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  • R5-920  (340)
  • Frontiers Media SA  (340)
  • 2020-2024  (340)
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  • 2020-2024  (340)
Year
  • 1
    Publication Date: 2024-04-01
    Description: The considerable number of viral infectious disease threats that have emerged since the beginning of the 21st century have shown the need to dispose global and coordinated responses to fight properly and efficiently against them. Severe acute respiratory syndrome (2003), avian influenza in humans (2005), A(H1N1) pandemic influenza (2009), Middle East respiratory syndrome coronavirus (MERS-CoV) (2012 onward) and Ebola virus disease (2014-2015) are some of the most important examples. The latest emerging and devastating threat was Zika virus, an arbovirus that provoked more than 500,000 suspicious cases in the Americas in 2016 and notable processes of social and medical alarms due to the evidence of a causal link between Zika virus and several congenital injuries, like microcephaly, as well as due to its association with neurological disorders such as Guillain-Barré syndrome in adults (PAHO, 2017). In the framework of this global response and multistrategic approach, the purpose of this Research Topic is to provide updated information and novel researches about control strategies, encompassing virological, entomological and epidemiological data, in order to reach the triad of protagonists of transmission cycles (virus, mosquitoes and humans).
    Keywords: RC346-429 ; R5-920 ; RA1-1270 ; QR1-502 ; Q1-390 ; RC109-216 ; Public Health ; Mosquitoes ; Zika virus ; Arbovirus ; Microcephaly ; Epidemiology ; Flavivirus ; Guillain-Barre Syndrome ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 2
    Publication Date: 2024-04-01
    Description: Understanding the role of sleep and the mechanisms at play in ageing are among the most exciting challenges in neuroscience. Although our understanding of the mechanisms governing sleep stages and their role in cognitive processes including memory functions is gradually increasing. most of the currently available data have been gathered in young adults. Still, substantial physiological changes in sleep are observed with increasing age, that may markedly impacts on daily functioning. This is why this Research Topic focuses on our current understanding of the impact of age-related changes in sleep architecture on various domains of cognition. The three editors Julie Carrier (Montréal, Canada), Philippe Peigneux (Brussels, Belgium) and Géraldine Rauchs (Caen, France) are specialized in various fields of sleep research. Here, they bring together an outstanding group of neuroscientist and clinical investigators engaged in the study of sleep, encompassing state-of-the-art studies of sleep disorders such as sleep apnoea or REM sleep behaviour disorder, studies assessing new treatments to improve sleep quality, together with experts in various domains of cognition such as vigilance, memory and dreams, in a perspective aimed at offering the interested reader a comprehensive view of the impact of age-related changes in sleep architecture on cognition.
    Keywords: RC346-429 ; R5-920 ; Sleep ; REM sleep behaviour disorder ; dream ; EEG ; Memory ; Sleep Disorders ; Sleep Apnea ; Aging ; Cognition ; insomnia ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 3
    Publication Date: 2024-04-01
    Description: Neuroimaging post-stroke has the potential to uncover underlying principles of disturbed hand function and recovery characterizing defined patient groups, including their long term course as well as individual variations. The methods comprise functional magnetic resonance imaging (MRI) measuring task related activation as well as resting state. Functional MRI may be complemented by arterial spin labeling (ASL) MRI to investigate slowly varying blood flow and associated changes in brain function. For structural MRI robust and accurate computational anatomical methods like voxel-based morphometry and surface based techniques are available. The investigation of the connectivity among brain regions and disruption after stroke is facilitated by diffusion tensor imaging (DTI). Intra- and interhemispheric coherence may be studied by electromagnetic techniques such as electroencephalography and transcranial magnetic stimulation. Consecutive phases of stroke recovery (acute, subacute, early chronic and late chronic stages) are each distinguished by intrinsic processes. The site and size of lesions entail partially different functional implications. New strategies to establish functional specificity of a lesion site include calculating contrast images between patients exhibiting a specific disorder and control subjects without the disorder. Large-size lesions often imply poor cerebral blood flow which impedes recovery significantly and possibly interferes with BOLD response of functional MRI. Thus, depending on the site and size of the infarct lesion the patterns of recovery will vary. These include recovery sensu stricto in the perilesional area, intrinsic compensatory mechanisms using alternative cortical and subcortical pathways, or behavioral compensatory strategies e.g. by using the non-affected limb. In this context, behavioral and neuroimaging measures should be developed and employed to delineate aspects of learning during recovery. Of special interest in recovery of hand paresis is the interplay between sensory and motor areas in the posterior parietal cortex involved during reaching and fine motor skills as well as the interaction with the contralesional hemisphere. The dominant disability should be characterized, from the level of elementary to hierarchically higher processes such as neglect, apraxia and motor planning. In summary, this Research Topic covers new trends in state of the art neuroimaging of stroke during recovery from upper limb paresis. Integration of behavioral and neuroimaging findings in probabilistic brain atlases will further advance knowledge about stroke recovery.
    Keywords: RC346-429 ; R5-920 ; stroke recovery ; Motor Imagery ; structural covariance ; Somatosensory Disorders ; perilesional plasticity ; network reorganization ; multimodal neuroimaging ; Neurorehabilitation ; computational biophysical modeling ; motor control ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 4
    Publication Date: 2024-04-01
    Description: Orexin/hypocretin neuropeptides, produced by a few thousand neurons in the lateral hypothalamus, are of critical importance for the control of vigilance and arousal of vertebrates, from fish to amphibians, birds and mammals. Two orexin peptides, called orexin-A and orexin-B, exist in mammals. They bind with different affinities to two distinct, widely distributed, excitatory G-protein- coupled receptors, orexin receptor type 1 and type 2 (OXR-1/2). The discovery of an OXR mutation causing canine narcolepsy, the narcolepsy-like phenotype of orexin peptide knockout mice, and the orexin neuron loss associated with human narcoleptic patients laid the foundation for the discovery of small molecule OXR antagonists as novel treatments for sleep disorders. Proof of concept studies from Glaxo Smith Kline, Actelion Pharmaceuticals Ltd. and Merck have now consistently demonstrated the efficacy of dual OXR antagonists (DORAs) in promoting sleep in rodents, dogs, non-human primates and humans. Some of these antagonists have completed late stage clinical testing in primary insomnia. Orexin drug discovery programs have also been initiated by other large pharmaceutical companies including Hoffmann La Roche, Novartis, Eli Lilly and Johnson & Johnson. Orexins are increasingly recognized for orchestrating the activity of the organism’s arousal system with appetite, reward and stress processing pathways. Therefore, in addition to models of insomnia, pharmacological effects of DORAs have begun to be investigated in rodent models of addiction, depression and anxiety. The first clinical trials in diabetic neuropathy, migraine and depression have been initiated with Merck’s MK-6096 (www.clinicaltrials.gov). Whereas the pharmacology of DORAs is established for their effects on wakefulness, pharmacological effects of selective OXR-1 or OXR-2 antagonists (SORAs) have remained less clear. From an evolutionary point of view, the OXR-2 was expressed first in most vertebrate lineages, whereas the OXR-1 is believed to result from a gene duplication event, when mammals emerged. Yet, both receptors do not have redundant function. Their brain expression pattern, their intracellular signaling, as well as their affinity for orexin-A and orexin-B differs. During the past decade most preclinical research on selective OXR-1 antagonism was performed with SB-334867. Only in recent years, other selective OXR-1 and OXR-2 antagonists with optimized selectivity profiles and pharmacokinetic properties have been discovered, and phenotypes of OXR-1 and OXR-2 knockout mice were described. The present Research Topic (referred to in the Editorial as “special topics issue”) comprises submissions of original research manuscripts as well as reviews, directed towards the neuropharmacology of OXR antagonists. The submissions are preclinical papers dealing with dual and/or selective OXR antagonists that shed light on the differential contribution of endogenous orexin signaling through both OXRs for cellular, physiological and behavioral processes. Some manuscripts also report on convergence or divergence of DORA vs. SORA effects with phenotypes expressed by OXR-1 or OXR-2 knockout animals. Ultimately these findings may help further define the potential of DORAs and SORAs in particular therapeutic areas in insomnia and beyond insomnia.
    Keywords: RC346-429 ; R5-920 ; RC321-571 ; RC435-571 ; RM1-950 ; Q1-390 ; Neuroscience ; Addiction ; hypocretin ; Anxiety ; orexin ; orexin receptor antagonist ; Neuropeptide ; insomnia ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 5
    Publication Date: 2024-04-01
    Keywords: RC346-429 ; R5-920 ; dizziness ; falls ; vestibular diseases ; aging ; vestibular function tests ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 6
    Publication Date: 2024-04-01
    Description: Inflammation of the brain in the context of neurodegenerative disorders is an area of intense debate and discussion, not least in terms of its pathogenic significance and the extent to which it drives disease processes and pathology. This inflammation can take several forms including innate responses recruiting microglia, humoral responses involving antibody, complement mediated processes and cellular T-cell activation, of which the role and extent of each may differ between diseases. Whilst some diseases have been more intensely linked to inflammation and long-term degeneration (e.g. MS), more traditional chronic neurodegenerative disorders have been thought of in terms of intrinsic neuronal pathology with a secondary innate response. However, it has been described that microglia activation is an early event of many degenerative disorders and evidence is accumulating that it may play a critical role in actually causing pathology and driving disease processes. If true, this would have major therapeutic implications, but what is the evidence that this is the case? The initial observations by Patrick McGeer’s group of post-mortem tissue from patients with Parkinson’s disease revealed the presence of activated brain microglia and has thus lead to the hypothesis that chronic inflammation could participate to neuronal degenerative processes. The significance of these original observations has only been recently revisited, and the development of more powerful tools to study the brain immune response has certainly contributed to this field of research. Chronic inflammation in the brain can take many forms but of particular interest has been the resident microglia and the role they play in this process. In this context, microglia have often been thought to become activated only after the disease has begun and then to contribute minimally to the degenerative process. Emerging new concepts challenge this view by proposing that microglial senescence, for example, may release the disease process and/or accelerate it. In addition, microglia, once activated, can adopt different phenotypes which can be both pro-inflammatory and pro-repair and may impact not only on the healthy adult neuronal population but on those new neurons derived from neurogenic niches of the adult brain. In this Research Topic, we attempt to explore this by first considering the innate immune responses in the brain and the methods by which they can be studied experimentally and in patients with various neurodegenerative disorders. This sets the scene for then discussing a range of different disorders including Alzheimer’s, Parkinson’s, Huntington’s disease and amyotrophic lateral sclerosis. These papers seek to discuss the evidence for an innate immune response and whether this is beneficial or detrimental, as well as its therapeutic implications.
    Keywords: RC346-429 ; R5-920 ; RC321-571 ; RC435-571 ; RM1-950 ; Q1-390 ; Therapeutics ; Inflammation ; Immunity ; Neurodegenerative disorders ; Animal Models ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 7
    Publication Date: 2024-04-01
    Description: Neurodegeneration is characterized by the progressive loss of neural tissue that result in various neurodegeneration-initiated cerebral failures and complex diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease. All these medical conditions are accompanied by the disruption of blood-brain barrier (BBB). The BBB is an interface, separating the brain from the circulatory system and protecting the central nervous system from potentially harmful chemicals while regulating transport of essential molecules and maintaining a stable environment. Owing to the inability of the neurons to regenerate on their own after neurodegeneration or severe damage to the neural tissue, neurodegenerative disorders do not have natural cures on their own. Neuroregeneration is a viable way to curb neurodegeneration. One of the current approaches is stem cell-based therapy that has been shown to be potentially helpful for the application of neuronal cell replacement for neuroregeneration. It is vital that the neurodegenerative disorder being detected at an early stage as it can provide a chance for treatment that may be helpful to prevent further progression of the fatal disease. Thus, research has focused on developing effective non-invasive diagnostic methods for early detection of these disorders. Molecular diagnostics can provide a powerful method to detect and diagnose various neurological disorders. Such diagnosis can enhance early detection, provide subsequent medical counsel based on medical pathway, as well as to gain better insight of neurogenesis and hopefully eventual cure of the neurodegenerative diseases. With research reports, reviews, mini-reviews and commentary, this research topic covers a wide range of areas in neurodegeneration research, including diagnosis and prognosis; regulating central nervous system; biomarkers and brain injury induced neurobehavioral outcomes among other timely reports on neurodegeneration.
    Keywords: RC346-429 ; R5-920 ; RC321-571 ; Q1-390 ; Stem Cells ; Neurodegenerative Diseases ; Neuroprotection ; Neurons ; biomarkers ; MicroRNAs ; neurodegeneration ; diagnosis ; Exosomes ; Hemorrhage ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 8
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    Frontiers Media SA
    Publication Date: 2024-04-01
    Description: Neurofibrillary tangles (NFTs) composed of intracellular aggregates of tau protein are a key neuropathological feature of Alzheimer's Disease (AD) and other neurodegenerative diseases, collectively termed tauopathies. The abundance of NFTs has been reported to correlate positively with the severity of cognitive impairment in AD. However, accumulating evidences derived from studies of experimental models have identified that NFTs themselves may not be neurotoxic. Now, many of tau researchers are seeking a "toxic" form of tau protein. Moreover, it was suggested that a "toxic" tau was capable to seed aggregation of native tau protein and to propagate in a prion-like manner. However, the exact neurotoxic tau species remain unclear. Because mature tangles seem to be non-toxic component, "tau oligomers" as the candidate of “toxic” tau have been investigated for more than one decade. In this topic, we will discuss our consensus of “tau oligomers” because the term of “tau oligomers” [e.g. dimer (disulfide bond-dependent or independent), multimer (more than dimer), granular (definition by EM or AFM) and maybe small filamentous aggregates] has been used by each researchers definition. From a biochemical point of view, tau protein has several unique characteristics such as natively unfolded conformation, thermo-stability, acid-stability, and capability of post-translational modifications. Although tau protein research has been continued for a long time, we are still missing the mechanisms of NFT formation. It is unclear how the conversion is occurred from natively unfolded protein to abnormally mis-folded protein. It remains unknown how tau protein can be formed filaments [e.g. paired helical filament (PHF), straight filament and twisted filament] in cells albeit in vitro studies confirmed tau self-assembly by several inducing factors. Researchers are still debating whether tau oligomerization is primary event rather than tau phosphorylation in the tau pathogenesis. Inhibition of either tau phosphorylation or aggregation has been investigated for the prevention of tauopathies, however, it will make an irrelevant result if we don’t know an exact target of neurotoxicity. It is a time to have a consensus of definition, terminology and methodology for the identification of "tau oligomers".
    Keywords: RC346-429 ; R5-920 ; RC321-571 ; RC435-571 ; Q1-390 ; Tau phosphorylation ; neurodegenerative disease ; propagation ; Tauopathy ; tau protein ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 9
    Publication Date: 2024-04-01
    Description: "Cells live together, but die singly", this sentence wrote the German physiologist Theodor Engelmann in 1875 and although he had no particular knowledge of gap junction channels (their structure was discovered around 100 years later) he described their functions very well: gap junction channels are essential for intercellular communication and crucial for the development of tissue and organs. But besides providing an opportunity for cells to communicate gap junction channels might also prevent intercellular communication by channel closure thereby preserving the surrounding healthy tissue in case of cellular necrosis. According to today’s understanding gap junction channels play an important role during embryonic development, during growth, wound healing and cell differentiation and are also involved in the process of learning. In the past decades most intensive research was done not only to unravel the physiological role of gap junction channels but also to extend our knowledge of the contribution of these channels in pathogenesis. A new frontier emerges in the field "pharmacology of gap junctions" with the aim to control growth, differentiation, or electrical coupling via targeting gap junction channels pharmacologically. As we know today disturbances in gap junction synthesis, assembly and cellular distribution may account for various organic disorders from most different medical fields, such as the Charcot-Marie-Tooth neuropathy, epilepsy, Chagas-disease, Naxos-syndrome, congenital cardiac malformations, arrhythmias, cancer and as a very common disease in industrial countries atherosclerosis. Point mutations in gap junction channels have been found to cause hereditary diseases like the congenital deafness or the Charcot-Marie-Tooth neuropathy but the exact molecular mechanisms of gap junction malfunction from most of the mentioned illnesses are not fully understood. Moreover, in the last few years research has expanded on the role and function of connexin hemichannels and on a relatively new field the pannexins. The purpose of this volume is to give a comprehensive overview of the involvement of gap junction channels, hemichannels and pannexins on pathogenesis of inborn and acquired diseases and on emerging pharmacological strategies to target these channels. We welcome our colleagues to contribute their findings on the influence of gap junctions on pathogenesis and to unravel the secrets of intercellular communication. Take the lid off!
    Keywords: RC346-429 ; R5-920 ; RM1-950 ; Q1-390 ; development ; differentiation ; Growth ; pannexins ; intercellular communication ; hemichannels ; Connexins ; gap junction ; Pharmacology ; human diseases ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 10
    Publication Date: 2024-04-01
    Description: This research topic aims at providing a state of the art update on neuroplasticity in humans with multiple sclerosis. It summarizes advances in plasticity research as achieved by a variety of techniques, in the motor as well as visual and cognitive domain. We are confident that this collection of articles broadens the view across systems and techniques and widens our understanding of this exciting field of research.
    Keywords: RC346-429 ; R5-920 ; Multiple Sclerosis ; motor ; cognitive ; Compensation ; Neurophysiological ; plasticity ; adaptation ; visual ; reorganization ; functional magnetic resonance imaging ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 11
    Publication Date: 2024-04-01
    Description: This Research Topic is devoted to arm and hand movement in health as well as in several disease conditions. It is a collection of several original research papers and reviews, clinical case studies, hypothesis and theory articles, opinions, commentaries, and methods papers that cover some important aspects of the topic from distinct scientific perspectives. We invite the readers to appreciate the range in methodologies and experimental designs that together have led to widen our understanding of this especially broad field of research.
    Keywords: RC346-429 ; R5-920 ; dexterity ; grasping ; arm and hand movement ; motor control of movement ; reaching ; Neuromuscular dysfunction ; reach to grasp ; Forelimb ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 12
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    Frontiers Media SA
    Publication Date: 2024-04-01
    Description: Dear Readers, If you are engaged in the treatment of patients with MS (pwMS), this e-book’s aim is to offer novel insights to improve on an understanding of one of the major problems of pwMS: fatigue. Although there is increasing research into fatigue and its impact on MS, this collection of ten articles supports a better understanding of fatigue in MS patients. It explores pathophysiological concepts, provoking mechanisms, objective measurements, personality interactions, pharmacological and non-pharmacological interventions and summarizes clinical management. It is written by neurologists, psychologists, scientists and therapists and addresses this group of people, who deal with pwMS in private, clinical, rehabilitation or scientific settings. Its aim is to communicate high-quality information, knowledge and experience on MS to healthcare professionals, while providing global support for the international MS community.
    Keywords: RC346-429 ; R5-920 ; Multiple Sclerosis ; cognitive fatigue ; motor fatigue ; Fatigue ; Depression ; Cognition ; Personality ; Rehabilitation ; gait analysis ; natalizumab ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 13
    Publication Date: 2024-04-01
    Description: Intractable epilepsy still remains the main issue despite new advances in medical and surgical treatment of epilepsy. Acute seizure management in a timely manner is crucial to prevent irreversible brain damage. Benzodiazepines still remain the first initial treatment to abort the seizure activity. The approval phenytoin, fosphenytoin, intravenous valproate, and rectal diazepam provided additional options. The approval of intravenous levetiracetam gave another option to physicians if and when the above treatment fails to control the seizure activity. In this Ebook, we have included chapters from renowned researchers in the field of neurology and epilepsy who have covered the various aspects of these agents in detail including the properties, mechanism of action, pharmacology, neurobehavioral effects, and the roles of these agents in special populations including traumatic brain injury and brain tumor related epilepsy. These data further show that intravenous levetiracetam can be used in acute seizure management and in special circumstances.
    Keywords: RC346-429 ; R5-920 ; Anticonvulsants ; Treatment ; Epilepsy ; acute seizure management ; levetiracetam ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 14
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    Frontiers Media SA
    Publication Date: 2024-04-01
    Description: An important area of current research in epilepsy focuses on identifying the specific regions within the brain that are affected in individuals with recurring seizures. The epileptogenic process may result not only in pathology in focal cortical regions, but abnormalities in subcortical structures, such as thalamus and basal ganglia, and in intercortical and intracortical connecting white matter pathways. Novel methods of treating refractory epilepsy are urgently needed. The goal of identifying for each affected individual the specific brain regions that are involved offers the promise that novel methods of treatment will one day be developed that specifically target those abnormal regions. Researchers from disparate fields are required to develop and advance this area of research, and this current topic proposes to place a spotlight on the “state of the art” of methods to identify the abnormal networks. Recent work covering a wide variety of disciplines and technologies, including dense array electroencephalography (dEEG), novel methods of analyses of both the interictal dEEG and intracranial EEG (icEEG), magnetoencephalography (MEG), high-resolution magnetic resonance imaging (MRI), functional MRI (fMRI), simultaneous fMRI-EEG, fMRI connectivity measures, simultaneous dEEG-icEEG, and techniques to coregister patient-specific MRI (including white matter pathways) and dEEG, are all examples of areas of research that have contributed to a greater understanding of potential epileptogenic regions. We asked for individuals with expertise in an area of research that expands an understanding of identifying epileptic networks to contribute to this research topic.
    Keywords: RC346-429 ; R5-920 ; tractography ; epileptic spikes ; functional connectivity ; Epilepsy ; cerebral networks ; EEG coherence analysis ; Seizure propagation ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 15
    Publication Date: 2024-04-01
    Description: This topic aims to pool the most recent advances in the phenomenology and pathophysiology of levodopa-induced dyskinesias. The papers in this eBook have strongly contributed to reduce the gaps in our knowledge of LIDs pathogenesis.
    Keywords: RC346-429 ; R5-920 ; Neuroimaging ; Transcranial Magnetic Stimulation ; Hyperkinetic Motor Disorders ; Deep Brain Stimulation ; Neurobiology ; Neuropsychology ; Levodopa Induced Dyskinesias ; striato cortical pathways ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 16
    Publication Date: 2024-04-01
    Description: The calcium-calmodulin dependent protein kinases (CaMKs) are a broadly expressed family of calcium-sensitive intracellular kinases, which are responsible for transducing cytosolic calcium signals into phosphorylation-based regulation of proteins and physiological functions. As the multifunctional member of the family, CaMKII has become the most prominent for its roles in the central nervous system and heart, where it controls a diverse range of calcium-dependent processes; from learning and memory at the neuronal synapse, to cellular growth and death in the myocardium. In the heart, CaMKII directly regulates many of the most important ion channels and calcium handling proteins, and controls the expression of an ever-increasing number of transcripts and their downstream products. Functionally, these actions are thought to orchestrate many of the electrophysiologic and contractile adaptations to common cardiac stressors, such as rapid pacing, chronic adrenergic stimulation, and oxidative challenge. In the context of disease, CaMKII has been shown to contribute to a remarkably wide variety of cardiac pathologies, of which heart failure (HF) is the most conspicuous. Hyperactivity of CaMKII is an established contributor to pathological cardiac remodeling, and is widely thought to directly promote arrhythmia and contractile dysfunction during HF. Moreover, several non-failing arrhythmia-susceptible phenotypes, which result from specific genetic channelopathies, functionally mimic constitutive channel phosphorylation by CaMKII. Because CaMKII contributes to both the acute and chronic manifestations of major cardiac diseases, but may be only minimally required for homeostasis in the absence of chronic stress, it has come to be one of the most promising therapeutic drug targets in cardiac biology. Thus, development of more specific and deliverable small molecule antagonists remains a key priority for the field. Here we provide a selection of articles to summarize the state of our knowledge regarding CaMKII in cardiac health and disease, with a particular view to highlighting recent developments in CaMKII activation, and new targets in CaMKII-mediated control of myocyte physiology.
    Keywords: RC346-429 ; R5-920 ; RM1-950 ; Q1-390 ; Phosphorylation ; Ion Channels ; Calcium ; arrhythmia ; Heart Failure ; Hypertrophy ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 17
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    Frontiers Media SA
    Publication Date: 2024-04-01
    Description: This Research Topic contains proceedings of the final conference for COST Action BM1101 “Network of dystonia syndromes”. The topic highlights consolidated knowledge and unmet needs in a field that is evolving very fast. This publication is based upon work from COST Action BM1101, supported by COST (European Cooperation in Science and Technology).
    Keywords: RC346-429 ; R5-920 ; Splitting ; Lumping ; Dystonia ; network ; cooperation ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
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  • 18
    Publication Date: 2024-03-31
    Description: Recognition and killing of aberrant, infected or tumor targets by Natural Killer (NK) cells is mediated by positive signals transduced by activating receptors upon engagement of ligands on target surface. These stimulatory pathways are counterbalanced by inhibitory receptors that raise NK cell activation threshold through negative antagonist signals. While regulatory effects are necessary for physiologic control of autoimmune aggression, they may restrain the ability of NK cells to activate against disease. Overcoming this barrier to immune surveillance, multiple approaches to enhance NK-mediated responses are being investigated since two decades. Propelled by considerable advances in the understanding of NK cell biology, these studies are critical for effective translation of NK-based immunotherapy principles into the clinic. In humans, dominant inhibitory signals are transduced by Killer Immunoglobulin Like Receptors (KIR) recognizing cognate HLA class I on target cells. Conversely, KIR recognition of “missing self-HLA” - due to HLA loss or HLA/ KIR mismatch - triggers NK-mediated tumor rejection. Initially observed in murine transplant models, these antitumor effects were later found to have important implications for the clinical outcome of haplotype-mismatched stemcell transplantation. Here, donor NK subsets protect against acute myeloid leukemia (AML) relapse through missing self recognition of donor HLA-C allele groups (C1 or C2) and/or Bw4 epitope. These studies were subsequently extended by trials investigating the antileukemia effects of adoptively transferred haplotype-mismatched NK cells in non-transplant settings. Other mechanisms have been found to induce clinically relevant NK cell alloreactivity in transplantation, e.g., post-reconstitution functional reversal of anergic NK cells. More recently, activating KIR came into the spotlight for their potential ability to directly activate donor NK cells through in vivo recognition of HLA or other ligands. Novel therapeutic monoclonal antibodies (mAb) may optimize NK-mediated effects. Examples include obinutuzumab (GA101), a glyco-engineered anti-CD20 mAb with increased affinity for the FcγRIIIA receptor, enhancing antibody-dependent cellular cytotoxicity; lirilumab (IPH2102), a first-in-class NK-specific checkpoint inhibitor, blocking the interaction between the major KIR and cognate HLA-C antigens; and elotuzumab (HuLuc63), a humanized monoclonal antibody specific for SLAMF7, whose anti-myeloma therapeutic effects are partly due to direct activation of SLAMF7-expressing NK cells. In addition to conventional antibodies, NK cell-targeted bispecific (BiKEs) and trispecific (TriKEs) killer engagers have also been developed. These proteins elicit potent effector functions by binding target ligands (e.g., CD19, CD22, CD30, CD133, HLA class II, EGFR) on one arm and NK receptors on the other. An additional innovative approach to direct NK cell activity is genetic reprogramming with chimeric antigen receptors (CAR). To date, primary NK cells and the NK92 cell line have been engineered with CAR specific for antigens expressed on multiple tumors. Encouraging preclinical results warrant further development of this approach. This Research Topic welcomes contributions addressing mechanisms of NK-mediated activation in response to disease as well as past and contemporary strategies to enhance NK mediated reactivity through control of the interactions between NK receptors and their ligands.
    Keywords: R5-920 ; RC581-607 ; Natural Killer cells ; Checkpoint inhibitors ; Immune Evasion ; Immunotherapy ; Transplantation ; chimeric antigen receptors ; Nk receptors ; bispecific antibodies ; Cancer ; thema EDItEUR::M Medicine and Nursing
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  • 19
    Publication Date: 2024-03-31
    Description: Oral health disparities are profound worldwide, and they affect the quality of life of individuals of all age groups. Disparities in oral health are seen in racial and ethnic minorities, at different socioeconomic levels and due to differences in environment and cultural factors. Several determinants of oral health have been identified at the population, community, family and individual levels. These determinants represent a complex interplay of the social, biological, cultural and economic factors that in turn affect the oral health behaviors, environmental exposures, health care utilization. To date, biological factors related to oral diseases have received much attention in oral health research; whilst social and cultural determinants have just started to receive recognition for their role in oral disease development and progression. This research highlights that interventions designed to reduce disparities should adopt a multi-level approach in order to identify the modifiable mechanisms and target all determinants of oral health disparities. In this Research Topic, we will focus on the role of social, environmental and cultural factors in the development and progression of oral diseases, their role in oral health disparities and interventions focusing on these factors to improve oral health and reduce disparities.
    Keywords: R5-920 ; RA1-1270 ; social determinants of oral health ; immigrant oral health ; interprofessional education ; oral health inequalities ; access to care ; thema EDItEUR::M Medicine and Nursing
    Language: English
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  • 20
    Publication Date: 2024-03-30
    Description: Fragmented, dissociated consciousness can characterize the mind in both wake and sleep states. Dissociative symptoms, during sleep, include vivid dreaming, nightmares, and alterations in objective sleep parameters (e.g., lengthening of REM sleep). During waking hours, dissociative symptoms exhibit disparate characteristics encompassing memory problems, excessive daydreaming, absentmindedness, and impairments and discontinuities in perceptions of the self, identity, and the environment. Llewellyn has theorized that a progressive and enduring de-differentiation of wake and dream states of consciousness eventually results in schizophrenia; a lesser degree of de-differentiation may have implications for dissociative symptoms. Against a background of de-differentiation between the dream and wake states, the papers in this volume link consciousness, memory, and mental illness with a special interest for dissociative symptoms.
    Keywords: R5-920 ; RC435-571 ; BF1-990 ; Q1-390 ; state de-differentiation ; Sleep ; dissociation ; Memory ; Psychopathology
    Language: English
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  • 21
    Publication Date: 2024-03-30
    Description: In the past decade, significant progresses have taken place in the field of cancer immunotherapy. Tumor-targeting immunotherapies are being developed for most human cancers, including melanoma, prostate cancer, glioblastoma, sarcoma, lung carcinoma and hepatocellular carcinoma. The FDA has approved multiple molecular immunotherapeutics, such as Ipilimumab; cellular immunotherapies (e.g. adoptive cell transfer) are being tested in phase II/III clinical trials. Immunotherapetics has evolved into a sophisticated field: Multimodal therapeutic regimens are administrated to induce focused responses, curtail side- effects and improve therapeutic efficacy. The lack of effective clinical assessment tools remains a major challenge. Because of the intricacy of antitumor response, it is essential to scrutinize individual tumor-targeting immune cells and their functions at the finest details - molecules. In this regard, flow cytometry analysis modernized hematology and allows characterization of surface molecular signature on individual cells. More recently, microchip technologies and new variations of cytometry have enormously expanded the spectrum, throughout and multiplexity of single cell analysis. Nowadays, tens of millions of readouts can be generated through the course of a cancer immunotherapy to monitor the abundance, phenotype and a myriad of effector functions of single immune cells. At the same time, big data analytics and data mining methodologies have been adapted to achieve sensible diagnostic interpretations. Such a marriage of technology and analytics opens the door for informative point-of-care assessment of therapeutic efficacy and ensures timely therapeutic decisions. The new generation of personalized clinical diagnostics will revolutionize healthcare in the years to come.
    Keywords: R5-920 ; RC254-282 ; immune assessment ; single cell analysis ; cancer immunotherapy ; tumor immunity ; immune suppression
    Language: English
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  • 22
    Publication Date: 2024-03-30
    Description: In the context of disease pathogenesis, it has been observed that after inadequate administration of antibiotics, animals become more susceptible to intestinal colonization and organ invasion by enteropathogens, these could be related to changes caused in the gastrointestinal microbial community. Therefore, we must reconsider the negative consequences that disruption of the microbiome has in the biology of metazoans (dysbacteriosis). Alternations of the intestinal microbiota composition in animals can be caused by multiple factors, including the misuse of antibiotics, having as a result a negative impact on the development and function of the immune, endocrine, nervous, and digestive systems. For this reason, social concerns regarding the development of antibiotic-resistant microorganisms have resulted in an urgent necessity to find feasible alternatives to maintain animal health and performance without the use of antibiotic growth promoters (AGP), in order to sustain livestock production as an economically viable source of food for human consumption. Hence, research about AGP alternatives such as probiotics, prebiotics, phytochemicals, organic acids, enzymes, and vaccines has become a priority for many scientists around the world.
    Keywords: R5-920 ; SF600-1100 ; Feed additives ; Antibiotics ; Livestock ; Antimicrobial resistance ; Microbiome
    Language: English
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  • 23
    Publication Date: 2024-03-30
    Description: Myotonic dystrophies (DMs) are pleotropic multisystemic diseases. These dominantly transmitted repeat disorders affect multiple organs of the human body at all ages – from the newborns to the elderly. The present Research Topic represents a timely addition to the expanding body of evidence which aims to provide novel perspectives in our understanding of myotonic dystrophies. This collection of original contributions and standpoint reviews from multiple leading DM centres in Europe describes the state of the art for the characterization of the DMs diseases, the development of molecular strategies to target its multisystemic nature, and provides evidence of screening and testing novel therapeutic avenues.
    Keywords: R5-920 ; RC346-429 ; brain imaging ; animal models ; phenotypes ; cell models ; myotonic dystrophy type 1 and type 2 ; DM2 ; DM1 ; CNS involvement ; multisystemic diseases ; repeat disorders
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  • 24
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    Frontiers Media SA
    Publication Date: 2024-03-30
    Description: In the ancient past, cocoa has been appreciated as a high-calorie food to boost energy in soldiers and for its undefined medicinal and mystical properties. During other times, chocolate has been considered as the forbidden “food of God”: a treasure of pleasure for the mind and the soul. The overall perception of the consumer for chocolate was of a “charming” and appealing food with lots of negative aspects related to high sugar content leading to consider chocolate as “junk food” for its “obesigen” calories. Recently, in association with the renewed interest of nutrition science in alternative source of health-promoting foods and ingredients, a large body of research has been conducted to unravel the pro and cons of cocoa in relation to human health. Epidemiological evidences indicate that cocoa consumption helps preventing cardiovascular disease for its high content in bioactive flavonoids. Clinical trials show that chocolate consumption might improve vascular function, decreasing platelet aggregation and display an antioxidant and anti-inflammatory effect. The putative protective action of cocoa seems to be multi-factorial and involving different aspects of vascular, antioxidant and endothelial function. However, the mechanism(s) that account for the benefits of cocoa it is still unclear. The aim of this Research Topic is therefore to provide the reader with an objective picture of the state of art on the association between cocoa and health, mainly through the evidences of human trials; overwhelmingly considered the golden standard for nutritional science. The Research Topic will cover the analysis of the manufacturing processes of the chocolate and the antioxidant effects in humans as well as the majority of the putative health effects of chocolate and cocoa, such as anti-inflammatory properties, effect on immunity, platelet aggregation, blood pressure, endothelial function and cognitive behavior. Unraveling the functional properties of cocoa will help to understand if the 'food of God' is a primordial gift for the health of mankind.
    Keywords: R5-920 ; RC581-607 ; TX341-641 ; Antioxidants ; Obesity ; Flavonoids ; Humans ; Chocolate ; Blood pressure ; Inflammation ; Cognitive function ; Cocoa ; Immunity
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  • 25
    Publication Date: 2024-03-30
    Description: The rapid development of new methods for immunological data collection - from multicolor flow cytometry, through single-cell imaging, to deep sequencing - presents us now, for the first time, with the ability to analyze and compare large amounts of immunological data in health, aging and disease. The exponential growth of these datasets, however, challenges the theoretical immunology community to develop methods for data organization and analysis. Furthermore, the need to test hypotheses regarding immune function, and generate predictions regarding the outcomes of medical interventions, necessitates the development of mathematical and computational models covering processes on multiple scales, from the genetic and molecular to the cellular and system scales. The last few decades have seen the development of methods for presentation and analysis of clonal repertoires (those of T and B lymphocytes) and phenotypic (surface-marker based) repertoires of all lymphocyte types, and for modeling the intricate network of molecular and cellular interactions within the immune systems. This e-Book, which has first appeared as a ‘Frontiers in Immunology’ research topic, provides a comprehensive, online, open access snapshot of the current state of the art on immune system modeling and analysis.
    Keywords: R5-920 ; RC581-607 ; Immune cell differentiation ; Immune cell population dynamics and turnover ; Immunological diseases ; activation and signaling ; mathematical modeling ; immunomics ; Immune cell receptors ; lymphocyte repertoires ; Immune cell migration and immune tissue organization ; Immune responses to pathogens ; high-throughput sequencing
    Language: English
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  • 26
    Publication Date: 2024-03-30
    Description: The repertoire of quantitative analytical techniques in disciplines such as ecology, decision science, and evolutionary biology has grown, in part enabled by the development and increased availability of computational resources. Integration of cutting-edge, quantitative tools into veterinary epidemiology that have been borrowed from such disciplines has offered opportunities to advance the study of disease dynamics in animal populations, to improve and guide decision-making related to disease prevention, control, or eradication. Furthermore, the need to explore new analytical methods for veterinary epidemiology has been driven by the increasing availability and complexity of animal disease data. The objective of this e-book is to contribute to current methods in epidemiology by 1) presenting and discussing novel analytical tools that help advance our understanding of epidemiology; and 2) demonstrating how inferences emerging from the application of novel analytical tools can be incorporated into decision-making related to animal health. The e-book constitutes a collection of articles that explore the applications of a variety of analytical methods such as machine learning, Bayesian risk assessment and an advanced form of social network analysis in the modern epidemiologic study of animal diseases.
    Keywords: R5-920 ; SF600-1100 ; Decision Making ; Risk Assessment ; social network analysis ; Spatial Epidemiology ; disease surveillance
    Language: English
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  • 27
    Publication Date: 2024-03-30
    Description: Millions of people worldwide are affected by neurological disorders which disrupt the connections within the brain and between brain and body causing impairments of primary functions and paralysis. Such a number is likely to increase in the next years and current assistive technology is yet limited. A possible response to such disabilities, offered by the neuroscience community, is given by Brain-Machine Interfaces (BMIs) and neuroprostheses. The latter field of research is highly multidisciplinary, since it involves very different and disperse scientific communities, making it fundamental to create connections and to join research efforts. Indeed, the design and development of neuroprosthetic devices span/involve different research topics such as: interfacing of neural systems at different levels of architectural complexity (from in vitro neuronal ensembles to human brain), bio-artificial interfaces for stimulation (e.g. micro-stimulation, DBS: Deep Brain Stimulation) and recording (e.g. EMG: Electromyography, EEG: Electroencephalography, LFP: Local Field Potential), innovative signal processing tools for coding and decoding of neural activity, biomimetic artificial Spiking Neural Networks (SNN) and neural network modeling. In order to develop functional communication with the nervous system and to create a new generation of neuroprostheses, the study of closed-loop systems is mandatory. It has been widely recognized that closed-loop neuroprosthetic systems achieve more favorable outcomes for users then equivalent open-loop devices. Improvements in task performance, usability, and embodiment have all been reported in systems utilizing some form of feedback. The bi-directional communication between living neurons and artificial devices is the main final goal of those studies. However, closed-loop systems are still uncommon in the literature, mostly due to requirement of multidisciplinary effort. Therefore, through eBook on closed-loop systems for next-generation neuroprostheses, we encourage an active discussion among neurobiologists, electrophysiologists, bioengineers, computational neuroscientists and neuromorphic engineers. This eBook aims to facilitate this process by ordering the 25 contributions of this research in which we highlighted in three different parts: (A) Optimization of different blocks composing the closed-loop system, (B) Systems for neuromodulation based on DBS, EMG and SNN and (C) Closed-loop BMIs for rehabilitation.
    Keywords: R5-920 ; RC346-429 ; RC321-571 ; Q1-390 ; neuromodulation ; closed-loop experiments ; artificial spiking neural network ; neuroprostheses ; neuronal circuits ; stimulation
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  • 28
    Publication Date: 2024-03-30
    Keywords: R5-920 ; RC435-571 ; Scientism ; causation ; mental disorder ; causal explanation ; Psychiatry
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  • 29
    Publication Date: 2024-03-30
    Description: 80% of the bodies’ immune cells are harbored within the intestine. They are only separated from 1014 microorganisms by a single layer of intestinal epithelial cells and a secreted superficial mucus layer. Therefore, the intestinal epithelial surface represents a main frontier in host defense. Providing an intact mucosal barrier is vital for the host to limit bacterial entry and spread to the circulation. This specialized localization requires dynamic responses of intestinal epithelial cells to both pathogen- and immune-derived signals. Moreover, emergency barriers are needed in the setting of epithelial damage, which allow provisional microbial control and a timely restitution of mucosal integrity. Epithelial cells constantly interact with subjacent immune cells and fibroblasts, actively directing the immune response and also shaping the luminal microbiota. Epithelial dysfunction has been appreciated in recent years as a driving element in the pathogenesis of Inflammatory Bowel Diseases (IBD). Additionally, primary immune deficiencies may manifest in the form of chronic intestinal inflammation mimicking features of IBD. Recent advances in the techniques of epithelial cell culture and the discovery of new immune cell types and cellular properties have tremendously advanced the understanding in this interesting field of research. In this research topic, we want to focus on the complex interaction of intestinal epithelial cells, luminal flora and adjacent immune cells and invite manuscripts which highlight the dynamic responses of both epithelium and immune cells under steady-state or inflammatory conditions, and envision how this may be translated to the benefit of patient-care.
    Keywords: R5-920 ; RC581-607 ; lymphocytes ; inflammatory bowel diseases ; immune system ; intestinal epithelium ; mucosal immunity
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  • 30
    Publication Date: 2024-03-30
    Description: Cancer and cardiovascular disease (CVD) are the two most common causes of mortality and morbidity worldwide. The incidence of both cancer and cardiovascular disease increases with age. With increased life expectancy, the burden of both these diseases will increase substantially in coming years. Patients with CVD share multiple common risk factors and lifestyle behaviors in addition to frequently suffering from multiple comorbid conditions. Tobacco use, hypertension, high cholesterol, diabetes, physical inactivity, and poor nutrition are all established risk factors of heart disease. Patients with diseases such as breast cancer may develop CVD from treatment, such as use of chemotherapy and RT. Effects on the heart are a potentially significant and serious clinical problem in radiation therapy treatment of breast cancer. Over the course of the past 50 years, there have been great advances in the delivery of RT due to the development of new techniques, beam energy, improvement in imaging modalities, and development of image registration strategies. It is hypothesized that cardiac damage from RT is correlated to the dose absorbed by the heart and differs between left- and right-breast radiotherapy. The damage to cardiac micro- and macro-vasculature is the pathophysiological cause of RT-related heart disease. Given the growing clinical relevance of cardio-oncology, this Frontiers in Oncology Research Topic provides a venue for disseminating focused reviews and cutting edge research in this quickly growing field. We encourage submission of original papers and reviews dealing with cardiac toxicity after breast cancer treatment, motion management to reduce cardiac exposure, imaging to evaluate potential cardiac toxicities and primary prevention of cardiac disease in the breast cancer patient.
    Keywords: R5-920 ; RC254-282 ; cardiac toxicity ; onco-cardiology ; biomarkers ; radiation therapy ; Cardio-oncology ; breast cancer ; Cardiac MRI ; chemotherapy ; Cardiac dose
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  • 31
    Publication Date: 2024-03-30
    Description: This special edition of Frontiers in Oncology reviews the current efficacy and limitations of surgical and radiotherapeutic management of lung cancer and provides insight into how local management options may change in the future.
    Keywords: R5-920 ; RC254-282 ; radiation techniques ; neo-adjuvant treatment ; heavy ion therapy ; small cell lung cancer ; surgery
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  • 32
    Publication Date: 2024-03-30
    Description: The term “immunobiotics” has been proposed to define microbial strains able to beneficially regulate the mucosal immune system. Research in immunobiotics has significantly evolved as researchers employed cutting-edge technologies to investigate the complex interactions of these beneficial microorganisms with the immune system. During the last decade, our understanding of immunobiotics-host interaction was profoundly transformed by the discovery of microbial molecules and host receptors involved in the modulation of gut associated immune system, as well as the systemic and distant mucosal immune systems. In recent years, there has been a substantial increase in the number of reports describing the beneficial effects of immunobiotics in diseases such as intestinal and respiratory infections, allergy, inflammatory bowel disease, obesity, immunosuppression, and several other immune-mediated conditions. Evidence is also emerging of immunobiotics related molecules with immunomodulatory functions leading to the production of pharmabiotics, which may positively influence human or animal health. Therefore, research in immunobiotics continue to contribute not only to food but also medical and pharmaceutical fields. The compilation of research articles included in this ebook should help reader to have an overview of the recent advances in immunobiotics.
    Keywords: R5-920 ; RC581-607 ; QR1-502 ; Q1-390 ; infection ; inflammation ; mucosal immune system ; beneficial microbes ; Immunobiotics ; lactic acid bacteria ; probiotics
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  • 33
    Publication Date: 2024-03-30
    Description: Children and companion animals seem to have a natural affinity towards each other. Most children desire a relationship with their own companion animals or at least demonstrate an interest to interact with animals in general. Living with companion animals or interacting with animals may have psychosocial, neurobiological, or medically relevant effects on typically developing children and juveniles as well as those with diverse and special needs.〈/p〉〈p〉〈br〉〈/p〉〈p〉In this eBook, we present several articles addressing the relationships between children/juveniles and animals in different countries, including Austria, Germany, Jamaica, Japan, the United Kingdom and the United States. Three articles discuss approaches in animal-assisted education, including animal keeping and animal assisted interventions in schools, and an experimental study investigating immediate effects of dogs on reading competence and accompanying stress reactions with cortisol and behavior. Other articles address topics involving children and their companion animals, including dog-walking by children and juveniles, risks of dog bites by the family dog, selection of pet dogs for families with a child with autism spectrum disorder (ASD) and the relationships that children with ASD have with their family cats. 〈/p〉〈p〉〈br〉〈/p〉〈p〉The interactions between children/juveniles and animals addressed in this eBook provide new insights into some scarcely investigated themes, and underline the significance of animals in children's lives.
    Keywords: R5-920 ; SF600-1100 ; Animal-Assisted Therapy ; Autism ; Animal-Assisted Intervention ; Dog Bite Prevention ; Companion Animals ; Children ; Animal-Assisted Education ; Human-Animal Interactions
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  • 34
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    Frontiers Media SA
    Publication Date: 2024-03-30
    Description: Monoclonal antibodies and Fc-fusion proteins used clinically are Fc-based therapeutics that grow fastest in the pharmaceutical industry. Since they both contain an Fc fragment, engineering of Fc fragments could be a platform for improving Fc-based drug efficacy. Fc engineering includes various aspects: stabilization of Fc; regulation of effector functions including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity; extension of serum half-life by modification of neonatal Fc receptor (FcRn) binding; monomerization or heterodimerization of Fc for design of new Fc formats. Currently, many new methods are being used in Fc engineering. Compared to traditional methods such as site mutagenesis on certain positions by amino acid replacement, new methods such as display-based technology can confer high throughput screening and obtain optimized variants relatively quickly, accelerating the drug development process. With the new methods, many new Fc variants were identified. On this Research Topic we are going to review the progress in current Fc engineering including the new engineering methods and the Fc variants or constructs they have produced, and the potential of these new Fcs in clinical use.
    Keywords: R5-920 ; RC581-607 ; effector function ; Fc receptor ; heterodimeric Fc ; Fc-fusion protein ; monomeric Fc ; Monoclonal antibody ; Fc engineering
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  • 35
    Publication Date: 2024-03-30
    Description: Stress proteins or heat-shock proteins (HSP) are evolutionary conserved proteins present in every prokaryotic and eukaryotic cell. Their main function is to protect cells and proteins from damage under stressful circumstances. The latter circumstances do include the cell and protein damaging effects of inflammation. The discovery of mycobacterial HSP60 being a critical antigen in the model of adjuvant arthritis, has led to studies that showed the immuno-dominance of microbial HSP60 and the potential of the microbial HSP induced repertoire of antibodies and T cells to cross-recognize the self-HSP homologues of stressed cells. Since then, the research in the immunology of stress proteins started to comprise a widening spectrum of topics with potential medical relevance. Interestingly, since stress proteins have their activities in both innate and adaptive immunity, they are key elements in the cross-roads between both arms of the immune system. Stress proteins or HSP can be considered as functional 'biomarkers' of inflammation. They are up-regulated locally during inflammation and interestingly, they seem to function as targets for anti-inflammatory regulatory T cells. In experimental models of autoimmunity, mainly arthritis, administration of HSP peptides have been shown to suppress disease. First clinical trials have shown the anti-inflammatory nature of T cell responses to Hsp. In type I diabetes and in rheumatoid arthritis, parenteral and oral administration of Hsp peptides were shown to induce a bias in pro-inflammatory T cells, switching them in the direction of regulatory cytokine production (IL4, IL5 and IL10). In addition a raised level of a marker of natural T regulatory cells, the transcription factor FoxP3, was noted in the RA trial. Other inflammatory diseases or diseases with inflammatory components which feature the immune imprint of the up-regulated Hsp are atherosclerosis, inflammatory bowel diseases, multiple sclerosis and atopic diseases such atopic dermatitis and allergic asthma.
    Keywords: R5-920 ; RC581-607 ; Autoimmunity ; Heat shock proteins ; T cells ; T cell regulation ; Cancer
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  • 36
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    Frontiers Media SA
    Publication Date: 2024-03-30
    Description: Cancer care delivery refers to the multiple layers of the health care system that interact to affect outcomes for patients with cancer and the quality of that care. The factors included in the care delivery system that potentially alter outcomes include social dynamics, financing systems, organizational structures and processes, health technologies, provider and individual behaviors. Because women’s health care has its own unique challenges, the intersection between cancer care delivery and women’s health is to be examined in this Frontiers in Oncology issue. The unique opportunities and challenges of improving the health care system for women with breast and gynecologic cancers are to be explored in depth. We will visit many topics of cancer care delivery with the unique perspective geared towards the care of women’s malignancies.
    Keywords: R5-920 ; RC254-282 ; survivorship ; health care delivery ; cancer prevention ; ovarian cancer ; endometrial cancer ; gynecologic cancer ; breast cancer ; cervical cancer
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  • 37
    Publication Date: 2024-03-30
    Description: Gilles de la Tourette Syndrome (TS) is a common, albeit severely under-diagnosed, neuropsychiatric disorder that is caused by a complex genetic basis, interacting with environmental factors. High comorbidity rates with other neurodevelopmental disorders such as attention deficit/hyperactivity disorder and obsessive compulsive disorder raise the intriguing hypothesis of a shared etiological background. Abnormalities of corticostriatal-thalamic-cortical circuits (CSTC) and dysfunction of both dopamine and serotonin neurotransmitter systems are assumed to be associated with TS. Recently, multiple lines of evidence also point towards an important role of additional neurotransmitters such as histamine and glutamate. For a very long time, efforts to elucidate the etiology and pathophysiology of TS have been fragmented and hampered by low statistical power. Finally, after more than two decades of active research aiming to identify the etiology and pathophysiology of TS, we are on the verge of a new era, promising exciting and rapid discoveries in the field. Investigators from around the world, representing multiple disciplines and scientific approaches, are joining their efforts in large-scale initiatives supported both by European Union and US National funding agencies, such as the European-funded EMTICS, TACTICS, and TSGeneSEE consortia, the Marie Curie Initial Training Network TS-EUROTRAIN and the European Society for the Study of TS joining forces with the NIH-funded TSAICG, GGRI, and Tic Genetics consortia. Importantly, all these initiatives are supported by TS patient support and advocacy groups. Multiple resources are being consolidated and coming together to serve the study of TS, including large well-characterized patient cohorts, and specialized epidemiological databases, such as the unique resource of the Netherlands Twin Register. This research topic showcases current large-scale collaborative efforts aiming to elucidate the genetic and neurobiological background of TS, through diverse approaches; from genomewide association studies aiming to identify common variants associated to the disorder to neuroimaging studies and animal models. Furthermore, current approaches on the clinical assessment and management of the disorder are presented. Propelled by the gradual availability of large scale TS cohorts, novel methodologies, and importantly, sheer enthusiasm by multiple researchers working together across different countries, the new era of the neurobiology of TS holds the promise to identify novel targets for improved therapies.
    Keywords: R5-920 ; RC321-571 ; RC435-571 ; RJ1-570 ; Q1-390 ; Treatment ; clinical research ; Neurobiology ; Collaborative studies ; Gilles de la Tourette syndrome ; Genetics
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  • 38
    Publication Date: 2023-12-21
    Description: It is now well appreciated that the immune system, in addition to its traditional role in defending the organism against pathogens, communicate in a well-organized fashion with the brain to maintain homeostasis and regulate a set of neural functions. Perturbation in this brain-immune interactions due to inflammatory responses may lead to psychiatric and neurological disorders. Microglia are one of the essential cells involved in the brain-immune interactions. Microglial cells are now not simply regarded as resident tissue macrophages in the brain. These cells are derived from myeloid progenitor cells in the yolk sac in early gestation, travel to the brain parenchyma and interact actively with neurons during the critical period of neurogenesis. Microglia provide a trophic support to developing neurons and take part in the neural wiring through the activity-dependent synapse elimination via direct neuron-microglia interactions. Altered microglial functions including changes in the gene expression due to early life inflammatory events or psychological and environmental stressors can be causally related to neurodevelopmental diseases and mental health disorders. This type of alterations in the neural functions can occur in the absence of infiltration of inflammatory cells in the brain parenchyma or leptomeninges. In this sense, the pathogenetic state underlying a significant part of psychiatric and neurological diseases may be similar to “para-inflammation”, an intermediate state between homeostatic and classical inflammatory states as defined by Ruslan Medzhitov (Nature 454:428-35, 2008). Therefore, it is important to study how systemic inflammation affects brain health and how local peripheral inflammation induces changes in the brain microenvironment. Chronic pain is also induced by disturbance in otherwise well-organized multisystem interplay comprising of reciprocal neural, endocrine and immune interactions. Especially, early-life insults including exposure to immune challenges can alter the neuroanatomical components of nociception, which induces altered pain response later in life. Recently the discrete roles of microglia and blood monocyte-derived macrophages are being defined. The distinction may be further highlighted by disorders in which the brain parenchymal tissue is damaged. Therefore, studies investigating the dynamics of immune cells in traumatic brain injury and neurotropic viral infections including human immunodeficiency virus, etc. as well as neurodegenerative diseases such as amyotrophic lateral sclerosis are promising to clarify the interplay between the central nervous and immune systems. The understanding of the histological architecture providing the infrastructure of such neuro-immune interplay is also essential. This Frontiers research topic brings together fourteen articles and aims to create a platform for researchers in the field of psychoneuroimmunology to share the recent theories, hypotheses and future perspectives regarding open questions on the mechanisms of cell-cell interactions with chemical mediators among the nervous, immune and endocrine systems. We hope that this platform would reveal the relevance of the studies on multisystem interactions to enhance the understanding of the mechanisms underlying a wide variety of neurological and psychiatric disorders.
    Keywords: R5-920 ; RC346-429 ; RC581-607 ; brain-immune interaction ; fatigue ; pain ; HIV ; neuroinflammation ; traumatic brain injury ; depression ; microglia ; amyotrophic lateral sclerosis ; autism ; bic Book Industry Communication::M Medicine
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  • 39
    Publication Date: 2023-12-21
    Description: Poly-ADP ribose polymerase (PARP) proteins are critical mediators of DNA repair. Many traditional anti-cancer chemotherapy agents overwhelm a cell’s ability to repair DNA damage in order to kill proliferating malignant cells. Recent evidence suggests that cancers within and across tissue types have specific defects in DNA repair pathways, and that these defects may predispose for sensitivity and resistance to various classes of cytotoxic agents. Breast, ovarian and other cancers develop in the setting of inherited DNA repair deficiency, and these cancers may be more sensitive to cytotoxic agents that induce DNA strand breaks, as well as to inhibitors of PARP activity. A series of recent clinical trials has tested whether PARP inhibitors can achieve synthetic lethality in hereditary DNA repair-deficient tumors. At the current time, mutation of BRCA serves as a potential, but not comprehensive, biomarker to predict response to PARP inhibitor therapy. Mechanisms of resistance to PARP inhibitors are only recently being uncovered. Future studies seek to identify sporadic cancers that harbor genomic instability rendering susceptibility to PARP inhibitors that compound lethal DNA damage.
    Keywords: R5-920 ; RC254-282 ; DNA reapir ; PARP inhibitor ; Homologous Recombination ; combination therapy ; DNA Damage ; Cancer ; bic Book Industry Communication::M Medicine
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  • 40
    Publication Date: 2023-12-21
    Description: This e-book provides the insight into occupational health and safety problems, challenges and solutions of the dairy sector. Thirty-two authors have been sharing their results and knowledge reflecting the challenges from small scale farming up to industrial style. The worldwide trend of growing farm sizes and a reduction in numbers is one of the major drivers for the changes in the working environment. Musculoskeletal disorders are among the most prevalent health problems of people working on farms. Nevertheless mechanisation has not reduced the number of complaints, and new problems arise due to the changing working environment.
    Keywords: R5-920 ; RA1-1270 ; immigrant workers ; Dairy farming ; OHS ; MSS ; MSD ; bic Book Industry Communication::M Medicine
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  • 41
    Publication Date: 2023-12-21
    Description: Microglia are essential for the development and function of the adult brain. Their ontogeny, together with the absence of turnover from the periphery and the singular environment of the central nervous system (CNS), make microglia a unique cell population compared to other tissue-macrophages. The unique properties and functions of microglial cells, such as their role in synaptic pruning or the exceptional capacity to scan the brain parenchyma and rapidly react to its perturbations, have emerged in recent years. In the coming years, understanding how microglia acquire and maintain their unique profiles in order to fulfil distinct tasks in the healthy CNS and how these are altered in disease, will be essential to develop strategies to diagnose or treat CNS disorders with an immunological component. This Research Topic covers several aspects of microglial biology, ranging from their origin and the functional role of microglia during development and lifespan, their molecular properties compared with other brain and peripheral immune cells to microglial phenotypes and functional states in neurodegenerative diseases and brain tumours. In conclusion, the present Research Topic provides a comprehensive overview of our current understanding of several cellular and molecular mechanisms that make microglia a unique immune cell population within the healthy CNS as well as under inflammatory, neurodegenerative and tumorigenic processes.
    Keywords: R5-920 ; RC346-429 ; RC581-607 ; inflammation ; brain tumour ; neurodegeneration ; microglia ; ontogeny ; bic Book Industry Communication::M Medicine
    Language: English
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  • 42
    Publication Date: 2023-12-21
    Description: The non-classical HLA class I molecule HLA-G is different from classical HLA class I molecules because of the low polymorphism in the coding region, the fact that HLA-G primary transcript is alternatively spliced in seven isoforms, and the inhibitory action on immune cells. Although HLA-G is low polymorphic, variants in both promoter and 3’ un-translated region (UTR) of HLA-G locus regulate its expression. In healthy conditions, a basal level of HLA-G gene transcription is observed in most cells and tissues; however, translation into HLA-G protein is restricted to trophoblasts in the placenta, where it participates in promoting tolerance at the fetal-maternal interface. HLA-G is also expressed by thymic epitelial, cornea, mesenchymal stem cells, nail matrix, pancreatic beta cells, erythroid, and endothelial precursors. HLA-G can be neo-expressed in adult tissues in pathological conditions, and its expression has been documented autoimmune disorders, viral infections, and cancer. In the latter setting de novo HLA-G expression is associated with the capability of tumor cells to evade the immune control. In the last decade it has become evident that HLA-G expression on T cells and antigenpresenting cells confers to these cells tolerogenic properties. This Research Topic focused on i) summarizing updated clinical and immunological evidences that HLA-G expression is associate with beneficial or detrimental tolerance, ii) gathering new insights into the mechanisms governing the expression of HLA-G in healthy and pathological conditions, such as pre-eclampsia, and iii) examining the mechanisms underlying HLA-G mediated tolerance.
    Keywords: R5-920 ; RC581-607 ; Pregnancy ; Autoimmunity ; Immuno-modulation ; Pre-Eclampsia ; Infections ; Exosomes ; HLA-G ; polymorphisms ; tolerance ; Cancer ; bic Book Industry Communication::M Medicine
    Language: English
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  • 43
    Publication Date: 2023-12-21
    Description: Lymphocytes constantly survey the lymph nodes in search for potential infection by a pathogen. They enter the afferent lymphatic vessel that serves as a conduit to transport the motile lymphocytes to the draining lymph node. Lymphatic vessels (LVs) are present in most vascularized tissues. They are traditionally regarded as passive conduits for soluble antigens and leukocytes. Afferent LVs begin as blind ended capillaries, which give rise to collecting vessels that merge and connect with draining lymph nodes (dLNs). Initial lymphatic capillaries are composed of Lymphatic Endothelial Cells (LECs) connected by discontinuous cell junctions, which join to form larger collecting lymphatic vessels, and ultimately feed into the LN subcapsular sinus. Within the LN, LECs are localized to the subcapsular, cortical, and medullary sinuses, where they interact with incoming and exiting leukocytes. LECs, and in general LN stromal cells, have emerged in the recent years as active players in the immune response. In support to this,studies have shown that the immune response generated during inflammation and under pathologic conditions is accompanied by modeling of the LVs and generation of new lymphatics, a process known as lymphangiogenesis. These facts strongly suggest that LECs and stromal LN cells in general, are not inert players but rather are part of the immune response by organizing immune cells movement, exchanging information and supplying survival factors. The purpose of this research topic is to review the role of the LECs during immune homeostasis and cancer. Considering the critical role of lymphangiogenesis in many pathologies like chronic and acute inflammation, autoimmunity, wound healing, graft rejection, and tumor metastasis, it is important to understand the molecular mechanisms that govern the cross talks between the LECs and immune cells during homeostasis and inflammation.
    Keywords: R5-920 ; RC581-607 ; Liver Injury ; Lymphatic Vessels ; Lymphatic Vasculature ; Tumor Microenvironment ; PD-L1 ; Antigen Presenting Cells ; Lymphatic Endothelial Cells ; T cell trafficking ; T cells ; bic Book Industry Communication::M Medicine
    Language: English
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  • 44
    Publication Date: 2023-12-21
    Description: It is long known that many cells can shed extracellular vesicles, small membrane-enclosed cell fragments. Although the existence of extracellular vesicles has been recognized for many years, researchers are only beginning to understand their physiologic significance. Several recent studies have demonstrated that extracellular vesicles released from cells serve as a mode of cellular communication. They can carry diverse molecular payload (e.g. nucleic acids, bioactive lipids and proteins) to distal organs and recipient cells. Extracellular vesicles can be classified into three major groups: exosomes, microvesicles, and apoptotic bodies. All these types of extracellular vesicles can be found in a variety of biologic specimen and their numbers, distribution and composition may serve as biomarkers for various disorders, including cardiovascular disease. Although extracellular vesicle-mediated processes are currently best characterized in the fields of cancer biology and neurobiology, evidence is accumulating that extracellular vesicles play a key role in the pathophysiology of diabetes, thrombosis, inflammation and cardiovascular calcification. In this Research Topic, we invited review and methodological articles that advance our understanding of extracellular vesicle-related processes in vascular biology.
    Keywords: R5-920 ; Angiogenesis ; Atherosclerosis ; Extracellular vesicles ; Calcification ; Biomarkers ; Cardiovascular disease ; Inflammation ; Exosomes ; Platelets ; Heart valve ; bic Book Industry Communication::M Medicine
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  • 45
    Publication Date: 2023-12-21
    Description: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is widely used in the treatment of haematological malignancies as a form of immunotherapy acting through a graft-versus-leukemia (GvL) reaction. This curative allogeneic response can be associated with severe drawbacks, such as frequent and severe graft-versus-host disease (GvHD) and a long-lasting immunodeficiency, especially now with the development of innovative strategies such as umbilical cord blood transplantation or transplants from haplo-identical family donors (Haplo-HSCT). In the long-term follow-up of these patients, severe post-transplant infections, relapse or secondary malignancies may be directly related to persistent immune defects.Reconstitution of the different lymphocyte populations (B, T, NK, NKT) and antigen presenting cells of myeloid origin (monocytes, macrophages and dendritic cells) should be considered not only quantitatively but especially qualitatively, in terms of functional subsets. Immune deficiency leading to an increased susceptibility to infections lasts for more than a year. Although infections that occur in the first month mostly result from a deficiency in both granulocytes and mononuclear cells (MNC), later post-engraftment infections are due to a deficiency in MNC subsets, primarily CD4 T-cells and B-cells. T-cell reconstitution has been extensively studied because of the central role of T-cells in mediating both GvHD, evidenced by the reduced incidence of this complication following T-Cell depletion, and a GvL effect as shown by DLI. In the recent years there has been renewed interest in the role of NK-cells, especially in the context of Haplo-HSCT, and in B-cell reconstitution.This Frontiers Research Topic will provide state of the art knowledge of the mechanisms of immune reconstitution in an allogeneic environment, in order to improve monitoring and therapeutic intervention in allo-HSCT patients.
    Keywords: R5-920 ; RC581-607 ; cell therapy ; Immune reconstitution ; Haplo-SCT ; HSCT ; Thymic function ; bic Book Industry Communication::M Medicine
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  • 46
    Publication Date: 2023-12-21
    Description: Gamma/delta (γδ) T-cells are a small subset of T-lymphocytes in the peripheral circulation but constitute a major T-cell population at other anatomical localizations such as the epithelial tissues. In contrast to conventional a/ß T-cells, the available number of germline genes coding for T-cell receptor (TCR) variable elements of γδ T-cells is very small. Moreover, there is a prefential localization of γδ T-cells expressing given Vgamma and Vdelta genes in certain tissues. In humans, γδ T-cells expressing the Vg9Vd2-encoded TCR account for anywhere between 50 and 〉95% of peripheral blood γδ T-cells, whereas cells expressing non-Vd2 genes dominate in mucosal tissues. In mice, there is an ordered appearance of γδ T-cell „waves“ during embryonic development, resulting in preferential localization of γδ T-cells expressing distinct VgammaVdelta genes in the skin, the reproductive organs, or gut epithelia. The major function of γδ T-cells resides in local immunosurveillance and immune defense against infection and malignancy. This is supported by the identification of ligands that are selectively recognized by the γδ TCR. As an example, human Vgamma9Vdelta2 T-cells recognize phosphorylated metabolites („phosphoantigens“) that are secreted by many pathogens but can also be overproduced by tumor cells, providing a basis for a role of these γδ T-cells in both anti-infective and anti-tumor immunity. Similarly, the recognition of endothelial protein C receptor by human non-Vdelta2 γδ T-cells has recently been identified to provide a link for the role for such γδ T-cells in immunity against epithelial tumor cells and cytomegalovirus-infected endothelial cells. In addition to „classical“ functions such as cytokine production and cytotoxicity, recent studies suggest that subsets of γδ T-cells can exert additional functions such as regulatory activity and – quite surpisingly – „professional“ antigen-presenting capacity. It is currently not well known how this tremendous extent of functional plasticity is regulated and what is the extent of γδ TCR ligand diversity. Due to their non-MHC-restricted recognition of unusual stress-associated ligands, γδ T-cells have raised great interest as to their potential translational application in cell-based immunotherapy. Topics of this Research Focus include: Molecular insights into the activation and differentiation requirements of γδ T-cells, role of pyrophosphates and butyrophilin molecules for the activation of human γδ T-cells, role of γδ T-cells in tumor immunity and in other infectious and non-infectious diseases, and many others. We are most grateful to all colleagues who agreed to write a manuscript. Thanks to their contributions, this E-book presents an up-to-date overview on many facets of the still exciting γδ T-cells.
    Keywords: R5-920 ; RC581-607 ; Infection ; Butyrophilin 3A1 ; Tumor-infiltrating lymphocytes ; cancer immunotherapy ; IL-17 ; Pyrophosphates ; bic Book Industry Communication::M Medicine
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  • 47
    Publication Date: 2023-12-21
    Description: Aflatoxins are a group of polyketide mycotoxins that are produced mainly by members of the genus Aspergillus. Production of these toxic secondary metabolites is closely related to fungal development (Keller et al., 2005; Jamali et al., 2012). Contamination of food, feed and agricultural commodities by aflatoxins poses enormous economic and serious health concerns because these chemicals are highly carcinogenic and can directly influence the structure of DNA. The resulting genetic defects can lead to fetal misdevelopment and miscarriages; aflatoxins are also known to suppress immune systems (Razzaghi-Abyaneh et al., 2013). In a global context, aflatoxin contamination is a constant concern between the 35N and 35S latitude where developing countries are mainly situated. With expanding boundaries of developing countries, aflatoxin contamination has become a persistent problem to those emerging areas (Shams-Ghahfarokhi et al., 2013). The continuing threat by aflatoxin contamination of food, feed and agricultural commodities to the world population has made aflatoxin research one of the most exciting and rapidly developing study areas of microbial toxins. The present research topic includes six review articles, three mini reviews and four original research articles. Contributors highlight current global health issues arising from aflatoxins and aflatoxigenic fungi and cover important aspects of aflatoxin research including contamination of crops, epidemiology, molecular biology and management strategies. Special attention is given to fungus-plant host interactions, biodiversity and biocontrol, sexual recombination in aflatoxigenic aspergilli, potential biomarkers for aflatoxin exposure in humans and safe storage programs.
    Keywords: R5-920 ; QR1-502 ; Q1-390 ; TX341-641 ; genetic diversity ; Public Health ; Aspergillus flavus ; Genomics ; MicroRNAs ; Fungus host interactions ; biological control ; aflatoxin ; agricultural crops ; bic Book Industry Communication::M Medicine
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  • 48
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: Epigenetics is the study of changes in gene activity that are heritable but not caused by changes in the DNA sequence. By modulating gene activities, epigenetic changes regulate cell functions. They include DNA methylation, histone posttranslational modifications and gene silencing by the action of non-coding RNAs, particularly microRNAs. It is now clear that epigenetic changes regulate B cell development. By acting in concert with networks of transcription factors, they modulate the activation of B cell lineage specific gene programs and repress inappropriate gene transcription in particular B cell differentiation states. A hallmark of B cell development in the bone marrow is the assembly of the B cell receptor (BCR) for antigen through rearrangement of immunoglobulin heavy (IgH) and light (IgL) chain V(D)J genes, as mediated by RAG1/RAG2 recombinases. Ig V(D)J rearrangement critically times the progression from pro-B cell to pre-B cell and, finally, mature B cell. Such progression is modulated by epigenetic marks, such as DNA methylation and histone posttranslational modifications, that increase chromatin accessibility and target RAG/RAG2 to V, D and J DNA. It is also dependent on the expression of multiple microRNAs. Mice deficient in Ago2, which is essential for microRNA biogenesis and function, have B cell development blocked at the pro-B cell stage. In agreement with this, B cell specific ablation of microRNA by B cell-specific knockout of Dicer virtually blocks B cell differentiation at the pro-B to pre-B cell transition. After mature B cells encounter antigen, changes of the epigenetic landscape are induced by the same stimuli that drive the antibody response; such epigenetic changes underpin the maturation of the antibody response itself. They instruct those B cell differentiation processes, somatic hypermutation (SHM), class switch DNA recombination (CSR) and plasma cell differentiation, that are central to the maturation of the antibody response as well as differentiation of memory B cells. Inducible histone modifications, together with DNA methylation and microRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase (AID), central to SHM and CSR, and B lymphocyte-induced maturation protein-1 (Blimp-1), which is central to plasma cell differentiation. Combinatorial histone modifications also function as histone codes in the targeting of the CSR and, possibly, the SHM machinery to the Ig locus by recruiting specific adaptors (histone code readers) that can in turn target and/or stabilize CSR/SHM factors. Epigenetic alterations in memory B cells contribute to their functionally distinction from their naive counterparts. Memory B cells inherit epigenetic information from their precursors and acquire new epigenetic marks, which make these resting B cells poised to promptly respond to antigen. The cross/feedback regulation of different epigenetic modifications/elements further increases the complexity of the B cell epigenome, which interacts with the genetic information for precise modulation of gene expression. It is increasingly evident that epigenetic dysregulation in B cells, including aberrant expression of microRNAs, can result in aberrant antibody responses to microbial pathogens, emergence of pathogenic autoantibodies or B cell neoplastic transformation. Epigenetic marks are potential targets for new therapeutics in autoimmunity and B cell malignancy.
    Keywords: R5-920 ; RC581-607 ; BLIMP-1 ; CSR ; immunoglobulin ; memory B cell ; Plasma cell ; V(D)J Recombination ; microRNA ; SHM ; AID ; epigenetics ; bic Book Industry Communication::M Medicine
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  • 49
    Publication Date: 2023-12-21
    Description: Excessive alcohol drinking represents a major social and public health problem for several countries. Alcohol abuse during pregnancy leads to a complex syndrome referred to as fetal alcohol spectrum disorders (FASD), chiefly characterized by mental retardation. The effects of early exposure to ethanol can be reproduced in laboratory animals and this helped to answer several key questions concerning the human pathology. The interest of experimental models of FASD is twofold. First, they increase our knowledge about the dose and modality of alcohol consumption able to induce damaging effects on the developing brain. Second, experimental models of FASD can provide useful hints to elucidate the basic mechanisms leading to the intellectual disability. In fact, experimental exposure to alcohol can be carried out during discrete, often very restricted, time windows. As a consequence, FASD models, though depending on the multifaceted interference of alcohol with several molecular pathways, can provide valuable information about which specific developmental periods and brain areas are critically involved in the genesis of mental retardation. Putting together data obtained through several experimental paradigms of alcohol exposure and those deriving from other genetic and non-genetic models, one can figure out to what extent different types of mental retardation share common pathogenetic mechanisms. The present Research Topic is aimed at establishing the state of the art of the current research on experimental FASD, focusing on differences and homologies with other types of intellectual disability. The ultimate goal is to find out a common roadmap in view of future therapeutical approaches.
    Keywords: R5-920 ; RC435-571 ; RJ1-570 ; glial cells ; development ; Amygdala ; Fetal Alcohol Spectrum Disorders ; Cerebral Cortex ; Intellectual Disability ; epigenetics ; Apoptosis ; bic Book Industry Communication::M Medicine
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  • 50
    Publication Date: 2023-12-21
    Description: The recent wave of clinical studies demonstrating long-term therapeutic efficacy highlights the enormous potential of gene therapy as an approach to the treatment of inherited disorders and cancer. While in recent years lentiviral vectors have dominated the field of ex vivo gene therapy in man, adeno-associated virus (AAV) vectors have become the platform of choice for the in vivo gene delivery, both local and systemic.Despite the achievements in the clinic however, a number of hurdles remain to be overcome in gene therapy, these include availability of scalable vector production systems, potential issues associated with insertional mutagenesis, and concerns related to immunogenicity of gene therapeutics. For AAV vectors, clinical trials showed that immunity directed against the vector could either prevent transduction of a target tissue or limit the duration of therapeutic efficacy. Initial observations in the context of a gene therapy trial for hemophilia spurred over a decade efforts by gene therapists and immunologists to understand the mechanism and identify factors that contribute to AAV’s immunogenicity, including the prevalence of B cell and T cell immunity to wild type AAV in humans and the interaction of AAV vectors with the innate and adaptive immune system. Despite a number of important contributions in particular in the more recent past, our knowledge on the immunology of gene transfer is still rudimental; this is partly due to the fact that the basic understanding of the complex balance between tolerance and immunity to an antigen, key aspect of gene transfer with AAV, keeps evolving rapidly. However, continuing work towards a better definition of the interaction of viral vectors with the immune system has led to significant advances in the knowledge of the factors influencing the outcome of gene transfer, such as the vector dose, the immune privilege of certain tissues, and the induction of tolerance to an antigen. A better understanding of the structure-function relationship of the viral capsid has boosted the development of novel immune-escape vector variants. In addition, novel immunomodulatory strategies were established to prevent or reduce anti-capsid immunity have been developed and are being tested in preclinical models and in clinical trials. Together, these advances are bringing us closer to the goal of achieving safe and sustained therapeutic gene transfer in humans. In this research topic, a collection of Original Research and Review Articles highlights critical aspects of the interaction between gene AAV vectors and the immune system, discussing how these interactions can be either detrimental or constitute an advantage, depending on the context of gene transfer, and providing tools and resources to better understand the issue of immunogenicity of AAV vectors in gene transfer.
    Keywords: R5-920 ; RC581-607 ; antibody response ; Clinical Trial ; Gene Therapy ; Regulatory T Cell ; Immunomodulation ; Tolerance induction ; adaptive and innate immunity ; adeno-associated virus ; Vaccine ; Epitopes ; bic Book Industry Communication::M Medicine
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  • 51
    Publication Date: 2023-12-21
    Description: CD4+ T lymphocytes play an essential role in host defense against bacterial, parasitic and viral infections. During infection, under the influence of intrinsic signals received through peptide-MHC/TCR interactions and extrinsic signals provided by pathogen-conditioned dendritic and other accessory cells, CD4+ T cells proliferate and differentiate into specialized T helper (Th) effectors, which produce distinct sets of cytokines tailored to combat a specific class of microbes. The concept of CD4+ T cell multi-functionality was developed after the seminal discovery of Th1 and Th2 cells nearly 30 years ago. Although the Th1/Th2 paradigm has successfully withstood the test of time, in the past decade additional Th subsets (Th17, Tfh, Th22, Th9) have been identified. Similarly, single cell analyses of cytokines and master transcriptional factors have revealed that, at the population level, CD4+ T cell responses are far more heterogeneous than initially anticipated. While some of the checkpoints in Th cell specification have been identified, recent studies of transcriptional and epigenetic regulation have uncovered a significant flexibility during the course CD4+ T lymphocyte polarization. In addition, Th cells expressing cytokines with counteracting functions, as a measure of self-regulation, display yet another level of diversity. Understanding the mechanisms that control the balance between stability vs. plasticity of Th effectors both at the time of initiation of immune response and during development of CD4 T cell memory is critical for the rational design of better vaccines and new immunotherapeutic strategies. This research topic will cover current views on Th cell development, with a focus on the mechanisms that govern differentiation, function and regulation of effector Th cells in the context of microbial infections.
    Keywords: R5-920 ; RC581-607 ; Infection ; Dendritic Cells ; Cytokines ; Immunoregulation ; CD4 lymphocytes ; Memory ; long noncoding RNA ; Macrophages ; Metabolism ; Th1 Th2 ; bic Book Industry Communication::M Medicine
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  • 52
    Publication Date: 2023-12-21
    Description: Lipids are best known as energy storing molecules and core-components of cellular membranes, but can also act as mediators of cellular signaling. This is most prominently illustrated by the paramount importance of the phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K) signaling pathways in many cells, including T cells and cancer cells. Both of these enzymes use the lipid phosphatidylinositol(4,5)bisphosphate (PIP2) as their substrate. PLCs produce the lipid product diacylglycerol (DAG) and soluble inositol(1,4,5)trisphosphate (IP3). DAG acts as a membrane tether for protein kinase C and RasGRP proteins. IP3 is released into the cytosol and controls calcium release from internal stores. The PI3K lipid product phosphatidylinositol(3,4,5)trisphosphate (PIP3) controls signaling by binding and recruiting effector proteins such as Akt and Itk to cellular membranes. Recent research has unveiled important signaling roles for many additional phosphoinositides and other lipids. The articles in this volume highlight how multiple different lipids govern T cell development and function through diverse mechanisms and effectors. In T cells, lipids can orchestrate signaling by organizing membrane topology in rafts or microdomains, direct protein function through covalent lipid-modification or non-covalent lipid binding, act as intracellular or extracellular messenger molecules, or govern T cell function at the level of metabolic regulation. The cellular activity of certain lipid messengers is moreover controlled by soluble counterparts, exemplified by symmetric PIP3/inositol(1,3,4,5)tetrakisphosphate (IP4) signaling in developing T cells. Not surprisingly, lipid producing and metabolizing enzymes have gained attention as potential therapeutic targets for immune disorders, leukemias and lymphomas.
    Keywords: R5-920 ; RC581-607 ; eicosanoid ; Inositol ; diacylglyerol ; PI3K ; Vitamin D ; T cell ; SHIP ; Pten ; Adipokine ; Lipid ; bic Book Industry Communication::M Medicine
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  • 53
    Publication Date: 2023-12-21
    Description: Experiences during early life program the central nervous- and endocrine-systems with consequences for susceptibility to physical and mental disorders. These programming effects depend on genetic and epigenetic factors, and their outcome leads to an adaptive or maladaptive phenotype to a given later environmental context. This Research Topic focused on the hypothalamus-pituitary-adrenal (HPA)-axis and stress-related phenotypes, and on how HPA-axis programming by the environment precisely occurs. We included original research, mini-review and review papers on a broad range of topics related to HPA-axis programming.
    Keywords: R5-920 ; RC648-665 ; RC321-571 ; Q1-390 ; HPA axis ; Vulnerability ; resilience ; early life stress ; materna ; bic Book Industry Communication::M Medicine
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  • 54
    Publication Date: 2023-12-21
    Description: Schistosomiasis is a severe parasitic disease, endemic in 74 developing countries with up to 600 million people, including many children, infected and 800 million at risk of contracting the disease following infection with Schistosoma mansoni, S. haematobium or S. japonicum. Disease burden is estimated to exceed 70 million disability-adjusted life-years, and leads to remarkably high YLD (years lived with disability) rates. Even more importantly, people with schistosomiasis are highly susceptible to malaria, tuberculosis and hepatic and acquired immunodeficiency viruses. There is only one drug, praziquantel, currently available for treatment and it has high efficacy, low cost, and limited side effects. However, only 13% of the target population has received the drug, and those treated are at continuous risk of reinfection necessitating repeated drug administration and the emergence of drug resistant parasites is a constant threat. There currently is no vaccine. While the target of 〉40% protection has been achieved with some molecules such as excretory-secretory proteins including calpain, glyceraldehyde 3-phosphate dehydrogenase, and cysteine peptidases, very recent articles reiterate the findings published during the last 2 decades of the last century, contradicting the established data of the pioneers of schistosome biology. A consensus should be reached without delay, in order to propose collaborative independent experiments and proceed ahead to pre- and clinical trials with efficacious candidate vaccine molecules. The proposed plan aims to finally reach an objective and fruitful agreement , via inviting established and young researchers from the United States, Brazil, China, Australia, and Europe who are working with different vaccine antigens, adjuvants, and approaches for immunization against S. mansoni, S. haematobium, and S. japonicum. It is hoped that the forum will end with a very few candidate antigens and a consensus approach regarding target immune responses, thus leading to encouraging the World Health Organization and other international foundations to sponsor the development and implementation of the urgently required, yet still elusive, vaccine for preventing and eliminating the transmission of schistosomiasis.
    Keywords: R5-920 ; RC581-607 ; Schistosomiasis ; Schistosoma mansoni ; Schistosoma haematobium ; Type 2 cytokines ; Vaccine ; Immune responses ; Schistosoma japonicum ; Vaccine candidates ; bic Book Industry Communication::M Medicine
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  • 55
    Publication Date: 2023-12-21
    Description: In the perioperative setting and in intensive care medicine, early and effective hemodynamic management including fluid therapy and administration of vasoactive drugs to maintain vital organ perfusion and oxygen delivery is mandatory. Understanding the different approaches in the management of critically ill patients during the resuscitation and further management is essential to initiate adequate context- and time-specific interventions. Optimization of hemodynamic variables to achieve a balance between organ oxygen delivery and consumption is a cornerstone. In general, cardiac output (i.e., the blood flow) is considered a major determinant of oxygen supply and thus its monitoring is regarded helpful. However, indicators of oxygen requirements are equally necessary to assess adequacy of oxygen supply. Currently, more and more less or even totally non-invasive monitoring systems have been developed and clinically introduced, but they require validation in particular clinical settings. Cardiac output monitors and surrogates of organ oxygenation only enable to adequately guide management, as patient’s outcome is determined by acquisition and interpretation of accurate measurements, and finally, suitable management decisions. This Research Topic focuses on the currently available techniques, especially the less and non-invasive ones, in the field of hemodynamic monitoring in the perioperative setting and in critically ill patients while summarizing their advantages and limitations.
    Keywords: R5-920 ; Blood Pressure ; Cardiovascular dynamics ; goal-directed therapy ; intensive care medicine ; Cardiac Output ; Anesthesiology ; bic Book Industry Communication::M Medicine
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  • 56
    Publication Date: 2023-12-21
    Description: Looking at "Horse in Motion", the iconic photograph by E. Muybridge, it is almost possible to hear the horse galloping. The pounding sound of the hoofs hitting the ground -like a drum- can also echo the rythmic beating of the human heart. That sound, that visceral rhythm, reminds us of the link between motion and performance: the perfectly executed stride of the horse, the incredible coordination of multiscale phenomena behind a heart beat. Furthermore, the decomposed sequence in Muybridge's photograph has become a well-known example of breaking motion into its components over time, and as such is reminiscent of those images that are routinely acquired in clinical practice, where the heart appears dilating and shirnking in a sequence of snapshots. The investigation of this motion and its subtleties is essential for refining our understanding of cardiac function, and the appreciation of how and when this motion is no longer perfectly executed can lead us to understand functional impairments and provide insight into the unfolding of pathology. In the presence of congenital heart disease (CHD), cardiac mechanics are altered: from single ventricle physiology to conduction abnormalities to different cardiomyopathies, it is important to both capture and interpret biomechanical changes that occur in the presence of a congenital defect. This special issue in Frontiers in Pediatrics, now an e-book, focuses on 'Ventricular mechanics in congenital heart disease' and looks at current knowledge of phenomena such as systolic/diastolic dysfuction and current methods (chiefly in cardiovascular magnetic resonance imaging and echocardiography) to evaluate cardiac function in the presence of CHD, and then presents a series of original studies that employ both medical imaging and computational modelling techniques to study specific CHD scenarios.
    Keywords: R5-920 ; RJ1-570 ; cardiovascular magnetic resonance imaging ; ventricular mechanics ; Congenital Heart Diseases ; hypoplastic left heart syndrome ; diastolic function ; computational modelling ; systolic function ; haemodynamics ; bic Book Industry Communication::M Medicine
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  • 57
    Publication Date: 2023-12-21
    Description: Natural antibodies (NAbs) are found in normal individuals in the absence of exogenous antigenic stimulation. Natural antibodies rapidly recognize and protect against pathogens that have not been previously encountered. NAbs also cross-react with several self-antigens, which, besides their role as a first line of defense against pathogens, affords them the ability to perform important housekeeping functions in healthy organisms. Such housekeeping functions include the clearance of oxidized damaged structures and/or apoptotic cells, which prevents the induction of pro-inflammatory effects. In addition, NAbs play a role in preventing the expansion of specific auto-reactive clones, thereby behaving as regulatory elements in acute or chronic inflammation. To maintain the non-pathogenic balance between the dual pathogen/self-antigen cross-reactivities of NAbs, a strict regulation in NAb secretion and function is necessary to avoid autoimmune disease. Actually, some of the NAbs related auto-reactivities, such as anti-DNA and anti-MOG, have been associated with autoimmunity. Furthermore, NAbs have been shown to bind to ‘neo-self’ carbohydrate antigens on glycolipids and glycoproteins found on malignant but not normal cells, which suggests NAbs may take part in tumor immunosurveillance. Many aspects regarding NAbs have yet to be studied in more detail: the reactivity and function of NAbs in health and disease, the behavior of the NAb repertoire with increasing age, the regulation of natural antibody production and auto-reactivity, the ways to specifically activate NAbs producing cells with desired specificities, the characteristics of human NAbs, among others. This special topics eBook consists of a number of articles exploring the cells that produce NAbs as well as the characteristics, function, specificity, and/or the role of natural antibodies in health and disease.
    Keywords: R5-920 ; RC581-607 ; innate immunity ; immunoglobulin ; Antibodies ; B cells ; IgM ; natural antibodies ; B-1 cells ; bic Book Industry Communication::M Medicine
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  • 58
    Publication Date: 2023-12-21
    Description: The discovery of the negative feedback of thyroid hormones on pituitary thyroid-stimulating hormone (TSH) secretion, a classical endocrine feedback control system, has shaped diagnosis and treatment of thyroid disease for the last decades. Based on this concept, a unique diagnostic category of subclinical thyroid disorders was introduced, being defined exclusively by an abnormal TSH response in the presence of thyroid hormone concentrations within the reference range. Although this approach was able to deliver a conceptually straightforward disease definition problems surfaced in clinical practice as neither the diagnostic reference range nor the appropriate threshold for initiating substitution treatment are universally agreed upon for subclinical thyroid disorders. The situation is further aggravated by the so-called syndrome T, which comprises a substantial but heterogeneous group of L-T4 treated patients with hypothyroidism with reduced quality of life despite “normal” TSH values.〈/p〉〈p〉A limited understanding of the physiological relationships between TSH and thyroid hormones may be a main reason for clinical difficulties in dealing with the causes of syndrome T and tailoring substitution therapy for hypothyroid patients with subclinical thyroid disorders. 〈/p〉〈p〉Feedback regulation has recently been shown to be much more complex than previously assumed. The concept of homeostatic control has also been extended to include the lesser known but equally important allostatic thyroid regulation.The latter aims at adaptive homeostasis or stability through changing setpoints and modulating structural parameters of feedback control, as may be appropriate to adapt to a vast array of conditions spanning from fetal life, aging, pregnancy, exercise, starvation, obesity, psychiatric disorders to the severe non-thyroidal illness syndrome.〈/p〉〈p〉A better understanding of homeostatic and allostatic mechanisms, which govern the behaviour of pituitary-thyroid feedback control, is on the horizon. This promises to improve the diagnostic utility of laboratory methods, laying the foundation for personalised methods to optimise dosage and modality of substitution therapy. The emerging new world of thyroid physiology is reflected on the side of clinical medicine in a new, relational paradigm for diagnosis and treatment.〈/p〉〈p〉Considerable progress has been made in this respect in the following key areas:〈/p〉〈p〉• the significance of complementary information processing structures within the feedback loop, in particular ultrashort feedback of TSH on its own secretion and the action of a TSH-T3 shunt unburdening the thyroid from T4 synthesis in imminent thyroid failure,〈/p〉〈p〉• the unravelling of spatio-temporal dynamics of hormone concentrations ranging from ultradian to circannual rhythms and including hysteresis effects,〈/p〉〈p〉• the emergence of “non-canonical” mechanisms of thyroid hormone signalling beyond transcriptional control of gene expression,〈/p〉〈p〉• the physiological actions of thyronine metabolites, which have been previously regarded as biologically inactive, such as thyronamines and iodothyroacetates,〈/p〉〈p〉• the characterisation of distinct patterns in the adaptive processes to stress and strain and their conclusive explanation through reactions to type 1 and type 2 allostatic load.〈/p〉〈p〉This collective volume contains the contributions to the Research Topic “Homeostasis and Allostasis of Thyroid Function”, which was originally published by the journal Frontiers in Endocrinology. Authored by an international team of experts from three continents ,the book provides a comprehensive overview on thyroid control from recent research in basic, computational and clinical thyroidology. Many aspects addressed here can be expected to stimulate future research. A more comprehensive view and better integration of in-vitro, in-silico and in-vivo investigations will be invaluable in paving the way to this new world of thyroidology.
    Keywords: R5-920 ; RC648-665 ; relational stability ; Thyronamines ; TSH-T3 Shunt ; thyroid allostasis ; precision medicine ; Stratified Medicine ; 3-T1AM ; Hypothyroidism ; Thyroid homeostasis ; Hysteresis ; bic Book Industry Communication::M Medicine
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  • 59
    Publication Date: 2023-12-21
    Description: Developing novel and more effective treatments that improve quality of life for individuals with autism spectrum disorders is urgently needed. To date a wide range of behavioral interventions have been shown to be safe and effective for improving language and cognition and adaptive behavior in children and adolescents with ASD. However many people with ASD can receive additional benefit from targeted pharmacological interventions. One of the major drawback in setting up therapeutics intervention is the remarkable individual differences found across individuals with ASD. As a matter of fact the medications that are currently available address only symptoms associated with ASD and not the core domains of social and communication dysfunction. The pathogenesis paradigm shift of ASD towards synaptic abnormalities moved the research to pathway to disease that involve multiple systems and that are becoming the forefront of ASD treatment and are pointing toward the development of new targeted treatments. Some new therapeutics have been tested and others are being studied. In this context single gene disorders frequently associated with ASD such as Rett Syndrome, Fragile X and Tuberous Sclerosis have been of significant aid as neurobiology of these disorders is more clear and has a potential to shed light on the altered signaling in ASD. However much research is needed to further understand the basic mechanisms of disease and the relationship to idiopathic ASD. Clinical trials in children are underway with agents directed to core symptoms and to the associated disorders in the search of new therapeutics and progress are expected with possible new option for therapeutics in ASD in the upcoming future. Children and Adolescents with ASD and their families can provide important information about their experience with new treatments and this should be a priority for future research. In addition, research performed on genetic mouse models of ASD will keep on providing useful information on the molecular pathways disrupted in the disease, thus contributing to identify novel drug targets.
    Keywords: R5-920 ; RJ1-570 ; Clinical Trial ; mouse model ; neurodevelopmental disorder ; Genetics ; autism ; bic Book Industry Communication::M Medicine
    Language: English
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  • 60
    Publication Date: 2023-12-21
    Description: Population aging and the associated burden of chronic diseases are one of the main challenges in public health worldwide. This Research Topic on "Active Aging and Disease Management" provides a comprehensive overview of population aging through fourteen comprehensive papers. Chapter 1 discusses an overview of health systems in active and healthy aging, while Chapter 2 focuses on the role of lifestyles, exercise and new technologies. Chapter 3 debates psychological and cognitive issues in aging and finally in Chapter 4, an older people self assessment is proposed and the role of communities and supporters are highlighted. We think that real social and health care integration at community level could be the key point to deliver effective health promotion and preventive intervention. Enjoy the reading!
    Keywords: R5-920 ; preventing disability ; dietary intake ; Active aging ; chronic diseases ; Life styles ; Mental Health ; Disease Management ; New technologies ; Elderly ; physical activity ; bic Book Industry Communication::M Medicine
    Language: English
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  • 61
    Publication Date: 2023-12-21
    Description: There is abundant evidence showing a strong association between trauma exposure, psychotic symptoms, and posttraumatic stress disorder (PTSD). Early trauma exposure contributes to the formation of psychotic symptoms and the development of psychotic disorders or severe mental illnesses such as schizophrenia, bipolar disorder, and treatment-refractory major depression. Furthermore, among persons with psychotic disorders, multiple traumatization over the lifetime is common, due to factors such as social stigma, the criminalization of severe mental illness, and increased vulnerability to interpersonal victimization. In addition to these factors is the traumatic nature of experiencing psychotic symptoms and coercive treatments such as involuntary hospitalization and being placed in seclusion or restraints. Not surprisingly, these high rates of trauma lead to high rates of PTSD in people with psychotic disorders, which are associated with more severe symptoms, worse functioning, and greater use of acute care services. In addition to the impact of trauma on the development of psychotic disorders and comorbid PTSD, traumatic experiences such as childhood sexual and physical abuse can shape the nature of prominent psychotic symptoms such as the content of auditory hallucinations and delusional beliefs. Additionally, traumatic experiences have been implicated in the role of ‘stress responsivity’ and increased risk for transition to psychosis in those identified as being at clinical high risk of developing psychosis. Finally, although the diagnostic criteria for PTSD primarily emphasize the effects of trauma on anxiety, avoidance, physiological over-arousal, and negative thoughts, it is well established that PTSD is frequently accompanied by psychotic symptoms such as hallucinations and delusions that cannot be attributed to another DSM-V Axis I disorder such as psychotic depression or schizophrenia. Understanding the contribution of traumatic experiences to the etiology of psychosis and other symptoms can inform the provision of cognitive behavioral therapy for psychosis, including the development of a shared formulation of the events leading up to the onset of the disorder, as well as other trauma-informed treatments that address distressing and disabling symptoms associated with trauma and psychosis. Until recently the trauma treatment needs of this population have been neglected, despite the high rates of trauma and PTSD in persons with psychotic disorders, and in spite of substantial gains made in the treatment of PTSD in the general population. Fortunately, progress in recent years has provided encouraging evidence that PTSD can be effectively treated in people with psychotic disorders using interventions adapted from PTSD treatments developed for the general population. In contrast to clinician fears about the untoward effects of trauma-focused treatments on persons with a psychotic disorder, research indicates that post-traumatic disorders can be safely treated, and that participants frequently experience symptom relief and improved functioning. There is a need to develop a better understanding of the interface between trauma, psychosis, and post-traumatic disorder. This Frontiers Research Topic is devoted to research addressing this interface.
    Keywords: R5-920 ; RC435-571 ; BF1-990 ; Q1-390 ; Psychosis ; PTSD ; Auditory Hallucinations ; Negative Symptoms ; Childhood Trauma ; Trauma ; Psychological Interventions ; Lived Experience ; bic Book Industry Communication::M Medicine
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  • 62
    Publication Date: 2023-12-21
    Description: The brainstem-limbic regions, including the superior colliculus, pulvinar and amygdala, receive direct perceptual information as a rapid, coarse, subcortical sensory system bypassing early sensory cortical systems, and play a central role in innate behaviors, including motivated and avoidance behaviors. Recent human neuropsychological studies including those on cortical blindness suggest that these subcortical sensory pathways are functional in the intact human brain and interact with more evolutionary recent cortical systems. This eBook presents up-to-date advancements in this area and to highlight the functions of the brainstem-limbic regions in a variety of perceptual, cognitive, affective and behavioral domains. We hope that this current Research Topic provides a comprehensive review to understand roles of the subcortical brainstem-limbic regions in some forms of sensory-motor coupling, cognitive and affective functions.
    Keywords: R5-920 ; RC321-571 ; RC435-571 ; BF1-990 ; Q1-390 ; Subcortical visual pathway ; Saccades ; Amygdala ; Pulvinar ; Superior colliculus ; Limbic system ; Cognition ; Emotion ; Faces ; Reward and aversion ; bic Book Industry Communication::M Medicine
    Language: English
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  • 63
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: In the highly competitive world of biomedical science, often the rush to publish and to be recognized as "first" with a new discovery, concept or method, is lost in the hurly-burly of the moment, as "the maddening crowd" moves on to the next "new thing". One of the great things about immunology today is that it has only become mature as a science within the last half-century, and especially within the past 35 years as a consequence of the revolution of molecular immunology, which has taken place only since 1980. Consequently, most of those who have contributed to our new understanding of how the immune system functions are still alive and well, and still contributing. Thus, "A Living History of Immunology" collates many stories from the investigators who actually performed the experiments that have established the frontiers of immunology. Accordingly, this volume combats "revisionist science", by those who want to alter history by telling the stories a different way than actually happened. In this regard, one of the good things about science vs. other disciplines is that we have the written record of what was done, when it was done and by whom. Even so, we do not have the complete story or narrative of how and why experiments were done, and what made the differences that led to success. This volume captures and chronicles some of these stories from the past fifty years in immunology.
    Keywords: R5-920 ; RC581-607 ; cytotoxic T lymphocytes (CTL) ; antibody ; Interleukins ; immunology history ; B cells ; Macrophages ; T cells ; Antibody Forming Cells (AFC) ; Thymus ; T cell receptor (TCR) ; bic Book Industry Communication::M Medicine
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  • 64
    Publication Date: 2023-12-21
    Description: While HIV/AIDS is a global public heath challenge, its impact is arguably greatest in the Sub-Saharan Africa (SSA), where new infections account for approximately 66% of the total number of HIV-positive persons globally. In SSA, medical, social, and economic resources are limited, thus necessitating innovative approaches to disease prevention. One of the mechanisms of prevention that is most promising occurs through HIV disclosure to family members (e.g., adult sexual partners) generally, and to children in particular. Our emphasis in this eBook is on HIV disclosure to children because it has multiple benefits, including improved adherence to antiretroviral medication treatment and understanding at an early age of the impact of sexual activity on the spread of HIV. While there is a noticeable gap in research on HIV disclosure to younger children, some of the general reasons for non-disclosure include concerns about fear of adult partners leaving relationships, and that children are too young to comprehend the severity of the situation and may tell others outside the family. Thus, it is critical to better understand how the HIV disclosure process happens (or does not happen) within HIV-affected families, as well as the best practices on how to disclose. In this eBook, we present a combination of empirical research studies and critical literature reviews that investigate the reasons for and for not disclosing HIV status within HIV-affected families and provide evidence-based practices that could be adopted by healthcare professionals to help HIV-positive parents facilitate disclosure activities within these families. This information can also be used by researchers, practitioners, and stakeholders who are in a position to influence policies on effective HIV disclosure practices, guidelines, and programs.
    Keywords: R5-920 ; RA1-1270 ; HIVAIDS ; Resource-poor setting ; HIV disclosure ; Parental HIV status disclosure ; Sub-Saharan Africa (SSA) ; Child HIV status disclosure ; HIV disclosure process ; bic Book Industry Communication::M Medicine
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  • 65
    Publication Date: 2023-12-21
    Description: During the recent few decades, global economic growth has been driven largely by developing world economies. The ones with the most intensive pace of development were marked as “emerging“ markets led by so called BRICS and N-11 countries. Such changes inevitably reflected the global health arena. A number of issues previously limited to established high-income economies became popularly discussed topics on the agendas of public health policy makers across these regions. Major challenges remain population aging, rising incidence of prosperity diseases, lack of universal insurance coverage and particularly provision of just and equitable access to medical care among the poor both in urban and rural communities. A significant part of the difficulties faced by these societies are attributed to inefficient resource allocation strategies in health care and unsatisfactory funding strategies. This Research Topic was created in order to address the core challenges of medical care financing and its affordability across the emerging global markets. Contributions of both undergoing or finished original research as well as review style papers are welcomed. All submitted manuscripts should deal with issues relevant to health care economics and policy in recognized global emerging markets. Outside the aforementioned key markets (BRICS- Brazil, Russia, India, China, South Africa; Next 11- Bangladesh, Egypt, Indonesia, Iran, South Korea, Mexico, Nigeria, Pakistan, the Philippines, Turkey and Vietnam) submissions referring to any of the dynamically developing Asian, Latin America, Eastern Europe or MENA countries are encouraged. In addition to a variety of health-economic evaluations and health policy analysis, methodological and resource use studies are within the Topic scope. Health policy considerations should be primarily focused on financing mechanisms and affordability of health care although other surrounding issues such as health insurance, reimbursement and cost-containment strategies will be considered.
    Keywords: R5-920 ; RA1-1270 ; Health Economics ; BRICS ; Hospitals ; cost ; Europe ; Emerging markets ; medical care ; Affordability ; Health financing ; Inequality ; bic Book Industry Communication::M Medicine
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  • 66
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: There is increased world-wide concern about the impact of multiple chronic conditions, especially among the rapidly aging population. Simultaneously, over the past decade there has been an emergence of state-wide and national initiatives to reduce the burden of chronic conditions that draw upon the translation of evidence-based programs (EPB) into community practice. Yet, little has been written about the national and international implementation, dissemination, and sustainability of such programs. This Research Topic features articles about EBPs for older adults, including a range of articles that focus on the infrastructure needed to widely disseminate EBP as well as individual participant impacts on physical, mental, and social aspects of health and well-being. Using a pragmatic research perspective, this Research Topic will advance knowledge that aims to enhance practice, inform policy and build systems of support and delivery in regard to the reach, effectiveness, adoption, implementation, and maintenance of evidence-based interventions for older adults. The focus is on knowledge transfer rather than knowledge generation but with a dual emphasis on the dissemination and sustainability of EBP that have been tested and shown effective as well as the adaptation of practice-based interventions into evidence-based programs. This Research Topic draws upon grand-scale efforts to deliver these programs, and include both U.S. as well as international examples. Commentaries discuss processes in the development and measurement of EBP and reflect perspectives from program developers and major national and regional funders of EBP as well as professionals and practitioners in the field. The full-length articles focus on four major programmatic areas: (1) chronic disease self-management programs; (2) fall prevention programs; (3) general wellness and physical activity programs; and (4) mental health programs. Additionally, articles are included to discuss cross-cutting issues related to building partnerships and the research infrastructure for the implementation, evaluation, and dissemination of evidence-based programming. The intent of this Research Topic is to enhance practice, inform policy, and build systems of support and delivery for EBP. It is written for a diverse audience and contains practical implications and recommendations for introducing, delivering, and sustaining EBP in a multitude of settings.
    Keywords: R5-920 ; RA1-1270 ; evidence based programming ; Fall prevention ; CDSMP ; older adults ; chronic disease self management CDSME programs ; healthy aging ; bic Book Industry Communication::M Medicine
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  • 67
    Publication Date: 2023-12-21
    Description: Traumatic brain injury (TBI) is a nondegenerative, noncongenital insult to the brain from an external mechanical force, possibly leading to permanent or temporary impairment of cognitive, physical, and psychosocial functions, with an associated diminished or altered state of consciousness. The definition of TBI has not been consistent and tends to vary according to specialties and circumstances. The term brain injury is often used synonymously with head injury, which may not be associated with neurological deficits. The definition has also been problematic due to variations in inclusion criteria. Both American and Brazilian data indicate that more than 700,000 people suffer TBI annually, with 20% afflicted with moderate or severe TBI. According to this data, 80% of people who suffered mild TBI can return to work, whist only 20% of moderate, and 10% of victims of severe TBI can return to their daily routine. Cognitive rehabilitation, a clinical area encompassing interdisciplinary action aimed at recovery as well as compensation of cognitive functions, altered as a result of cerebral injury, is extremely important for these individuals. The aim of a cognitive and motor rehabilitation program is to recover an individual's ability to process, interpret and respond appropriately to environmental inputs, as well as to create strategies and procedures to compensate for lost functions that are necessary in familial, social, educational and occupational relationships. In general, the cognitive rehabilitation programs tend to focus on specific cognitive domains, such as memory, motor, language and executive functions. By contrast, the focus of compensatory training procedures is generally on making environmental adaptations and changes to provide grater autonomy for patients. Successful cognitive rehabilitation programs are those whose aim is both recovery and compensation based on an integrated and interdisciplinary approach. The purpose of this Research Topic is to review the basic concepts related to TBI, including mechanisms of injury, severity levels of TBI, the most common findings in mild, moderate and severe TBI survivors, and the most cognitive and motor impairments following TBI, and also to discuss the strategies used to handle patients post-TBI. Within this context, the importance of an interdisciplinary rehabilitation for TBI is underlined.
    Keywords: R5-920 ; RC346-429 ; Traumatic Brain Injury ; Diffuse Axonal Injury ; concussion ; cognitive impairment ; bic Book Industry Communication::M Medicine
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  • 68
    Publication Date: 2023-12-21
    Description: This eBook contains a collection of peer-reviewed original and review articles published in either Frontiers in Endocrinology or Frontiers in Physiology focused on the research topic Optimizing Exercise for the Prevention and Treatment of Type 2 Diabetes.
    Keywords: R5-920 ; RC648-665 ; QP1-981 ; Q1-390 ; treatment ; glucose ; type 2 diabetes ; interval training ; exercise ; metabolism ; cardiometabolic health ; diabetes ; lifestyle ; physical activity ; bic Book Industry Communication::M Medicine
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  • 69
    Publication Date: 2023-12-21
    Description: TP53 gene mutations are present in more than half of all human cancers. The resulting proteins are mostly full-length with a single amino acid change and are abundantly expressed in cancer cells. Some of the mutant p53 proteins gain oncogenic functions (GOF) through which it actively contribute to the aberrant cell proliferation, increased resistance to apoptotic stimuli and ability to metastasize. Gain of function mutant p53 proteins can transcriptionally regulate the expression of a large plethora of target genes. This mainly occurs through the formation of oncogenic transcriptional competent complexes that include mutant p53 protein, known transcription factors, posttranslational modifiers and scaffold proteins. Mutant p53 protein can also transcriptionally regulate the expression of microRNAs, small non-coding RNAs that regulate gene expression at the posttranscriptional level. Each microRNA can putatively target the expression of hundred mRNAs and consequently impact on many cellular functions. Thus, gain of function mutant p53 proteins can exert their oncogenic activities through the modulation of both non-coding and coding regions of human genome. Over the past 3 decades, the regulation of p53 has been extensively studied. However, the regulation of mutant p53 remained largely unexplored. This snapshot focuses on recent discovery of mutant p53 GOF and regulation.
    Keywords: R5-920 ; RC254-282 ; mouse models ; mutant p53 ; dominant netagive ; therapies ; Oncogenic addiction ; gain of function ; bic Book Industry Communication::M Medicine
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  • 70
    Publication Date: 2023-12-21
    Description: The use of radical prostatectomy in patients with high risk of recurrence has significantly increased during the past 10 years. Thus, adjuvant radiation as a part of multimodality treatment or salvage radiation at the evidence of prostate-specific antigen (PSA) progression represents mainstay curative-intent options for a great number of prostate cancer patients. Although, few randomized trials and many retrospective studies have been published, many uncertainties still mold the discussions on the best treatment management for men after prostatectomy. This research topic successfully intended to foster discussions on current controversies in the use of postoperative radiotherapy and to present novel perspectives for treatment optimization.
    Keywords: R5-920 ; RC254-282 ; prostate cancer ; PSMA ; Choline PET ; LH-RH agonists ; salvage prostate bed radiotherapy ; Intra-operative radiotherapy ; rising PSA ; bic Book Industry Communication::M Medicine
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  • 71
    Publication Date: 2023-12-21
    Description: Gut health and specifically the gut microbiome-host interaction is currently a major research topic across the life sciences. In the case of animal sciences research into animal production and health, the gut has been a continuous area of interest. Production parameters such as growth and feed efficiency are entirely dependent on optimum gut health. In addition, the gut is a major immune organ and one of the first lines of defense in animal disease. Recent changes in animal production management and feed regulations, both regulatory and consumer driven, have placed added emphasis on finding ways to optimize gut health in novel and effective ways. In this volume we bring together original research and review articles covering three major categories of gut health and animal production: the gut microbiome, mucosal immunology, and feed-based interventions. Included within these categories is a broad range of scientific expertise and experimental approaches that span food animal production. Our goal in bringing together the articles on this research topic is to survey the current knowledge on gut health in animal production. The following 15 articles include knowledge and perspectives from researchers from multiple countries and research perspectives, all with the central goal of improving animal health and production.
    Keywords: R5-920 ; SF600-1100 ; gut health ; production animals ; Swine ; Cattle ; Chickens ; microbiome ; mucosal immunity ; bic Book Industry Communication::M Medicine
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  • 72
    Publication Date: 2023-12-21
    Description: Immune molecules have evolved to distinguish “self “molecules from “non-self”, “altered self” and “danger” molecules. Recognition is mediated via interactions between pattern recognition receptor molecules (PPRs) and their ligands, which include hydrophobic and electrostatic interactions between amino acid residues on the PPRs and uncharged or charged groups on amino acid residues, sugar rings or DNA/RNA molecules. Recognition in innate immunity range from cases (C1q, mannin-binding protein etc) where recognition is orchestrated by interaction between many ligands with one receptor molecule, and density of interaction is necessary for strong specific recognition, distinct from weak non-specific binding, and cases such as TLRs and NLRs where recognition involves complexation of single receptor and ligand, followed by oligomerisation of the receptor molecule. The majority of PPR molecules bind and recognise a wide variety of ligands, e.g TLR4 recognises LPS (gram negative bacteria), Lipotechoic acid (gram positive bacteria), heat shock protein hsp60, respiratory syncytial virus fusion protein etc, molecules that are structurally dissimilar to each other. This indicates considerable flexibility in their binding domains (amino acid residue variations) and modes (hydrophobic and charged, direct or mediated via an adaptor molecule). However, in many cases there is a dearth of structural and molecular data available, required to delineate the mechanism of ligand binding underlining recognition in pathogen receptors in innate immunity. Insights into requirements of conformation, charge, surface etc in the recognition and function of innate immunity receptors and their activation pathways, based on current data can suggest valuable avenues for future work.
    Keywords: R5-920 ; RC581-607 ; HIV-1 ; host-pathogen interactions ; zebrafish model system ; innate immunity ; protein-protein interaction ; complement ; malaria ; pattern recognition ; bic Book Industry Communication::M Medicine
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  • 73
    Publication Date: 2023-12-21
    Description: Tobacco smoking is a major risk factor for a number of chronic diseases, including a variety of cancers, lung disease and damage to the cardiovascular system. The World Health Organization recently calculated that there were 6 million smoking-attributable deaths per year and that this number is due to rise to about eight million per year by the end of 2030. Recent work has demonstrated that habitual smoking in adults is not only associated with a range of health problems, but may also contribute to a number of neurocognitive deficits, including deficits in memory and attention. One area of growing concern is the health and neurocognitive consequences of exposure to second-hand smoke or “passive smoking” (where a non-smoker inhales another person’s smoke, mainly in the form of side-stream smoke). In terms of tackling smoking-related problems, there has been a rise in the amount and range of smoking cessation and interventions techniques, including the emergence of e-cigarettes as one of the most popular forms of nicotine replacement therapies. The present book comprises a collection of manuscripts discussing (1) the impact of active and passive smoking upon health and neurocognitive function, (2) smoking cessation techniques and interventions used to tackle smoking-related problems, and (3) a critical consideration of current issues surrounding the use of e-cigarettes as nicotine-replacement therapy. This collection of papers includes empirical, theoretical, and review papers. This Research Topic demonstrates the broad nature of research currently being undertaken in this field and should pave the way for future work.
    Keywords: R5-920 ; RC435-571 ; Active smoking ; neurocognitive ; Health ; E-cigarettes ; passive smoking ; Smoking Cessation ; bic Book Industry Communication::M Medicine
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  • 74
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: "Intrinsic Clocks" presents an array of current research activities on intrinsic clocks and their contributions to biology and physiology. It elucidates the current models for the intrinsic clocks, their molecular components and key mechanisms as well as the key brain regions and animal models for their behavioral analysis. It provides a timely view on how these clocks guide behavior, and how their disruption may cause depressive-like behavior and impairment in cognitive functions. Thereby, any specific method by which the mood-related functions of the intrinsic clocks might be influenced bears therapeutic potential and has clinical interest. The importance of some of these mechanisms was highlighted by the 2017 award of the Nobel Prize in Physiology or Medicine to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for their discoveries of the genetic control of the daily biological rhythm. The key to the explanation was the discovery of transcription-translation feedback loops of the so-called “clock genes.”
    Keywords: R5-920 ; RC346-429 ; nocturnal ; circadian ; tanycytes ; hippocampus ; mood ; diurnal ; seasonal ; cryptochrome ; oscillation ; small-molecule ; bic Book Industry Communication::M Medicine
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  • 75
    Publication Date: 2023-12-21
    Description: Approximately 40% of lung cancer patients will develop central nervous system (CNS) metastases during the course of their disease. Most of these are brain metastases, but up to 10% will develop leptomeningeal metastases. Known risk factors for CNS metastases development are small cell lung cancer (SCLC), adenocarcinoma histology, epidermal growth factor receptor (EGFR) mutant or anaplastic lymphoma kinase (ALK) rearranged lung cancer, advanced nodal status, tumor stage and younger age. CNS metastases can have a negative impact on quality of life (QoL) and overall survival (OS). The proportion of lung cancer patients diagnosed with CNS metastases has increased over the years due to increased use of brain imaging as part of initial cancer staging, advances in imaging techniques and better systemic disease control. Post contrast gadolinium enhanced magnetic resonance imaging (gd-MRI) is preferred, however when this is contra-indicated a contrast enhanced computed tomography (CE-CT) is mentioned as an alternative option. When CNS metastases are diagnosed, local treatment options consist of radiotherapy (stereotactic or whole brain) and surgery. Local treatment can be complicated by symptomatic radiation necrosis for which no high level evidence based treatment exists. Moreover, differential diagnosis with metastasis progression is difficult. Systemic treatment options have expanded over the last years. Until recently, chemotherapy was the only treatment option with a poor penetration in the CNS. Angiogenesis inhibitors are promising in the treatment of primary CNS tumors as well as radiation necrosis but clinical trials of anti-angiogenic agents in NSCLC have largely excluded patients with CNS metastases. Furthermore, research has also focused on methods to prevent development of CNS disease, for example with prophylactic cranial irradiation. Recently, checkpoint inhibitors have become available for NSCLC patients, and tyrosine kinase inhibitors (TKIs) have improved prognosis significantly in those with a druggable driver mutation. Newer TKIs are often designed to have better CNS penetration compared to first-generation TKIs. Despite advances in treatment options CNS metastases remain a problem in lung cancer and cause morbidity and mortality. This Research Topic provides an extensive resource of articles describing advances in CNS metastases management in lung cancer patients, from prevention to diagnosis and treatment.
    Keywords: R5-920 ; RC254-282 ; lung cancer ; driver mutations ; treatment ; brain metastases ; leptomeningeal metastases ; cranial radiation ; prediction ; diagnosis ; bic Book Industry Communication::M Medicine
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  • 76
    Publication Date: 2023-12-21
    Description: A critical problem in resource-scarce countries across the globe is the shortage of appropriately trained health care providers. According to the World Health Organization, the current global health workforce shortage of 7.2 million providers is estimated to increase to 12.9 million by 2035. This disproportionately affects resource-scarce countries, denying basic health care to millions and limiting access to life-saving treatments. Due to limited resources in these countries, not enough health professionals receive training, few have the opportunity for continuing education, and the ability to develop or implement educational programs and curricula is constrained. Additionally, many existing providers choose to emigrate in pursuit of professional advancement opportunities, contributing to the overall shortage of qualified health care providers in these environments. Efforts to strengthen health workforce capacity not only increases access, safety and availability of care, but is critical to building resilient health systems capable of caring for the world’s neediest populations. This requires not only cultivating new health care providers, but also providing ongoing professional development to retain and support current providers, advancing the level of practice in accordance with current clinical science, cultivating educators, and enhancing training curricula. It is critical also to contribute to the limited body of research documenting the effectiveness and impact of various models of collaborative education and partnership to improve health worker training and retention. This Research Topic examines strategies for building health workforce capacity through the prism of educational partnerships, offering significant examples of effective models of international collaborative education as well as insight and guidance on the structure and operation of successful global partnerships. Collectively, the 31 articles accepted and included in this eBook represent a diversity of health professions and geographies across academic, non-governmental organizations and other global partnership forms. The published manuscripts highlight various elements of partnerships with several consistent themes emerging: capacity building, local empowerment, mutual trust and respect, long-term commitment, equity, collaboration, and the importance of integrating theory and practice, for a balance of academic and clinical development. The manuscripts provide examples of partnership and educational programs that are in the formative, early stages of implementation and others which have been sustained long term, some for decades. The following eBook is divided into two parts, with each part broken down into sections. Part I of the eBook includes 18 manuscripts that showcase long-term educational programs that strongly exemplify multiple, foundational aspects of international partnerships in education including mutual collaboration and project management, empowerment of host partners to lead and sustain programs, and capacity building. While individual manuscripts included in Part I look broadly at multiple aspects of successful, international partnerships in education, Part II manuscripts focus intently on one-two elements. Part II includes 13 articles that highlight partnership through short- rather than long-term educational initiatives as well as program development and broad academic partnerships. This Research Topic was sponsored by Health Volunteers Overseas – a United States based non-profit that collaborates with over eighty international universities and health institutions to send volunteer health professionals to low-resource countries to provide continuing education, train the trainer courses, professional support, and consultation on academic program and curricula development.
    Keywords: R5-920 ; RA1-1270 ; Medicine ; global health ; Nursing ; partnerships ; Education ; collaboration ; Physical Therapy ; Health Workforce ; international ; sustainability ; bic Book Industry Communication::M Medicine
    Language: English
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  • 77
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: Surgical infections are caused by the breakdown of the equilibrium existing between organisms and the host. This may occur after a breach in a protective surface, as occurs after surgical trauma, changes in host resistance, or particular characteristics of the organism. The possible outcomes are abscess formation, local spread with/without tissue death, distant spread or resolution. A surgical infection is an infection requiring operative treatment (excision or drainage), and occupies an unvascularized space in tissue, or may occur in an operated site. Common examples of the former group are furuncles and carbuncles, hollow viscus inflammations, such as appendicitis, cholecystitis, and most abscesses. The latter group comprises all surgical site infections. This Research Topic provides comprehensive information on the biology, mechanisms, prevention and treatment of surgery-related infections.
    Keywords: R5-920 ; RD1-811 ; surgical infections ; bacteria ; necrosis ; culture ; surgery ; bic Book Industry Communication::M Medicine
    Language: English
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  • 78
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: Signaling through the cell surface antigen receptor is a hallmark of various stages of lymphocyte development and adaptive immunity. Besides the adaptive immune system, the innate immunity is equally important for protection. However, the mechanistic connection between signaling, chromatin changes and downstream transcriptional pathways in both innate and adaptive immune system remains incompletely understood in hematopoiesis. A related issue is how the enhancers communicate to the promoters in a stage specific fashion and in the context of chromatin. Because the factors that regulate chromatin are generally present and active in most cell types, how could cell type and/or stage specific chromatin architecture is achieved in response to a particular immune signal?The genetic loci that encode lymphocyte cell surface receptors are in an "unrearranged” or “germline” configuration during the early stages of development. Thus, in addition to expressing lineage and/or stage specific transcription factors during each developmental stage, lymphocytes also need to rearrange their cognate receptor loci in a strictly ordered fashion. Hence, there must be a tightly coordinated communication between the recombination machinery and the transcriptional machinery (including chromatin regulators) at every developmental step. Mature B cells also undergo classswitch recombination and somatic hypermutation. Importantly, along the way, these cells must avoid autoimmune responses and only those cells capable of recognizing foreignantigens are preserved to reach peripheral organs where they must function. The exquisite regulation that govern chromatin accessibility, recombination and transcription regulation in response to the environmental signals in the immune system is discussed here is a series of articles.
    Keywords: R5-920 ; RC581-607 ; Promoter ; Chromatin ; transcription ; Enhancer ; immune response ; bic Book Industry Communication::M Medicine
    Language: English
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  • 79
    Publication Date: 2023-12-21
    Description: More than 90% of diseases possess immunological abnormalities. Disorders such as inflammation, hypersensitivity, autoimmunity and immunodeficiency are simple examples of how the immune system misinterprets its surroundings and goes awry. Multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, among many others are manifestations of immune cells attacking normal tissues. On the other hand, damping the immune system leads to diseases such as cancer, AIDS, and severe combined immunodeficiency. The last ten years witnessed an explosion in developing drugs that target the immune system. Several novel monoclonal antibodies have been approved for treatment of various diseases confirming that personalized medicine approach is robust in combating diseases. Hence, the future holds great promise for using personalized and targeted medicine rather than generalized medications that, in most circumstances, proven to be ineffective and characteristically exert side effects. Approaches such as generating novel adjuvants that can stimulate the immune system without harmful side effects, targeting inflammatory cytokines and chemokines, harnessing and activating innate immune cells such as natural killer cells or dendritic cells, are examples of future approaches to treat autoimmune diseases, AIDS, and various forms of cancer resulting from chronic inflammation. More recently, targeting immune checkpoint molecules have shown therapeutic response against lung cancer and melanoma. Identifying molecules involved in autophagy is another example of how personalized medicine might help treat patients with refractory asthma and autoimmune diseases. This topic introduces the reader to these novel approaches of manipulating the immune system and developing targeted therapeutic strategies for treatment of various diseases.
    Keywords: R5-920 ; RC581-607 ; Drugs ; Multiple sclerosis ; NK cells ; Leukemia ; AIDS ; Adjuvants ; Lymphoma ; Autophagy ; Chemokines ; Cancer ; bic Book Industry Communication::M Medicine
    Language: English
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  • 80
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: The PI3Ks control many key functions in immune cells. PI3Ks phosphorylate PtdIns(4,5)P2 to yield PtdIns(3,4,5)P3. Initially, PI3K inhibitors such as Wortmannin, LY294002 and Rapamycin were used to establish a central role for Pi3K pathway in immune cells. Considerable progress in understanding the role of this pathway in cells of the immune system has been made in recent years, starting with analysis of various PI3K and Pten knockout mice and subsequently mTOR and Foxo knockout mice. Together, these experiments have revealed how PI3Ks control B cell and T cell development, T helper cell differentiation, regulatory T cell development and function, B cell and T cell trafficking, immunoglobulin class switching and much, much more. The PI3Kd inhibitor idelalisib has recently been approved for the treatment of B cell lymphoma. Clinical trials of other PI3K inhibitors in autoimmune and inflammatory diseases are also in progress. This is an opportune time to consider a Research Topic considering when what we have learned about the PI3K signalling module in lymphocyte biology and how this is making an impact on clinical immunology and haematology.
    Keywords: R5-920 ; RC581-607 ; B cell ; PI3K/AKT/mTOR ; Signal Transduction ; T cell ; PI3K pathway inhibitors ; bic Book Industry Communication::M Medicine
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  • 81
    Publication Date: 2023-12-21
    Description: The immune system employs TLOs to elicit highly localized and forceful responses to unresolvable peripheral tissue inflammation. Current data indicate that TLOs are protective but they may also lead to collateral tissue injury and serve as nesting places to generate autoreactive lymphocytes. A better comprehension of these powerhouses of disease immunity will likely facilitate development to unprecedented and specific therapies to fight chronic inflammatory diseases.
    Keywords: R5-920 ; RC581-607 ; Autoimmunity ; nonresolving peripheral tissue inflammation ; Autoinflammation ; Tertiary lymphoid organs ; dichotomies of immune responses ; disease immunity ; Immune Tolerance ; antigen ; bic Book Industry Communication::M Medicine
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  • 82
    Publication Date: 2023-12-21
    Description: The immunological synapse (IS) is a specialised cell-cell adhesion that mediates antigen acquisition and regulates the activation of lymphocytes. Initial studies of the IS showed a structure composed of stable supra-molecular activation clusters (SMAC) organised during the interaction of helper T lymphocytes with B lymphocytes, working as antigen presenting cells. A central SMAC of coalesced T cell receptors (TCRs) and a peripheral SMAC for cell-cell adhesion were observed. IS with similar structure was later described during antigen acquisition by B cells and during the interaction of NK cells with target and healthy cells. More recent research developed with microscopy systems that improve the spatial and temporal resolution has showed the complex molecular dynamics at the IS that governs lymphocyte activation. Currently, the IS is seen as a three-dimensional structure where signalling networks for lymphocyte activation and endosomal and cytoskeleton machinery are polarised. A view has emerged in which dynamic microclusters of signalling complexes are composed of molecular components attached to the plasma membrane and other components conveyed on sub-synaptic vesicles transported to the membrane by cytoskeletal fibers and motor proteins. Much information is nonetheless missing about how the dynamics of the endosomal compartment, the cytoskeleton, and signalling complexes are reciprocally regulated to achieve the function of lymphocytes. Experimental evidence also suggests that the environment surrounding lymphocytes exposed to different antigenic challenge regulates IS assembly and functional output, making an even more complex scenario still far from being completely understood. Also, although some signalling molecular components for lymphocyte activation have been identified and thoroughly studied, the function of other molecules has not been yet uncovered or deeply characterised. This research topic aims to provide the reader with the latest information about the molecular dynamics governing lymphocyte activation. These molecular dynamics dictate cell decisions. Thus, we expect that understanding them will provide new avenues for cell manipulation in therapies to treat different immune-related pathologies.
    Keywords: R5-920 ; RC581-607 ; cytoskeleton dynamics ; intracellular signalling ; Immunological Synapse ; endosomal dynamics ; bic Book Industry Communication::M Medicine
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  • 83
    Publication Date: 2023-12-21
    Description: The pathogenic mechanisms underlying primary T-cell disorders are mainly related to molecular alterations of genes whose expression is intrinsic to hematopoietic cells. However, since the differentiation process requires a crosstalk among thymocytes and the thymic microenvironment, molecular alterations of genes, involved in the differentiation and functionality of the stromal component of the thymus, may lead to a severe T-cell defect or failure of central tolerance, as well. The first example of severe combined immunodeficiency (SCID) not related to an intrinsic alteration of the hematopoietic cell but rather of the thymic epithelial component is the Nude/SCID phenotype, inherited as an autosomal recessive disorder, whose hallmarks are the T-cell defect and the absence of the thymus. The clinical and immunological phenotype is the human equivalent of the murine Nude/SCID syndrome, which represents the first spontaneous SCID identified in nude mice in 1966. For over 3 decades studies of immune system in these mice enormously contributed to the overall knowledge of cell mediated immunity, in the assumption that the athymia of these mice was solely responsible for the T-cell immunological defect. This syndrome is due to mutations of the transcription factor FOXN1, belonging to the forkhead-box gene family, which is mainly expressed in the thymus and skin epithelial cells, where it plays a critical role in differentiation and survival. An alteration of the thymic structure is also a feature of the DiGeorge syndrome (DGS), which has been long considered the human counterpart of the nude mice phenotype. This syndrome is frequently associated to a deletion of the 22q11 region, which contains approximately 30 genes, including the TBX1 gene, which is responsible for most of the clinical features of DGS in humans and mice. In this syndrome common manifestations are cardiac malformations, speech delay, hypoparathyrodism and immunodeficiency, even though the immunological hallmarks of the T-cell defect in DiGeorge syndrome are profoundly different from those reported in human Nude/SCID. The divergence of the phenotype among these 2 entities raised the possibility that the FOXN1 transcription factor represents the real key stromal molecule implicated in directing the hematopoietic stem cell toward a proper T-cell fate. Thymic stromal component of the primary lymphoid organ is also required to negatively select the autoreactive clones, a process driven by the expression of tissue specific antigens (TSA) by medullary thymic epithelial cells (mTECs). The expression of genes encoding TSA antigens is mediated by autoimmune regulator (AIRE) gene, encoding a transcription factor expressed in mTECs. Molecular alterations of this gene are associated to autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a rare autosomal disorder, which may be considered the prototype of an autoimmune disease due to the failure of central tolerance homeostasis. All these "experiments of nature" led to unravel novel pathogenic mechanisms underlying inherited disorders of immune system and, of note, to clarify the pivotal role of epithelial cells in the maturation and education process of T-cell precursors.
    Keywords: R5-920 ; RC581-607 ; Central Tolerance ; Rag defects ; Combined immunodeficiency ; DiGeorge Syndrome ; Foxn1 ; medullary thymic epithelial cells ; APECED ; bic Book Industry Communication::M Medicine
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  • 84
    Publication Date: 2023-12-21
    Description: In multicellular organisms, states with a high degree of tissue turnover like embryogenesis, development, and adult tissue homeostasis need an instantaneous, tightly regulated and immunologically silent clearance of these dying cells to ensure appropriate development of the embryo and adult tissue remodelling. The proper and swift clearance of apoptotic cells is essential to prevent cellular leakage of damage associated molecular patterns (DAMPs) which would lead to the stimulation of inflammatory cytokine responses. In addition to the clearance of apoptotic cells (efferocytosis), backup mechanisms are required to cope with DAMPs (HMGB-1, DNA, RNA, S100 molecules, ATP and adenosine) and other intracellular material (uric acid, intracellular proteins and their aggregates) released from cells, that were not properly cleared and have entered the stage of secondary necrosis. Furthermore, under certain pathologic conditions (e.g. gout, cancer, diabetes) non-apoptotic cell death may transiently occur (NETosis, necroptosis, pyroptosis) which generates material that also has to be cleared to avoid overloading tissues with non-functional cellular waste. Efficient efferocytosis is therefore indispensable for normal tissue turnover and homeostasis. The characterization of various signalling pathways that regulate this complex and evolutionary conserved process has shed light on new pathogenetic mechanisms of many diseases. Impaired clearance promotes initiation of autoimmunity as well as the perpetuation of chronic inflammation, but may also foster anti-tumor immunity under certain microenvironmental conditions. Immunological tolerance is continuously being challenged by the presence of post-apoptotic remnants in peripheral lymphoid tissues. Besides the autoimmune phenotype of chronic inflammatory rheumatoid disorders a plethora of pathologies have been associated with defects in genes involved in clearance, e.g. atherosclerosis, cancer, gout, diabetes, some forms of blindness, neuropathy, schizophrenia and Alzheimer’s disease. The main goal of this research topic is to collect contributions from various disciplines committed to studying pathogenetic mechanisms of the aforementioned disorders and dealing with alterations in the clearance of dying and dead cells, their remnants, and their constituents that leak out after membrane rupture. Integrating the combined collection of knowledge on efferocytosis and clearance of dead cells and their derived waste from different fields of research in physiology and pathophysiology could improve the molecular understanding of these increasingly prevalent diseases and may ultimately result in new therapeutic strategies.
    Keywords: R5-920 ; RC581-607 ; Autoimmunity ; NETs ; Efferocytosis ; Inflammation ; cell-remnants ; Phagocytosis ; Apoptosis ; Cancer ; Asthma ; bic Book Industry Communication::M Medicine
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  • 85
    Publication Date: 2023-12-21
    Description: Endocrinological research early recognized the importance of intercellular interactions and realized the importance of glutamatergic and GABAergic signaling. In turn this signalling depends on elaborate interactions between astrocytes and neurons, without which neurons would be unable to produce, reuse and metabolize transmitter glutamate and GABA. Details of these subjects are described in this Research Topic by key investigators in this field. It focuses on the intricate and extremely swift pathway producing these amino acid transmitters from glucose in brain but also discusses difficulties in determining expression of some of the necessary genes in astrocytes and related processes in pancreatic islets. However, it does not discuss how closely associated astrocytes and neurons are anatomically, enabling these interactions. This is elegantly shown in this cover image, kindly provided by Professor Andreas Reichenbach (University of Leipzig, Germany).
    Keywords: R5-920 ; RC648-665 ; QH301-705.5 ; Q1-390 ; Brain glutamine ; brain metabolism ; Appetite Regulation ; Astrocyte-oligdendrocyte interaction ; Brain ammonia ; GABA ; Astrocytic gene expression ; pancreatic islets ; Brain aspartate ; Brain glutamate ; bic Book Industry Communication::M Medicine
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  • 86
    Publication Date: 2023-12-21
    Description: Successful containment of an infection is dependent on both innate and adaptive immune response. Cytokines are essential effectors of both of these systems. In particular, type I interferons (IFN-I) are important components of early innate immunity against an infection. However, the production of IFN-I could serve as a double edge sword, either containing an infection or enhancing susceptibility. For example, IFN-I, which is essential for early containment of viral infections, has been shown to be detrimental to the host during bacterial infections. In fact, recent significant reports have shown that influenza virus induced IFN-I responses can enhance the host susceptibility to secondary bacterial infections. These recent reports highlight the expanding immunoregulatory role of IFN-I in the host immunity. With these recent findings in mind, the aim of this research topic is to welcome novel data, opinion and literature reviews on the newly identified dual functions of IFN-I. This research topic wills focus on the following areas of IFN-I: 1) a detrimental role of IFN-I during primary bacterial infection; 2) a detrimental role of viral infection induced IFN-I during secondary bacterial infections; 3) evolutionary pressure that drove detrimental IFN-I response during primary bacterial infection; and 4) does benefit of IFN-I responses during primary viral infections outweigh the adverse consequences of IFN-I mediated enhanced susceptibility to secondary bacterial infections.
    Keywords: R5-920 ; RC581-607 ; Autoimmunity ; adjuvant ; bacterial and viral infections ; Vaccine ; type I IFN ; bic Book Industry Communication::M Medicine
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  • 87
    Publication Date: 2023-12-21
    Description: Plasticity is the hallmark of stem cells. At the same time, stem cells, like any other cell type, are influenced by their microenvironment and respond to it accordingly. A specific microenvironment is defined by a variety of factors, including biological and chemical factors, cell-cell interactions, but also metabolic and mechanical cues. Such dynamic and specialized microenvironment where the stem cells reside is considered a stem cell niche. Tissue injury as well as malignant tissue alterations lead to changes in the niche influencing the plasticity and biology of residing stem cells. Similarly, the niche changes upon tissue damage, which eventually induces differentiation of stem cells and ultimately regeneration of the tissue.
    Keywords: R5-920 ; QH301-705.5 ; RC581-607 ; Q1-390 ; microenvironment ; stem cells ; tissue regeneration ; immunomodulation ; extracellular vesicles (EVs) ; oxygen tension ; plasticity ; imaging ; bic Book Industry Communication::M Medicine
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  • 88
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: Articles within this e-book are focused on the health of children with disabilities. Various frameworks have been used to articulate the dynamic interaction of the individual, environment and the task as it relates to child health. A majority of the contributing authors in this special topic are researchers within the field of adapted physical activity. This field embraces a broad perspective of inclusiveness and attitudes of acceptance.
    Keywords: R5-920 ; RA1-1270 ; Disability ; Development ; Children ; Adapted Physical Activity ; bic Book Industry Communication::M Medicine
    Language: English
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  • 89
    Publication Date: 2023-12-21
    Description: NETosis, a form of cell death that manifests by the release of decondensed chromatin to the extracellular space, provides valuable insights into mechanisms and consequences of cellular demise. Because extracellular chromatin can immobilize microbes, the extended nucleohistone network was called a neutrophil extracellular trap (NET), and the process of chromatin release was proposed to serve an innate immune defense function. Extracellular chromatin NETs were initially observed in studies of neutrophils and are most prominent in these types of granulocytes. Subsequent studies showed that other granulocytes and, in a limited way, other cells of the innate immune response may also release nuclear chromatin following certain kinds of stimulation. Variations of NETosis were noted with cells that remain temporarily motile after the release of chromatin. Numerous stimuli for NETosis were discovered, including bacterial breakdown products, inflammatory stimuli, particulate matter, certain crystals, immune complexes and activated thrombocytes. Fundamental explorations into the mechanisms of NETosis observed that neutrophil enzyme activity (PAD4, neutrophil elastase, proteinase 3 and myeloperoxidase) and signal transduction pathways contribute to the regulation of NETosis. Histones in NET chromatin become modified by peptidylarginine deiminase 4 (PAD4) and cleaved at specific sites by proteases, leading to extensive chromatin externalization. In addition, NETs serve for attachment of bactericidal enzymes including myeloperoxidase, leukocyte proteases, and the cathelicidin LL-37. NETs are decorated with proteases and may thus contribute to tissue destruction. However, the attachment of these enzymes to NET-associated supramolecular structures restricts systemic spread of the proteolytic activity. While the benefit of NETs in an infection appears obvious, NETs also participate as key protagonists in various pathologic states. Therefore, it is essential for NETs to be efficiently cleared; otherwise digestive enzymes may gain access to tissues where inflammation takes place. Persistent NET exposure at sites of inflammation may lead to a further complication: NET antigens may provoke acquired immune responses and, over time, could initiate autoimmune reactions, serve as antigen for nuclear autoantibodies and foster DNA immune complex-related inflammation. Neutrophil products and deiminated proteins comprise an important group of autoantigens in musculoskeletal disorders. Aberrant NET synthesis and/or clearance are often associated with inflammatory and autoimmune conditions. Recent evidence also implicates aberrant NET formation in the development of endothelial damage, atherosclerosis and thrombosis. Intravital microscopy provides evidence for conditions that induce NETosis in vivo. Furthermore, NETs can easily be detected in synovial fluid and tissue sections of patients with arthritis and gout. NETosis is thus of interest to researchers who investigate innate immune responses, host-pathogen interactions, chronic inflammatory disorders, cell and vascular biology, biochemistry, and autoimmunity. As we enter the second decade of research on NETosis, it is useful and timely to review the mechanisms and pathways of NET formation, their role in bacterial and fungal defense and their importance as inducers of autoimmune responses.
    Keywords: R5-920 ; RC581-607 ; Infection ; Autoimmunity ; Microscopy ; Immune Cell Interactions ; Neutrophil Extracellular Traps ; Inflammation ; Mechanisms of Cell Death ; Chronic Disease ; bic Book Industry Communication::M Medicine
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  • 90
    Publication Date: 2023-12-21
    Description: Early studies recognized the unique phenotype and attributes of T cells found in mucosal tissues, such as the intestines, skin, lung and female reproductive tract. This special topic issue will cover many aspects of mucosal-resident T cell biology during infection and disease and is dedicated to Leo Lefrancois, a pioneer in this field who recently passed away. A major proportion of these mucosal T cells are memory T cells, now recognized as a major constituent of memory T cells referred to as tissue-resident memory T cells. Unlike central and effector memory T cell subsets, tissue-resident memory T cells exhibit tissue specificity with minimal systemic migration. Nonetheless, tissue-resident memory T cells share a similar origin and display some overlapping phenotypes with their other memory T cell counterparts. Articles in this issue will describe the different types of memory T cells residing in mucosal tissues, their origins and functions as well as how they vary among discrete mucosal sites. Manuscripts will consider the unique physiological environments and cellular constituents which facilitate tissue residency while preserving tissue function. Additionally, there will be descriptions of the various mechanisms responsible for the migration and segregation of tissue resident memory CD8 T cells from the peripheral T cell pool. Although the mechanisms facilitating the sequestration of tissue-resident memory T cells within a respective tissue has not well characterized, various theories will also be discussed. Lastly, how these T cells contribute to immunity to pathogens, cancer, and autoimmunity and could be modified through vaccination or therapeutic intervention will be described. As mucosal tissues are the major portals of pathogen entry and frequent transformation, the activities and persistence of tissue resident memory T cells is crucial for mediating protection at these sites.
    Keywords: R5-920 ; RC581-607 ; pathogens ; Microscopy ; Migration ; Mucosa ; T cell differentiation ; Vaccination ; Inflammation ; Epithelium ; CD103 ; bic Book Industry Communication::M Medicine
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  • 91
    Publication Date: 2023-12-21
    Description: Biological engagement programs are a set of projects or activities between partner countries that strengthen global health security to achieve mutually beneficial outcomes. Engagement programs are an effective way to work collaboratively towards a common threat reduction goal, usually with a strong focus on strengthening health systems and making the world a safer place. Cooperative programs are built upon trust and sharing of information and resources to increase the capacity and capabilities of partner countries. Biological engagement programs reduce the threat of infectious disease with a focus on pathogens of security concern, such as those pathogens identified by the U.S. Government as Biological Select Agent and Toxins. These programs seek to develop technical or scientific relationships between countries to combat infectious diseases both in humans and animals. Through laboratory biorisk management, diagnostics, pathogen detection, biosurveillance and countermeasure development for infectious diseases, deep relationships are fostered between countries. Biological engagement programs are designed to address dual-use issues in pathogen research by promoting responsible science methodologies and cultures. Scientific collaboration is a core mechanism for engagement programs are designed to strengthen global health security, including prevention of avoidable epidemics; detection of threats as early as possible; and rapid and effective outbreak response. This Research Topic discusses Biological Engagement Programs, highlighting the successes and challenges of these cooperative programs. Articles in this topic outlined established engagement programs as well as described what has been learned from historical cooperative engagement programs not focused on infectious diseases. Articles in this topic highlighted selected research, trainings, and programs in Biological Engagement Programs from around the world. This Topic eBook first delves into Policies and Lessons Learned; then describes Initiatives in Biosafety & Biosecurity; the core of this work documents Cooperative Research Results from the field; then lastly the Topic lays out potential Future Directions to the continued success of the World’s cooperative science in reducing the threat of infectious diseases.
    Keywords: R5-920 ; RA1-1270 ; QR1-502 ; Q1-390 ; Infectious disease ; biosecurity ; Cooperative Biological Engagement ; select agents ; biosafety ; bic Book Industry Communication::M Medicine
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  • 92
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: Trypanosoma cruzi is a pathogenic protozoan of the Trypanosomatidade Family, which is the etiological agent of Chagas’ disease. Chagas’ disease stands out for being endemic among countries in Latin America, affecting about 15 million people. Recently, Chagas has become remarkable in European countries as well due to cases of transmission via infected blood transfusion. An important factor that has exacerbated the epidemiological picture in Brazil, Colombia and Venezuela is infection after the oral intake of contaminated foods such as sugar cane, açai and bacaba juices. Trypanosoma cruzi is an intracellular protozoan that exhibits a complex life cycle, involving multiple developmental stages found in both vertebrate and invertebrate hosts. In vertebrate hosts, the trypomastigote form invades a large variety of nucleated cells using multiple mechanisms. The invasion process involves several steps: (a) attraction of the protozoan to interact with the host cell surface; (b) parasite-host cell recognition; (c) adhesion of the parasite to the host cell surface; (d) cell signalling events that culminate in the internalization of the parasite through endocytic processes; (e) biogenesis of a large vacuole where the parasite is initially located, and is also known as parasitophorous vacuole (PV); (f) participation of endocytic pathway components in the internalization process; (g) participation of cytoskeleton components in the internalization process; (h) transformation of the trypomastigote into the amastigote form within the PV; (i) lysis of the membrane of the PV; (j) multiplication of amastigotes within the host cell in direct contact with cell structures and organelles; (k) transformation of amastigotes into trypomastigotes, and (l) rupture of the host cell releasing trypomastigotes into the extracellular space. The kinetics of the interaction process and even the fate of the parasite within the cell vary according to the nature of the host cell and its state of immunological activation.
    Keywords: R5-920 ; RC581-607 ; QR1-502 ; Q1-390 ; Chagas Disease ; Parasite-host cell interaction ; cell-to-cell recognition ; Parasitic protozoa ; Trypanosoma cruzi ; bic Book Industry Communication::M Medicine
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  • 93
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: The field of arthroscopy, originating from Denmark in 1912, has rapidly evolved to diagnose and treat a wide range of musculoskeletal pathologies. Although around for sometime, arthroscopy in the field of orthopedics has traditionally focused on the knee, shoulder, or elbow, as arthroscopy of the hip is technically challenging; the deep structures of the hip, including neurovascular bundles, require specialized training and equipment to access. However, with advances in surgical techniques, hip arthroscopy has become increasingly popular given its ability to treat pathologies with previously poor prognoses such as labral tears, hip arthritis and femoroacetabular impingement (FAI). When indicated, hip arthroscopy results in shorter recovery times, low complication rates, and excellent outcomes in quality of life and pain regardless of age, gender or activity level. The purpose of this e-book is to shed light on this expanding field by delving into the common hip pathology femoroacetabular impingement, its clinical relevance, and to explore various surgical techniques and postoperative rehabilitation. It is our hope that this textbook provides valuable knowledge to advance the field of hip arthroscopy, enhance surgical techniques, and ultimately increase the quality of patient care.
    Keywords: R5-920 ; RD1-811 ; labral ; preservation ; capsular ; management ; femoroacetabular impingement ; hip arthroscopy ; FAI ; bic Book Industry Communication::M Medicine
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  • 94
    Publication Date: 2023-12-21
    Description: Over the last years it has become evident that many neurological diseases of the central nervous system (CNS) are induced by a specific adaptive immune response directed against molecules expressed on CNS-resident cells. Well-recognized examples are anti-N-Methyl-D-Aspartate Receptor (NMDAR) encephalitis which is characterized by the presence of antibodies against neuron-expressed NMDAR, or neuromyelitis optica (NMO), induced by antibodies to astrocyte-expressed aquaporin-4. Many more examples exist, and antibodies, and T or/and B cells have increasingly been associated with CNS disease. Often the symptoms of these diseases have not been typically reported to have an immune aetiology. Beside classical neurological symptoms like ataxia, vision disturbance, and motor or sensory symptoms, these can include cognitive disturbances, behavioral abnormalities, or/and epileptic seizures. Although much has been learned regarding the pathophysiology of prototypic examples of these disorders, there are still major gaps in our understanding of their biology. This may be due to the fact that they are rare diseases, and their therapies are still very limited. This research topic includes contributions addressing the analysis of the adaptive immune response driving disease including target antigens, molecular epitope mapping, and factors involved in the disease pathogenesis such as complement activation cascades, genetic and genomic regulation, as well as environmental triggers. Diagnostic criteria and methods, and treatment are also discussed. The overall aim of the volume is to review progress in our pathophysiological understanding of immune-mediated CNS disorders in order to advance diagnostic and therapeutic approaches, and ultimately improve outcomes for patients.
    Keywords: R5-920 ; RC346-429 ; RC581-607 ; autoimmune encephalitis ; autophagy ; aquaporin-4 ; multiple sclerosis ; neuromyelitis optica spectrum disorder ; T cell ; thyroid gland ; B cells ; NMDA receptor ; myelin oligodendrocyte glycoprotein ; bic Book Industry Communication::M Medicine
    Language: English
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  • 95
    Publication Date: 2023-12-21
    Description: The mononuclear phagocyte system (MPS) comprises dendritic cells (DCs), monocytes and macrophages (MØs) that together play crucial roles in tissue immunity and homeostasis, but also contribute to a broad spectrum of pathologies. They are thus attractive therapeutic targets for immune therapy. However, the distinction between DCs, monocytes and MØ subpopulations has been a matter of controversy and the current nomenclature has been a confounding factor. DCs are remarkably heterogeneous and consist of multiple subsets traditionally defined by their expression of various surface markers. While markers are important to define various populations of the MPS, they do not specifically define the intrinsic nature of a cell population and do not always segregate a bona fide cell type of relative homogeneity. Markers are redundant, or simply define distinct activation states within one subset rather than independent subpopulations. One example are the steady-state CD11b+ DCs which are often not distinguished from monocytes, monocyte-derived cells, and macrophages due to their overlapping phenotype. Lastly, monocyte fate during inflammation results in cells bearing the phenotypic and functional features of both DCs and MØs significantly adding to the confusion. In fact, depending on the context of the study and the focus of the laboratory, a monocyte-derived cell will be either be called "monocyte-derived DCs" or "macrophages". Because the names we give to cells are often associated with a functional connotation, this is much more than simple semantics. The "name" we give to a population fundamentally changes the perception of its biology and can impact on research design and interpretation. Recent evidence in the ontogeny and transcriptional regulation of DCs and MØs, combined with the identification of DC- and MØ-specific markers has dramatically changed our understanding of their interrelationship in the steady state and inflammation. In steady state, DCs are constantly replaced by circulating blood precursors that arise from committed progenitors in the bone marrow. Similarly, some MØ populations are also constantly replaced by circulating blood monocytes. However, others tissue MØs are derived from embryonic precursors, are seeded before birth and maintain themselves in adults by self-renewal. In inflammation, such differentiation pathways are fundamentally changed and unique monocyte-derived inflammatory cells are generated. Current DC, monocyte and MØ nomenclature does not take into account these new developments and as a consequence is quite confusing. We believe that the field is in need of a fresh view on this topic as well as an upfront debate on DC and MØ nomenclature. Our aim is to bring expert junior and senior scientists to revisit this topic in light of these recent developments. This Research Topic will cover all aspects of DC, monocyte and MØ biology including development, transcriptional regulation, functional specializations, in lymphoid and non-lymphoid tissues, and in both human and mouse models. Given the central position of DCs, monocytes and MØs in tissue homeostasis, immunity and disease, this topic should be of interest to a large spectrum of the biomedical community.
    Keywords: R5-920 ; RC581-607 ; nomenclature ; Monocytes ; development ; Dendritic Cells ; Subset ; differentiation ; Antigen Presentation ; Mononuclear Phagocyte System ; Ontogeny ; Macrophages ; bic Book Industry Communication::M Medicine
    Language: English
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  • 96
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    Frontiers Media SA
    Publication Date: 2023-12-21
    Description: Although at first glance mechanisms used to create the variable domains of immunoglobulin appear to be designed to generate diversity at random, closer inspection reveals striking evolutionary constraints on the sequence and structure of these antigen receptors, suggesting that natural selection is operating to create a repertoire that anticipates or is biased towards recognition of specific antigenic properties. This Research Topics issue will be devoted to an examination of the evolution of antigen receptor sequence at the germline level, an evaluation of the repertoire in B cells from fish, pigs and human, an introduction into bioinformatics approaches to the evaluation and analysis of the repertoire as ascertained by high throughput sequencing, and a discussion of how study of the normal repertoire informs the construction or selection of in vitro antibodies for applied purposes.
    Keywords: R5-920 ; RC581-607 ; Antibody repertoire ; immunoglobulin ; B cells ; sequence analysis software ; comparative immunology ; natural antibodies ; bic Book Industry Communication::M Medicine
    Language: English
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  • 97
    Publication Date: 2023-12-21
    Description: There is a growing body of evidence that infectious agents or their products contribute to events leading to unexpected infant deaths. This issue summarizes the current information on the interactions between genetic background of the infant, environmental and developmental risk factors, and the microbial flora of the infant that could trigger lethal responses to common infections.
    Keywords: R5-920 ; RC581-607 ; Virus infection ; Sudden unexpected death in infancy ; sudden infant death syndrome ; Stillbirths ; cigarette smoke ; Risk factors ; Animal Models ; Mechanisms of Death ; sex of infant ; interactions between environmental and genetic risk factors ; bic Book Industry Communication::M Medicine
    Language: English
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  • 98
    Publication Date: 2023-12-21
    Description: It has not been yet clarified whether allergy and asthma are part of the same condition or they follow a parallel path. This Research Topic aims to try and put some light in this parallel march going through crucial topics: from prenatal events to later risk factors such as obesity; and from basic immunology to immunotherapy, both subcutaneous and sublingual. We hope the readers can infer their own conclusions as what is first: egg or chicken.
    Keywords: R5-920 ; RJ1-570 ; Allergy ; Obesity ; Food allergy ; Oxidative stress ; Mediterranean diet ; Immunotherapy ; Genetics ; Epidemiology ; Asthma ; Atopy ; bic Book Industry Communication::M Medicine
    Language: English
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  • 99
    Publication Date: 2023-12-21
    Description: Proliferating cells must adapt their metabolism to fulfill the increased requirements for energy demands and biosynthetic intermediates. This adaptation is particularly relevant in cancer, where sustained rapid proliferation combined with the harsh conditions of the tumor microenvironment represent a major metabolic challenge. Noteworthy, metabolic reprogramming is now considered one of the hallmarks of cancer. However, the one size fits all rarely applies to the metabolic rewiring occurring in cancer cells, which ultimately depends on the combination of several factors such as the tumor’s origin, the specific genetic alterations and the surrounding microenvironment. In the present Research Topic, we compile a series of articles that discuss different metabolic adaptations that proliferating cells undergo to sustain growth and division, as well as the potential therapeutic window to treat certain pathologies, with a special focus on cancer.
    Keywords: R5-920 ; RC648-665 ; cancer metabolism ; proliferation ; mitochondria ; lipogenesis ; metabolic adaptation ; obesity ; Warburg effect ; bic Book Industry Communication::M Medicine
    Language: English
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  • 100
    Publication Date: 2023-12-21
    Description: Alcohol is the sixth leading risk factor for disability and premature death all over the world, and one of the leading causes of premature mortality in western societies; it is a leading risk factor for death in young and middle-age males. Heavy drinking accounts for about two thirds of the burden of disease attributable to alcohol. In the early 1980s, screening and brief interventions (SBI) in primary health care settings were proposed as effective strategies to identify risky drinkers and to help them reduce their drinking. Since then, a growing body of evidence, including several meta-analysis and Cochrane reviews, has shown the efficacy and effectiveness of SBI in primary health settings. However, demonstrating the effectiveness of SBI has not been insufficient to facilitate its general implementation in the routines of primary health care physicians, and in fact the dissemination of SBI has proven to be a difficult business. Qualitative and quantitative research has identified most of the facilitators and barriers for its implementation, and publicly funded research has been earmarked to address the dissemination problems worldwide. Some examples are the World Health Organization Phase III and Phase IV studies on the identification and management of alcohol-related problems in primary care, EU funded projects (PHEPA, AMPHORA, ODHIN, BISTAIRS), the UK SIPS trials and the SBIRT developments sponsored by the Substance Abuse & Mental Health Services Administration (SAMHSA) in the USA. The efficacy and effectiveness of SBI in primary health is now well established, but there are still some questions that remain unsolved: which practitioners should deliver them; what length should they be; is there a need for booster sessions; is there added value of a motivational approach? These questions, together with other relevant aspects of SBI, need ongoing research. In recent years, SBIs have been tested in settings other than primary health care, including hospitals, accident and emergency rooms, criminal justice, colleges and universities, social services and pharmacies. In some of those areas, the evidence is scarce (for example, pharmacies) while in others it is very promising (for example, students and hospitals). New technologies have also offered the possibility of online tools, and, in the last few years, different digital-based applications have been tested successfully as new ways to deliver effective SBIs to larger amounts of people. Brief interventions have also spread to drugs other than alcohol. This book aims to be an update of the state-of-the art of brief advice. It is a compilation of articles published by some of the most relevant researchers in the field in Frontiers in Psychiatry between 2014 and 2016.
    Keywords: R5-920 ; RC435-571 ; brief intervention ; hazardous drinking ; brief advice ; Alcohol Drinking ; At-risk drinking ; bic Book Industry Communication::M Medicine
    Language: English
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