Advancing Open Science
for more than 25 years
Supporting academic communities
since 1996
 
12 pages, 5175 KiB  
Article
Unselective Measurement of Tumor-to-Stroma Proportion in Colon Cancer at the Invasion Front—An Elusive Prognostic Factor: Original Patient Data and Review of the Literature
by Zsolt Fekete, Patricia Ignat, Amelia Cristina Resiga, Nicolae Todor, Alina-Simona Muntean, Liliana Resiga, Sebastian Curcean, Gabriel Lazar, Alexandra Gherman and Dan Eniu
Diagnostics 2024, 14(8), 836; https://doi.org/10.3390/diagnostics14080836 (registering DOI) - 18 Apr 2024
Abstract
The tumor-to-stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study, we proposed confirming or dismissing the hypothesis that a simple measurement of stroma quantity is [...] Read more.
The tumor-to-stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study, we proposed confirming or dismissing the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma < 10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients, had stroma-rich tumors, 4% had stroma-poor tumors and 89.2% had tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease-specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation between stroma proportion and tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma–tumor interaction has to be further elucidated. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Gastrointestinal Diseases—Volume 2)
Show Figures

Figure 1

18 pages, 6400 KiB  
Article
Vegetation–Lake–Sand Landscape of Northeast China Sandy Land between 1980 and 2022: Pattern, Evolution, and Driving Forces
by Weiyi Lu, Geer Teni and Huishi Du
Sustainability 2024, 16(8), 3382; https://doi.org/10.3390/su16083382 (registering DOI) - 18 Apr 2024
Abstract
Northeast China’s sandy region is an arid and semi-arid zone highly susceptible to climate change. Investigating the long-term changes in the Northeast China sandy land (Northeast China sandy land, DBSL) landscape can provide an important basis for the ecological restoration of this region. [...] Read more.
Northeast China’s sandy region is an arid and semi-arid zone highly susceptible to climate change. Investigating the long-term changes in the Northeast China sandy land (Northeast China sandy land, DBSL) landscape can provide an important basis for the ecological restoration of this region. This study analyzed long-term remote sensing data of the DBSL from 1980 to 2022 and explored the spatial pattern, evolution, and driving mechanisms. In 2022, vegetation was mainly distributed in the northwest, center, and southwest, covering a total area of 30,508.82 km2. Areas with high and medium vegetation cover showed strong aggregation characteristics and were mainly distributed in the southwest, whereas those with low vegetation coverage were highly dispersed and widely distributed in the central region. Lakes were widely distributed in the northwest and central regions, with a total area of 2736.43 km2. In the last 42 years, the vegetation cover decreased by 24.48%. Areas with high and medium vegetation coverage decreased in size, and those with low vegetation coverage first increased and then decreased, with overall decreases of 35.35%, 19.16%, and 6.88%, respectively. The overall area of the DBSL showed various degrees of degradation. Shrinking and dry lakes were concentrated in the sandy hinterland. The lake landscape changed significantly from 1990 to 2010, with a decrease in lake area of 27.41%. In contrast, the sandy area increased by 25.65%, indicating a high degree of desertification. However, from 2005 to 2022, desertification decelerated. The most important factors driving the evolution of the DBSL were socio-economic factors. The increase in human disturbance will have a certain impact on the landscape changes in the region in the short term. The national policy of returning farmland to fields and grasslands will affect the increase of vegetation and lake landscape area in the short term, and the sand area and excessive animal husbandry will be reduced. This study provides a scientific basis for ecological restoration and sustainable development in Northeast China. Full article
Show Figures

Figure 1

20 pages, 638 KiB  
Systematic Review
Pharmacological Treatment for Terminal Agitation, Delirium and Anxiety in Frail Older Patients
by Dine A. D. Jennes, Tim Biesbrouck, Maaike L. De Roo, Tinne Smets and Nele Van Den Noortgate
Geriatrics 2024, 9(2), 51; https://doi.org/10.3390/geriatrics9020051 (registering DOI) - 18 Apr 2024
Abstract
Context: Psychological distress symptoms in the last days of life often contribute to the overall symptom burden in frail older patients. Good symptom management practices are crucial to ensure high-quality end-of-life care in an aging population, though the best pharmacological approach to treat [...] Read more.
Context: Psychological distress symptoms in the last days of life often contribute to the overall symptom burden in frail older patients. Good symptom management practices are crucial to ensure high-quality end-of-life care in an aging population, though the best pharmacological approach to treat these psychological symptoms has yet to be established. Objectives: To identify current evidence-based and practice-based knowledge of pharmacological interventions for the treatment of agitation, delirium, and anxiety during the last days of life in frail older patients. Methods: A systematic, mixed methods review was performed through MEDLINE via PubMed and EMBASE from inception until February 2022 and updated through March 2023. National and international guideline databases and grey literature were searched for additional studies and guidelines. Results: Four quantitative studies, two non-randomized and two descriptive, were identified. No randomized controlled trials met inclusion criteria. No qualitative studies were withheld. The three consensus-based protocols that were found through citation searching and screening of grey literature did not meet the standards for inclusion. Haloperidol is recommended in consensus-based guidelines for delirium and is widely used, but high-quality evidence about its efficacy is missing. Better control of agitation or refractory delirium might be achieved with the addition of a benzodiazepine. There is no evidence available about the treatment of anxiety in the last days of life in frail older patients. Conclusions: This mixed methods review demonstrates the lack of good quality evidence that is needed to help clinicians with pharmacological treatment decisions when confronted with psychological symptoms in the last days of life in frail older patients. Population aging will only emphasize the need for further research in this specific population. Full article
(This article belongs to the Special Issue Enriching Lives: Palliative Care in Geriatrics)
Show Figures

Figure 1

14 pages, 5032 KiB  
Article
Antiproliferative Activity of N-Acylhydrazone Derivative on Hepatocellular Carcinoma Cells Involves Transcriptional Regulation of Genes Required for G2/M Transition
by Amanda Aparecida Ribeiro Andrade, Fernanda Pauli, Carolina Girotto Pressete, Bruno Zavan, João Adolfo Costa Hanemann, Marta Miyazawa, Rafael Fonseca, Ester Siqueira Caixeta, Julia Louise Moreira Nacif, Alexandre Ferro Aissa, Eliezer J. Barreiro and Marisa Ionta
Biomedicines 2024, 12(4), 892; https://doi.org/10.3390/biomedicines12040892 (registering DOI) - 18 Apr 2024
Abstract
Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed [...] Read more.
Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage. The drug arsenal used in systemic therapy for HCC is very limited. Multikinase inhibitors sorafenib (Nexavar®) and lenvatinib (Lenvima®) have been used as first-line drugs with modest therapeutic effects. In this scenario, it is imperative to search for new therapeutic strategies for HCC. Herein, the antiproliferative activity of N-acylhydrazone derivatives was evaluated on HCC cells (HepG2 and Hep3B), which were chemically planned on the ALL-993 scaffold, a potent inhibitor of vascular endothelial growth factor 2 (VEGFR2). The substances efficiently reduced the viability of HCC cells, and the LASSBio-2052 derivative was the most effective. Further, we demonstrated that LASSBio-2052 treatment induced FOXM1 downregulation, which compromises the transcriptional activation of genes required for G2/M transition, such as AURKA and AURKB, PLK1, and CDK1. In addition, LASSBio-2052 significantly reduced CCNB1 and CCND1 expression in HCC cells. Our findings indicate that LASSBio-2052 is a promising prototype for further in vivo studies. Full article
(This article belongs to the Special Issue Signaling Pathways That Regulate Cell Proliferation and Apoptosis)
Show Figures

Figure 1

23 pages, 618 KiB  
Article
Translation and Validation of the Dutch Version of the Spiritual Care Competence Questionnaire (SCCQ-NL)
by Merel Schoot, Agna Bartels-Velthuis, Daniela Rodrigues Recchia, Eckhard Frick, Arndt Büssing and Rogier Hoenders
Religions 2024, 15(4), 496; https://doi.org/10.3390/rel15040496 (registering DOI) - 18 Apr 2024
Abstract
The importance of spirituality in the treatment of mental illness is increasingly acknowledged, but mental healthcare professionals often feel they lack specific competence. An instrument is missing to quantify the spiritual care competence of mental healthcare professionals in the Netherlands. The aim of [...] Read more.
The importance of spirituality in the treatment of mental illness is increasingly acknowledged, but mental healthcare professionals often feel they lack specific competence. An instrument is missing to quantify the spiritual care competence of mental healthcare professionals in the Netherlands. The aim of this study was thus to translate the Spiritual Care Competence Questionnaire (SCCQ) into Dutch and validate it for use in mental healthcare. After translation, the SCCQ-NL was distributed in a cross-sectional design among 3497 healthcare professionals in two mental healthcare institutions (MHIs) in the Netherlands. In the sample of 730 completed questionnaires, exploratory factor analysis revealed seven factors: perception of spiritual needs competencies, team spirit, spiritual self-awareness, documentation competencies, empowerment and proactive opening competencies, knowledge about other religions, and conversation competencies. One item was deleted during the process. Internal consistency for the 25-item SCCQ-NL subscales is sufficient with Cronbach’s alpha ranging from 0.64 to 0.81. Conversation competencies and perception of spiritual needs scored highest in the sample, next to knowledge about other religions and empowerment competencies, while spiritual self-awareness, team spirit and documentation competencies scored the lowest. Small but significant differences in several subscale scores were found for profession, identifying oneself as a believer, practicing prayer and/or meditation, age and working years. The SCCQ-NL can be used for the assessment of spiritual care competencies and for the planning and evaluation of training and improvement strategies. Full article
(This article belongs to the Special Issue Spirituality in Psychiatry)
Show Figures

Figure 1

24 pages, 1723 KiB  
Review
New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review
by Jorge E. Jalil, Luigi Gabrielli, María Paz Ocaranza, Paul MacNab, Rodrigo Fernández, Bruno Grassi, Paulina Jofré, Hugo Verdejo, Monica Acevedo, Samuel Cordova, Luis Sanhueza and Douglas Greig
Int. J. Mol. Sci. 2024, 25(8), 4407; https://doi.org/10.3390/ijms25084407 - 17 Apr 2024
Abstract
This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including [...] Read more.
This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of β-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans. Full article
(This article belongs to the Special Issue New Cardiovascular Risk Factors)
Show Figures

Figure 1

27 pages, 1109 KiB  
Article
Defining Self-Management for Solid Organ Transplantation Recipients: A Mixed Method Study
by Katie Brunner, Lydia Weisschuh, Stefan Jobst, Christiane Kugler and Anne Rebafka
Nurs. Rep. 2024, 14(2), 961-987; https://doi.org/10.3390/nursrep14020073 (registering DOI) - 17 Apr 2024
Abstract
Patients with Solid Organ Transplantations (SOTx) face long-term lifestyle adaptations, psychological and social adjustments, and complex self-care regimes to maintain health post-transplant. Self-management (SM) skills represent important aspects of nursing communication with SOTx patients; however, there is potential for SM to be defined [...] Read more.
Patients with Solid Organ Transplantations (SOTx) face long-term lifestyle adaptations, psychological and social adjustments, and complex self-care regimes to maintain health post-transplant. Self-management (SM) skills represent important aspects of nursing communication with SOTx patients; however, there is potential for SM to be defined narrowly in terms of medication adherence. The study presented here collated the existing definitions in a mixed method review in order to identify SM attributes for this group (including those unique to this population). Secondary analysis of a dataset and bibliographic analysis and an expert panel were used to develop a comprehensive working definition of SOTx patients. The analysis comprised critical interpretation of the evolving definition content, concepts, and contexts of application in current usages and over time. We identified eight definitions and 63 cited definition sources from bibliographic analysis. Findings identified limitations of the existing definitions. Population-specific attributes included optimisation of transplant outcomes, active engagement in healthy behaviours, control, structure, and discipline characteristics, and moderating factors of patient motivation, self-efficacy, and cognitive function. A critical appraisal of definitions indicated inadequately defined aspects such as setting, temporal dimension, concept interaction, interventions, and measurable outcomes. The bibliographic analysis highlighted the influence of broader chronic illness constructions of SM, underpinning the generalisable SM attributes in current definitions. Further research may advance the development of a definition in exploring the relevance of SOTx-specific attributes of the definition. Full article
(This article belongs to the Special Issue Self-Management of Chronic Disease)
Show Figures

Figure 1

17 pages, 8939 KiB  
Article
ANNs Predicting Noisy Signals in Electronic Circuits: A Model Predicting the Signal Trend in Amplification Systems
by Alessandro Massaro
AI 2024, 5(2), 533-549; https://doi.org/10.3390/ai5020027 - 17 Apr 2024
Abstract
In the proposed paper, an artificial neural network (ANN) algorithm is applied to predict the electronic circuit outputs of voltage signals in Industry 4.0/5.0 scenarios. This approach is suitable to predict possible uncorrected behavior of control circuits affected by unknown noises, and to [...] Read more.
In the proposed paper, an artificial neural network (ANN) algorithm is applied to predict the electronic circuit outputs of voltage signals in Industry 4.0/5.0 scenarios. This approach is suitable to predict possible uncorrected behavior of control circuits affected by unknown noises, and to reproduce a testbed method simulating the noise effect influencing the amplification of an input sinusoidal voltage signal, which is a basic and fundamental signal for controlled manufacturing systems. The performed simulations take into account different noise signals changing their time-domain trend and frequency behavior to prove the possibility of predicting voltage outputs when complex signals are considered at the control circuit input, including additive disturbs and noises. The results highlight that it is possible to construct a good ANN training model by processing only the registered voltage output signals without considering the noise profile (which is typically unknown). The proposed model behaves as an electronic black box for Industry 5.0 manufacturing processes automating circuit and machine tuning procedures. By analyzing state-of-the-art ANNs, the study offers an innovative ANN-based versatile solution that is able to process various noise profiles without requiring prior knowledge of the noise characteristics. Full article
Show Figures

Figure 1

25 pages, 17881 KiB  
Article
Adapting the Segment Anything Model for Volumetric X-ray Data-Sets of Arbitrary Sizes
by Roland Gruber, Steffen Rüger and Thomas Wittenberg
Appl. Sci. 2024, 14(8), 3391; https://doi.org/10.3390/app14083391 - 17 Apr 2024
Abstract
We propose a new approach for volumetric instance segmentation in X-ray Computed Tomography (CT) data for Non-Destructive Testing (NDT) by combining the Segment Anything Model (SAM) with tile-based Flood Filling Networks (FFN). Our work evaluates the performance of SAM on volumetric NDT data-sets [...] Read more.
We propose a new approach for volumetric instance segmentation in X-ray Computed Tomography (CT) data for Non-Destructive Testing (NDT) by combining the Segment Anything Model (SAM) with tile-based Flood Filling Networks (FFN). Our work evaluates the performance of SAM on volumetric NDT data-sets and demonstrates its effectiveness to segment instances in challenging imaging scenarios. We implemented and evaluated techniques to extend the image-based SAM algorithm for the use with volumetric data-sets, enabling the segmentation of three-dimensional objects using FFN’s spatial adaptability. The tile-based approach for SAM leverages FFN’s capabilities to segment objects of any size. We also explore the use of dense prompts to guide SAM in combining segmented tiles for improved segmentation accuracy. Our research indicates the potential of combining SAM with FFN for volumetric instance segmentation tasks, particularly in NDT scenarios and segmenting large entities and objects. While acknowledging remaining limitations, our study provides insights and establishes a foundation for advancements in instance segmentation in NDT scenarios. Full article
(This article belongs to the Special Issue Digital Image Processing: Advanced Technologies and Applications)
Show Figures

Figure 1

10 pages, 1544 KiB  
Article
Biallelic NDUFA4 Deletion Causes Mitochondrial Complex IV Deficiency in a Patient with Leigh Syndrome
by Doriana Misceo, Petter Strømme, Fatemeh Bitarafan, Maninder Singh Chawla, Ying Sheng, Sandra Monica Bach de Courtade, Lars Eide and Eirik Frengen
Genes 2024, 15(4), 500; https://doi.org/10.3390/genes15040500 (registering DOI) - 17 Apr 2024
Abstract
Oxidative phosphorylation involves a complex multi-enzymatic mitochondrial machinery critical for proper functioning of the cell, and defects herein cause a wide range of diseases called “primary mitochondrial disorders” (PMDs). Mutations in about 400 nuclear and 37 mitochondrial genes have been documented to cause [...] Read more.
Oxidative phosphorylation involves a complex multi-enzymatic mitochondrial machinery critical for proper functioning of the cell, and defects herein cause a wide range of diseases called “primary mitochondrial disorders” (PMDs). Mutations in about 400 nuclear and 37 mitochondrial genes have been documented to cause PMDs, which have an estimated birth prevalence of 1:5000. Here, we describe a 4-year-old female presenting from early childhood with psychomotor delay and white matter signal changes affecting several brain regions, including the brainstem, in addition to lactic and phytanic acidosis, compatible with Leigh syndrome, a genetically heterogeneous subgroup of PMDs. Whole genome sequencing of the family trio identified a homozygous 12.9 Kb deletion, entirely overlapping the NDUFA4 gene. Sanger sequencing of the breakpoints revealed that the genomic rearrangement was likely triggered by Alu elements flanking the gene. NDUFA4 encodes for a subunit of the respiratory chain Complex IV, whose activity was significantly reduced in the patient’s fibroblasts. In one family, dysfunction of NDUFA4 was previously documented as causing mitochondrial Complex IV deficiency nuclear type 21 (MC4DN21, OMIM 619065), a relatively mild form of Leigh syndrome. Our finding confirms the loss of NDUFA4 function as an ultra-rare cause of Complex IV defect, clinically presenting as Leigh syndrome. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
Show Figures

Figure 1

15 pages, 2379 KiB  
Article
Enhancing Apple Cultivar Classification Using Multiview Images
by Silvia Krug and Tino Hutschenreuther
J. Imaging 2024, 10(4), 94; https://doi.org/10.3390/jimaging10040094 - 17 Apr 2024
Abstract
Apple cultivar classification is challenging due to the inter-class similarity and high intra-class variations. Human experts do not rely on single-view features but rather study each viewpoint of the apple to identify a cultivar, paying close attention to various details. Following our previous [...] Read more.
Apple cultivar classification is challenging due to the inter-class similarity and high intra-class variations. Human experts do not rely on single-view features but rather study each viewpoint of the apple to identify a cultivar, paying close attention to various details. Following our previous work, we try to establish a similar multiview approach for machine-learning (ML)-based apple classification in this paper. In our previous work, we studied apple classification using one single view. While these results were promising, it also became clear that one view alone might not contain enough information in the case of many classes or cultivars. Therefore, exploring multiview classification for this task is the next logical step. Multiview classification is nothing new, and we use state-of-the-art approaches as a base. Our goal is to find the best approach for the specific apple classification task and study what is achievable with the given methods towards our future goal of applying this on a mobile device without the need for internet connectivity. In this study, we compare an ensemble model with two cases where we use single networks: one without view specialization trained on all available images without view assignment and one where we combine the separate views into a single image of one specific instance. The two latter options reflect dataset organization and preprocessing to allow the use of smaller models in terms of stored weights and number of operations than an ensemble model. We compare the different approaches based on our custom apple cultivar dataset. The results show that the state-of-the-art ensemble provides the best result. However, using images with combined views shows a decrease in accuracy by 3% while requiring only 60% of the memory for weights. Thus, simpler approaches with enhanced preprocessing can open a trade-off for classification tasks on mobile devices. Full article
Show Figures

Figure 1

10 pages, 356 KiB  
Article
Development of a Targeted NGS Assay for the Detection of Respiratory Pathogens including SARS-CoV-2 in Felines
by Jobin J. Kattoor, Mothomang Mlalazi-Oyinloye, Sarah M. Nemser and Rebecca P. Wilkes
Pathogens 2024, 13(4), 335; https://doi.org/10.3390/pathogens13040335 (registering DOI) - 17 Apr 2024
Abstract
Acute respiratory diseases in felines can be attributed to a diverse range of pathogens. The recent emergence of novel viruses, particularly SARS-CoV-2 and its variants, has also been associated with respiratory ailments in cats and other pets, underscoring the need for a highly [...] Read more.
Acute respiratory diseases in felines can be attributed to a diverse range of pathogens. The recent emergence of novel viruses, particularly SARS-CoV-2 and its variants, has also been associated with respiratory ailments in cats and other pets, underscoring the need for a highly sensitive diagnostic assay capable of concurrently detecting multiple respiratory pathogens. In this study, we developed a targeted next generation sequencing panel using Ion Torrent Ampliseq technology to detect multiple respiratory pathogens, including recent SARS-CoV-2 variants and Feline herpesvirus-1, Feline calicivirus, Bordetella bronchiseptica, Mycoplasmopsis (previously Mycoplasma) felis, and Chlamydia felis. A PCR amplification-based library preparation, employing primers designed for pathogen target regions, was synthesized and divided into two pools, followed by sequencing and assembly to a repertoire of target pathogen genomes. Analytical sensitivity was assessed based on Ct values from real-time PCR for the corresponding pathogens, indicating an equivalent detection limit. Most of the pathogens under study were positively identified to a limit of approximately Ct 36, whereas for Feline herpesvirus-1 and SARS-CoV-2, positive reads were observed in samples with a Ct of 37. Based on a limited number of samples, the diagnostic sensitivity values for the SARS-CoV-2, Feline herpesvirus-1, and M. felis samples were 100% with no false negative results. The diagnostic specificity of SARS-CoV-2, Feline herpesvirus-1, Feline calicivirus, and C. felis were 100%. Importantly, none of the target primers exhibited non-specific amplification, ensuring the absence of false positive results for other pathogens within the study. Additionally, the assay’s specificity was validated by cross-referencing the raw sequencing data with established databases like BLAST, affirming the high specificity of the targeted Next-Generation Sequencing (tNGS) assay. Variations in the sequencing reads of different pathogens were observed when subjected to diverse extraction methods. Rigorous assessment of the assay’s reliability involved reproducibility across testing personnel and repeated runs. The developed assay’s clinical applicability was tested using samples submitted to the diagnostic laboratory from cat shelters and suspected cases. The developed targeted next-generation sequencing methodology empowers the detection of multiple respiratory pathogens manifesting similar clinical symptoms while offering confirmation of results through genome sequencing. Full article
(This article belongs to the Special Issue Diagnostics of Animal Viral Infectious Diseases)
22 pages, 4938 KiB  
Article
Functional and Molecular Analysis of Human Osteoarthritic Chondrocytes Treated with Bone Marrow-Derived MSC-EVs
by Annachiara Scalzone, Clara Sanjurjo-Rodríguez, Rolando Berlinguer-Palmini, Anne M. Dickinson, Elena Jones, Xiao-Nong Wang and Rachel E. Crossland
Bioengineering 2024, 11(4), 388; https://doi.org/10.3390/bioengineering11040388 (registering DOI) - 17 Apr 2024
Abstract
Osteoarthritis (OA) is a degenerative joint disease, causing impaired mobility. There are currently no effective therapies other than palliative treatment. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have shown promise in attenuating OA progression, promoting chondral regeneration, and modulating joint [...] Read more.
Osteoarthritis (OA) is a degenerative joint disease, causing impaired mobility. There are currently no effective therapies other than palliative treatment. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have shown promise in attenuating OA progression, promoting chondral regeneration, and modulating joint inflammation. However, the precise molecular mechanism of action driving their beneficial effects has not been fully elucidated. In this study, we analyzed MSC-EV-treated human OA chondrocytes (OACs) to assess viability, proliferation, migration, cytokine and catabolic protein expression, and microRNA and mRNA profiles. We observed that MSC-EV-treated OACs displayed increased metabolic activity, proliferation, and migration compared to the controls. They produced decreased proinflammatory (Il-8 and IFN-γ) and increased anti-inflammatory (IL-13) cytokines, and lower levels of MMP13 protein coupled with reduced expression of MMP13 mRNA, as well as negative microRNA regulators of chondrogenesis (miR-145-5p and miR-21-5p). In 3D models, MSC-EV-treated OACs exhibited enhanced chondrogenesis-promoting features (elevated sGAG, ACAN, and aggrecan). MSC-EV treatment also reversed the pathological impact of IL-1β on chondrogenic gene expression and extracellular matrix component (ECM) production. Finally, MSC-EV-treated OACs demonstrated the enhanced expression of genes associated with cartilage function, collagen biosynthesis, and ECM organization and exhibited a signature of 24 differentially expressed microRNAs, associated with chondrogenesis-associated pathways and ECM interactions. In conclusion, our data provide new insights on the potential mechanism of action of MSC-EVs as a treatment option for early-stage OA, including transcriptomic analysis of MSC-EV-treated OA, which may pave the way for more targeted novel therapeutics. Full article
(This article belongs to the Section Regenerative Engineering)
Show Figures

Figure 1

18 pages, 3912 KiB  
Article
NLRX1 Inhibits LPS-Induced Microglial Death via Inducing p62-Dependent HO-1 Expression, Inhibiting MLKL and Activating PARP-1
by Yu-Ling Huang, Duen-Yi Huang, Vladlen Klochkov, Chi-Ming Chan, Yuan-Shen Chen and Wan-Wan Lin
Antioxidants 2024, 13(4), 481; https://doi.org/10.3390/antiox13040481 (registering DOI) - 17 Apr 2024
Abstract
The activation of microglia and the production of cytokines are key factors contributing to progressive neurodegeneration. Despite the well-recognized neuronal programmed cell death regulated by microglial activation, the death of microglia themselves is less investigated. Nucleotide-binding oligomerization domain, leucine-rich repeat-containing X1 (NLRX1) functions [...] Read more.
The activation of microglia and the production of cytokines are key factors contributing to progressive neurodegeneration. Despite the well-recognized neuronal programmed cell death regulated by microglial activation, the death of microglia themselves is less investigated. Nucleotide-binding oligomerization domain, leucine-rich repeat-containing X1 (NLRX1) functions as a scaffolding protein and is involved in various central nervous system diseases. In this study, we used the SM826 microglial cells to understand the role of NLRX1 in lipopolysaccharide (LPS)-induced cell death. We found LPS-induced cell death is blocked by necrostatin-1 and zVAD. Meanwhile, LPS can activate poly (ADP-ribose) polymerase-1 (PARP-1) to reduce DNA damage and induce heme oxygenase (HO)-1 expression to counteract cell death. NLRX1 silencing and PARP-1 inhibition by olaparib enhance LPS-induced SM826 microglial cell death in an additive manner. Less PARylation and higher DNA damage are observed in NLRX1-silencing cells. Moreover, LPS-induced HO-1 gene and protein expression through the p62-Keap1-Nrf2 axis are attenuated by NLRX1 silencing. In addition, the Nrf2-mediated positive feedback regulation of p62 is accordingly reduced by NLRX1 silencing. Of note, NLRX1 silencing does not affect LPS-induced cellular reactive oxygen species (ROS) production but increases mixed lineage kinase domain-like pseudokinase (MLKL) activation and cell necroptosis. In addition, NLRX1 silencing blocks bafilomycin A1-induced PARP-1 activation. Taken together, for the first time, we demonstrate the role of NLRX1 in protecting microglia from LPS-induced cell death. The underlying protective mechanisms of NLRX1 include upregulating LPS-induced HO-1 expression via Nrf2-dependent p62 expression and downstream Keap1-Nrf2 axis, mediating PARP-1 activation for DNA repair via ROS- and autophagy-independent pathway, and reducing MLKL activation. Full article
(This article belongs to the Special Issue Oxidative Stress and Nrf2-Mediated Cellular Inflammation)
Show Figures

Graphical abstract

24 pages, 919 KiB  
Article
Building the Resilience of Marginal Rural Areas Using a Complementary Characterization Approach: Possible Beneficial Health Effects and Stress Tolerance of Italian Common Bean (Phaseolus vulgaris L.) Landraces
by Martina Falcione, Alessandra Renella, Vadym Samukha, Mayra Colardo, Melissa Simiele, Gabriella Stefania Scippa, Marco Segatto and Dalila Trupiano
Diversity 2024, 16(4), 240; https://doi.org/10.3390/d16040240 (registering DOI) - 17 Apr 2024
Abstract
Common bean landraces, besides contributing to the preservation of the social and cultural identity of the local communities of the production area, typically display adaptability to adverse agro-climatic conditions. This adapted germplasm is a repository of the gene pool and also shows typical [...] Read more.
Common bean landraces, besides contributing to the preservation of the social and cultural identity of the local communities of the production area, typically display adaptability to adverse agro-climatic conditions. This adapted germplasm is a repository of the gene pool and also shows typical phytochemical profiles, representing an essential source of bioactive components. However, genetic erosion is progressively affecting this genetic material, creating serious threats to its cultivation in marginal rural areas and use as a source of biodiversity and bioproducts. In the present work, a comprehensive approach was used to characterize the seed morpho-colorimetric traits, genetic diversity, and NMR metabolomic profiles of three Italian common bean landraces. Specific physiological and biochemical features (antioxidant molecules, osmolytes, structural reorganization of photosynthetic pigment, etc.), together with the accumulation of distinctive metabolites, contribute to the description of the observed diversity among the landraces in terms of the salt stress response and antiproliferative abilities on intestinal human cancer cells. This information could be useful in establishing their value in terms of environmental and/or human health “service”, both essential to translating landraces into competitive products, a prerequisite for envisioning appropriate strategies for their conservation and a driving force for the revitalization of marginal rural areas. Full article
(This article belongs to the Special Issue Advances in Crop Genetic Diversity: Challenges and Opportunities)
12 pages, 1090 KiB  
Article
Comparative Bioactive Compounds and Mineral Properties of South African and Lesotho Artemisia afra (Jacq.) Genotypes
by Matumelo Rafiri, Moosa Mahmood Sedibe and Goitsemang Mahlomola Hendry Dikane
Plants 2024, 13(8), 1126; https://doi.org/10.3390/plants13081126 (registering DOI) - 17 Apr 2024
Abstract
Artemisia afra is a plant that grows in the northern, central, and coastal regions of South Africa, as well as in neighboring countries such as Eswatini and Lesotho. These phytochemicals can be used as active compounds in plant-based medicine. Therefore, it is important [...] Read more.
Artemisia afra is a plant that grows in the northern, central, and coastal regions of South Africa, as well as in neighboring countries such as Eswatini and Lesotho. These phytochemicals can be used as active compounds in plant-based medicine. Therefore, it is important to determine how plant minerals and phytochemicals, particularly bioactive compounds, are affected by the geolocation in which they grow. This study aimed to evaluate the mineral and phytochemical properties of A. afra genotypes in the southern regions of Africa. Leaf samples of A. afra genotypes were collected from Lesotho, in Mohale’s Hoek and Roma. In South Africa, leaf samples were collected in Wepener and Hobhouse, and 80 plants were randomly selected for phytochemical and mineral analyses. This study reveals that phosphorus, calcium, potassium, iron, and zinc loaded positively to the first principal component, while copper loaded positively to the second principal component with variabilities of 29.95% and 21.12%, respectively. Furthermore, both the Mohale’s Hoek and Hobhouse genotypes exhibited relatively high levels of ascorbic acid, phenolic compounds, flavonoids, and tannins. It is worth noting that genotypes from Roma and Wepener showed higher levels of foliar magnesium. Thus, the Mohale’s Hoek and Hobhouse genotypes could be recommended for their better phytochemical contents. Full article
(This article belongs to the Special Issue Advanced Research on African Medicinal Plants)
Show Figures

Figure 1

24 pages, 3148 KiB  
Article
Sustainability Evaluation of Residential Buildings Based on the Footprint Family: Application to Case Studies in Andalusia
by Jaime Solís-Guzmán, Paula Garzón-González, Patricia González-Vallejo and Madelyn Marrero
Buildings 2024, 14(4), 1131; https://doi.org/10.3390/buildings14041131 (registering DOI) - 17 Apr 2024
Abstract
The criteria on green public procurement of the European Union establish that the economic budgets of building projects must be complemented by their derived environmental and social costs. These criteria are currently being adapted to the requirements related to the circular economy, such [...] Read more.
The criteria on green public procurement of the European Union establish that the economic budgets of building projects must be complemented by their derived environmental and social costs. These criteria are currently being adapted to the requirements related to the circular economy, such as the use of methods to evaluate buildings environmentally. However, most methods available in the European and Spanish markets require prior training, which makes their use difficult. This paper presents an evaluation method, CEACE, for housing construction based on the determination of their footprints (ecological, carbon, and water footprints), also called the footprint family, to which the economic and social evaluation is added, as is the quantification of the construction and demolition waste generated. This method is validated with the assessment of fifteen residential buildings in Andalusia and creates an indicator that will allow technicians, companies, and administrations to evaluate projects in accordance with the criteria of green public procurement. The method is sensitive to changes in the type of building, foundation solution, and underground construction. Full article
(This article belongs to the Special Issue Advances in Project Development and Construction Management)
Show Figures

Figure 1

15 pages, 1394 KiB  
Article
The Relation between Atmospheric Aerosol Concentration and SARS-CoV-2 Variants’ Infection and Mortality Rates in the United States: A Remote-Sensing Perspective
by Yasin Elshorbany, Sarah Mixson, Laila Marcum and Jason L. Salemi
Sustainability 2024, 16(8), 3381; https://doi.org/10.3390/su16083381 (registering DOI) - 17 Apr 2024
Abstract
Numerous studies have highlighted the health benefits associated with reducing aerosol particles and other pollutants. Recent studies have shown a positive correlation between exposure to aerosol particles and COVID-19 cases. In this study, we investigate the relationship between aerosol particle concentration and COVID-19 [...] Read more.
Numerous studies have highlighted the health benefits associated with reducing aerosol particles and other pollutants. Recent studies have shown a positive correlation between exposure to aerosol particles and COVID-19 cases. In this study, we investigate the relationship between aerosol particle concentration and COVID-19 variants’ infection and mortality rates. Remote-sensing data on aerosol optical depth (AOD), a surrogate for atmospheric aerosol levels, were collected and analyzed in three regions within the states of California, Illinois, and North and South Carolina. These regions were selected to reflect the variability in aerosol concentration and anomalies during the COVID-19 period (2020–2022) compared to a reference period (2010–2019). We found consistent positive linear correlations across most regions between COVID-19 mortality rates and AOD levels below 0.2. These correlations were found to be independent of the change in aerosol levels relative to the reference period. In North and South Carolina, the Delta variant was associated with not only a high mortality rate but also a steeper increase in mortality rate per AOD of 39.6 ± 1.5 (R2 = 0.87) compared to Alpha at 10.5 ± 0.3 (R2 = 0.85). However, due to the lower mortality rate of the Delta variant compared to the Alpha variant in Illinois, the Delta variant has a lower correlation slope of 28.3 ± 1 (R2 = 0.94) compared to the Alpha variant at 52.1 ± 1.8 (R2 = 0.78). No correlation between mortality rate and AOD was observed for the Omicron variants in any of the investigated counties except in California where a weak positive correlation was evident. Our findings establish a compelling link between aerosol concentrations and SARS-CoV-2 infection and mortality. Our results underscore the urgent need for further research to elucidate the underlying mechanisms and broader implications, leading to more sustainable solutions to curb the airborne transmission of COVID-19 viruses and other viral infections in general. Full article
(This article belongs to the Special Issue Environmental Pollution and Impacts on Human Health)
26 pages, 3028 KiB  
Article
A Comprehensive Evaluation of Resilience in Abandoned Open-Pit Mine Slopes Based on a Two-Dimensional Cloud Model with Combination Weighting
by Liangxing Jin, Pingting Liu, Wenbing Yao and Junjie Wei
Mathematics 2024, 12(8), 1213; https://doi.org/10.3390/math12081213 (registering DOI) - 17 Apr 2024
Abstract
The stability of abandoned open-pit mine slopes and their ecological environment are threatened owing to their fragile, complicated, and uncertain characteristics. This study establishes a novel evaluation indicator system for enhancing mine design and environmental protection insight. The weights in the system are [...] Read more.
The stability of abandoned open-pit mine slopes and their ecological environment are threatened owing to their fragile, complicated, and uncertain characteristics. This study establishes a novel evaluation indicator system for enhancing mine design and environmental protection insight. The weights in the system are assigned using a combined method, which consists of the game theory, the interval analytic hierarchy process (IAHP), and the entropy weight method (EWM). The IAHP is optimized by the improved radial movement optimal (IRMO) algorithm and the simulated annealing (SA) algorithm to ensure calculation stability and efficiency. Meanwhile, a two-dimensional cloud model (TDCM) is developed to obtain the slope resilience level and visualize the result. This comprehensive evaluation method is applied to three abandoned mine slopes in the Yellow River Basin, and the results demonstrate that the method can provide crucial insights for rational mine slope stabilization and ecological restoration. Full article
11 pages, 283 KiB  
Article
Study of Salmonella spp. from Cage Papers Belonging to Pet Birds in an Argentinean Canary Breeder Championship
by Dante J. Bueno, Francisco I. Rodríguez, Luciana C. Machado, Mario A. Soria, Francisco Procura, Silvana C. Gómez, Teresa M. Hoffmann, Andrea Alcain, María I. Caffer, Juan D. Latorre and Javier O. Quintar
Animals 2024, 14(8), 1207; https://doi.org/10.3390/ani14081207 (registering DOI) - 17 Apr 2024
Abstract
Birds, including canaries and other birds, have become increasingly popular as pets. Bird fairs, where breeders gather and show their production in a championship setting, present a setting for possible Salmonella spp. contamination and transmission. Therefore, this study estimated the rate of Salmonella [...] Read more.
Birds, including canaries and other birds, have become increasingly popular as pets. Bird fairs, where breeders gather and show their production in a championship setting, present a setting for possible Salmonella spp. contamination and transmission. Therefore, this study estimated the rate of Salmonella spp. isolation from cage papers, located in the bottom of cages of exotic pet birds, including canaries. Collected Salmonella isolates were used to determine the antimicrobial resistance profile to 52 antibiotics and 17 commercial disinfectants, based on pure or a mixture of acids, alcohols, aldehydes, alkalis, halogens, peroxygen, and quaternary ammonium compounds. The samples consisted of 774 cage papers taken in the 2015 Argentinean canary breeder championship, pooling three cage papers into one sterile sampling bag. Only one pool of the cage papers was positive for Salmonella spp. (0.4%), which belonged to the sample from three frill canary cages. Two strains of Salmonella serotype Glostrup were isolated, which were only resistant to sulfonamides and erythromycin and sensitive to alkali-based product PL301 AS. Although the rate of Salmonella spp. isolation from cage papers in an Argentinean canary breeder championship is low, it should not be discounted because Salmonella ser. Glostrup can be a source of human Salmonella outbreaks and they show high resistance to disinfecting products. Full article
(This article belongs to the Section Birds)
16 pages, 364 KiB  
Article
The EU Interreg Project “ADRINET”: Assessment of Well-Known and Emerging Pollutants in Seafood and Their Potential Effects for Food Safety
by Elisabetta Bonerba, Fatmira Shehu, Annamaria Pandiscia, Patrizio Lorusso, Alessio Manfredi, Aleksandra Huter, Giuseppina M. Tantillo, Sara Panseri, Maria Nobile and Valentina Terio
Foods 2024, 13(8), 1235; https://doi.org/10.3390/foods13081235 (registering DOI) - 17 Apr 2024
Abstract
Anthropogenic activities lead to the spread of chemicals and biological materials, including plastic waste, toxic metals, and pharmaceuticals, of which the impact on the Mediterranean Sea is of high concern. In this context, the EU Interreg Italy-Albania- Montenegro Project “ADRINET (Adriatic Network for [...] Read more.
Anthropogenic activities lead to the spread of chemicals and biological materials, including plastic waste, toxic metals, and pharmaceuticals, of which the impact on the Mediterranean Sea is of high concern. In this context, the EU Interreg Italy-Albania- Montenegro Project “ADRINET (Adriatic Network for Marine Ecosystem) _244” (2018–2020) arises. It aims to carry out biomonitoring campaigns in the main commercial interest of fish and cephalopod species, such as Sparus aurata, Dicentrarchus labrax, Sepia spp., and Loligo spp. sampled in three different subregions of the Mediterranean Sea. The presence of the main environmental contaminants, such as cadmium, microplastics, and antibiotics was investigated in these seafood samples. Contamination by cadmium and antibiotics in the seafood investigated in our study was negligible. However, a high value of microplastics was detected in the stomach and gut of Sparus aurata and Dicentrarchus labrax. Overall, even though the presence of microplastics needs to be investigated by further studies, the results confirmed that the environmental conditions of the three bays investigated by the ADRINET project partners (Italy, Albania, Montenegro) are positive and not affected by intensive anthropogenic activity. Full article
32 pages, 1053 KiB  
Review
Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma
by Joon Hyuk Choi and Swan N. Thung
Cancers 2024, 16(8), 1537; https://doi.org/10.3390/cancers16081537 (registering DOI) - 17 Apr 2024
Abstract
Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified [...] Read more.
Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: the small-duct type and large-duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes—inflammation and proliferation—have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches. Full article
18 pages, 573 KiB  
Article
Health Literacy of Children and Adolescents with Inflammatory Bowel Disease (IBD) and Parents of IBD Patients—Coping and Information Needs
by Kalina Kaul, Stefan Schumann, Cornelia Sander, Jan Däbritz and Jan de Laffolie
Children 2024, 11(4), 481; https://doi.org/10.3390/children11040481 (registering DOI) - 17 Apr 2024
Abstract
Background: The number of children and adolescents with inflammatory bowel disease (IBD) is increasing. Many chronically ill children and adolescents have low health literacy. Patient empowerment (PE) enables positive changes and control over one’s disease through specific activities, information, and counseling. The CEDNA [...] Read more.
Background: The number of children and adolescents with inflammatory bowel disease (IBD) is increasing. Many chronically ill children and adolescents have low health literacy. Patient empowerment (PE) enables positive changes and control over one’s disease through specific activities, information, and counseling. The CEDNA (IBD Needs Assessment) Survey aimed to provide the necessary data to improve PE in pediatric IBD (PIBD). Methods: Questionnaires were distributed to adolescent IBD patients and parents of children and adolescents with IBD throughout Germany. The answers were given anonymously. Based on the available data, a subgroup analysis was conducted in relation to the age of the patients and the period since diagnosis. For the parents’ responses, the same age groups were analyzed for comparison with the patients’ responses. Results: From October 2021 to April 2022, 2810 questionnaires were distributed and 1158 questionnaires were completed (n = 708 parents [61.1%], n = 450 patients [38.9%]). The results indicate that health literacy in children with IBD is low. Significant gaps in knowledge of important IBD topics were identified, and a comparison of responses regarding preferred methods and timing of obtaining information revealed differences between patient and parent preferences. The greatest need for knowledge on IBD topics was found in the group of 16–17-year-old patients on transition (n = 214, 31.8%) and in the group of patients diagnosed 1–2 years ago on the causes of IBD (n = 288, 17.4%). The willingness to seek advice was unexpectedly low. Conclusions: The analysis of all findings according to the patient’s age structure and duration since diagnosis can be used to enable age-appropriate communication at certain stages of the disease. This tailored information should increase patients’ health literacy, improve their management of the disease, and reduce the burden on their families. Full article
(This article belongs to the Special Issue Health Behaviour, Health Literacy and Mental Health in Children)
Show Figures

Graphical abstract

Open Access Journals

Browse by Indexing Browse by Subject Selected Journals
Back to TopTop