(1) Background: Alzheimer’s disease (AD) is characterized by β-amyloid (Aβ) peptide accumulation and mitochondrial dysfunction during the early stage of disease. PINK1 regulates the balance between mitochondrial homeostasis and bioenergy supply and demand via the PINK1/Parkin pathway, Na⁺/Ca²⁺ exchange, and other pathways. (2) Methods: In this study, we synthesized positively charged carbon dots (CA-PEI CDs) using citric acid (CA) and polyethyleneimine (PEI) and used them as vectors to express PINK1 genes in the APP/PS1-N2a cell line to determine mitochondrial function, electron transport chain (ETC) activity, and ATP-related metabolomics. (3) Results: Our findings showed that the CA-PEI CDs exhibit the characteristics of photoluminescence, low toxicity, and concentrated DNA. They are ideal biological carriers for gene delivery. PINK1 overexpression significantly increased the mitochondrial membrane potential in APP/PS1-N2a cells and reduced reactive-oxygen-species generation and Aβ1-40 and Aβ1-42 levels. An increase in the activity of NADH ubiquinone oxidoreductase (complex I, CI) and cytochrome C oxidase (complex IV, CIV) induces the oxidative phosphorylation of mitochondria, increasing ATP generation. (4) Conclusions: These findings indicate that the PINK gene can alleviate AD by increasing bioenergetic metabolism, reducing Aβ1-40 and Aβ1-42, and increasing ATP production. Full article

This study explores a nanoemulsion formulated with açaí seed oil, known for its rich fatty acid composition and diverse biological activities. This study aimed to characterise a nanoemulsion formulated with açaí seed oil and explore its cytotoxic effects on HeLa and SiHa cervical cancer cell lines, alongside assessing its antioxidant and toxicity properties both in vitro and in vivo. Extracted from fruits sourced in Brazil, the oil underwent thorough chemical characterization using gas chromatography–mass spectrometry. The resulting nanoemulsion was prepared and evaluated for stability, particle size, and antioxidant properties. The nanoemulsion exhibited translucency, fluidity, and stability post centrifugation and temperature tests, with a droplet size of 238.37, PDI -9.59, pH 7, and turbidity 0.267. In vitro assessments on cervical cancer cell lines revealed antitumour effects, including inhibition of cell proliferation, migration, and colony formation. Toxicity tests conducted in cell cultures and female Swiss mice demonstrated no adverse effects of both açaí seed oil and nanoemulsion. Overall, açaí seed oil, particularly when formulated into a nanoemulsion, presents potential for cancer treatment due to its bioactive properties and safety profile. Full article

Rat animal models are widely used owing to their relatively superior cognitive abilities and higher similarity compared with mouse models to human physiological characteristics. However, their use is limited because of difficulties in establishing embryonic stem cells and performing genetic modifications, and insufficient embryological research. In this study, we established optimal superovulation and fertilized–egg transfer conditions, including optimal hormone injection concentration (≥150 IU/kg of PMSG and hCG) and culture medium (mR1ECM), to obtain high-quality zygotes and establish in vitro fertilization conditions for rats. Next, sgRNA with optimal targeting activity was selected by performing PCR analysis and the T7E1 assay, and the CRISPR/Cas9 system was used to construct a rat model for muscular dystrophy by inducing a deficiency in the fukutin gene without any off-target effect detected. The production of fukutin knockout rats was phenotypically confirmed by observing a drop-in body weight to one-third of that of the control group. In summary, we succeeded in constructing the first muscular dystrophy disease rat model using the CRISPR/CAS9 system for increasing future prospects of producing various animal disease models and encouraging disease research using rats. Full article

Background: Breast cancer (BC) is frequently diagnosed among Canadian women. While targeted therapies are available for most BC patients; treatment resistance is common and novel therapeutic targets are of interest. Thyroid hormones (TH) bound to thyroid hormone receptors (THR) influence cell proliferation and differentiation; they are also involved in the growth and development of normal breast tissue. Evidence suggests that THRβ is a tumor suppressor in various solid tumors. Purpose: This narrative review discusses retrospective studies regarding the clinical relevance of THRβ as a potential prognostic biomarker and therapeutic target in BC. Methods: We consulted with an information specialist to develop a search strategy to find all literature related to THRα expression as a potential prognostic and therapeutic biomarker in breast cancer. The primary search was developed for Medline and translated to Embase. The searches were conducted on the Ovid platform on 18 August 2023. Results: Across seven retrospective studies identified, several have shown an association between higher THRβ1 expression with a lower risk of BC recurrence and with longer overall survival. Conclusions: Some evidence suggests that THRβ expression is associated with a lower risk of BC recurrence and death. Validation of THRβ as an independent prognostic biomarker and possible predictive biomarker of response to endocrine therapy and/or chemotherapy is of interest. Given that THRβ is upstream of the AKT/PI3K pathway, its potential as a predictive biomarker of response to AKT inhibitors and/or PI3K inhibitors may also be of value. Finally, the potential re-purposing of THRβ agonists as anti-cancer agents warrants investigation. Full article

Myelodysplastic neoplasm (MDS) is a heterogeneous group of clonal hematological disorders that originate from the hematopoietic and progenitor cells and present with cytopenias and morphologic dysplasia with a propensity to progress to bone marrow failure or acute myeloid leukemia (AML). Genetic evolution plays a critical role in the pathogenesis, progression, and clinical outcomes of MDS. This process involves the acquisition of genetic mutations in stem cells that confer a selective growth advantage, leading to clonal expansion and the eventual development of MDS. With the advent of next-generation sequencing (NGS) assays, an increasing number of molecular aberrations have been discovered in recent years. The knowledge of molecular events in MDS has led to an improved understanding of the disease process, including the evolution of the disease and prognosis, and has paved the way for targeted therapy. The 2022 World Health Organization (WHO) Classification and the International Consensus Classification (ICC) have incorporated the molecular signature into the classification system for MDS. In addition, specific germline mutations are associated with MDS development, especially in pediatrics and young adults. This article reviews the genetic abnormalities of MDS in adults with a brief review of germline predisposition syndromes. Full article

Many people experience intense fear of COVID-19. The purpose of this study was to provide a comprehensive visual overview of the published literature from 2020 to 2022 assessing fear of COVID-19. From 2020 to 2022, we employed the Scopus database to conduct a bibliometric analysis. We used the VOSviewer program to perform the author co-citation analysis, Mapchart to produce a worldwide map, and Wordart to make a word cloud image. From the 1769 records examined, 1654 (93.50%) were articles, with English being the most common language (96.31%). From 2020 to 2022, annual citations experienced significant growth (R² = 99.91%; p = 0.0195). The Institut National de la Santé et de la Recherche Médicale (INSERM, France) and China led in terms of publication output (n = 36; n = 255). M. D. Griffiths authored the highest number of articles (n = 21). The most active journal was the International Journal of Environmental Research and Public Health (n = 146), and the most prevalent keyword was “human/s” (11.51%). This bibliometric analysis evaluates the quality of the research on fear of the pandemic and the crisis management of COVID-19, which can provide managers and researchers with crucial insights for future decision making. Full article

Aim and Objectives: We aimed to test the predictive value of readily accessible and easily performed post-surgical “bedside tests” on their validity of long-term urinary incontinence (UI) (≥12 months) in patients following robot-assisted laparoscopic radical prostatectomy (RALP). Material and Methods: Patients undergoing RALP between July 2020 and March 2021 were prospectively included and subdivided into two groups based on their pad usage after 12 months (0 vs. ≥1 pad). After catheter removal, patients performed a 1 h pad test, documented the need for pad change in a micturition protocol and received post-voiding residual urine volume ultrasound. Univariate and multivariable analyses were used to demonstrate the predictive value of easily accessible tests applied after catheter removal for UI following RALP. Results: Of 109 patients, 47 (43%) had to use at least one pad (vs. 62 (57%) zero pads) after 12 months. Univariate testing showed a significant difference in urine loss between both groups evaluated by the 1 h pad test performed within 24 h after catheter removal (70% < 10 mL, vs. 30% ≥ 10 mL, p = 0.004) and in the need for pad change within the first 24 h after catheter removal (14% dry pads vs. 86% wet pads, p = 0.003). In multivariable analyses, the combination of both tests (synoptical incontinence score) could be confirmed as an independent predictor for UI after 12 months (p = 0.011). Conclusions: Readily accessible “everyday” diagnostics (pad test/change of pads after catheter removal) following RALP seem to be associated with a higher rate of long-term UI. This finding is crucial since patients with a potentially higher need for patient education and counselling can be identified using these readily accessible tests. This could lead to a higher patient satisfaction and improved outcomes. Full article

Despite a rhetorical turn towards prevention in homelessness policy and research, the work of youth homelessness prevention continues to be frustrated by persistent structural barriers. In this article, we examine how youth homelessness prevention is being implemented in the province of Ontario, with a focus on targeted provincial support programs and local shelter diversion practices. Drawing on interviews with workers in the homeless-serving sector, we describe the implementation of these initiatives and identify points of frustration and potential that workers encounter as they try to prevent experiences of homelessness for youth. We contend that these points of frustration illuminate persistent structural barriers that continue to forestall the work of youth homelessness prevention. Meanwhile, points of potential demonstrate the importance of empowering workers to creatively adapt and offer responsive services. Taken together, these signal the critical importance of two aspects of contemporary homelessness prevention typologies—primordial prevention and empowerment. We end by offering aspirations for action, a political reframing of the policy recommendations sections more typical of social science research articles. We do so to affirm our commitment to advancing the work of structural transformation that is required to achieve the right to housing for all, including youth. Full article

This study investigated the effect of compaction effort and soaking time on the shear strength properties of fine-grained gypsum-containing soils. The objective was to demonstrate that increasing compaction effort increases soil strength, specifically cohesion and the angle of shear strength, when subjected to soaking in freshwater. Unconsolidated undrained triaxial tests were carried out on CBR soil samples with different soaking times. The results showed a transition from brittle to ductile failure behaviour as the soaking time increased. Mohr–Coulomb failure envelopes showed reduced cohesion and angle of shear strength with increasing soak time. Regression models were developed to establish correlations between soaked and unsoaked strength parameters. Strong relationships were found between soil strength properties, compaction effort and soaking time. Empirical equations were proposed to estimate the cohesion and angle of shear strength from compaction effort and soaking time. This study highlighted the importance of considering gypsum-rich soils in civil engineering design. Gypsum dissolution during wetting significantly affected soil strength parameters. The regression models and empirical equations provide engineers with tools to assess the influence of compaction effort and soaking time on soil strength, thus aiding decision making when designing structures on gypsum-rich soils. Full article

(1) Current literature on ethnic minorities, comorbidities, and COVID-19 tends to investigate these factors separately, leaving gaps in our understanding about their interactions. Our review seeks to identify a relationship between ethnicity, comorbidities, and severe COVID-19 outcomes (ICU admission and mortality). We hope to enhance our understanding of the various factors that exacerbate COVID-19 severity and mortality in ethnic minorities in Canada and the USA. (2) All articles were received from PubMed, Scopus, CINAHL, and Ovid EMBASE from November 2020 to June 2022. Included articles contain information regarding comorbidities among ethnic minorities in relation to COVID-19 severity and mortality. (3) A total of 59 articles were included that examined various ethnic groups, including Black/African American, Asian, Hispanic, White/Caucasian, and Indigenous people. We found that the most examined comorbidities were diabetes, hypertension, obesity, and chronic kidney disease. A total of 76.9% of the articles (40 out of 52) found a significant association between different races and COVID-19 mortality, whereas 21.2% of the articles (11 out of 52) did not. (4) COVID-19 ICU admissions and mortality affect various ethnic groups differently, with Black patients generally having the most adverse outcomes. These outcomes may also interact with sex and age, though more research is needed assessing these variables together with ethnicity. Full article

The tree species Salix caprea shows high adaptability to different habitat conditions and is economically valuable as a woody crop for biomass production. Moreover, S. caprea is dependent on mycorrhizal fungi, which are crucial for its growth and adaptability in different environments. Hence, this study explores the ectomycorrhizal diversity of S. caprea by utilizing the taxonomy (morphotyping and a molecular approach using the ITS and LSU regions) and trait diversity (exploration types) at two test sites in Germany and Poland. In total, 19 ectomycorrhizal (EM) morphotypes of S. caprea were characterized. Seven taxa were identified at the species level (Hebeloma populinum, Cortinarius atrocoerulaeus, Inocybe hirtella, Laccaria cf. ochropurpurea, Tuber maculatum, Cenococcum geophilum, and Phialophora finlandia) and twelve at the genus level (Tomentella spp. 1–8, Hebeloma sp. 1, Inocybe sp. 1, and Tuber spp. 1–2). The EM colonization ranged from 14 to 28% of the fine root tips. At both test sites, the largest portion of the total EM colonization consisted of Thelephoraceae. The exploration types were classified as medium-distance smooth (Tomentella sp. 1–8 and L. ochropurpurea) and medium-distance fringe (C. atrocoerulaeus), while the other taxa were short-distance exploration types, highlighting their potential functional role in the adaptation and growth of S. caprea. Full article

Marine hermit crabs inhabiting different species of shells in the rocky intertidal may receive varied benefits and costs. Thick shell walls, sculpture, and certain silhouettes may increase protection against crushing predators and waves, but also the energy cost for bearing such a shell. To determine the relative energy demands on Pagurus granosimanus supporting one of three different species of shells commonly inhabited in nature, we measured the consumption of food by free-roaming, size-matched individuals after four days of food deprivation in the laboratory. Surprisingly, while all hermit crabs consumed a significant amount of food, that amount did not differ significantly across the types of shells inhabited, despite the significantly heavier weight of one type of shell (>150% of each of the other two species), and markedly different shell silhouettes. Whether our results were due to the inherent abilities of arthropods to support proportionally immense weights (physiology), reduced movements by animals in heavier shells (plastic behavior), or the way the hermit crabs bear the burden of the shell requires further investigation. Regardless, our results suggest that individuals of P. granosimanus that inhabit heavier shells that likely provide increased protection do not experience corresponding elevated food consumption requirements over the short term, even if those shells are not centered over the body mass of the hermit crab. Pagurus granosimanus crabs can bear the burden. Full article

(1) The aim of our study was to determine the attitudes of medical students toward organ donation in the case of brain death. (2) The study was conducted among 1348 medical students from three medical universities in Poland. The research tool was the Polish version of the standardized questionnaire concerning attitudes toward organ donation and transplantation (ODT) [PCID-DTO RIOS: A questionnaire designed by the ‘International Collaborative Organ Donation project about organ transplantation and donation]. (3) Some sources of information on organ donation were found to have a significant impact on the recipients’ knowledge of brain death. These were books, friends, family, lectures in other centers, social media, and the Church. Medical students holding the opinion that recovery and leading a normal lifestyle after brain death is impossible were significantly more likely to donate their organs after death, not for religious reasons and not because they wanted to survive their own death. (4) The medical students in our study showed a high level of awareness and favorable attitudes toward ODT. However, the number of registered donors was low. It is important to educate students on these issues to raise the awareness of both future medical professionals and the public on organ transplantation procedures. The public should be made aware that transplantation procedures are of a high standard, and that the law protects both donors and recipients. These measures would reduce recipients’ waiting time, and certainly increase the statistics of the number of life-saving and health-saving procedures. Full article

Some of the earliest known engravings are described, analyzed, and interpreted, following their microscopic examination. They are of significance in exploring the cognitive evolution of hominins several hundred thousand years ago and have not been described together before. The Steinrinne site near Bilzingsleben, north of Weimar, Germany, is one of Europe’s most important Lower Paleolithic occupation sites. Its extensive human habitation floor, excavated over 1000 square meters, comprises some of the world’s oldest evidence of dwellings, broadly matching or exceeding the age of examples proposed in Africa, India, and France. It has yielded numerous hominin remains, many wooden artefacts, other exquisitely preserved organic remains, and more portable engravings than any other Middle Pleistocene site. The latter are reviewed here, presenting the results of a detailed microscopic examination of the main finds. Bilzingsleben has so far produced the largest number of engraved Lower Paleolithic objects reported, which are particularly important to exploring the cognitive developments of hominins. Full article

The allure of team scale and functional diversity has led to the promising adoption of heterogeneous multi-robot systems (HMRS) in complex, large-scale operations such as disaster search and rescue, site surveillance, and social security. These systems, which coordinate multiple robots of varying functions and quantities, face the significant challenge of accurately assembling robot teams that meet the dynamic needs of tasks with respect to size and functionality, all while maintaining minimal resource expenditure. This paper introduces a pioneering adaptive cooperation method named inner attention (innerATT), crafted to dynamically configure teams of heterogeneous robots in response to evolving task types and environmental conditions. The innerATT method is articulated through the integration of an innovative attention mechanism within a multi-agent actor–critic reinforcement learning framework, enabling the strategic analysis of robot capabilities to efficiently form teams that fulfill specific task demands. To demonstrate the efficacy of innerATT in facilitating cooperation, experimental scenarios encompassing variations in task type (“Single Task”, “Double Task”, and “Mixed Task”) and robot availability are constructed under the themes of “task variety” and “robot availability variety.” The findings affirm that innerATT significantly enhances flexible cooperation, diminishes resource usage, and bolsters robustness in task fulfillment. Full article

There is an urgent need for valid and reliable measures of physical activity (PA) participation for use among people with physical and/or sensory disabilities. This study involved adapting the Leisure Time PA Questionnaire for People with Spinal Cord Injury for use in individuals with disabilities (i.e., the LTPAQ-D) and performing a preliminary evaluation of its content validity, construct validity, and same-day test–retest reliability in people with disabilities. User interviews assessed the content validity (n = 5). A cross-sectional study assessed the construct validity and same-day test–retest reliability (n = 27, 45 ± 21 years). Participants completed the LTPAQ-D, other self-report measures of aerobic and strength training PA, as well as tests of cardiorespiratory fitness (i.e., peak oxygen consumption ($\dot{\mathrm{V}}$O_2peak)) and muscular strength. LTPAQ-D measures of min/week of aerobic LTPA, aerobic moderate-to-vigorous PA (MVPA), and strength training shared medium-to-large correlations with other self-report measures of aerobic and strength training PA (r = 0.458–0.942, ps < 0.01). After controlling for age, aerobic LTPA and MVPA shared moderate partial correlations with $\dot{\mathrm{V}}$O_2peak (r = 0.341 and 0.356, respectively). Min/week of strength training, measured by the LTPAQ-D, was associated with predicted maximal strength on the chest press (r = 0.621, p = 0.009). All LTPAQ-D measures demonstrated good-to-excellent test–retest reliability (intraclass correlations = 0.709–0.948, ps < 0.01). This study provides preliminary evidence of the validity and reliability of the LTPAQ-D as a measure of LTPA among people with disabilities. Full article

In this review, in addition to the potential cardiovascular applications of β-blockers and, more specifically, propranolol, we wanted to list the more recent applications in psychiatry as well as current knowledge on the impact of oxidative stress on propranolol hydrochloride and the oxidative stress that could be limited by the latter. In fact, a number of studies show that this molecule is modified by oxidative stress but is also able to limit it. Mention is also made to studies on the increasingly important problem of eliminating drug waste and its impact on the environment, particularly the marine environment. Given the increase in the consumption of medicines, more rigorous waste management is needed to avoid impacting biodiversity. Full article

In this work, an enzyme cocktail with β-mannanase as the main activity was immobilized on epoxy resin foams filled with fibers from annatto capsules. The catalytic system was characterized by SEM, FTIR, and a mechanical crush resistance test. The behavior of the pH and temperature for the hydrolysis of the locust bean gum were also studied. With the same substrate and with respect to the free enzyme, the immobilized enzyme showed an activity retention of 79.61%. Its operational stability in ten reuse cycles did not show any statistically significant loss of activity. This catalytic system was used to study the preferential release of MOS of two to five degrees of polymerization from mannan present in dried and ground açaí seeds, which were not subjected to any other pretreatment. Using an experimental response surface design, the predicted quadratic models for the M2–M5 MOS content were obtained and they fit well with the experimental data, predicting a production range between 0.435 and 20 g/L of MOS (M2–M5). In addition, the production reached about 12 g/L under the optimized conditions. These results indicate that the used foamed epoxy resin supports and immobilization methodology are suitable for catalyzing the hydrolysis of mannan from açaí seeds. Full article

Starting from the dynamics of a bouncing ball in classical and quantum regime, we have suggested in a previous paper to add an arbitrary function of time to the standard expression of the probability current in quantum mechanics. In this paper, we suggest a way to determine this function: imposing a suitable normalization condition. The application of our proposal to the case of the harmonic oscillator is discussed. Full article

This article examines the performance of the proposed complex-order, conventional and fractional-order controllers for process automation and control in process plants. The controllers are compared regarding disturbance rejection and set-point tracking, considering variables such as response time, robustness to uncertainty, and steady-state error. The study shows that a complex PI-PD controller has better accuracy, faster response time, and better noise rejection. Still, implementation is challenging due to increased complexity and processing requirements. In contrast, a standard PI-PD controller is a known solution but may have problems with accuracy and robustness. Fractional-order controllers based on fractional computations have the potential to improve control accuracy and robustness of non-linear and time-varying systems. Experimental insights and real-world case studies are used to highlight the strengths and weaknesses of each controller. The findings provide valuable insights into the strengths and weaknesses of complex-order and fractional-order controllers and help to select the appropriate controller for specific process plant requirements. Future perspectives on controller design and performance optimization are detailed, identifying the potential benefits of using complex and fractional-order controllers in process plants. Full article

Anterior cruciate ligament (ACL) injuries mainly arise from non-contact mechanisms during sport performance, with most injuries occurring among youth or adolescent-age athletes, particularly females. The growing popularity of elite-level sport training has increased the total volume, intensity and frequency of exercise and competition loading to levels that may exceed natural healing capacity. Growing evidence suggests that the prevailing mechanism that leads to non-contact ACL injury from sudden mechanical fatigue failure may be accumulated microtrauma. Given the consequences of primary ACL injury on the future health and quality of life of youth and adolescent athletes, the objective of this review is to identify key “recovery science” factors that can help prevent these injuries. Recovery science is any aspect of sports training (type, volume, intensity, frequency), nutrition, and sleep/rest or other therapeutic modalities that may prevent the accumulated microtrauma that precedes non-contact ACL injury from sudden mechanical fatigue failure. This review discusses ACL injury epidemiology, current surgical efficacy, the native ACL vascular network, regional ACL histological complexities such as the entheses and crimp patterns, extracellular matrix remodeling, the concept of causal histogenesis, exercise dosage and ligament metabolism, central nervous system reorganization post-ACL rupture, homeostasis regulation, nutrition, sleep and the autonomic nervous system. Based on this information, now may be a good time to re-think primary ACL injury prevention strategies with greater use of modified sport training, improved active recovery that includes well-planned nutrition, and healthy sleep patterns. The scientific rationale behind the efficacy of regenerative orthobiologics and concomitant therapies for primary ACL injury prevention in youth and adolescent athletes are also discussed. Full article

Multimetric indices play a pivotal role in assessing river ecological quality, aligning with the European Water Framework Directive (EU WFD) requirements. However, indices developed specifically for large rivers are uncommon. Our objective was to develop a fish-based tool specifically tailored to assess the ecological quality in Portuguese large rivers. Data were collected from seven sites in each of three Portuguese large rivers (Minho, Guadiana, and Tagus). Each site was classified using an environmental disturbance score, combining different pressure types, such as water chemistry, land use, and hydromorphological alterations. The Fish-based Multimetric Index for Portuguese Large Rivers (F-MMIP-LR) comprises four metrics: % native lithophilic individuals; % alien individuals; % migrant individuals; and % freshwater native individuals, representing compositional, reproductive, and migratory guilds. The index showed good performance in separating least- and most-disturbed sites. Least-disturbed sites were rated ‘high’ or ‘good’ by F-MMIP-LR, contrasting with no such classification for most-disturbed sites, highlighting index robustness. The three rivers presented a wide range of F-MMIP-LR values across the gradient of ‘bad’ to ‘high’, indicating that, on a large spatial extent, the biological condition was substantially altered. The F-MMIP-LR provides vital information for managers and decision-makers, guiding restoration efforts and strengthening conservation initiatives in line with the WFD. Full article