Miracle-dz/UniFAR-FTUs huggingface dataset:
Identifying Occupational Therapy Research Priorities in Trinidad and Tobago: A Group Concept Mapping Study

In Trinidad and Tobago, occupational therapy is an emerging profession with limitations in the number of practitioners and the scope of practice. With the development of a new Master of Science Occupational Therapy programme in the country, the profession is continuously growing. There has been an increased demand for culturally relevant research to build the occupational therapy evidence base locally. However, the narrow range of occupational therapy literature in the country makes it difficult to highlight research gaps and decipher what research areas should be prioritised to best impact occupational therapy practice at present. This group concept mapping study is aimed at identifying priority areas for occupational therapy research in Trinidad and Tobago from the perspectives of occupational therapy students and practitioners. Participants brainstormed and contributed specific research ideas they would like to see developed in the country. Individually, participants sorted these ideas into themes and rated each idea based on perceived importance and feasibility. Using the GroupWisdom™ software, multidimensional scaling and hierarchical cluster analyses were applied to the sort data to create idea clusters within a concept map. Rating values were analysed to determine priority research themes within the concept map. The resulting concept map illustrated seven research priorities: Contextualising Practitioner Development, The Realities of Emerging OT Practice, Localising Mental Health OT, Occupation and Participation of Children and Youth, School-based OT in the Local Context, OT with Special Populations, and OT Contributions to the Public Health Sector. These findings represent the research needs of the occupational therapy profession in Trinidad and Tobago and will help to focus future researchers' efforts to expand the local evidence base.
The prevalence of DNA microsatellite instability in anaplastic thyroid carcinoma – systematic review and discussion of current therapeutic options

Introduction Anaplastic thyroid carcinoma is a rare, rapidly progressing, highly aggressive thyroid malignancy. Responses to immune checkpoint inhibitors in mismatch repair-deficient/microsatellite instability-high tumours of other locations have shown promising results, and with the extended approval of the PD-1 receptor inhibitor pembrolizumab by the Food and Drug Administration, also anaplastic thyroid cancer (ATC) requires analysis for microsatellite instability (MSI) status. Material and methods Systematic research for relevant literature was conducted in different databases. Prevalence, detection methods, and the potential prognostic/predictive value of MSI in view of the available targeted therapies were of special focus. Results Selected citations revealed the prevalence of MSI in 7.4%, with mutations in the MSH2 gene (33%) being the most frequent, followed by MSH6 (25%) and MLH1 (16.7%) occurring in the following combinations: MLH1-MSH2 (8.3%), MSH2-MSH6 (8.3%), and MLH3-MSH5 (8.3%). No mutations in the PMS2 gene were reported. Sixty-six co-mutations in 9 cases were found, with TP53 (88.9%), NF1 (44.4 %), ATM (33.3%), and RB1 (33.3%) being the most frequent. No RAS mutations were noted. Survival ranged between 2.8 and 48 months, and patient age varied between 49 and 84 years. There are insufficient and heterogenous data concerning the predictive or prognostic value of mismatch repair-deficient/microsatellite instability status. Conclusions Tumour molecular profiling is fundamental in ATC for predictive, prognostic, as well as therapeutic reasons, and analysis of MSI status is strongly suggested because a small subgroup show the MSI signature and might profit from recently approved targeted therapies.
Factors Associated with Quality of Life among Caregivers of People with Spinal Cord Injury

Purpose Often people with spinal cord injury (SCI) require help from their caregivers to carry out activities of daily living. Such assistance may affect caregiver quality of life (QoL). This study investigates the QoL and its associated risk factors among caregivers of people with SCI to find possible ways to increase their QoL. Material and Method. A convenience sample of 135 Iranian caregivers of people with SCI participated in a cross-sectional study from the Brain and Spinal Injury Repair Research Center of Tehran (BASIR), Iran, from June 2018 to October 2019. The World Health Organization's Quality of Life Questionnaire (WHOQoL-BREF), the Beck Depression Inventory-II (BDI-II), the Caregiver Burden Scale (CBS), and a demographic questionnaire were administered. Hierarchical multiple linear regression analysis was then applied to identify risk factors associated with caregiver QoL. Results Moderate to highly significant negative correlations were observed between all domains of the WHOQoL scale and subscales of the CBS and the BDI-II. After controlling for demographic and clinical variables, depression, burden, and level of injury were found to predict caregiver QoL significantly. Furthermore, QoL was lower in caregivers of people with quadriplegia than paraplegia (p < 0.05). Conclusions The level of injury, self-perceived caregiver burden, and depression are associated with QoL for the caregivers of people with SCI. A holistic approach incorporating caregiver training, psychological interventions, and adequate support may enable better QoL for these caregivers.
Downregulation of Src-family tyrosine kinases by Srcasm and c-Cbl: A comparative analysis

AIM: Elevated Src-Family tyrosine kinase (SFK) activity drives carcinogenesis in vivo and elevated SFK activity is found ubiquitously in human cancers. Although human squamous cell carcinomas (SCCs) demonstrate increased SFK activity, in silico analysis of SCCs demonstrates that only 0.4% of lesions contain mutations that could potentially increase SFK activity; similarly, a low frequency of activating SFK mutations is found in other major cancers. These findings indicate that SFK activation in cancers likely is not due to activating mutations but alternative mechanisms. To evaluate potential alternative mechanisms, we evaluated the selectivity of c-Cbl and Srcasm in downregulating native and activated mutant forms of SFKs. MATERIALS AND METHODS: We co-transfected native and activated forms of Src and Fyn with c-Cbl and Srcasm into HaCaT cells and monitored the ability of Srcasm and c-Cbl to downregulate native and activated forms of SFKs by Western blotting. The mechanism of downregulation was probed using mutant forms of Srcasm and c-Cbl and using proteosomal and lysosomal inhibition. RESULTS: The data indicate that Srcasm downregulates native Fyn and Src more effectively than c-Cbl, whereas c-Cbl preferentially downregulates activated SFK mutants, including Fyn Y528F, more effectively than Srcasm. Srcasm downregulates SFKs through a lysosomal-dependent mechanism while c-Cbl utilizes a proteosomal-dependent mechanism. CONCLUSION: Given the rarity of activating SFK mutations in human cancer, these data indicate that decreasing Srcasm level/function may represent a mechanism for increasing SFK activity in SCC and other human tumors.
Fetuin-A regulates adipose tissue macrophage content and activation in insulin resistant mice through MCP-1 and iNOS: Involvement of IFNγ-JAK2-STAT1 pathway.

In the context of obesity-induced adipose tissue inflammation, migration of macrophages and their polarization from predominantly anti-inflammatory to proinflammatory subtype is considered a pivotal event in the loss of adipose insulin sensitivity. Two major chemoattractants, monocyte chemoattractant protein-1 (MCP-1) and Fetuin A (FetA), have been reported to stimulate macrophage migration into inflamed adipose tissue instigating inflammation. Moreover, FetA could notably modulate macrophage polarization, yet the mechanism(s) is unknown. The present study was undertaken to elucidate the mechanistic pathway involved in the actions of FetA and MCP-1 in obese adipose tissue. We found that FetA knockdown in high fat diet (HFD) fed mice could significantly subdue the augmented MCP-1 expression and reduce adipose tissue macrophage (ATM) content thereby indicating that MCP-1 is being regulated by FetA. Additionally, knockdown of FetA in HFD mice impeded the expression of inducible nitric oxide synthase (iNOS) reverting macrophage activation from mostly proinflammatory to anti-inflammatory state. It was observed that the stimulating effect of FetA on MCP-1 and iNOS was mediated through interferon γ (IFNγ) induced activation of JAK2-STAT1-NOX4 pathway. Furthermore, we detected that the enhanced IFNγ expression was accounted by the stimulatory effect of FetA upon the activities of both cJun and JNK. Taken together, our findings revealed that obesity-induced FetA acts as a master upstream regulator of adipose tissue inflammation by regulating MCP-1 and iNOS expression through JNK-cJun-IFNγ-JAK2-STAT1 signaling pathway. This study opened a new horizon in understanding the regulation of ATM content and activation in conditions of obesity-induced insulin resistance.
Glomerular endothelial cell senescence drives age‐related kidney disease through PAI‐1

The mechanisms underlying the development of glomerular lesions during aging are largely unknown. It has been suggested that senescence might play a role, but the pathophysiological link between senescence and lesion development remains unexplained. Here, we uncovered an unexpected role for glomerular endothelial cells during aging. In fact, we discovered a detrimental cross‐talk between senescent endothelial cells and podocytes, through PAI‐1. In vivo, selective inactivation of PAI‐1 in endothelial cells protected glomeruli from lesion development and podocyte loss in aged mice. In vitro, blocking PAI‐1 in supernatants from senescent endothelial cells prevented podocyte apoptosis. Consistently, depletion of senescent cells prevented podocyte loss in old p16 INK‐ATTAC transgenic mice. Importantly, these experimental findings are relevant to humans. We showed that glomerular PAI‐1 expression was predictive of poor outcomes in transplanted kidneys from elderly donors. In addition, we observed that in elderly patients, urinary PAI‐1 was associated with age‐related chronic kidney disease. Altogether, these results uncover a novel mechanism of kidney disease and identify PAI‐1 as a promising biomarker of kidney dysfunction in allografts from elderly donors.
NEW MARKETING TOOLS IN THE BLOOD SERVICE TO OPTIMIZE QUALITY MANAGEMENT.

OBJECTIVE The aim: To identify the main fears of donation among young people in the city and ways to eliminate these phobias with the help of modern marketing tools. PATIENTS AND METHODS Materials and methods: It was conducted the questionnaire among Sumy State University students on donation fears. The questionnaire included questions about experience of donation, reason for non donation and age. After that a focus group among students who feared donation was organized. Participants were shown a 360 degree video recorded in the blood center and discussed how to donate blood after watching the video. RESULTS Results: The main phobias were fear of becoming infected during the procedure (37.7%), fear of the procedure itself due to ignorance and misunderstanding of what to expect (14.0%), and fear of the needle, blood, and the discomfort possibility during the procedure (10.0%); 26.7% indicated that they could not be donors due to poor health, and 11.6% due to personal laziness. It was developed a 360o video, which demonstrates the blood donation process, showing the next steps with the selected blood in facilities. Its continues for 20 minutes. This video was shown in the focus group for ten non-donors with some donation fear. 60% of them reported a change from blood to a positive, which may indicate this tool's effectiveness. CONCLUSION Conclusions: Due a 360o video some non-donor people can ensure safety, sterility of the process, reduce the fear of donation and further increase the likelihood of becoming regular donors.
Astragalus polysacharin inhibits hepatocellular carcinoma-like phenotypes in a murine HCC model through repression of M2 polarization of tumour-associated macrophages

Abstract Context Astragalus polysaccharin (APS), an extract of Astragalus propinquus Schischk, exerts antitumor effects in hepatocellular carcinoma (HCC). Objective This study investigated the mechanism of action of APS in HCC. Materials and methods Tumour-associated macrophages (TAMs) were treated with APS (0, 8, 16 mg/mL) for 24 h. APS (16 mg/mL)-treated TAMs were co-cultured with MHCC97H/Huh7 cells for 24 h. Finally, BALB/c nude mice were divided into PBS, APS (50 mg/kg), APS (100 mg/kg), APS (200 mg/kg) groups: mice were inoculated with Huh7 cells to construct tumour xenograft model, followed by administration of APS (50, 100, 200 mg/kg) or PBS daily for 30 days. Cell proliferation, migration, invasion, tumour growth, macrophage markers and proportions were measured. Results APS 16 mg/mL treatment enhanced the expression of M1 macrophage markers (iNOS, IL-1β and TNF-α) and M1 macrophage proportions, while reducing the expression of M2 macrophage markers (IL-10, Arg-1) and M2 macrophage proportions in TAMs. Moreover, the APS-mediated M1 phenotype of TAMs significantly repressed cell proliferation, migration and invasion of MHCC97H and Huh7 cells. Moreover, APS (50, 100, 200 mg/kg) enhanced M1 macrophage proportions and reduced M2 macrophage proportions in the tumour tissues, and thus inhibited tumour growth of HCC. Discussion and conclusions APS inhibits HCC-like phenotypes in a murine HCC model through repression of M2 polarization of TAMs. This work provides a novel theoretical basis for the application of APS in the clinical treatment of HCC.
Spatial modulation of individual behaviors enables an ordered structure of diverse phenotypes during bacterial group migration

Coordination of diverse individuals often requires sophisticated communications and high-order computational abilities. Microbial populations can exhibit diverse individualistic behaviors, and yet can engage in collective migratory patterns with a spatially sorted arrangement of phenotypes. However, it is unclear how such spatially sorted patterns emerge from diverse individuals without complex computational abilities. Here, by investigating the single-cell trajectories during group migration, we discovered that, despite the constant migrating speed of a group, the drift velocities of individual bacteria decrease from the back to the front. With a Langevin-type modeling framework, we showed that this decreasing profile of drift velocities implies the spatial modulation of individual run-and-tumble random motions, and enables the bacterial population to migrate as a pushed wave front. Theoretical analysis and stochastic simulations further predicted that the pushed wave front can help a diverse population to stay in a tight group, while diverse individuals perform the same type of mean reverting processes around centers orderly aligned by their chemotactic abilities. This mechanism about the emergence of orderly collective migration from diverse individuals is experimentally demonstrated by titration of bacterial chemoreceptor abundance. These results reveal a simple computational principle for emergent ordered behaviors from heterogeneous individuals.
Univariate and Multivariate Base Rates of Score Elevations, Reliable Change, and Inter-Rater Discrepancies in the BRIEF-A Standardization Samples

The Behavior Rating Inventory of Executive Function–Adult Version (BRIEF-A) is a standardized rating scale of subjective executive functioning. We provide univariate and multivariate base rates (BRs) for scale/index scores in the clinical range (T scores ≥65), reliable change, and inter-rater information not included in the Professional Manual. Participants were adults (ages = 18–90 years) from the BRIEF-A self-report (N = 1,050) and informant report (N = 1,200) standardization samples, as well as test–retest (n = 50 for self, n = 44 for informant) and inter-rater (n = 180) samples. Univariate BRs of elevated T scores were low (self-report = 3.3%–15.4%, informant report = 4.5%–16.3%). Multivariate BRs revealed the common occurrence of obtaining at least one elevated T-score across scales (self-report = 26.5%–37.3%, informant report = 22.7%–30.3%), whereas virtually none had elevated scores on all scales. Test–retest scores were highly correlated (self = .82–.94; informant = .91–.96). Inter-rater correlations ranged from . 44 to . 68. Significant (p < .05) test–retest T-score differences ranged from 7 to 12 for self-report, from 6 to 8 for informant report, and from 16 to 21 points for inter-rater T-score differences. Applications of these findings are discussed.
Effectiveness of early versus delayed rehabilitation following total shoulder replacement: A systematic review

Objective To investigate the effectiveness of early versus delayed rehabilitation following total shoulder replacement. Design Intervention systematic review with narrative synthesis. Literature search MEDLINE, EMBASE, CINAHL, Scopus and the Cochrane Library were searched from inception to the 29th of July 2021. Study selection criteria Randomised controlled trials comparing early versus delayed rehabilitation following primary anatomic, primary reverse, or revision total shoulder replacement. Data synthesis A revised Cochrane risk of bias assessment tool for randomised controlled trials was used, as well as the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the quality of evidence. A narrative synthesis was undertaken. Results Three eligible randomised controlled trials (n = 230) were included. There was very low-quality evidence of no statistically significant difference (P > 0.05) in pain, shoulder function, health-related quality of life or lesser tuberosity osteotomy healing at 12 months between early or delayed rehabilitation. There was conflicting and very low-quality evidence of a difference between the effect of early and delayed rehabilitation on shoulder range of movement. There was limited, very low-quality evidence of statistically significantly improved pain and function (P < 0.05) in the early post-operative period with early rehabilitation following anatomic total shoulder replacement. Conclusions No differences were seen in patient-reported or clinician-reported outcomes at 12 months post-surgery between early and delayed rehabilitation following total shoulder replacement. There is very low-quality evidence that early rehabilitation may improve shoulder pain and function in the early post-operative phase following anatomic total shoulder replacement.
Prevalence, main serovars and antimicrobial resistance profiles of Non-typhoidal Salmonella in poultry samples from the Americas: A systematic review and meta-analysis.

Poultry and poultry-derived products such as meat and eggs are among the main sources of non-typhoidal Salmonella (NTS) transmission to the human. Therefore, we performed a systematic review and used random-effects meta-analyses to 1) estimate the prevalence of NTS in poultry samples from birds, products and subproducts and environmental samples, 2) examine the diversity and frequency of their serovars and 3) estimate the prevalence and profiles of antimicrobial resistance (AMR) in NTS isolates reported in studies from the Americas. We included 157 studies from 15 countries comprising 261,408 poultry samples and estimated an overall pooled prevalence of 17.9% (95% CI: 10.8-26.3) in birds, 21.8% (17.7-26.1) in products and subproducts and 29.5% (24.2-35.1) in environmental samples. At the national level, the prevalence of NTS was heterogenous across countries with the highest values in Mexico, the USA and Canada. In total, 131 serovars were identified from 13,388 isolates, Heidelberg, Kentucky, Enteritidis and Typhimurium were the most prevalent in the overall top 10 ranking (range 6.5-20.8%). At the national level, Enteritidis and Typhimurium were identified in most of the countries, though with national differences in their ranks. The prevalence of AMR increased from 24.1% for 1 antibiotic, to 36.2% for 2-3 antibiotics and 49.6% for ≥ 4 antibiotics. Kentucky, Heidelberg, Typhimurium and Enteritidis were the serovars with the highest prevalence of AMR. Besides, tetracycline, ampicillin, streptomycin, ceftiofur and amoxicillin-clavulanic acid were the most frequent antibiotics to which NTS showed resistance. In conclusion, NTS was distributed through the avian production chain with high and heterogenous values of prevalence in poultry samples. Besides, there were distinctive patterns of serovars distribution across countries and an alarming prevalence of AMR among zoonotic serovars. This article is protected by copyright. All rights reserved.
Transferrin binding protein-B from Neisseria meningitidis C as a novel carrier protein in glycoconjugate preparation: an in silico approach

Abstract The linking of polysaccharide in glycoconjugate vaccine with carrier protein is an imperative step to develop a strong memory response. The excessive use of similar carrier protein known to result in bystander immunity warrants an urgent need for new carrier protein. The preparation of the glycoconjugate vaccine using cyanylation chemistry is to link the active cyanate ester site of polysaccharide with the carrier protein. In the present study, transferrin binding protein-B (Tbp-B) has been explored as a new carrier protein to develop in silico pneumococcal polysaccharide serotype-5 (PnPs-5) conjugate vaccine. The homology model of Tbp-B was constructed using the Prime module and stereochemically validated using ProSA, PDBsum and ProQ. The selected model revealed a Z-score of −5.6 within the X-ray region in ProSA analysis, LGscore: 9.776, and MaxSub: 0.8 in protein quality predictor suggesting its preferred use. Loop modeling and active site analysis followed by in silico PnPs-5 activation with cyanalyting agent CDAP was docked with Tbp-B using Glide module. The complex stability of cyanate esters with Tbp-B, analyzed by molecular dynamics (MD) simulation, revealed an average RMSD of 2.49 Å for its binding to the receptor. The RMSF values of cyanate ester-1, -2, and -3 were observed to be 1.06, 1.39 and 0.79 Å, respectively. The higher RMSF of 1.39 Å of cyanate ester-2 was further found unstable which corroborates its non-binding to the protein and also incurring conformational changes to a carrier protein. Molecular simulations revealed that cyanate ester-1 and cyanate ester-3 formed stable conjugates with carrier protein Tbp-B. Communicated by Ramaswamy H. Sarma
Genuine and non‐genuine smiles in individuals meeting criteria for a clinical high‐risk syndrome

Psychosis is characterized by both alterations in emotional functioning and environmental stressors including bullying victimization. Recent evidence suggests that some alterations in emotional functioning (e.g., blunted positive facial expressions) are already present in the psychosis risk period. Yet, some clinically relevant facial emotions have not been investigated such as genuine smiles (thought to reflect genuine positive emotions) and non‐genuine smiles (thought to fake positive or mask negative emotions) in individuals meeting criteria for a clinical high‐risk (CHR) syndrome. Further, despite a compelling conceptual basis to suggest a link between affective expression and exposure to environmental stress, to date, no investigations have sought to examine this association. Here, we aim to assess differences between a sample of CHR (N = 65) and control (N = 67) individuals in genuine and non‐genuine smiles and associations with bullying victimization.