Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence and Genetic Diversity of Toxin Genes in Clinical Isolates of Clostridium perfringens: Coexistence of Alpha-Toxin Variant and Binary Enterotoxin Genes (bec/cpile)

Clostridium perfringens (C. perfringens) is responsible for food-borne gastroenteritis and other infectious diseases, and toxins produced by this bacterium play a key role in pathogenesis. Although various toxins have been described for C. perfringens isolates from humans and animals, prevalence of individual toxins among clinical isolates has not yet been well explored. In the present study, a total of 798 C. perfringens clinical isolates were investigated for prevalence of eight toxin genes and their genetic diversity by PCR, nucleotide sequencing, and phylogenetic analysis. Besides the alpha-toxin gene (plc) present in all the isolates, the most common toxin gene was cpe (enterotoxin) (34.2%), followed by cpb2 (beta2 toxin) (1.4%), netB (NetB) (0.3%), and bec/cpile (binary enterotoxin BEC/CPILE) (0.1%), while beta-, epsilon-, and iota-toxin genes were not detected. Genetic analysis of toxin genes indicated a high level of conservation of plc, cpe, and netB. In contrast, cpb2 was revealed to be considerably divergent, containing at least two lineages. Alpha-toxin among 46 isolates was classified into ten sequence types, among which common types were distinct from those reported for avian isolates. A single isolate with bec/cpile harbored a plc variant containing an insertion of 834-bp sequence, suggesting its putative origin from chickens.
Early squamous cell carcinoma of the oral tongue with histologically benign lymph nodes: A model predicting local control and vetting of the eighth edition of the American Joint Committee on Cancer pathologic T stage

The eighth edition of the American Joint Committee on Cancer staging manual (AJCC8) added depth of invasion to the definition of pathologic T stage (pT). In the current study, the authors assess pT stage migration and the prognostic performance of the updated pT stage and compare it with other clinicopathologic variables in patients with early squamous cell carcinoma of the oral tongue (OTSCC; tumors measuring ≤4 cm) with histologically benign lymph nodes (pN0).
Gut Microbiota Alteration and Its Time Course in a Tauopathy Mouse Model.

Emerging evidence suggests that gut microbiota dysbiosis plays a role in neurodegenerative disorders. However, whether the composition and diversity of the gut microbiota are altered in tauopathies remains largely unknown. This study was aimed to examine the diversity and composition of the gut microbiota in tauopathies, as well as the correlation with pathological changes in the brain. We collected fecal samples from 32 P301L tau transgenic mice and 32 age- and gender-matched littermate mice at different ages. The 16S ribosomal RNA sequencing technique was used to analyze the microbiota composition in feces. Brain tau pathology levels were measured by immunohistochemistry. The diversity and composition of the gut microbiota significantly changed with aging. At the phylum level, the relative abundance of Bacteroidetes was increased, while Firmicutes were decreased in P301L mice compared with that in Wt mice after 3 months of age. In addition, Actinobacteria was decreased in P301L mice at 3 and 6 months of age, meanwhile Tenericutes was decreased in P301L mice at 10 months of age. Moreover, several specific macrobiota were highly associated with the levels of paired helical filament-tau or pT231-tau protein in the brain. Our findings suggest that gut microbiota changed with aging, as well as in the tauopathy mice model. Modulation of the gut microbiota may be a potential strategy for treatment of tauopathy.
Systematic Literature Review of Health Impact Assessments in Low and Middle-Income Countries

Health Impact Assessments (HIAs) motivate effective measures for safeguarding public health. There is consensus that HIAs in low and middle-income countries (LMICs) are lacking, but no study systematically focuses on those that have been successfully conducted across all regions of the world, nor do they highlight factors that may enable or hinder their implementation. Our objectives are to (1) systematically review, geographically map, and characterize HIA activity in LMICs; and (2) apply a process evaluation method to identify factors which are important to improve HIA implementation in LMICs. A systematic review of peer-reviewed HIAs in 156 LMICs was performed in Scopus, Medline, Web of Science, Sociological abstracts, and LILACs (Latin American and Caribbean Health Sciences) databases. The search used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and covered HIAs across all type of interventions, topics, and health outcomes. HIAs were included if they reported a clear intervention and health outcome to be assessed. No time restriction was applied, and grey literature was not included. The eligible studies were subjected to six process evaluation criteria. The search yielded 3178 hits and 57 studies were retained. HIAs were conducted in 26 out of 156 countries. There was an unequal distribution of HIAs across regions and within LMICs countries. The leading topics of HIA in LMICs were air pollution, development projects, and urban transport planning. Most of the HIAs reported quantitative approaches (72%), focused on air pollution (46%), appraised policies (60%), and were conducted at the city level (36%). The process evaluation showed important variations in the way HIAs have been conducted and low uniformity in the reporting of six criteria. No study reported the time, money, and staff used to perform HIAs. Only 12% of HIAs were based on participatory approaches; 92% of HIAs considered multiple outcomes; and 61% of HIAs provided recommendations and fostered cross-national collaboration. The limited transparency in process, weak participation, and inconsistent delivery of recommendations were potential limitations to HIA implementation in low and middle-income countries. Scaling and improving HIA implementation in low and middle-income countries in the upcoming years will depend on expanding geographically by increasing HIA governance, adapting models and tools in quantitative methods, and adopting better reporting practices.
Clinical Genomic Sequencing of Pediatric and Adult Osteosarcoma Reveals Distinct Molecular Subsets with Potentially Targetable Alterations

Purpose: Although multimodal chemotherapy has improved outcomes for patients with osteosarcoma, the prognosis for patients who present with metastatic and/or recurrent disease remains poor. In this study, we sought to define how often clinical genomic sequencing of osteosarcoma samples could identify potentially actionable alterations. Experimental Design: We analyzed genomic data from 71 osteosarcoma samples from 66 pediatric and adult patients sequenced using MSK-IMPACT, a hybridization capture-based large panel next-generation sequencing assay. Potentially actionable genetic events were categorized according to the OncoKB precision oncology knowledge base, of which levels 1 to 3 were considered clinically actionable. Results: We found at least one potentially actionable alteration in 14 of 66 patients (21%), including amplification of CDK4 (n = 9, 14%: level 2B) and/or MDM2 (n = 9, 14%: level 3B), and somatic truncating mutations/deletions in BRCA2 (n = 3, 5%: level 2B) and PTCH1 (n = 1, level 3B). In addition, we observed mutually exclusive patterns of alterations suggesting distinct biological subsets defined by gains at 4q12 and 6p12-21. Specifically, potentially targetable gene amplifications at 4q12 involving KIT, KDR, and PDGFRA were identified in 13 of 66 patients (20%), which showed strong PDGFRA expression by IHC. In another largely nonoverlapping subset of 14 patients (24%) with gains at 6p12-21, VEGFA amplification was identified. Conclusions: We found potentially clinically actionable alterations in approximately 21% of patients with osteosarcoma. In addition, at least 40% of patients have tumors harboring PDGFRA or VEGFA amplification, representing candidate subsets for clinical evaluation of additional therapeutic options. We propose a new genomically based algorithm for directing patients with osteosarcoma to clinical trial options.
Do fuel type and place of cooking matter for acute respiratory infection among Afghan children? Evidence from the Afghanistan DHS 2015

Abstract In Afghanistan, acute respiratory infection (ARI) is a leading cause of under-five mortality. Previous studies on the effects of cooking fuel on ARI have only looked at the types of cooking fuel, and not the effects of the location of the cooking place. The present study aimed to assess the effects of fuel type and place of cooking on the prevalence of ARI among under-five children in Afghanistan. Descriptive statistics and multilevel logistic regression analysis were performed for 31,063 children using data from the first round of the Afghanistan Demographic and Health Survey conducted in 2015. Overall, 13% of the children suffered from ARI symptoms in the 2 weeks before the survey, but this varied widely across the country. The multilevel analysis showed that, compared with households using clean cooking fuel in a separate building or outside, households using clean cooking fuel within the house and without a separate kitchen had a 32% lower risk [95% confidence interval (CI)=0.51–0.91] of having under-five children with ARI, and those using clean fuel in a separate kitchen in the house had a 17% lower risk (95% CI=0.67–1.03). On the other hand, households using polluting cooking fuel in the house without a kitchen had a 14% (95% CI=0.91–1.44) higher risk of having under-five children with ARI, and those using polluting cooking fuel in the house with a separate kitchen had a 5% (95% CI=0.85–1.30) higher risk, after adjusting for other covariates. The findings indicate that type of cooking fuel is not the only issue affecting ARI in children. Place of cooking (in a house with or without a separate kitchen versus outside) also affects the risk of ARI among under-five children. The study also found that mother’s education and occupational status, community poverty and ethnicity are other important factors affecting the prevalence of ARI in under-five children in Afghanistan.
Factors Associated with Compliance among Methadone Maintenance Treatment Transfers: Evidence from Audit Records at Clinics in Guangdong, China

Methadone maintenance treatment (MMT) requires patients to intake their daily dose in person at their clinic. Therefore, transfer services are vital for patients who need temporary leave from their primary MMT clinic. However, studies have shown that transfer patients might delay return after temporary leave, leading to missed doses and putting them at risk of increased harm. In this study, we aimed to explore the transfer rates and factors associated with MMT patients who delayed return during a transfer period. In this retrospective analysis, we used audit records from the web-based management system from six MMT clinics in Guangdong, China. Multilevel logistic regression and multilevel Poisson regression analyses were used to examine the factors associated with patients who delayed return to their primary MMT clinic. A total of 459 people used the transfer system 2940 times between January 2006 and December 2016. Of those, patients delayed return to their primary MMT clinic 1199 times (40.78%). Patients who transferred regularly had poor compliance rates with MMT treatment. Those who once dropped out from and then re-enrolled in MMT were more likely to delay return. Most patients (82.71%) who used the transfer service for “work” were more likely to prolong their delay length. The findings highlight that a more flexible transfer system would minimize inconvenience to the patients.
Metabolic regulation through the endosomal system

The endosomal system plays an essential role in cell homeostasis by controlling cellular signaling, nutrient sensing, cell polarity and cell migration. However, its place in the regulation of tissue, organ and whole body physiology is less well understood. Recent studies have revealed an important role for the endosomal system in regulating glucose and lipid homeostasis, with implications for metabolic disorders such as type 2 diabetes, hypercholesterolemia and non‐alcoholic fatty liver disease. By taking insights from in vitro studies of endocytosis and exploring their effects on metabolism, we can begin to connect the fields of endosomal transport and metabolic homeostasis. In this review, we explore current understanding of how the endosomal system influences the systemic regulation of glucose and lipid metabolism in mice and humans. We highlight exciting new insights that help translate findings from single cells to a wider physiological level and open up new directions for endosomal research.
Host species and site of collection shape the microbiota of Rift Valley fever vectors in Kenya

The composition and structure of microbial communities associated with mosquitoes remain poorly understood despite their important role in host biology and potential to be harnessed as novel strategies for mosquito-borne disease control. We employed MiSeq sequencing of the 16S rRNA gene amplicons to characterize the bacterial flora of field-collected populations of Aedes mcintoshi and Aedes ochraceus, the primary vectors of Rift Valley fever (RVF) virus in Kenya. Proteobacteria (53.5%), Firmicutes (22.0%) and Actinobacteria (10.0%) were the most abundant bacterial phyla accounting for 85.5% of the total sequences. Non-metric multi-dimensional scaling plots based on Bray-Curtis dissimilarities revealed a clear grouping of the samples by mosquito species, indicating that the two mosquito species harbored distinct microbial communities. Microbial diversity, richness and composition was strongly influenced by the site of mosquito collection and overall, Ae. ochraceus had significantly higher microbial diversity and richness than Ae. mcintoshi. Our findings suggest that host species and site of collection are important determinants of bacterial community composition and diversity in RVF virus vectors and these differences likely contribute to the spatio-temporal transmission dynamics of RVF virus.
Evaluation of attention in APP/PS1 mice shows impulsive and compulsive behaviours

While Alzheimer's disease (AD) is traditionally associated with deficits in episodic memory, early changes in other cognitive domains, such as attention, have been gaining interest. In line with clinical observations, some animal models of AD have been shown to develop attentional deficits, but this is not consistent across all models. The APPswe/PS1ΔE9 (APP/PS1) mouse is one of the most commonly used AD models and attention has not yet been scrutinised in this model. We set out to assess attention using the 5‐choice serial reaction time task (5CSRTT) early in the progression of cognitive symptoms in APP/PS1 mice, using clinically translatable touchscreen chambers. APP/PS1 mice showed no attentional changes across 5CSRTT training or any probes from 9 to 11 months of age. Interestingly, APP/PS1 mice showed increased impulsive and compulsive responding when task difficulty was high. This suggests that while the APP/PS1 mouse model may not be a good model of attentional changes in AD, it may be useful to study the early changes in impulsive and compulsive behaviour that have been identified in patient studies. As these changes have not previously been reported without attentional deficits in the clinic, the APP/PS1 mouse model may provide a unique opportunity to study these specific behavioural changes seen in AD, including their mechanistic underpinnings and therapeutic implications.
Household Food Insecurity is Associated with Higher Adiposity among US Schoolchildren Ages 10-15 Years: The Healthy Communities Study.

BACKGROUND Limited research exists on the relationship between food insecurity and children's adiposity and diet and how it varies by demographic characteristics in the United States. OBJECTIVE The aim of this study was to assess the relationship between household food insecurity and child adiposity-related outcomes, measured as BMI (kg/m2) z score (BMI-z), weight status, and waist circumference, and diet outcomes, and examined if the associations differ by age, sex, and race/ethnicity. METHODS Data collected in 2013-2015 from 5138 US schoolchildren ages 4-15 y from 130 communities in the cross-sectional Healthy Communities Study were analyzed. Household food insecurity was self-reported using a validated 2-item screener. Dietary intake was assessed using the 26-item National Cancer Institute's Dietary Screener Questionnaire, and dietary behaviors were assessed using a household survey. Data were analyzed using multilevel statistical models, including tests for interaction by age, sex, and race/ethnicity. RESULTS Children from food-insecure households had higher BMI-z (β: 0.14; 95% CI: 0.06, 0.21), waist circumference (β: 0.91 cm; 95% CI: 0.18, 1.63), odds of being overweight or obese (OR: 1.17; 95% CI: 1.02, 1.34), consumed more sugar from sugar-sweetened beverages (β: 1.44 g/d; 95% CI: 0.35, 2.54), and less frequently ate breakfast (β: -0.28 d/wk; 95% CI: -0.39, -0.17) and dinner with family (β: -0.22 d/wk; 95% CI: -0.37, -0.06) compared to children from food-secure households. When examined by age groups (4-9 and 10-15 y), significant relationships were observed only for older children. There were no significant interactions by sex or race/ethnicity. CONCLUSIONS Household food insecurity was associated with higher child adiposity-related outcomes and several nutrition behaviors, particularly among older children, 10-15 y old.
A bibliometric analysis of the 103 top-cited articles in endodontics

Abstract Objective: The purpose of this study was to identify the 100 top-cited articles in endodontics and analyse their bibliometric characteristics. Material and methods: The Web of Science database was reviewed to identify the relevant articles. Results: One hundred and three articles were included because the last four articles had the same number of citations. The top-cited article received 2115 citations. The articles were published in 28 different journals, with the most popular publication being the Journal of Endodontics (n = 36). The most prolific country was the United States (n = 41), followed by Sweden (n = 17) and Switzerland (n = 8). The most prolific author and institution were M. Torabinejad (n = 12) and Umeå University (n = 9), respectively. The majority of articles were of a basic science nature (n = 55), while endodontic microbiology (n = 24) was the most frequent subspecialty. The most common study design used in clinical articles was non-randomized experimental study (n = 5). Half of the clinical articles (n = 11) had a level III evidence score. Conclusions: The present citation analysis provides insights into the historical progress and current trends in endodontics.
Indirect Effects in Sequential Mediation Models: Evaluating Methods for Hypothesis Testing and Confidence Interval Formation

Abstract Complex mediation models, such as a two-mediator sequential model, have become more prevalent in the literature. To test an indirect effect in a two-mediator model, we conducted a large-scale Monte Carlo simulation study of the Type I error, statistical power, and confidence interval coverage rates of 10 frequentist and Bayesian confidence/credible intervals (CIs) for normally and nonnormally distributed data. The simulation included never-studied methods and conditions (e.g., Bayesian CI with flat and weakly informative prior methods, two model-based bootstrap methods, and two nonnormality conditions) as well as understudied methods (e.g., profile-likelihood, Monte Carlo with maximum likelihood standard error [MC-ML] and robust standard error [MC-Robust]). The popular BC bootstrap showed inflated Type I error rates and CI under-coverage. We recommend different methods depending on the purpose of the analysis. For testing the null hypothesis of no mediation, we recommend MC-ML, profile-likelihood, and two Bayesian methods. To report a CI, if data has a multivariate normal distribution, we recommend MC-ML, profile-likelihood, and the two Bayesian methods; otherwise, for multivariate nonnormal data we recommend the percentile bootstrap. We argue that the best method for testing hypotheses is not necessarily the best method for CI construction, which is consistent with the findings we present.
Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis

New three-dimensionally-structured hybrid phospholipid vesicles, able to load clotrimazole in a high amount (10 mg/mL), were obtained for the first time in this work by significantly reducing the amount of water (≤10%), which was replaced with a mixture of glycerol and ethanol (≈90%). A pre-formulation study was carried out to evaluate the effect of both the composition of the hydrating medium and the concentration of the phospholipid on the physico-chemical properties of hybrid vesicles. Four different three-dimensionally-structured hybrid vesicles were selected as ideal systems for the topical application of clotrimazole. An extensive physico-chemical characterization performed using transmission electron microscopy (TEM), cryogenic transmission electron microscopy (cryo-TEM), 31P-NMR, and small-angle X-ray scattering (SAXS) displayed the formation of small, multi-, and unilamellar vesicles very close to each other, and was capable of forming a three-dimensional network, which stabilized the dispersion. Additionally, the dilution of the dispersion with water reduced the interactions between vesicles, leading to the formation of single unilamellar vesicles. The evaluation of the in vitro percutaneous delivery of clotrimazole showed an improved drug deposition in the skin strata provided by the three-dimensionally-structured vesicles with respect to the commercial cream (Canesten®) used as a reference. Hybrid vesicles were highly biocompatible and showed a significant antifungal activity in vitro, greater than the commercial cream Canesten®. The antimycotic efficacy of formulations was confirmed by the reduced proliferation of the yeast cells at the site of infection in vivo. In light of these results, clotrimazole-loaded, three-dimensionally-structured hybrid vesicles appear to be one of the most innovative and promising formulations for the treatment of candidiasis infections.
Psychosocial Mediators Between Intimate Partner Violence and Alcohol Abuse in Low-Income African American Women

Intimate partner violence (IPV) exposure can increase alcohol use. Although African Americans use less alcohol compared with European Americans, African American women experience disparate rates of IPV, potentially intensifying their alcohol abuse. We used data from 171 African American women to test if IPV was related to alcohol abuse and if psychosocial factors—loneliness, embarrassment, fear of harm, hope, social support, childcare needs, and finances—mediated this link. IPV and alcohol abuse were related, and several factors were related to either IPV or alcohol abuse. Social support was related to both, and it mediated the IPV–alcohol abuse link, explaining women’s alcohol abuse relating to IPV.