Miracle-dz/UniFAR-FTUs huggingface dataset:
The internal structure of handwriting proficiency in beginning writers

Fluent and automatized handwriting frees cognitive resources for more complex elements of writing (i.e., spelling or text generation) or even math tasks (i.e., operating) and is therefore a central objective in primary school years. Most previous research has focused on the development of handwriting automaticity across the school years and characteristics of handwriting difficulties in advanced writers. However, the relative and absolute predictive power of the different kinematic aspects for typically developing beginning handwriting remains unclear. The purpose of the present study was to investigate whether and to what extent different kinematic aspects contribute to handwriting proficiency in typically developing beginning handwriters. Further, we investigated whether gender, socioeconomic background, or interindividual differences in executive functions and visuomotor integration contribute to children’s acquisition of handwriting. Therefore, 853 first-grade children aged seven copied words on a digitized tablet and completed cognitive performance tasks. We used a confirmatory factor analysis to investigate how predefined kinematic aspects of handwriting, specifically the number of inversions in velocity (NIV), pen stops, pen lifts, and pressure on the paper, are linked to an underlying handwriting factor. NIV, pen stops, and pen lifts showed the highest factor loadings and therefore appear to best explain handwriting proficiency in beginning writers. Handwriting proficiency was superior in girls than boys but, surprisingly, did not differ between children from low versus high socioeconomic backgrounds. Handwriting proficiency was related to working memory but unrelated to inhibition, shifting, and visuomotor integration. Overall, these findings highlight the importance of considering different kinematic aspects in children who have not yet automatized pen movements. Results are also important from an applied perspective, as the early detection of handwriting difficulties has not yet received much research attention, although it is the base for tailoring early interventions for children at risk for handwriting difficulties.
Time trends and geographical variation in major lower limb amputation related to peripheral arterial disease in England

Abstract Background Above and below knee amputation (AKA, BKA) are treatments of last resort for peripheral arterial disease (PAD). The aim was to examine amputation rates, AKA:BKA ratios, previous revascularization and minor amputation, lengths of stay in hospital, mortality following amputation, and regional variation in people with and without diabetes in England. Methods The study used population-based ecological and cohort study designs, 31 672 census areas, hospital admissions from 2006 to 2018 and Poisson, logistic and Cox regression. Results There were 47 249 major lower limb amputations (50.7% AKA; 48% had diabetes), giving an annual PAD-related amputation rate of 11 per 100 000 in the population aged 25+ years. Amputation rates were higher in men and substantially higher in people with diabetes. The AKA:BKA ratio was 0.63 in patients with diabetes (n = 22 702) and 1.62 in patients without diabetes (n = 24 547). Of patients having AKA, 25.3% died within 90 days of amputation compared with 11.9% for BKA. Median survival following amputation ranged from only 1.68 years following AKA in patients with diabetes to 5.72 years following BKA in patients without diabetes. Amputation rates decreased over time mainly in the population with diabetes. Short-term mortality and lengths of stay in hospital also decreased over time, while the percentage with previous revascularization generally increased. Amputation rates and AKA:BKA ratios were highest in the North. Adjustment for age, sex and deprivation did not substantially alter geographical patterns. Adjusted 90-day mortality was generally higher in the North and the Midlands but also high in London. There were also regional variations in adjusted duration from admission to amputation, duration from amputation to discharge or death in hospital, previous revascularization and previous minor amputation. Conclusions There were large variations in amputation rates and survival following amputation in relation to diabetes status and amputation level, and regional variations which remained after adjustment for deprivation.
Validity and reliability of the persian version of the modified telephone interview for cognitive status among community-dwelling older adults in Iran

ABSTRACT. Due to the increase in the population of the elderly, there is a growing trend in some diseases such as cognitive disorders (dementia) which are common in this era, and the diagnosis and treatment of this disease are still facing challenges. Therefore, early identification of cognitive disorders is of particular importance. In this regard, the use of any tool or cognitive tests may not be enough to diagnose dementia in the early stages and a special tool is needed. Objective: The validity and reliability of the Persian version of the Modified Telephone Interview for Cognitive Status (P-TICS-M) in older adults living in the Iranian community for a comprehensive screening of mild cognitive impairment and dementia was investigated. Methods: In the first phase, translation, re-translation, and word-taking were performed by using the face validity and content validity. In the second phase, a stratified convenient sampling with 150 participants aged ≥60 years was conducted based on cognitive status using the global deterioration scale in 2018. The external and internal reliability of the P-TICS-M using the interclass correlation coefficient and Cronbach's alpha coefﬁcient of total items of this tool were estimated. Results: The mean age of the participants was 68.6 (standard deviation±7.4) years. According to global deterioration scale, 87 (58.0%) had normal cognition, 40 (26.7%) had mild cognitive impairment, and 23 (15.3%) had dementia. The Spearman's correlation coefficient between P-TICS-M scores and Mini-Mental State Examination scale was 0.764. In exploratory factor analysis, seven domains were detected, which were compatible with those defined by the tool developer. The Cronbach's alpha of the P-TICS-M was 0.920. The absolute agreement between test-retest score was >0.90. The sensitivity of 92.2, 94.8, and 100%, and also the specificity of 79.4, 88.2, and 89.8% were calculated for detecting subjects with dementia, respectively. Furthermore, a mild cognitive impairment cutoff of >28 was determined. Conclusion: The development and validation of a P-TICS-M tool can be useful in identifying older adult people with cognitive impairment. Demographic characteristics (level of education, age) can also affect the cutoff point of this tool.
Teaching of sexual medicine and gender issues in medical courses: students’ perception

SUMMARY INTRODUCTION: In addition to reproductive purposes, human sexuality and sexual health are matters of great importance in the medical office. Despite this, there is still a deficiency in the training of Brazilian medical students regarding sexual medicine and gender issues. OBJECTIVE: The objective of this study was to analyze the perception of fifth- and sixth-year students in relation to the teaching of sexual medicine and gender issues in medical courses. METHODS: This is a descriptive and cross-sectional study with students from the last 2 years of medical schools in the State of Santa Catarina (internship classes), through the application of a self-administered, semi-structured online questionnaire. RESULTS: A total of 164 students answered the questionnaire, with 83.5% (137/164) saying they had taken classes on sexual medicine and 47% (77/164) saying they had taken classes on gender issues. The participants judged the teaching inadequate in most of the topics addressed, and there was no significant difference between students from public and private schools. Notably, 79.9% (131/164) of the students considered the teaching of sexual medicine insufficient or inadequate, while 87.8% (144/164) considered the teaching of gender issues insufficient or inadequate. CONCLUSION: The vast majority of students consider the teaching of sexual medicine and gender issues insufficient and inadequate.
Factors associated with barriers to healthcare access among ever-married women of reproductive age in Bangladesh: Analysis from the 2017–2018 Bangladesh Demographic and Health Survey

Background Globally, women experience healthcare inequalities, which may contribute to excessive mortality rates at various stages of their lives. Though Bangladesh has achieved excellent progress in providing healthcare, the country still has some critical challenges that need immediate attention. The objective of this study is to examine the association between social determinants and barriers to accessing healthcare among ever-married women aged 15–49 in Bangladesh. Methods The study was conducted among 20,127 women aged 15–49, using data from the 2017–2018 Bangladesh Demographic and Health Survey. Four barriers to healthcare were considered: whether women face problems with permission, obtaining money, distance, and companionship. The multivariable logistic regression analysis was used, with a broad array of independent variables (such as age, and educational level) to identify the determinants of barriers to healthcare access. The associations were expressed as adjusted odds ratios (AOR) with a 95% confidence interval (CI). Results More than two-thirds (66.3%) of women reported having at least one perceived barrier to accessing healthcare. Women with a higher level of education (AOR = 0.49, 95% CI: 0.41–0.57), owning a mobile telephone (AOR = 0.78, 95% CI: 0.73–0.84), and those in the richest wealth quintile (AOR = 0.45, 95% CI: 0.38–0.52) had lower odds of having barriers to accessing healthcare. In addition, widowed (AOR = 1.53, 95% CI: 1.26–1.84), divorced (AOR = 1.91, 95% CI:1.47–2.48), or separated (AOR = 1.98, 95% CI: 1.46–2.69) women had higher odds of having a money barrier to accessing healthcare, than married women. Conclusions This study shows that individual-, household-, and community-level factors are associated with barriers to healthcare accessibility. To improve the state of women’s health in Bangladesh, it is vital to consider these socio-economic factors and implement fundamental measures, such as supporting the national health policy, empowering women’s socio-economic situation, and spreading the flexible way of healthcare access.
Screening with urine Histoplasma antigen test in asymptomatic patients starting TNF-alpha inhibitor therapy: a cohort study

Background: Histoplasmosis is the second most frequent granulomatous disease in patients treated with tumor necrosis factor (TNF)-α inhibitors, second only to tuberculosis. However, there is limited information about pre-therapy screening procedures and the need for preventive treatments for patients who will start immunobiologicals. Methods: This is a cohort study that evaluated the prevalence of histoplasmosis in asymptomatic HIV-negative patients before initiation of TNF-α inhibitors by testing for Histoplasma antigen in urine samples. The patients included completed a 180-day follow-up after the initiation of the biologics to assess the onset of symptoms suggestive of histoplasmosis. Results: From January 2021 to December 2022, 54 patients who were prescribed a TNF-α inhibitor agent for treating autoimmune diseases in centers in southern Brazil were included. In the screening before therapy, the prevalence of a positive urinary Histoplasma antigen test was 14.8%. None of the 54 patients developed histoplasmosis after 6 months of immunobiological therapy, including the eight patients who tested positive. Conclusion: The prevalence of Histoplasma capsulatum infection in chronic patients may be higher than expected, but the impact of latent infection in asymptomatic patients is still uncertain, including those starting treatment with immunobiological drugs such as TNF-α inhibitors. Our study did not identify risk factors for the diagnosis of disseminated histoplasmosis in this group, including a positive result in an antigen test performed before immunobiological therapy. To date, there is no evidence to recommend routine antigen-based screening or preventive therapy for histoplasmosis before initiating a TNF-α inhibitor.
The Influence of Anthropometrics on Cardiac Mechanics in Healthy Women With Opposite Obesity Phenotypes (Android vs Gynoid)

Background: The possible influence exerted by mechanical factors and/or compressive phenomena on myocardial strain parameters in healthy individuals with opposite obesity phenotypes (android vs gynoid) has never been previously investigated. Accordingly, we aimed at evaluating the relationship between anthropometrics, such as the waist-to-hip ratio (WHR), modified Haller index (MHI, the ratio of chest transverse diameter over the distance between sternum and spine), and epicardial adipose tissue (EAT), and left ventricular (LV)-global longitudinal strain (GLS), in healthy women with opposite obesity phenotypes (android vs gynoid). Methods: Forty healthy women with obesity (body mass index (BMI) ≥30 Kg/m2) and WHR ≥0.85 (“android group”) (52.5±13.2 yrs), 40 age- and BMI-matched healthy women with obesityand WHR <0.78 (“gynoid group”) (49.8±13.4 yrs) and 40 age-matched healthy women without obesity (BMI <30 Kg/m2) (controls) (50.3±12.5 yrs) were retrospectively analyzed. All women underwent transthoracic echocardiography implemented with echocardiographic strain analysis of all cardiac chambers. Correlation between LV-GLS and anthropometrics (WHR, MHI, and EAT) was assessed in both groups of obese women. Age, WHR, homeostasis model assessment for insulin resistance (HOMA-IR), and left ventricular mass index (LVMi) were included in the logistic regression analysis performed for evaluating the independent predictors of reduced LV-GLS magnitude (less negative than -20%) in women with android obesity. Results: Compared to the other groups of women, those with android obesity were found with significantly greater LVMi, higher LV filling pressures, and lower biventricular and biatrial deformation indices. A strong inverse correlation between LV-GLS and all anthropometrics (WHR, MHI, and EAT) was demonstrated in both groups of women with obesity. Univariate logistic regression analysis revealed that WHR (OR 1.58, 95%CI 1.22-2.03, p<0.001) and LVMi (OR 1.09, 95%CI 1.02-1.16, p=0.006) were independently correlated with LV-GLS impairment in women with android obesity. On multivariate logistic regression analysis, the WHR maintained a statistically significant association with the above-mentioned outcome (OR 1.68, 95%CI 1.14-2.48, p=0.009). Receiver operating characteristic (ROC) curve analysis showed that a WHR value ≥1.01 had 93% sensitivity and 100% specificity for detecting LV-GLS impairment in women with android obesity (AUC=0.98; 95%CI 0.96-1.00). Conclusions: Anthropometrics may strongly influence cardiac mechanics in healthy women with obesity. The WHR is associated with reduced LV-GLS magnitude in healthy women with android obesity, independent of age, glycometabolic status, and LV size.
Sex hormone therapy in Multiple Sclerosis: A systematic review of randomized clinical trials

Background In spite of the observed immunomodulatory properties of different sex hormones on Multiple Sclerosis (MS) in different investigations, to date, there has been no study to systematically review the documents to add more powerful data to the field. Objectives Therefore, in this paper we aim to systematically review clinical and randomized controlled trials (RCT) assessing the effect of sex hormone therapies on individuals with MS. Design A comprehensive search of electronic databases including PubMed, EMBASE, and Scopus was conducted. Clinical trials and RCTs that assessed the impact of sex hormones on individuals with MS were selected and included in the systematic review. Data sources and methods In the final phase of the search strategy, 9 papers reached the criteria for entering in the systematic review. Two independent reviewers extracted the relevant data from each article according to the standardized data extraction form. Two reviewers also assessed the quality of each study independently using PEDro scale. Results We categorized three different classifications of outcomes including clinical, MRI, and immune system findings and put each measured outcome in the category which matched best. Conclusion In conclusion, the existed investigations on the effect of sex hormones on inflammatory and neurodegenerative components of MS are promising particularly in relapsing-remitting MS (RRMS).
Low Neutralizing Activities to the Omicron Subvariants BN.1 and XBB.1.5 of Sera From the Individuals Vaccinated With a BA.4/5-Containing Bivalent mRNA Vaccine

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1. 5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster. Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1. 5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1. 5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1. 5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.
World Journal of Gastroenterology

BACKGROUND Although the usefulness of endoscopic scores, such as the Mayo Endoscopic Subscore (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS), and biomarkers such as fecal calprotectin (FC) for predicting relapse in ulcerative colitis (UC) has been reported, few studies have included endoscopic scores for evaluating the entire colon. AIM To compare the usefulness of FC value and MES, UCEIS, and UCCIS for predicting relapse in patients with UC in clinical remission.
World Journal of Psychiatry

BACKGROUND The literature has discussed the relationship between environmental factors and depressive disorders; however, the results are inconsistent in different studies and regions, as are the interaction effects between environmental factors. We hypothesized that meteorological factors and ambient air pollution individually affect and interact to affect depressive disorder morbidity. AIM To investigate the effects of meteorological factors and air pollution on depressive disorders, including their lagged effects and interactions.
Achaete‐scute family bHLH transcription factor 2 activation promotes hepatoblastoma progression

Abstract Achaete‐scute family bHLH transcription factor 2 (ASCL2) is highly expressed in hepatoblastoma (HB) tissues, but its role remains unclear. Thus, biological changes in the HB cell line HepG2 in response to induced ASCL2 expression were assessed. ASCL2 expression was induced in HepG2 cells using the Tet‐On 3G system, which includes doxycycline. Cell viability, proliferation activity, mobility, and stemness were evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, colony‐formation, migration, invasion, and sphere‐formation assays. Quantitative reverse‐transcription polymerase chain reaction was used to assess the expression of markers for proliferation (CCND1 and MYC), epithelial‐mesenchymal transition (EMT; SNAI1, TWIST1, and ZEB1), mesenchymal‐epithelial transition (CDH1), and stemness (KLF4, POU5F1, and SOX9). Compared with the non‐induced HepG2 cells, cells with induced ASCL2 expression showed significant increases in viability, colony number, migration area (%), and sphere number on days 7, 14, 8, and 7, respectively, and invasion area (%) after 90 h. Furthermore, induction of ASCL2 expression significantly upregulated CCND1, MYC, POU5F1, SOX9, and KLF4 expression on days 2, 2, 3, 3, and 5, respectively, and increased the ratios of SNAI1, TWIST1, and ZEB1 to CDH1 on day 5. ASCL2 promoted the formation of malignant phenotypes in HepG2 cells, which may be correlated with the upregulation of the Wnt signaling pathway‐, EMT‐, and stemness‐related genes. ASCL2 activation may therefore be involved in the progression of HB.
The role of cryptic ancestral symmetry in histone folding mechanisms across Eukarya and Archaea

Histones compact and store DNA in both Eukarya and Archaea, forming heterodimers in Eukarya and homodimers in Archaea. Despite this, the folding mechanism of histones across species remains unclear. Our study addresses this gap by investigating 11 types of histone and histone-like proteins across humans, Drosophila, and Archaea through multiscale molecular dynamics (MD) simulations, complemented by NMR and circular dichroism experiments. We confirm and elaborate on the widely applied “folding upon binding” mechanism of histone dimeric proteins and report a new alternative conformation, namely, the inverted non-native dimer, which may be a thermodynamically metastable configuration. Protein sequence analysis indicated that the inverted conformation arises from the hidden ancestral head-tail sequence symmetry underlying all histone proteins, which is congruent with the previously proposed histone evolution hypotheses. Finally, to explore the potential formations of homodimers in Eukarya, we utilized MD-based AWSEM and AI-based AlphaFold-Multimer models to predict their structures and conducted extensive all-atom MD simulations to examine their respective structural stabilities. Our results suggest that eukaryotic histones may also form stable homodimers, whereas their disordered tails bring significant structural asymmetry and tip the balance towards the formation of commonly observed heterotypic dimers.