Miracle-dz/UniFAR-FTUs huggingface dataset:
Protocol and statistical analysis plan for the PREOXI trial of preoxygenation with noninvasive ventilation vs oxygen mask

Background: Hypoxemia is a common and life-threatening complication during emergency tracheal intubation of critically ill adults. The administration of supplemental oxygen prior to the procedure (preoxygenation) decreases the risk of hypoxemia during intubation. Research Question: Whether preoxygenation with noninvasive ventilation prevents hypoxemia during tracheal intubation of critically ill adults, compared to preoxygenation with oxygen mask, remains uncertain. Study Design and Methods: The PRagmatic trial Examining OXygenation prior to Intubation (PREOXI) is a prospective, multicenter, non-blinded randomized comparative effectiveness trial being conducted in 7 emergency departments and 17 intensive care units across the United States. The trial compares preoxygenation with noninvasive ventilation versus oxygen mask among 1300 critically ill adults undergoing emergency tracheal intubation. Eligible patients are randomized in a 1:1 ratio to receive either noninvasive ventilation or an oxygen mask prior to induction. The primary outcome is the incidence of hypoxemia, defined as a peripheral oxygen saturation <85% between induction and 2 minutes after intubation. The secondary outcome is the lowest oxygen saturation between induction and 2 minutes after intubation. Enrollment began on 10 March 2022 and is expected to conclude in 2023. Interpretation: The PREOXI trial will provide important data on the effectiveness of noninvasive ventilation and oxygen mask preoxygenation for the prevention of hypoxemia during emergency tracheal intubation. Specifying the protocol and statistical analysis plan prior to the conclusion of enrollment increases the rigor, reproducibility, and interpretability of the trial. Clinical trial registration number: NCT05267652
Altered sleep architecture in diabetes and prediabetes: findings from the Baependi Heart Study

Objective: People with diabetes are more likely to have obstructive sleep apnea, but there are few studies examining sleep architecture in people with diabetes, especially in the absence of moderate-severe sleep apnea. Therefore, we compared sleep architecture among people with diabetes, prediabetes or neither condition, whilst excluding people with moderate-severe sleep apnea. Research design and methods: This sample is from the Baependi Heart Study, a prospective, family-based cohort of adults in Brazil. 1,074 participants underwent at-home polysomnography (PSG). Diabetes was defined as 1) FBG>125 OR 2) HbA1c>6.4 OR 3) taking diabetic medication, and prediabetes was defined as 1) [(5.7[≤]HbA1c[≤]6.4) OR (100[≤]FBG[≤]125)] AND 2) not taking diabetic medication. We excluded participants that had an apnea-hypopnea index (AHI)>30 from these analyses to reduce confounding due to severe sleep apnea. We compared sleep stages among the 3 groups. Results: Compared to those without diabetes, we found shorter REM duration for participants with diabetes (-6.7min, 95%CI -13.2, -0.1) or prediabetes (-5.9min, 95%CI -10.5, -1.3), even after adjusting for age, gender, BMI, and AHI. Diabetes was also associated with lower total sleep time (-13.7min, 95%CI -26.8, -0.6), longer slow-wave sleep (N3) duration (+7.6min, 95%CI 0.6, 14.6) and higher N3 percentage (+2.4%, 95%CI 0.6, 4.2), compared to those without diabetes. Conclusions: People with diabetes and prediabetes had less REM sleep after taking into account potential confounders, including AHI. People with diabetes also had more N3 sleep. These results suggest that diabetes is associated with different sleep architecture, even in the absence of moderate-severe sleep apnea.
Discrete Isoperimetric Problems

It is shown that there exists a linear ordering of the points in $I_ + ^n $ or $I^n $ (Cartesian products of nonnegative integers or integers) such that the first j points in this ordering is a configuration that minimizes the number of boundary points (points not in the set that have Euclidean distance one from the set) among sets of size j. The relation of the $I_ + ^n $ result to Macaulay’s theorem is deduced also.
Genetic regulation of fetal hemoglobin across global populations

Human genetic variation has enabled the identification of several key regulators of fetal-to-adult hemoglobin switching, including BCL11A, resulting in therapeutic advances. However, despite the progress made, limited further insights have been obtained to provide a fuller accounting of how genetic variation contributes to the global mechanisms of fetal hemoglobin (HbF) gene regulation. Here, we have conducted a multi-ancestry genome-wide association study of 28,279 individuals from several cohorts spanning 5 continents to define the architecture of human genetic variation impacting HbF. We have identified a total of 178 conditionally independent genome-wide significant or suggestive variants across 14 genomic windows. Importantly, these new data enable us to better define the mechanisms by which HbF switching occurs in vivo. We conduct targeted perturbations to define BACH2 as a new genetically-nominated regulator of hemoglobin switching. We define putative causal variants and underlying mechanisms at the well-studied BCL11A and HBS1L-MYB loci, illuminating the complex variant-driven regulation present at these loci. We additionally show how rare large-effect deletions in the HBB locus can interact with polygenic variation to influence HbF levels. Our study paves the way for the next generation of therapies to more effectively induce HbF in sickle cell disease and {beta}-thalassemia.
BAYESIAN REASONING IN DATA ANALYSIS: A CRITICAL INTRODUCTION

Critical review and outline of the Bayesian alternative: uncertainty in physics and the usual methods of handling it a probabilistic theory of measurement uncertainty. A Bayesian primer: subjective probability and Bayes' theorem probability distributions (a concise reminder) Bayesian inference of continuous quantities Gaussian likelihood counting experiments bypassing Bayes' theorem for routine applications Bayesian unfolding. Further comments, examples and applications: miscellanea on general issues in probability and inference combination of experimental results - a closer look asymmetric uncertainties and nonlinear propagation which priors for frontier physics? Concluding matter: conclusions and bibliography.
VISTA+/CD8+ status correlates with favorable prognosis in Epithelial ovarian cancer

Immunotherapy by blocking immune checkpoint regulators has emerged as a new targeted therapy for some cancers. Among them V-domain Ig suppressor of Tcell activation (VISTA) which is identified as a novel checkpoint regulator in ovarian cancer. This study aimed to investigate the VISTA role in Epithelial ovarian cancer (EOC), and its relationship with tumor-infiltrating lymphocytes (TILs) markers and its prognostic value. The expression of VISTA, CD3, CD8, CD4, FOXP3, and CD56 was assessed in 168 EOC tissue microarrays (TMA) by immunohistochemistry (IHC). In addition, associations between VISTA, TILs, clinicopathological variables, and overall survival (OS) were analyzed. VISTA expression in IGRov1 cells, as well as in PBMC of EOC patient, was evaluated by western blot. VISTA expression was detected in 64,28% of tissues, among which 42.3% were positive for tumor cells (TCs), and 47,9% were positive for immune cells (ICs). In univariate analysis, VISTA expression was significantly associated with a high density of TILs:CD3+ (p = 0,001), CD4+ (p = 0,002) and CD8+ (p≤0,001), in ICs but not in TCs. In terms of OS, multivariate analysis showed a significant association between the high density of CD8+ TILs and VISTA positive staining in ICs (p = 0,044), but not in TCs (p = 0,108). Kaplan-Meier curves demonstrated no correlation between VISTA expression and prolonged OS in both ICs (p = 0,841) and TCs (p = 0,090). Classification of EOC tumor microenvironment based on VISTA and CD8+TILs expression, demonstrated four immune subtypes: VISTA+/CD8+, VISTA+/CD8-, VISTA-/CD8+ and VISTA-/CD8-. The dual positive VISTA+/CD8+ subtype was significantly associated with prolonged OS in both TCs and ICs (p = 0,012 and p≤0,01, respectively), whereas patients with VISTA+/CD8- had the worst OS. Our results showed that VISTA is highly expressed in the IGRov1 cell line and LT-CD8 from a patient with EOC. Our results highlighted the association of VISTA expression and CD8+ TILs in EOC, with prolonged OS in patients with VISTA+/CD8+ and proposed VISTA as a potential immunotherapeutic target in EOC.
Identification PMS1 and PMS2 as potential meiotic substrates of CDK2 activity

Cyclin dependent-kinase 2 (CDK2) plays important functions during the mitotic cell cycle and also facilitates several key events during germ cell development. The majority of CDK2’s known meiotic functions occur during prophase of the first meiotic division. Here, CDK2 is involved in the regulation of meiotic transcription, the pairing of homologous chromosomes, and the maturation of meiotic crossover sites. Despite that some of the CDK2 substrates are known, few of them display functions in meiosis. Here, we investigate potential meiotic CDK2 substrates using in silico and in vitro approaches. We find that CDK2 phosphorylates PMS2 at Thr337, PMS1 at Thr331, and MLH1 in vitro. Phosphorylation of PMS2 affects its interaction with MLH1 to some degree. In testis extracts from mice lacking Cdk2, there are changes in expression of PMS2, MSH2, and HEI10, which may be reflective of the loss of CDK2 phosphorylation. Our work has uncovered a few CDK2 substrates with meiotic functions, which will have to be verified in vivo. A better understanding of the CDK2 substrates will help us to gain deeper insight into the functions of this universal kinase.
Prevalence of depression and its association with health-related quality of life in people with heart failure in low- and middle-income countries: A systematic review and meta-analysis

Introduction Heart failure is a growing public health concern around the world. People with heart failure have a high symptom burden, such as depression, which affects health-related quality of life (HRQoL). The objective of this systematic review and meta-analysis was to estimate the pooled prevalence of depression and evaluate its association with HRQoL among people with heart failure in low- and middle-income countries (LMICs). Methods This systematic review was conducted in accordance with the JBI methodology. Electronic databases such as MEDLINE, PsycINFO, EMBASE, CINAHL, Web of Science, Scopus and JBI EBP were searched to identify relevant studies published from January 2012 to August 2022. The methodological quality of each article was assessed using relevant JBI critical appraisal instruments. A random-effects model was employed to estimate the pooled prevalence of depression. Heterogeneity across the studies was investigated using Cochrane’s Q test and I2 statistic. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines 2020 were followed for reporting the results. All statistical analyses were performed using STATA version 17 software. Results After screening, a total of 21 eligible articles with 5074 participants with heart failure were included in this review. The pooled prevalence of depression among people with heart failure in LMICs was 51.5% (95% CI = 39.7, 63.3%, I2 = 99.00%). Subgroup analysis revealed, the highest prevalence in studies whose participants were in-patients, and from the Middle East and North Africa, and studies utilizing Becks Depression Inventory (BDI). Depression was positively associated with HRQoL. Conclusion This review revealed that almost half of all people with heart failure in low- and middle-income countries have comorbid depression. People with heart failure and depressive symptoms had poor HRQoL. Therefore, early screening of depression is critical for improving HRQoL in this population. Systematic review registration: PROSPERO CRD42022361759.
Multiple sclerosis and COVID-19: A retrospective study in Iran

Objectives Previous studies suggested a higher rate of COVID-19 infection in patients with multiple sclerosis than in the general population, and limited studies addressed the impact of COVID-19 and its vaccination in patients with multiple sclerosis in Iran. We decided to investigate the factors associated with COVID-19 infection, the effects and side effects of the COVID-19 vaccination in patients with multiple sclerosis (MS). Methods We used the data of the patients with multiple sclerosis registered in a referral clinic in Kerman, one of the large cities in Iran (a population of 537,000 inhabitants), to explore the association between demographic variables, the history of COVID-19 vaccination, and the clinical outcomes. Results Of the 367 participants in this study, 88.3% received the COVID-19 vaccine, 35.4% were confirmed COVID-19 cases, and the incidence of COVID-19 was much higher before vaccination (24.5% before vaccination versus 10.1% after vaccination). The multivariable logistic regression model showed that male gender (OR = 2.64, 95% confidence interval: 1.21, 5.74) and current employment (OR = 3.04, 95% confidence interval: 1.59, 5.80) were associated with an increased risk of COVID-19. The only factor associated with the adverse effects of COVID-19 vaccination was the type of vaccine (AstraZeneca). Conclusion Our findings showed that the vaccination protected MS cases considerably against COVID-19. In addition, the side effects of the vaccines were not noticeably high in these cases as well. Among all COVID-19 vaccines, AstraZeneca had the most common side effects, so people must be aware of them before vaccination. The male gender and employment were the most important variables in the prevalence of COVID-19 in patients with multiple sclerosis in our study.
The temporal structure of male freestyle wrestling bouts in 65, 86 and 125 kg categories

In freestyle wrestling, how regulatory breaks and micro pauses affect the efforts during combat has been studied very little. The objective of the study was to determine the temporal structure of fights in male freestyle wrestling in the 65, 86 and 125 kg categories. All wrestlers from the categories (n = 115) who competed in the 2019 senior wrestling world championship (Nur-Sultan, Kazakhstan) participated. Using observational methodology, we analyzed all fights (n = 127). We used different statistical techniques: descriptive, normality tests, Kruskall-Wallis, one-way ANOVA and chi-square. The significance level was ρ<0.05. The results show that most fights finish in the last minute (73.5% in 65 kg, 74.5% in 86 kg and 80.6% in 125 kg) and the total fight time is consumed (67.3% in 65 kg, 70.2% in 86 kg and 77.4% in 125 kg). Differences in 18 variables were found when comparing the three weights were found in the temporal and sequential parameters of the combat. When we compare these parameters to the different fight minutes, we find that there are differences in 17 variables in 65 kg, 20 variables in 86 kg and 10 variables in 125 kg. The results define a temporal structure of male freestyle wrestling bouts in the three categories, and therefore, it will be possible to prepare adequate trainings for these athletes. We conclude that in the three weight categories, they wrestle longer standing than while on the ground. There are clear differences between the three categories. In the 125 kg category, the temporal and sequential parameters are more stable throughout the different minutes of the fight, and in 65 and 86 kg, there is an instability. In the three weights, the regulatory break modulates the duration of the pauses and the actions performed by the wrestlers in different fight minutes.
Effect of silvopasture system on fearfulness and leg health in fast-growing broiler chickens

A silvopasture system intentionally integrates trees, forages, and livestock, allowing dual land use. These systems can provide high-quality habitat for broiler chickens; however, such systems have not been widely adopted by the broiler industry in the United States. The objective of this study was to examine the effect of silvopasture versus open pasture access on fearfulness and leg health in fast-growing broiler chickens. A total of 886 mixed-sex Ross 708 chicks in Experiment 1 (Exp 1) and 648 chicks in Experiment 2 (Exp 2) were housed in coops and had access to 16 (Exp 1) or 12 (Exp 2) 125m2 silvopasture plots (x̄ = 32% canopy cover) or open pasture plots (no canopy cover) from day 24 of age. Fearfulness was measured using a tonic immobility test (tonic immobility duration), and leg health was assessed by quantifying footpad dermatitis, hock burns, gait, and performing a latency-to-lie test on days 37–39 of age. Birds in the silvopasture treatment were less fearful than birds in the open pasture treatment. Overall, birds in both silvopasture and open pasture systems had excellent leg health. Silvopasture birds had lower footpad dermatitis scores than open pasture birds. Silvopasture birds tended to have worse gait than open pasture birds in Exp 1, but not in Exp 2. Hock burn scores and latency-to-lie did not differ between treatments in Exp 1 or Exp 2. Raising birds in silvopasture reduced fear and improved footpad health compared to birds raised in open pastures, which indicates that silvopasture systems provide some benefits for affective state and leg health in fast-growing broilers.
The association of prenatal amniotic sex hormones and digit ratio (2D:4D) in children aged 5 to 70 months: A longitudinal study

The sex difference of the 2D:4D digit ratio (female > male)–a proposed marker for prenatal testosterone exposure—is well established. Studies suggest it already exists in utero and is of moderate effect size in adulthood. However, evidence for the claim that 2D:4D reflects prenatal androgen action is limited, and the sex difference may exhibit lability during childhood. In the present study, 244 mothers were recruited in the course of an amniocentesis examination (performed between gestational weeks 14 and 18). Prenatal testosterone (T) and estradiol (E) levels were determined from amniotic fluid for boys and girls. The majority (97.4%, n = 114) of available female T levels (n = 117) were found below the level of quantification. Therefore, only male amniotic fluid data (n = 117) could be included for the analysis of associations between amniotic sex hormones (T levels and T to E ratio (T/E)) and 2D:4D. The families were then invited to each of the five consecutive follow-ups (ages: 5, 9, 20, 40, and 70 months) where children’s 2D:4D was measured for both hands. The alternative marker D[r-l] reflects the directional asymmetry of 2D:4D (right subtracted by left 2D:4D) and was subsequently calculated as an additional measure for prenatal T exposure. No significant correlations between amniotic T or the T/E ratio (measured between week 14 and 18 of gestation) with 2D:4D respectively D[r-l] were observed for any time point. There was a significant sex difference (females > males) and a significant age effect with moderate correlations of 2D:4D between time points. 2D:4D increased between 20 and 40 months and between 40 and 70 months of age. The findings raise questions regarding the applicability of 2D:4D as a marker for prenatal androgen action and are discussed in terms of the reliability of obtained digit ratio data as well as in terms of the developmental timing of amniocentesis.
The relative age effect is widespread among European adult professional soccer players but does not affect their market value

Background The relative age effect (RAE) is most prevalent in highly competitive youth soccer and persists to a lesser extent in senior soccer. However, it is known that soccer players born in the second half of the year are as successful at senior level, indicating that they are equally talented although under-represented at youth level due to bias during the selection process, in which the emphasis is on more pronounced physical qualities in a specific period of time. Examining the prevalence of the RAE among professional soccer players depending on the level of competition and playing position, as well as analyzing the relationship between the player’s birth quarter and market value, are of scientific interest. Methods The dates of birth, playing position, and market value of all adult male soccer players included in the final rosters of teams from the top-division of 54 European countries, listed on www.transfermarkt. com on August 15th, 2020, were analyzed (18,429 soccer players in total). All players were categorized into four groups according to the quarter of birth (Q) and playing position. All teams were further sub-divided in groups depending on the soccer clubs’ level of representation in the UEFA Champions League. Results Of 18,429 players, 30.9% were born in Q1, 25.7% in Q2, 23.8% in Q3 and 19.6% in Q4. The number of soccer players born in Q1 was lower in less competitive leagues. The number of players born in Q1 decreased as the level of competition decreased; the highest percentage of these players was observed in clubs that are among the top 50 ranked in UEFA or compete in the most prestigious European championships. The RAE was less pronounced in teams that participate in lower competitive championships. There was no significant difference in market value between players playing position and level of competition when born in different quarters. Although, the most expensive soccer players in the European championships were late-born forwards. Players of various groups differed in their market value. Conclusions The RAE is currently prevalent in all the most competitive senior soccer leagues and teams in Europe regardless of playing position. There are no significant differences in market value between players of the same playing position and level of competition when born in different quarters. The most expensive soccer players in the European championships are forwards born in Q4. These findings may indicate that the under-representation of “late-born” soccer players in youth, and then consequently in adult soccer, is not associated with lower talent, but with other factors, possibly based on physiological characteristics and socio-cultural factors. Further measures are needed to mitigate the discriminatory effects of selection bias based on the RAE.