Miracle-dz/UniFAR-FTUs huggingface dataset:
Algebraic Statistics for Computational Biology: Preface

Preface Part I. Introduction to the Four Themes: 1. Statistics L. Pachter and B. Sturmfels 2. Computation L. Pachter and B. Sturmfels 3. Algebra L. Pachter and B. Sturmfels 4. Biology L. Pachter and B. Sturmfels Part II. Studies on the Four Themes: 5. Parametric inference R. Mihaescu 6. Polytope propagation on graphs M. Joswig 7. Parametric sequence alignment C. Dewey and K. Woods 8. Bounds for optimal sequence alignment S. Elizalde 9. Inference functions S. Elizalde 10. Geometry of Markov chains E. Kuo 11. Equations defining hidden Markov models N. Bray and J. Morton 12. The EM algorithm for hidden Markov models I. B. Hallgrimsdottir, A. Milowski and J. Yu 13. Homology mapping with Markov random fields A. Caspi 14. Mutagenetic tree models N. Beerenwinkel and M. Drton 15. Catalog of small trees M. Casanellas, L. Garcia and S. Sullivant 16. The strand symmetric model M. Casanellas and S. Sullivant 17. Extending statistical models from trees to splits graphs D. Bryant 18. Small trees and generalized neighbor-joining M. Contois and D. Levy 19. Tree construction using Singular Value Decomposition N. Eriksson 20. Applications of interval methods to phylogenetics R. Sainudiin and R. Yoshida 21. Analysis of point mutations in vertebrate genomes J. Al-Aidroos and S. Snir 22. Ultra-conserved elements in vertebrate genomes M. Drton, N. Eriksson and G. Leung Index.
Hypoxia-Inducible Factors and Diabetic Kidney Disease—How Deep Can We Go?

Diabetes is one of the leading causes of chronic kidney disease (CKD), and multiple underlying mechanisms involved in pathogenesis of diabetic nephropathy (DN) have been described. Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden, considering that about 40% of type 2 diabetes patients will develop nephropathy. In the past years, some research found that hypoxia response and hypoxia-inducible factors (HIFs) play critical roles in the pathogenesis of DN. Hypoxia-inducible factors (HIFs) HIF-1, HIF-2, and HIF-3 are the main mediators of metabolic responses to the state of hypoxia, which seems to be the one of the earliest events in the occurrence and progression of diabetic kidney disease (DKD). The abnormal activity of HIFs seems to be of crucial importance in the pathogenesis of diseases, including nephropathies. Studies using transcriptome analysis confirmed by metabolome analysis revealed that HIF stabilizers (HIF-prolyl hydroxylase inhibitors) are novel therapeutic agents used to treat anemia in CKD patients that not only increase endogenous erythropoietin production, but also could act by counteracting the metabolic alterations in incipient diabetic kidney disease and relieve oxidative stress in the renal tissue. In this review, we present the newest data regarding hypoxia response and HIF involvement in the pathogenesis of diabetic nephropathy and new therapeutic insights, starting from improving kidney oxygen homeostasis.
Effectiveness of theta burst versus high frequency repetitive transcranial magnetic stimulation in reducing symptoms of post-traumatic stress disorder in Veterans with depression: a retrospective case series.

Abstract Background: Two commonly used forms of repetitive transcranial magnetic stimulation (rTMS) were recently shown to be equivalent for the treatment of treatment-resistant depression (TRD): high-frequency stimulation (10 Hz), a protocol that lasts between 19-38 minutes, and intermittent Theta-Burst Stimulation (iTBS), a protocol that can be delivered in just 3 minutes. Intermittent TBS offers significant advantages to patients and clinics and has thus become a default treatment in many clinics. However, it is unclear whether iTBS treatment offers the same benefits as standard 10 Hz rTMS for comorbid symptoms, such as post-traumatic-stress-disorder (PTSD). Methods: In this retrospective case series, we analyzed treatment outcomes in Veterans from the VA San Diego Healthcare system (VASDHS) who received 10 Hz (n = 47) or iTBS (n = 51) rTMS treatments for TRD between the dates of Jan 2017 to June 2022. We compared outcomes between these two stimulation protocols used between these dates on symptoms of depression (using changes in the patient health questionnaire-9, or PHQ-9) and PTSD (using changes in the PTSD Checklist for DSM-5, or PCL-5). We hypothesized that there would be no differences in treatment outcomes between 10 Hz and iTBS protocols for either depression (confirming prior RCT) or PTSD. Results: We found that both types of stimulation showed a clinically meaningful reduction in symptoms with no difference in outcomes based on the type of stimulation. The mean reduction on the PHQ-9 scale was 5.8 +/- 0.93 (p <0.001, n = 47) in Veterans receiving 10 Hz stimulation and 6.6 +/- 0.71 (p < 0.001, n = 51) in the Veterans receiving iTBS. There were no difference between stimulation protocols (p = 0.5). The mean reduction on the PCL-5 symptom scale was 8.1 +/- 2.1 in Veterans receiving 10 Hz stimulation (p <0.001, n =47) and -13.2 +/- 2.4 the Veterans receiving iTBS (p <0.001, n = 51). This difference was not significant (p=0.11) and had a small effect size (eta^2 = 0.026). Follow-up analyses restricting the sample in various ways did not meaningfully change these results. Conclusions: While limited by small sample size, non-blinded and pseudo-randomized assignment, our data suggests that iTBS can be expected to have similar if not slightly greater reductions in PTSD symptoms compared with 10 Hz stimulation. Our findings pave the way for further research trials to validate and optimize iTBS for PTSD symptoms.
The Systematics and Distribution of Molecular Hydrogen in Planetary Nebulae

The infrared S(l) line of molecular hydrogen has been searched for in twenty-two planetary nebulae using the imaging mode of the AngloAustralian Telescope. The line was detected and mapped in eleven objects. It has been demonstrated that all those with strong excited molecular hydrogen belong to a subclass of the Type I planetary nebulae, morphologically consisting of an equatorial toroid with faint bipolar extensions. Furthermore, nearly all planetaries with these characteristics have strong molecular hydrogen. The molecular line ratios in the 2.0 to 2.5 micron window are consistent with shock excitation. The observations suggest that the morphology of these planetaries has been controlled by a fast stellar wind interacting with a disc of gas concentrated in the equatorial plane.
Enhanced closure scheme for lattice Boltzmann equation hydrodynamics

A simple and adaptable closure algorithm for the edge nodes of a lattice Boltzmann fluid simulation space is presented. Its rules are designed to be correct at every instant, to maintain local mass and to produce a specified fluid velocity and, crucially, the correct strain rate tensor at the resulting fluid boundary. Further, our algorithm models the fluid on boundary nodes to the same accuracy as on the bulk nodes and in a demonstrably equivalent manner, requiring only a specified boundary velocity, the fluid boundary pressure emerging. Illustrative results for steady and time-dependent flows, together with outline generalizations, are presented.
A study of mandibular premolar root and canal morphology in a Black South African population using cone-beam computed tomography and two classification systems.

PURPOSE An investigation of the configurations of mandibular premolar roots and canals in a population of Black South Africans. METHODS Cone-beam computed tomography analysis of 772 mandibular premolars was performed, and the premolars were classified according to the systems proposed by Vertucci and Ahmed et al. Root number, canal morphology, age, and sex were recorded. Fisher's exact test was used to determine relationships based on age and sex (P < 0.05). RESULTS Single roots were seen in the majority of mandibular premolars (97.1%). Single canal configurations (i.e., Vertucci Type 1/Ahmed et al. 1MP1) were observed in 48.5% of first and 81.3% of second mandibular premolars. Mandibular first premolars demonstrated multiple canals in more than half of the sample (51.5%), and C-shaped morphology in more than one-tenth (11.1%). A relationship between sex and the presence of radicular grooves was demonstrated (P = 0.049), males being more likely to demonstrate this feature (P = 0.051). Multiple canals in mandibular first premolars also showed a relationship with sex (P = 0.005), a male predilection being evident (P = 0.007). The Ahmed et al. system proved superior to the Vertucci classification for reporting complex configurations and anatomical variations, although a greater number of unique categories were created. CONCLUSION Diverse mandibular premolar root and canal morphology was observed in the studied population. Clinicians must be aware of common morphological features as well as possible anatomical variations in mandibular premolars, as failure to treat complete root canal systems may negatively impact endodontic treatment outcomes.
Patient safety in medical education: Tunisian students’ attitudes

ABSTRACT Health care delivery continues to be unsafe despite major patient safety (PS) improvement efforts over the past decade. Medical school education plays an important role in promoting this culture during initial training. To determine undergraduate medical students’ attitudes toward PS at a Tunisian medical school. We carried out a cross-sectional study among undergraduate medical students at Ibn Al Jazzar Medical School in Sousse, Tunisia, using a self-administered questionnaire inspired from the valid tool: Attitudes to Patient Safety Questionnaire (APSQ III). A total of 178 medical students responded to the questionnaire. Medical students tend to have an overall positive perceptions of PS culture with a global mean score 5.33 ± 0.5. Among the individual domains ‘Working hours as a cause of error’ earned the highest score (6.38 ± 1.0) followed in order by ‘Team functioning’ (6.24 ± 0.8), ‘Error inevitability’ (5.91 ± 1.0) and ‘Patient involvement in reducing error’ (5.50 ± 1.0). The lowest score was for ‘Professional incompetence as a cause of error’ (4.01 ± 1.0). A PS domain’s mean scores comparison based on socio-demographic variables: gender, age, academic year and on PS training revealed a statistically significant difference (p < 0.05) for five PS key dimensions: ‘ Error reporting confidence ’, ‘ Working hours as a cause of error ’, ‘ Professional incompetence as a cause of error ’, ‘ Team functioning ’ and ‘PS training received’. Tunisian medical students showed positive attitude towards PS. Nevermore, intensive in terms of frequency and duration sessions, based on various teaching methods may be needed to fulfill students’ educational needs.
Effects of a Neonicotinoid Insecticide and Population Density on Behavior and Development of Wood Frogs (Rana sylvatica)

Amphibians have been facing global declines over the last decades from direct and indirect effects of anthropogenic activities. A contributor to declines is waterway contamination from agricultural runoffs of pesticides such as neonicotinoids. Beyond direct and indirect effects of the pesticide, few studies have investigated the possible interactions between neonicotinoids and natural environmental stressors across larval development, which could alter the strength and direction of observed neonicotinoid effects. The present study used a fully crossed design to investigate how a concentration of imidacloprid (a neonicotinoid; 10 µg/L) measured in surface waters interacted with low and high population densities (0.33 and 1 tadpole/L, respectively), an important environmental stressor, to influence behavior and development across metamorphosis in wood frogs (Rana sylvatica), known to breed in agricultural landscapes. Behaviors were measured in the absence and presence of predation cues using open‐field tests at three distinct developmental stages, up to the metamorph stage. We found that imidacloprid did not interact with population density or independently affect behaviors in the absence of predation cues. However, individuals raised at high density compared with low density were more active at an early developmental stage but less active at metamorphic climax. Furthermore, both density and imidacloprid independently decreased the natural freezing response of tadpoles to predation cues. Finally, we found that distance traveled in the open‐field test was weakly repeatable between aquatic stages but not repeatable across metamorphosis, a pattern that was not affected by treatments. The present study provides novel insights on the ecotoxicology of imidacloprid in the presence of a natural stressor, highlighting the importance of including behavioral assays and natural stressors in studies of amphibian ecotoxicology. Environ Toxicol Chem 2022;41:2968–2980. © 2022 SETAC
Impact of HbA1c Followed 32 Years From Diagnosis of Type 1 Diabetes on Development of Severe Retinopathy and Nephropathy: The VISS Study.

OBJECTIVE To evaluate HbA1c followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]). RESEARCH DESIGN AND METHODS In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA1c (wHbA1c) was calculated by integrating the area under all HbA1c values. Complications were analyzed in relation to wHbA1c categorized into five levels. RESULTS After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA1c did not develop PDR or macroalbuminuria. The lowest wHbA1c values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA1c, being 74% and 44% in the highest category, wHbA1c >9.5% (>80 mmol/mol). In comparison with the follow-up done after 20-24 years' duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA1c values. CONCLUSIONS wHbA1c followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA1c <7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life.
Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma.

BACKGROUND In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings. METHODS We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events. RESULTS A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%). CONCLUSIONS Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).
Clinical features and management of animal bites in an emergency department: a single-center experience

ABSTRACT Objectives This study aimed to evaluate the clinical features, management, and outcomes of patients with animal bites presented to the pediatric emergency department of a tertiary center. Methods Patients with ICD-10 code W54 (contact with dog) and W55 (contact with other mammals) between March 1st, 2017, and July 1st, 2021, were included in the study. Demographic characteristics of the patients, type of contacted animal, wound characteristics (muscle involvement, soft tissue defect, vascular injury, type of nerve injury, and Lackmann’s classification), wound care measurements, tetanus prophylaxis, administration of rabies immunoglobulin and antibiotics, location of the injury, existing fractures, suturing, splinting, surgical consultations and hospitalization status were recorded. Results Four hundred and nineteen incidents of animal bites (240 males and 179 females) occurred over a four-year period. 51% was due to a dog bite; 47% was by a cat. The median age was nine years (IQR: 5–14 years). Most bites (91.6%) involved only a single anatomical site. The extremities were the commonly involved part (right upper limb [35.3%], left upper limb [21.2%], right lower limb [12.6%], left lower limb [16%]). Head-neck and face injury ratio was 17.6%. Torso (5.7%) and genitalia (5.2%) were uncommonly involved. A consultation was requested from at least one surgical department for 8% of the patients. 97.1% of patients received a rabies vaccine. Most attacks were trivial and did not require hospitalization. Conclusion Animal bites often cause minor injuries. However, multiple dog attacks can be seen related to a high number of stray animals in our country. Therefore, these patients may present with major traumas. Surgical intervention and hospitalization may be required. Emergency physicians play an essential role in acute management and rabies prophylaxis in these patients.
Circulating irisin in nonalcoholic fatty liver disease: an updated meta-analysis.

INTRODUCTION Exogenous administration of recombinant irisin may reverse hepatic steatosis and steatohepatitis. However, it remains controversial as to whether nonalcoholic fatty liver disease (NAFLD) shows reduced circulating (serum/plasma) irisin levels. A meta-analysis was conducted to address this issue. MATERIAL AND METHODS A literature search of databases was performed up to June 2021. Observational studies that reported circulating irisin in NAFLD ascertained by any methods (e.g. ultrasonography or magnetic resonance) and compared with any controls were eligible for inclusion. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were obtained using a random-effects meta-analysis model. RESULTS Eleven studies enrolling 1277 NAFLD cases and 944 non-NAFLD controls were included. The approaches used for NAFLD ascertainment included ultrasonography (4 studies), magnetic resonance (3 studies), and liver biopsy (5 studies). Meta-analysis showed that circulating irisin in NAFLD was comparable to any non-NAFLD controls (10 studies with 11 datasets; SMD -0.09, 95% CI: -0.48 to 0.29), including the body mass index (BMI)-matched and lean controls (both p ≥ 0.80). Restricting studies to NAFLD ascertained by magnetic resonance or liver biopsy rather than ultrasonography showed that serum irisin was reduced in NAFLD (5 studies, SMD -0.63, 95% CI: -1.14 to -0.13). Meta-analysis also suggested that circulating irisin did not differ between mild and moderate-to-severe NAFLD (7 studies; SMD 0.02, 95% CI: -0.25 to 0.30), and this association was not significantly moderated by study location (Europe versus Asia). CONCLUSIONS Circulating irisin in NAFLD did not differ from any non-NAFLD controls and was unlikely to be affected by disease severity or racial-ethnic difference.
Validity testing of the conspiratorial thinking and anti-expert sentiment scales during the COVID-19 pandemic across 24 languages from a large-scale global dataset

Abstract In this study, we tested the validity across two scales addressing conspiratorial thinking that may influence behaviours related to public health and the COVID-19 pandemic. Using the COVIDiSTRESSII Global Survey data from 12 261 participants, we validated the 4-item Conspiratorial Thinking Scale and 3-item Anti-Expert Sentiment Scale across 24 languages and dialects that were used by at least 100 participants per language. We employed confirmatory factor analysis, measurement invariance test and measurement alignment for internal consistency testing. To test convergent validity of the two scales, we assessed correlations with trust in seven agents related to government, science and public health. Although scalar invariance was not achieved when measurement invariance test was conducted initially, we found that both scales can be employed in further international studies with measurement alignment. Moreover, both conspiratorial thinking and anti-expert sentiments were significantly and negatively correlated with trust in all agents. Findings from this study provide supporting evidence for the validity of both scales across 24 languages for future large-scale international research.
Brain age vector: A measure of brain aging with enhanced neurodegenerative disorder specificity

Neuroimaging‐driven brain age estimation has become popular in measuring brain aging and identifying neurodegenerations. However, the single estimated brain age (gap) compromises regional variations of brain aging, losing spatial specificity across diseases which is valuable for early screening. In this study, we combined brain age modeling with Shapley Additive Explanations to measure brain aging as a feature contribution vector underlying spatial pathological aging mechanism. Specifically, we regressed age with volumetric brain features using machine learning to construct the brain age model, and model‐agnostic Shapley values were calculated to attribute regional brain aging for each subject's age estimation, forming the brain age vector. Spatial specificity of the brain age vector was evaluated among groups of normal aging, prodromal Parkinson disease (PD), stable mild cognitive impairment (sMCI), and progressive mild cognitive impairment (pMCI). Machine learning methods were adopted to examine the discriminability of the brain age vector in early disease screening, compared with the other two brain aging metrics (single brain age gap, regional brain age gaps) and brain volumes. Results showed that the proposed brain age vector accurately reflected disorder‐specific abnormal aging patterns related to the medial temporal and the striatum for prodromal AD (sMCI vs. pMCI) and PD (healthy controls [HC] vs. prodromal PD), respectively, and demonstrated outstanding performance in early disease screening, with area under the curves of 83.39% and 72.28% in detecting pMCI and prodromal PD, respectively. In conclusion, the proposed brain age vector effectively improves spatial specificity of brain aging measurement and enables individual screening of neurodegenerative diseases.