Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing the social patterning and magnitude of inequalities in sexual violence among young women in Uganda: Findings from 2016 demographic and health survey

ABSTRACT Sexual violence (SV) is a significant global public health problem. To develop effectively targeted interventions to prevent SV and allocate resources equitably requires identifying the most vulnerable groups and the magnitude of these social inequities. However, these data are currently lacking. Using the Uganda Demographic and Health Survey, we examined SV among all young women and ever-married young women. We conducted univariate and bivariate analyses to characterise the prevalence and social patterning of SV, and then utilised the World Health Organization Health Equity Assessment Toolkit (HEAT) to assess the magnitude of social inequities in SV. At the national level, 5.5% among all young women and 20.5% of ever-married young women had experienced SV. For all young women, the largest inequities in SV were based on sub-national region of residence. Among the ever-married young women, we found profound education, wealth and place-based inequities in SV, which favoured young women with higher education, in wealthier households, and within central regions of Uganda. Our findings suggest a need for regionally targeted multi-sectoral interventions that take into consideration that multiple intersecting social dimensions such as education, poverty and the safe built environment, to address young women's risk for SV.
Vaginal mucositis in patients with gynaecological cancer undergoing (chemo-)radiotherapy: a retrospective analysis

Abstract The objective of this retrospective analysis was to determine the incidence and extent of vaginal mucositis (VM) in women with gynaecological cancer undergoing external (chemo)radiation therapy (CRT). A retrospective analysis was set up to collect data on the incidence and severity of VM in women treated with external pelvic RT for gynaecological cancer at the Jessa Hospital, Hasselt and ZOL, Genk, BE between January 2017 and June 2018. At the start and end of their external (C)RT, they rated the frequency and intensity of five common symptoms of VM. Thirty-three patients treated with RT for gynaecological cancer met the inclusion criteria. A non-negligible proportion of patients already experienced at least one VM symptom to any degree before the start of RT, a proportion that further increased towards the end of the RT (73%). At the end of RT, on average, about 25% of these patients reported moderate-to-severe symptoms (against about 7% before the (C)RT). These results suggest that VM is a rather frequent side effect in gynaecological cancer patients that aggravates during treatment up to a moderate severity level. Although the small sample size, these data highlight the need for attention to VM. Impact Statement What is already known about this topic? Radiotherapy plays an important role in the treatment of gynaecological malignancies. A debilitating complication in patients undergoing pelvic radiotherapy is vaginal mucositis, an inflammation of the vaginal mucosal lining. To date, the incidence of vaginal mucositis is still not well documented. What this paper adds? A non-negligible proportion of patients already experienced at least one symptom related to vaginal mucositis before the start of radiotherapy. Most patients presented mild to moderate vaginal mucositis symptoms at the end of external pelvic radiotherapy. Burning sensation, pruritus, and pain were the most frequently documented radiotherapy-induced complications. The implications of this paper: Vaginal mucositis is an underrated side effect of pelvic radiotherapy that needs to be tackled multidisciplinary by a team of nurses, radiotherapists, oncologists, and gynaecologists. The team should tackle the complication from the start of radiotherapy by using the most appropriate measures. Due to a possible link between acute vaginal mucositis and late vaginal toxicity, the team needs to follow-up patient’s post-radiotherapy to support patients in late complications and advise/encourage patients in performing vaginal dilatation to prevent vaginal stenosis.
Katacine Is a New Ligand of CLEC-2 that Acts as a Platelet Agonist

Background CLEC-2 is a platelet receptor with an important role in thromboinflammation but a minor role in hemostasis. Two endogenous ligands of CLEC-2 have been identified, the transmembrane protein podoplanin and iron-containing porphyrin hemin, which is formed following hemolysis from red blood cells. Other exogenous ligands such as rhodocytin have contributed to our understanding of the role of CLEC-2. Objectives To identify novel CLEC-2 small-molecule ligands to aid therapeutic targeting of CLEC-2. Methods ALPHA screen technology has been used for the development of a high-throughput screening (HTS) assay recapitulating the podoplanin–CLEC-2 interaction. Light transmission aggregometry was used to evaluate platelet aggregation. Immunoprecipitation and western blot were used to evaluate direct phosphorylation of CLEC-2 and downstream protein phosphorylation. Autodock vina software was used to predict the molecular binding site of katacine and mass spectrometry to determine the polymeric nature of the ligand. Results and Conclusion We developed a CLEC-2–podoplanin interaction assay in a HTS format and screened 5,016 compounds from a European Union-open screen library. We identified katacine, a mixture of polymers of proanthocyanidins, as a novel ligand for CLEC-2 and showed that it induces platelet aggregation and CLEC-2 phosphorylation via Syk and Src kinases. Platelet aggregation induced by katacine is inhibited by the anti-CLEC-2 monoclonal antibody fragment AYP1 F(ab)′2. Katacine is a novel nonprotein ligand of CLEC-2 that could contribute to a better understanding of CLEC-2 activation in human platelets.
Habit and Automaticity in Medical Alert Override: Cohort Study

Background Prior literature suggests that alert dismissal could be linked to physicians’ habits and automaticity. The evidence for this perspective has been mainly observational data. This study uses log data from an electronic medical records system to empirically validate this perspective. Objective We seek to quantify the association between habit and alert dismissal in physicians. Methods We conducted a retrospective analysis using the log data comprising 66,049 alerts generated from hospitalized patients in a hospital from March 2017 to December 2018. We analyzed 1152 physicians exposed to a specific clinical support alert triggered in a hospital’s electronic medical record system to estimate the extent to which the physicians’ habit strength, which had been developed from habitual learning, impacted their propensity toward alert dismissal. We further examined the association between a physician’s habit strength and their subsequent incidences of alert dismissal. Additionally, we recorded the time taken by the physician to respond to the alert and collected data on other clinical and environmental factors related to the alerts as covariates for the analysis. Results We found that a physician’s prior dismissal of alerts leads to their increased habit strength to dismiss alerts. Furthermore, a physician’s habit strength to dismiss alerts was found to be positively associated with incidences of subsequent alert dismissals after their initial alert dismissal. Alert dismissal due to habitual learning was also found to be pervasive across all physician ranks, from junior interns to senior attending specialists. Further, the dismissal of alerts had been observed to typically occur after a very short processing time. Our study found that 72.5% of alerts were dismissed in under 3 seconds after the alert appeared, and 13.2% of all alerts were dismissed in under 1 second after the alert appeared. We found empirical support that habitual dismissal is one of the key factors associated with alert dismissal. We also found that habitual dismissal of alerts is self-reinforcing, which suggests significant challenges in disrupting or changing alert dismissal habits once they are formed. Conclusions Habitual tendencies are associated with the dismissal of alerts. This relationship is pervasive across all levels of physician rank and experience, and the effect is self-reinforcing.
Thirty years of resistance: Zig-zag through the plant immune system

Abstract Understanding the plant immune system is crucial for using genetics to protect crops from diseases. Plants resist pathogens via a two-tiered innate immune detection-and-response system. The first plant Resistance (R) gene was cloned in 1992 . Since then, many cell-surface pattern recognition receptors (PRRs) have been identified, and R genes that encode intracellular nucleotide-binding leucine-rich repeat receptors (NLRs) have been cloned. Here, we provide a list of characterized PRRs and NLRs. In addition to immune receptors, many components of immune signaling networks were discovered over the last 30 years. We review the signaling pathways, physiological responses, and molecular regulation of both PRR- and NLR-mediated immunity. Recent studies have reinforced the importance of interactions between the two immune systems. We provide an overview of interactions between PRR- and NLR-mediated immunity, highlighting challenges and perspectives for future research.
Pre‐synaptic and post‐synaptic A‐type K+ channels regulate glutamatergic transmission and switching of the network into epileptiform oscillations

Anticonvulsants targeting K+ channels have not been clinically available, although neuronal hyperexcitability in seizures could be suppressed by activation of K+ channels. Voltage‐gated A‐type K+ channel (A‐channel) inhibitors may be prescribed for diseases of neuromuscular junction but could cause seizures. Consistently, genetic loss of function of A‐channels may also cause seizures. It is unclear why inhibition of A‐channels, compared with other types of K+ channels, is particularly prone to seizure induction. This hinders the development of relevant therapeutic interventions.
Global benefits of non‐continuous flooding to reduce greenhouse gases and irrigation water use without rice yield penalty

Non‐continuous flooding is an effective practice for reducing greenhouse gas (GHG) emissions and irrigation water use (IRR) in rice fields. However, advancing global implementation is hampered by the lack of comprehensive understanding of GHGs and IRR reduction benefits without compromising rice yield. Here, we present the largest observational data set for such effects as of yet. By using Random Forest regression models based on 636 field trials at 105 globally georeferenced sites, we identified the key drivers of effects of non‐continuous flooding practices and mapped maximum GHGs or IRR reduction benefits under optimal non‐continuous flooding strategies. The results show that variation in effects of non‐continuous flooding practices are primarily explained by the UnFlooded days Ratio (UFR, that is the ratio of the number of days without standing water in the field to total days of the growing period). Non‐continuous flooding practices could be feasible to be adopted in 76% of global rice harvested areas. This would reduce the global warming potential (GWP) of CH4 and N2O combined from rice production by 47% or the total GWP by 7% and alleviate IRR by 25%, while maintaining yield levels. The identified UFR targets far exceed currently observed levels particularly in South and Southeast Asia, suggesting large opportunities for climate mitigation and water use conservation, associated with the rigorous implementation of non‐continuous flooding practices in global rice cultivation.
Association of Iatrogenic Infarcts With Clinical and Cognitive Outcomes in the Evaluating Neuroprotection in Aneurysm Coiling Therapy Trial

Background and Objectives Small iatrogenic brain infarcts are often seen on diffusion-weighted MRI (DWI) following surgical or endovascular procedures, but there are few data on their clinical effects. We examined the association of iatrogenic infarcts with outcomes in the ENACT (Evaluating Neuroprotection in Aneurysm Coiling Therapy) randomized controlled trial of nerinetide in patients undergoing endovascular repair of intracranial aneurysms. Methods In this post hoc analysis, we used multivariable models to evaluate the association of the presence and number of iatrogenic infarcts on DWI with neurologic impairment (NIH Stroke Scale [NIHSS]), functional status (modified Rankin Scale [mRS]), and cognitive and neuropsychiatric outcomes (30-minute test battery) at 1–4 days and 30 days postprocedure. We also related infarct number to a z score–derived composite outcome score using quantile regression. Results Among 184 patients (median age 56 years [interquartile range (IQR) 50–64]), 124 (67.4%) had postprocedural DWI lesions (median 4, IQR 2–10.5). Nerinetide treatment was associated with fewer iatrogenic infarcts but no overall significant clinical treatment effects. Patients with infarcts had lower Mini-Mental State Examination (MMSE) scores at 2–4 days (median 28 vs 29, adjusted coefficient [acoef] −1.11, 95% CI −1.88 to −0.34, p = 0.005). Higher lesion counts were associated with worse day 1 NIHSS (adjusted odds ratio for NIHSS ≥1: 1.07, 1.02–1.12, p = 0.009), day 2–4 mRS (adjusted common odds ratio [acOR] 1.05, 1.01–1.09, p = 0.005), and day 2–4 MMSE (acoef −0.07, −0.13 to −0.003, p = 0.040) scores. At 30 days, infarct number remained associated with worse mRS (acOR 1.04, 1.01–1.07, p = 0.016) and Hopkins Verbal Learning Test (HVLT) delayed recall scores (acoef −0.21, −0.39 to −0.03, p = 0.020). Patients with infarcts trended towards lower 30-day Digit Symbol Substitution Test (DSST) scores (acoef −3.73, −7.36 to −0.10, p = 0.044). Higher lesion count was associated with worse composite outcome scores at both 1–4 days and 30 days (30-day acoef −0.12, 95% CI −0.21 to −0.03, p = 0.008). Among those with infarcts, day 1 NIHSS and day 2–4 mRS correlated with 30-day NIHSS, DSST, HVLT, and mRS scores, whereas day 2–4 MMSE correlated with 30-day NIHSS and DSST scores (Spearman ρ 0.47, p = 0.001). Discussion Iatrogenic brain infarcts were associated with subtle differences in postprocedural (1–4 days) and 30-day outcomes on different measures in this middle-aged cohort, with earlier dysfunction correlating with later differences. Trial Registration Information Clinical trials registration NCT00728182.
Ultra‐Tough Elastomers from Stereochemistry‐Directed Hydrogen Bonding in Isosorbide‐Based Polymers

Abstract The remarkable elasticity and tensile strength found in natural elastomers are challenging to mimic. Synthetic elastomers typically feature covalently cross‐linked networks (rubbers), but this hinders their reprocessability. Physical cross‐linking via hydrogen bonding or ordered crystallite domains can afford reprocessable elastomers, but often at the cost of performance. Herein, we report the synthesis of ultra‐tough, reprocessable elastomers based on linear alternating polymers. The incorporation of a rigid isohexide adjacent to urethane moieties affords elastomers with exceptional strain hardening, strain rate dependent behavior, and high optical clarity. Distinct differences were observed between isomannide and isosorbide‐based elastomers where the latter displays superior tensile strength and strain recovery. These phenomena are attributed to the regiochemical irregularities in the polymers arising from their distinct stereochemistry and respective inter‐chain hydrogen bonding.
High visceral adiposity index is associated with female orgasmic disorder in premenopausal women: a cross-sectional study

Abstract This study aimed to evaluate the association between the visceral adiposity index (VAI) and female sexual dysfunction (FSD). This cross-sectional study included 165 premenopausal, sexually active women admitted to the gynaecology outpatient clinic between January 2021 and April 2021. Female Sexual Function Index (FSFI) was used to assess the sexual function of the women. After measuring body mass index (BMI) and waist circumference (WC), biochemical serum analysis was performed. The VAI was calculated for all participants. The relationship between VAI and total FSFI and subdomain scores was investigated. Of the participants, FSD was detected in 65.5%. There was no relationship between the total FSFI scores and age, BMI, WC and VAI (p = .126, p = .675, p = .790, p = .220, respectively). Increased VAI levels were associated with dysfunction in orgasm (p = .008). Although VAI seems not to be directly related to FSD, it may predict the orgasmic disorder in women. Impact Statement What is already known on this subject? Obesity and female sexual dysfunction (FSD) are common health problems which adversely affect the biopsychosocial well-being. Although the relationship between FSD and obesity, body mass index (BMI) and waist circumference (WC) has been widely discussed in the literature to date, there is not enough evidence for the link between FSD and visceral adiposity index (VAI) which is a reliable indicator of visceral fat dysfunction. What do the results of this study add? The results of this study showed that none of the factors indicating obesity such as BMI, WC and VAI were correlated with the total FSFI scores. However, a significant positive correlation was found between the VAI and female orgasmic disorder (FOD). What are the implications of these findings for clinical practice and/or further research? The VAI may be a useful tool for detecting FOD patients. Diagnosis and treatment of orgasmic disorder would significantly improve the patient’s quality of life and general well-being. Further large-scale and high-evidence studies are needed to clarify the impact of obesity on FSD and the relationship between VAI and FOD.
Stability Analysis for Earth-rock Dam Slope Based on Broken Line Method

Based on the broken line method,the Visual Basic programming language is used to compile a program so as to get the value of minimum safety coefficient Kc under risk working conditions.Through calculation,it is found that in three working cases,the water level is in 1/3 of the dam height,and the design flood level in steady seepage stage as well as and the normal storage level and earthquake,and Kc value could meet the requirements of design.Based on this,the influence on the stability of dam slope due to the change of upstream water level and the turning point's position is discussed.At the same time,the conclusion from Literature [8] is tested,in which the formula is used for calculation,and the results are consistent,that is,the bending surface to the Kcmin value could not pass through the dam crest level and just be limited to the range of dam slope.
S-Nitrosylation of p62 Inhibits Autophagic Flux to Promote α-Synuclein Secretion and Spread in Parkinson's Disease and Lewy Body Dementia

Dysregulation of autophagic pathways leads to accumulation of abnormal proteins and damaged organelles in many neurodegenerative disorders, including Parkinson's disease (PD) and Lewy body dementia (LBD). Autophagy-related dysfunction may also trigger secretion and spread of misfolded proteins, such as α-synuclein (α-syn), the major misfolded protein found in PD/LBD. However, the mechanism underlying these phenomena remains largely unknown. Here, we used cell-based models, including human induced pluripotent stem cell-derived neurons, CRISPR/Cas9 technology, and male transgenic PD/LBD mice, plus vetting in human postmortem brains (both male and female). We provide mechanistic insight into this pathologic pathway. We find that aberrant S-nitrosylation of the autophagic adaptor protein p62 causes inhibition of autophagic flux and intracellular buildup of misfolded proteins, with consequent secretion resulting in cell-to-cell spread. Thus, our data show that pathologic protein S-nitrosylation of p62 represents a critical factor not only for autophagic inhibition and demise of individual neurons, but also for α-syn release and spread of disease throughout the nervous system. SIGNIFICANCE STATEMENT In Parkinson's disease and Lewy body dementia, dysfunctional autophagy contributes to accumulation and spread of aggregated α-synuclein. Here, we provide evidence that protein S-nitrosylation of p62 inhibits autophagic flux, contributing to α-synuclein aggregation and spread.
Effect of serum vitamin D on metabolic associated fatty liver disease: a large population-based study

Abstract Background Several studies have revealed that serum vitamin D is an important factor for metabolic associated fatty liver disease (MAFLD), but there had been no consistent conclusion. Methods Of 427,507 subjects who underwent health examination, 83,625 who met the inclusion criteria were included in a cross-sectional analysis. Clinical and laboratory data were collected for analysis. MAFLD was diagnosed by abdominal imaging. Results Multivariate linear regression models discovered a negative association between serum vitamin D and MAFLD (OR: 0.92, 95% CI: 0.90 to 0.94, p = .001), after adjusting for other well-identified risk factors. The same result was found when serum vitamin D was handled as a categorical variable (quartile, Q1–Q4) (Q4 vs. Q1, OR: 0.82, 95% CI: 0.77 to 0.87, p < .001), and a significant linear trend was observed (p for trend <.001). After analysis, a nonlinear relationship was detected between serum vitamin D and MAFLD, with an inflection point of 2.23 (44.6 nmol/L or 17.84 ng/mL). The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.16 (1.06 to 1.28) and 0.89 (0.86 to 0.91), respectively. All interactions with MAFLD were not significant for age, sex, diabetes, hypertension, smoking and body mass index (p for interaction = .110, .558, .335, .195, .616 and .401, respectively). Conclusions There was a nonlinear relationship between serum vitamin D and MAFLD. When the serum vitamin D level was ≥44.6 nmol/L (17.84 ng/mL), a negative correlation between serum vitamin D and MAFLD was detected. Below this level, serum vitamin D might promote the progression of MAFLD.
Stigma, lost opportunities, and growth: Understanding experiences of caregivers of persons with mental illness in Tamil Nadu, India

This study aimed to address gaps in understanding of the lived experiences of caregivers of persons with mental illness in low-income countries. It was conducted among caregivers of persons with mental illness making use of a free non-governmental clinic in and around Chennai, India. The study adopted a qualitative methodology, with semi-structured interviews and life history exercises (n = 29) and six focus group discussions with caregivers (n = 21) and mental health professionals and community-based workers (n = 39). The experiences of caregivers were analyzed in the framework of “The Banyan model of caregiving,” which identifies six phases. Major themes in caregivers’ experience were: embarrassment and losing honor; fear; awareness; stigma and social exclusion; and reduced social interaction and loneliness. Posttraumatic growth considered as the result of caregiver experiences was found to consist mainly of personal growth and focusing on positive life experiences. Lost opportunities particular to the context of Tamil Nadu were described as the inability to get married, obtaining less education than desired, and loss of employment. Siblings faced lower levels of burden, while elderly mothers experienced especially high levels of burden and lack of happiness in life. Caregiver gains were identified as greater compassion for other people with disabilities, resulting in a desire to help others, as well as increased personal strength and confidence. Understanding the nuances of the caregiving experiences over time can provide a framework to devise more fine-tuned support structures that aim to prevent reductions in social interaction and lost opportunities, and improve a sense of meaning, in order to assist caregivers to continue providing care for their relatives with mental illness in a context with scarce mental health resources.