Miracle-dz/UniFAR-FTUs huggingface dataset:
Household- and community-level determinants of low-risk Caesarean deliveries among women in India

Abstract Caesarean section delivery rates in India have doubled from 9% in 2005–06 to 17% in 2015–16, increasing the clinical and economic burden on the health care system. This study applied multilevel models to assess the role of household- and community-level factors in Caesarean section (CS) deliveries among low-risk women in India using data from Round 4 of the National Family Health Survey (NFHS-4) conducted in 2015–16. The sample size was 59,318 low-risk women who had their last birth in an institution during the 5 years preceding the survey. These women were nested in 57,279 households, which were nested in 22,183 communities, which were further nested in 640 districts in India. Around 21% of the low-risk women and 24% of all women who had delivered in an institution had undergone CS. The CS rates among low-risk women were extremely high in private institutions (40%) and in southern India (43%). The explanatory variables age, education of women, household wealth and number of antenatal visits were significantly positively associated, while women’s parity was negatively associated, with CS delivery among low-risk women. The multilevel analysis suggested that the likelihood of a low-risk woman opting for CS was influenced by a similar decision of another woman from the same household (37%) and/or community (18%). Furthermore, women with low-risk pregnancies from higher educated communities were less likely (OR 0.92) to undergo CS. There is therefore a need for a community-level awareness programme on the risks and benefits of low-risk CS and vaginal delivery, particularly in the southern region of India.
Sleep-Related Movement Disorders In A Population Of Patients With Epilepsy: Prevalence And Impact Of Restless Legs Syndrome And Sleep Bruxism.

STUDY OBJECTIVES Sleep disorders are frequent co-occurrences in patients with epilepsy (PWE), but sleep-disordered breathing and insomnia are better studied than others. Our aim was to study sleep-related movement disorders in epilepsy. METHODS We interviewed 175 PWE (age 18-71, mean age - 35.4, females - 47.4%) and 130 control subjects (age 18-72, mean age - 33.6, females - 47.7%). Restless legs syndrome (RLS) and sleep bruxism (SB) were diagnosed by IRLSSG's diagnostic criteria and ICSD-3 criteria respectively. We also utilized Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Berlin Questionnaire (BQ). RESULTS Our findings suggest that RLS and SB are encountered strikingly more frequently in PWE than controls: 20.6% vs. 6.1% for RLS, and 23.7% vs. 5.4% for SB (p<0.05). Also insomnia was more prevalent in epilepsy (46.2% vs. 24.6%, p<0.05) while poor sleep hygiene occurred more frequently in controls (28.3% vs. 53.8%), (p<0.05). PWE had poorer sleep by PSQI 61.7% vs 41.5% (p<0.05). Sleepiness (38.7% vs. 39.2%) and snoring (42.8% vs. 40.8%) were equally distributed in both groups, also ESS and BQ not showing significant differences (p>0.05). CONCLUSIONS Our study demonstrates that sleep disorders comprise important part of epilepsy co-morbidity. We demonstrated that unselected PWE had higher prevalence of RLS. For the first time we show higher prevalence of sleep bruxism in epilepsy population. Also complaints of insomnia are seen more in PWE, while snoring and poor sleep hygiene not.
Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience.

OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.
Critical Impact of Drug-Drug Interactions via Intestinal CYP3A in the Risk Assessment of Weak Perpetrators Using Physiologically Based Pharmacokinetic Models

A great deal of effort has been being made to improve the accuracy of the prediction of drug-drug interactions (DDIs). In this study, we addressed CYP3A-mediated weak DDIs, in which a relatively high false prediction rate was pointed out. We selected 17 orally administered drugs that have been reported to alter area under the curve (AUC) of midazolam, a typical CYP3A substrate, 0.84–1.47 times. For weak CYP3A perpetrators, the predicted AUC ratio mainly depends on intestinal DDIs rather than hepatic DDIs because the drug concentration in the enterocytes is higher. Thus, DDI prediction using simulated concentration-time profiles in each segment of the digestive tract was made by physiologically based pharmacokinetic (PBPK) modeling software GastroPlus. Although mechanistic static models tend to overestimate the risk to ensure the safety of patients, some underestimation is reported about PBPK modeling. Our in vitro studies revealed that 16 out of 17 tested drugs exhibited time-dependent inhibition (TDI) of CYP3A, and the subsequent DDI simulation that ignored these TDIs provided false-negative results. This is considered to be the cause of past underestimation. Inclusion of the DDI parameters of all the known DDI mechanisms, reversible inhibition, TDI, and induction, which have opposite effects on midazolam AUC, to PBPK model was successful in improving predictability of the DDI without increasing false-negative prediction as trade-off. This comprehensive model-based analysis suggests the importance of the intestine in assessing weak DDIs via CYP3A and the usefulness of PBPK in predicting intestinal DDIs. SIGNIFICANCE STATEMENT Although drug-drug interaction (DDI) prediction has been extensively performed previously, the accuracy of prediction for weak interactions via CYP3A has not been thoroughly investigated. In this study, we simulate DDIs considering drug concentration-time profile in the enterocytes and discuss the importance and the predictability of intestinal DDIs about weak CYP3A perpetrators.
An update on pharmacotherapies in active development for the management of cancer regimen-associated oral mucositis

ABSTRACT Introduction Oral mucositis (OM) is a common toxicity of cytotoxic cancer regimens and remains one of the most painful, injurious, and treatment-disrupting side effects of radiation and ablative therapy. Despite its frequency and impact, approved definitive preventive or therapeutic options remain limited. Areas covered This review focuses on mechanistically active small molecules and biologicals that are under clinical development for the prevention of oral mucositis. The authors have excluded those compounds and devices for which their indication is limited to symptoms management. Expert opinion OM remains a significant unmet clinical need. The commercial opportunities for an effective treatment have been characterized as a global market of $1 billion (US). The formulations of drugs under development vary considerably but share some several commonalities in their development scheme. All new agents are given prophylactically and are being evaluated in patients treated with concomitant chemoradiation therapy for head and neck cancer. The primary efficacy outcome for most trials is dependent on the assessment of mucositis using the scoring scale established years ago by the World Health Organization. The development activity for OM is robust with a diverse range of agents. New drug applications for effective therapeutic options for OM should be ready for review within the next few years.
Preventing injuries among recreational adult volleyball players: Results of a prospective randomised controlled trial

ABSTRACT The objective was to evaluate the effectiveness of an exercise-based warm-up programme (“VolleyVeilig”) on the one-season occurrence of musculoskeletal injuries among recreational adult volleyball players. A prospective randomised controlled trial was conducted over the 2017–2018 volleyball season. Recreational adult volleyball players were allocated either to an intervention or control group. The Dutch version of the Oslo Sports Trauma Research Centre questionnaire was used to register and monitor acute and overuse injuries. A total of 672 volleyball players were enrolled: 348 in the intervention group (mean age: 30) and 324 in the control group (mean age: 27). The incidence rate of acute injury was 21% lower in the intervention group, namely 8.9 versus 11.3 per 1,000 h in the control group (Cox mixed effects crude model: hazard ratio = 0.82 [95%CI: 0.69–0.98]; Cox mixed effects adjusted model: 0.85 [95%CI: 0.71–1.02]). No significant difference in mean prevalence of overuse injury was found between the intervention (4.8%) and control (4.2%) groups. The severity of injuries was not significantly different between groups, while injury burden was slightly lower in the intervention group. The exercise-based warm-up programme led to a trend in less acute injuries among recreational adult volleyball players.
The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases

Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2–4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases.
Brain networks mediating the influence of background music on selective attention

Abstract Prevalent across societies and times, music has the ability to enhance attention, a property relevant to clinical applications, but the underlying brain mechanisms remain unknown. It is also unclear whether music produces similar or differential effects with advancing age. Here, we used event-related functional magnetic resonance imaging to investigate the influence of music exposure evoking four types of emotions on distinct attentional components measured with a modified attention network test, across 19 young (21 ± 2.6) and 33 old participants (72 ± 5.4). We then determined whether music-related effects differed across age groups and whether they were associated with particular acoustic features. Background music during selective attention requiring distractor conflict resolution was associated with faster response times and greater activations of fronto-parietal areas during happy and high-arousing music, whereas sad and low-valence music was associated with slower responses and greater occipital recruitment. Shifting and altering components of attention were unaffected. The influence of music on performance and brain networks was similar between age groups. These behavioral and neuroimaging results demonstrate the importance of affective music dimensions, particularly arousal, in enhancing selective attention processes. This study adds novel support to the benefits of music in the rehabilitation of attention functions.
Maternal stress level when a baby is admitted to the neonatal intensive care unit at Teaching Hospital Jaffna and the influence of maternal and infant characteristics on this level

Background : Currently, little is known about the maternal stress when a neonate is admitted to a Neonatal Intensive Care Unit (NICU) in Sri Lanka. Objective: To assess the maternal stress level when a baby is admitted to the NICU at Teaching Hospital Jaffna (THJ) and the influence of maternal and infant characteristics on this level. Method: A prospective cross sectional descriptive study was conducted in NICU at THJ on 75 mother-baby pairs using the Parental Stressor Scale: Neonatal Intensive Care Unit to measure the maternal stress level. A parent/infant demographic sheet provided information for determining which characteristic resulted in a different response. Results: Seventy six percent of mothers experienced severe and extreme stress level for overall stress. The mean for overall stress experienced by the mothers was 4.01 + 0.87. The highest levels of stress experienced were in the sight and sound subscale with a mean of 3.04 + 1.04 and the relationship with the baby–parental role (mean 2.93 + 1.28). The infant characteristic of gestational age resulted in a significant different score concerning the appearance and behaviour of the baby, even though there were no significant differences in the score experienced in the overall stress level. There was no significant difference in the overall stress score with maternal characteristics such as age, parity, maternal level of education and income, but a previous baby being admitted to the NICU had a significant correlation with the overall stress level (p =0.04). Conclusions: Mothers suffer significantly high stress levels when their babies need NICU admission. NICU physical environment and alteration in parental role are the main sources of stress. Infant characteristics like gestational age, birth asphyxia and sepsis are related to high maternal stress levels. Previous baby needing NICU admission and previous neonatal deaths have strong associations with high maternal stress levels. (Key words: maternal stress, NICU) DOI: http://dx.doi. org/10.4038/sljch.v45i2. 8003
Predictive Features of Thymic Carcinoma and High-Risk Thymomas Using Random Forest Analysis.

PURPOSE To determine the predictive features of thymic carcinomas and high-risk thymomas using random forest algorithm. METHODS A total of 137 patients with pathologically confirmed high-risk thymomas and thymic carcinomas were enrolled in this study. Three clinical features and 20 computed tomography features were reviewed. The association between computed tomography features and pathological patterns was analyzed by univariate analysis and random forest. The predictive efficiency of the random forest algorithm was evaluated by receiver operating characteristic curve analysis. RESULTS There were 92 thymic carcinomas and 45 high-risk thymomas in this study. In univariate analysis, patient age, presence of myasthenia gravis, lesion shape, enhancement pattern, presence of necrosis or cystic change, mediastinal invasion, vessel invasion, lymphadenopathy, pericardial effusion, and distant organ metastasis were found to be statistically different between high-risk thymomas and thymic carcinomas (all P < 0.01). Random forest suggested that tumor shape, lymphadenopathy, and the presence of pericardial effusion were the key features in tumor differentiation. The predictive accuracy for the test data and whole data was 94.73% and 96.35%, respectively. Further receiver operating characteristic curve analysis showed the area under the curve was 0.957 (95% confidence interval, 0.986-0.929). CONCLUSIONS The random forest model in the present study has high efficiency in predictive diagnosis of thymic carcinomas and high-risk thymomas. Tumor shape, lymphadenopathy, and pericardial effusion are the key features for tumor differentiation. Thymic tumors with irregular shape, the presence of lymphadenopathy, and pericardial effusion are highly indicative of thymic carcinomas.
An integrated experimental‐computational study of the microclimate under dressings applied to intact weight‐bearing skin

Pressure ulcers (PUs) are one of the most prevalent adverse events in acute and chronic care. The root aetiological cause of PUs is sustained cell and tissue deformations, which triggers a synergistic tissue damage cascade that accelerates over relatively short time periods. Changes in skin microclimate conditions are known to indirectly contribute to PU‐risk levels or to exacerbation of existing wounds. It is therefore surprising that information concerning heat accumulation under dressings is poor. Here, we aimed to investigate the effects of dressings on the microclimate of weight‐bearing buttocks skin in 1‐hour supine lying sessions. Using a novel and originally developed experimental‐computational approach, we compared the combined influence of the mechanical and thermal properties of a polymeric membrane dressing (PolyMem, Ferris Mfg. Corp., Fort Worth, TX) on skin microclimate under and near the dressings with those of a standard placebo foam dressing. We specifically identified the thermal conductivity properties of dressings as being highly important in the context of protective dressing performances, given its association with potential heat accumulation under dressings. Accordingly, this article highlights, for the first time in the literature, the relevance of thermal properties of a dressing in effectively mitigating the risk of developing PUs or aggravating an injury, and offers a systematic, methodological bioengineering process for assessing the thermal performances of dressings.
Alternative splicing of the bicistronic gene molybdenum cofactor synthesis 1 (MOCS1) uncovers a novel mitochondrial protein maturation mechanism

Molybdenum cofactor (Moco) biosynthesis is a highly conserved multistep pathway. The first step, the conversion of GTP to cyclic pyranopterin monophosphate (cPMP), requires the bicistronic gene molybdenum cofactor synthesis 1 (MOCS1). Alternative splicing of MOCS1 within exons 1 and 9 produces four different N-terminal and three different C-terminal products (type I–III). Type I splicing results in bicistronic transcripts with two open reading frames, of which only the first, MOCS1A, is translated, whereas type II/III splicing produces MOCS1AB proteins. Here, we first report the cellular localization of alternatively spliced human MOCS1 proteins. Using fluorescence microscopy, fluorescence spectroscopy, and cell fractionation experiments, we found that depending on the alternative splicing of exon 1, type I splice variants (MOCS1A) either localize to the mitochondrial matrix (exon 1a) or remain cytosolic (exon 1b). MOCS1A proteins required exon 1a for mitochondrial translocation, but fluorescence microscopy of MOCS1AB variants (types II and III) revealed that they were targeted to mitochondria independently of exon 1 splicing. In the latter case, cell fractionation experiments displayed that mitochondrial matrix import was facilitated via an internal motif overriding the N-terminal targeting signal. Within mitochondria, MOCS1AB underwent proteolytic cleavage resulting in mitochondrial matrix localization of the MOCS1B domain. In conclusion, MOCS1 produces two functional proteins, MOCS1A and MOCS1B, which follow different translocation routes before mitochondrial matrix import for cPMP biosynthesis involving both proteins. MOCS1 protein maturation provides a novel alternative splicing mechanism that ensures the coordinated mitochondrial targeting of two functionally related proteins encoded by a single gene.
Lifetime history of traumatic brain injury is associated with increased loneliness in adults: A US nationally representative study

An estimated 55 million individuals worldwide live with chronic disability associated with traumatic brain injury (TBI), which may include cognitive, behavioral, and social impairments. Reduced participation in social activities is common after TBI; however, few studies have evaluated loneliness among survivors of TBI. The current study aimed to evaluate the association between history of TBI and loneliness and to identify mediators of this association.
Semiparametric modelling and estimation of covariate‐adjusted dependence between bivariate recurrent events

A time‐dependent measure, termed the rate ratio, was proposed to assess the local dependence between two types of recurrent event processes in one‐sample settings. However, the one‐sample work does not consider modeling the dependence by covariates such as subject characteristics and treatments received. The focus of this paper is to understand how and in what magnitude the covariates influence the dependence strength for bivariate recurrent events. We propose the covariate‐adjusted rate ratio, a measure of covariate‐adjusted dependence. We propose a semiparametric regression model for jointly modeling the frequency and dependence of bivariate recurrent events: the first level is a proportional rates model for the marginal rates and the second level is a proportional rate ratio model for the dependence structure. We develop a pseudo‐partial likelihood to estimate the parameters in the proportional rate ratio model. We establish the asymptotic properties of the estimators and evaluate the finite sample performance via simulation studies. We illustrate the proposed models and methods using a soft tissue sarcoma study that examines the effects of initial treatments on the marginal frequencies of local/distant sarcoma recurrence and the dependence structure between the two types of cancer recurrence.