Miracle-dz/UniFAR-FTUs huggingface dataset:
Epithelial delamination is protective during pharmaceutical-induced enteropathy

Significance The intestinal epithelium is a protective barrier against ingested pharmaceuticals and microbiota. Delamination of intestinal epithelial cells (IEC) is a common feature of pharmaceutical-induced enteropathies, but physiological functions and underlying mechanisms remain unknown. Using zebrafish, we define the mechanisms underlying intestinal toxicity of a human pharmaceutical, the NSAID Glafenine. Glafenine induced IEC delamination independent of microbiota colonization, yet Glafenine treatment in colonized animals caused inflammation and microbiota dysbiosis. Glafenine-induced IEC delamination was mediated by the unfolded protein response and protected from excessive inflammation and mortality. Glafenine toxicity resulted not from NSAID activity but from off-target inhibition of multidrug-resistance efflux pumps. These results reveal the mechanisms of Glafenine toxicity, and implicate IEC delamination as a protective response to pharmaceutical-induced enteropathies. Intestinal epithelial cell (IEC) shedding is a fundamental response to intestinal damage, yet underlying mechanisms and functions have been difficult to define. Here we model chronic intestinal damage in zebrafish larvae using the nonsteroidal antiinflammatory drug (NSAID) Glafenine. Glafenine induced the unfolded protein response (UPR) and inflammatory pathways in IECs, leading to delamination. Glafenine-induced inflammation was augmented by microbial colonization and associated with changes in intestinal and environmental microbiotas. IEC shedding was a UPR-dependent protective response to Glafenine that restricts inflammation and promotes animal survival. Other NSAIDs did not induce IEC delamination; however, Glafenine also displays off-target inhibition of multidrug resistance (MDR) efflux pumps. We found a subset of MDR inhibitors also induced IEC delamination, implicating MDR efflux pumps as cellular targets underlying Glafenine-induced enteropathy. These results implicate IEC delamination as a protective UPR-mediated response to chemical injury, and uncover an essential role for MDR efflux pumps in intestinal homeostasis.
A meta-analysis of neuroimaging studies on pain empathy: investigating the role of visual information and observers’ perspective

Abstract Empathy relies on brain systems that support the interaction between an observer’s mental state and cues about the others’ experience. Beyond the core brain areas typically activated in pain empathy studies (insular and anterior cingulate cortices), the diversity of paradigms used may reveal secondary networks that subserve other more specific processes. A coordinate-based meta-analysis of fMRI experiments on pain empathy was conducted to obtain activation likelihood estimates along three factors and seven conditions: visual cues (body parts, facial expressions), visuospatial (first-person, thirdperson), and cognitive (self-, stimuli-, other-oriented tasks) perspectives. The core network was found across cues and perspectives, and common activation was observed in higher-order visual areas. Body-parts distinctly activated areas related with sensorimotor processing (superior and inferior parietal lobules, anterior insula) while facial expression distinctly involved the inferior frontal gyrus. Self- compared to other-perspective produced distinct activations in the left insula while stimulus- versus other-perspective produced distinctive responses in the inferior frontal and parietal lobules, precentral gyrus, and cerebellum. Pain empathy relies on a core network which is modulated by several secondary networks. The involvement of the latter seems to depend on the visual cues available and the observer's mental state that can be influenced by specific instructions.
Association of ideal cardiovascular health at age 50 with incidence of dementia: 25 year follow-up of Whitehall II cohort study

Abstract Objectives To examine the association between the Life Simple 7 cardiovascular health score at age 50 and incidence of dementia. Design Prospective cohort study. Setting Civil service departments in London (Whitehall II study; study inception 1985-88). Participants 7899 participants with data on the cardiovascular health score at age 50. Exposures The cardiovascular health score included four behavioural (smoking, diet, physical activity, body mass index) and three biological (fasting glucose, blood cholesterol, blood pressure) metrics, coded on a three point scale (0, 1, 2). The cardiovascular health score was the sum of seven metrics (score range 0-14) and was categorised into poor (scores 0-6), intermediate (7-11), and optimal (12-14) cardiovascular health. Main outcome measure Incident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017. Results 347 incident cases of dementia were recorded over a median follow-up of 24.7 years. Compared with an incidence rate of dementia of 3.2 (95% confidence interval 2.5 to 4.0) per 1000 person years among the group with poor cardiovascular health, the absolute rate differences per 1000 person years were −1.5 (95% confidence interval −2.3 to −0.7) for the group with intermediate cardiovascular health and −1.9 (−2.8 to −1.1) for the group with optimal cardiovascular health. Higher cardiovascular health score was associated with a lower risk of dementia (hazard ratio 0.89 (0.85 to 0.95) per 1 point increment in the cardiovascular health score). Similar associations with dementia were observed for the behavioural and biological subscales (hazard ratios per 1 point increment in the subscores 0.87 (0.81 to 0.93) and 0.91 (0.83 to 1.00), respectively). The association between cardiovascular health at age 50 and dementia was also seen in people who remained free of cardiovascular disease over the follow-up (hazard ratio 0.89 (0.84 to 0.95) per 1 point increment in the cardiovascular health score). Conclusion Adherence to the Life Simple 7 ideal cardiovascular health recommendations in midlife was associated with a lower risk of dementia later in life.
Clinical Variability in P102L Gerstmann–Sträussler–Scheinker Syndrome

Gerstmann–Sträussler–Scheinker syndrome (GSS) with the P102L mutation is a rare genetic prion disease caused by a pathogenic mutation at codon 102 in the prion protein gene. Cluster analysis encompassing data from 7 Czech patients and 87 published cases suggests the existence of 4 clinical phenotypes (typical GSS, GSS with areflexia and paresthesia, pure dementia GSS, and Creutzfeldt–Jakob disease–like GSS); GSS may be more common than previously estimated. In making a clinical diagnosis or progression estimates of GSS, magnetic resonance imaging and real‐time quaking‐induced conversion may be helpful, but the results should be evaluated with respect to the overall clinical context. ANN NEUROL 2019;86:643–652
Phenotypic and Genetic Characteristics of Five Korean Patients with Costello Syndrome

Costello syndrome (CS) is a rare genetic disorder characterized by distinctive facial appearance, cardiopulmonary complications, severe growth retardation, skin and skeletal defects, developmental delay, and tumor predisposition. CS is caused by heterozygous de novo mutations in the proto-oncogene HRAS, which is a component of the RAS/mitogen-activated protein kinase pathway. Herein, we reviewed the phenotypic and genetic features of 5 Korean patients who were genetically diagnosed with CS. Atrial tachycardia and polyhydramnios, which are important prenatal features for CS, were observed in 4 and 5 patients, respectively. The distinctive coarse facial appearances of the patients and presence of deep palmoplantar creases supported the clinical diagnosis of CS, which was confirmed by HRAS sequence analysis. Extremely poor postnatal growth was observed in all 5 patients. Further, all patients exhibited cardiac abnormalities; left ventricular hypertrophy and hypertrophic cardiomyopathy were observed in 3 patients. All 5 patients suffered from airway problems; 3 of them required intubation right after birth, and 2 of them received tracheostomy. One patient with a p.Gly12Ser mutation was diagnosed with retroperitoneal rhabdomyosarcoma alveolar type at the age of 5 years. Consistent with previous reports, both patients with p.Gly12Cys mutations died within the first year of life due to cardiopulmonary failure. Our study summarizes the characteristics of these 5 Korean patients with CS and, along with previous studies, provides clues for genotype-phenotype correlation in patients with CS.
Predicting the effects of supplemental EPA and DHA on the omega-3 index.

BACKGROUND Supplemental long-chain omega-3 (n-3) fatty acids (EPA and DHA) raise erythrocyte EPA + DHA [omega-3 index (O3I)] concentrations, but the magnitude or variability of this effect is unclear. OBJECTIVE The purpose of this study was to model the effects of supplemental EPA + DHA on the O3I. METHODS Deidentified data from 1422 individuals from 14 published n-3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, chemical form [ethyl ester (EE) compared with triglyceride (TG)], and duration of treatment. The O3I was measured by the same method in all included studies. Variables were selected by stepwise regression using the Bayesian information criterion. RESULTS Individuals supplemented with EPA + DHA (n = 846) took a mean ± SD of 1983 ± 1297 mg/d, and the placebo controls (n = 576) took none. The mean duration of supplementation was 13.6 ± 6.0 wk. The O3I increased from 4.9% ± 1.7% to 8.1% ± 2.7% in the supplemented individuals ( P < 0.0001). The final model included dose, baseline O3I, and chemical formulation type (EE or TG), and these explained 62% of the variance in response (P < 0.0001). The model predicted that the final O3I (and 95% CI) for a population like this, with a baseline concentration of 4.9%, given 850 mg/d of EPA + DHA EE would be ∼6.5% (95% CI: 6.3%, 6.7%). Gram for gram, TG-based supplements increased the O3I by about 1 percentage point more than EE products. CONCLUSIONS Of the factors tested, only baseline O3I, dose, and chemical formulation were significant predictors of O3I response to supplementation. The model developed here can be used by researchers to help estimate the O3I response to a given EPA + DHA dose and chemical form.
Electrical Impedance Tomography for Cardio-Pulmonary Monitoring

Electrical impedance tomography (EIT) is a bedside monitoring tool that noninvasively visualizes local ventilation and arguably lung perfusion distribution. This article reviews and discusses both methodological and clinical aspects of thoracic EIT. Initially, investigators addressed the validation of EIT to measure regional ventilation. Current studies focus mainly on its clinical applications to quantify lung collapse, tidal recruitment, and lung overdistension to titrate positive end-expiratory pressure (PEEP) and tidal volume. In addition, EIT may help to detect pneumothorax. Recent studies evaluated EIT as a tool to measure regional lung perfusion. Indicator-free EIT measurements might be sufficient to continuously measure cardiac stroke volume. The use of a contrast agent such as saline might be required to assess regional lung perfusion. As a result, EIT-based monitoring of regional ventilation and lung perfusion may visualize local ventilation and perfusion matching, which can be helpful in the treatment of patients with acute respiratory distress syndrome (ARDS).
Generating Poetry Title Based on Semantic Relevance with Convolutional Neural Network

Several approaches have been proposed to automatically generate Chinese classical poetry (CCP) in the past few years, but automatically generating the title of CCP is still a difficult problem. The difficulties are mainly reflected in two aspects. First, the words used in CCP are very different from modern Chinese words and there are no valid word segmentation tools. Second, the semantic relevance of characters in CCP not only exists in one sentence but also exists between the same positions of adjacent sentences, which is hard to grasp by the traditional text summarization models. In this paper, we propose an encoder-decoder model for generating the title of CCP. Our model encoder is a convolutional neural network (CNN) with two kinds of filters. To capture the commonly used words in one sentence, one kind of filters covers two characters horizontally at each step. The other covers two characters vertically at each step and can grasp the semantic relevance of characters between adjacent sentences. Experimental results show that our model is better than several other related models and can capture the semantic relevance of CCP more accurately.
Reading Instruction for Students with Emotional Disturbance: A Mixed-Methods Investigation

Although there is a substantial body of observation research investigating the manner in which reading instruction is provided to students with learning disabilities, there is little research in this area involving students with and at risk for emotional disturbance. The purpose of this investigation was to contribute to the limited corpus of observation studies investigating school-based practice in reading for this student population. In this investigation, 11 teachers from two states were systematically observed while providing reading instruction over the course of the 2017-2018 school year. Participating students were also observed over the course of the year and completed two standardized reading assessments at the beginning and end of this investigation. Teachers were also interviewed to identify contextual factors that promote or impede the provision of high quality reading instruction to this student population. Study findings suggest that teachers are in need of additional training, support, and resources to maximize instructional time. Students in this sample tended to make no or minimal progress in reading and were frequently observed displaying low levels of academic engagement across settings. Implications for school practice and areas for future research are discussed.
Making sense of subclinical cardiac alterations in patients with diabetes.

Patients with diabetes are prone to develop a distinct primary myocardial condition, diabetic cardiomyopathy, placing them at an increased risk for heart failure (1-3). This occurs independently of hypertension, coronary artery disease, and other established causes of heart failure. Pertinent findings include increased mass, concentric changes, and diastolic dysfunction of the left ventricle (4,5). Such adverse remodeling is common among patients with diabetes and appears to be strongly associated with its duration, suggesting a role for persistent metabolic stress (6-8). However, which exact components of the diabetic syndrome determine these cardiac alterations is not clear. Moreover, most studies have investigated patients with type 2 diabetes, and it is uncertain whether patients with type 1 diabetes experience similar myocardial changes. Continue reading full text in the preliminary PDF version.
Assessing the Relative Biological Effectiveness of Neutrons across Organs of Varying Depth among the Atomic Bomb Survivors.

When assessing radiation-related risk among the atomic bomb survivors, choices in modeling approach can have an important impact on the results, which are then used to inform radiation protection standards throughout the world. The atomic bombings of Hiroshima and Nagasaki produced a mixed-field radiation exposure from two sources: neutrons and gamma rays. Neutrons are more densely ionizing and cause greater biological damage per unit absorbed dose, resulting in greater relative biological effectiveness (RBE) than gamma rays. To account for this, a combined weighted dose is typically calculated as the sum of the gamma-ray dose and 10 times the neutron dose in the Radiation Effects Research Foundation's reports of mortality, solid cancer incidence and other outcomes. In addition, the colon, which is often chosen as the whole-body representative organ in these analyses, is relatively deep in the body and therefore its dose calculation involves heavy body shielding of neutrons and a low neutron/gamma-ray ratio. With added follow-up and recently updated doses, we used a data-driven approach to determine the best-fitting neutron RBE for a range of organs of varying depth. Aggregated person-year tables of solid cancer incidence (1958-2009) from the Life Span Study were created with separate neutron and gamma-ray DS02R1 doses for several organs including breast, brain, thyroid, bone marrow, lung, liver and colon. Typical excess relative risk models estimating the linear effect of radiation dose were fitted using a range of neutron weights (1-250) to calculate combined dose for each organ, and model deviations were compared to assess fit. Furthermore, models using separate terms for gamma-ray and neutron dose were also examined, wherein the ratio of the neutron/gamma-ray linear terms indicated the best estimate of the RBE. The best-fitting RBE value for the traditional weighted colon dose was 80 [95% confidence interval (CI): 20-190], while the RBEs for other organs using weighted doses ranged from 25 to 60, with the best-fitting weights and confidence interval widths both incrementally increasing with greater depth of organ. Models using separate neutron- and gamma-ray-dose terms gave similar results to weighted linear combinations, with a neutron/gamma-ray term ratio of 79.9 (95% CI: 18.8-192.3) for colon. These results indicated that the traditionally modeled RBE of 10 may underestimate the effect of neutrons across the full dose range, although these updated estimates still have fairly wide confidence bounds. Furthermore, the colon is among the deepest of organs and may not be the best choice as a single surrogate organ dose, as it may minimize the role of the neutrons. Future work with more refined organ doses could shed more light on RBE-related information available in the Life Span Study data.
Powerful statistical method to detect disease‐associated genes using publicly available genome‐wide association studies summary data

Genome‐wide association studies (GWAS) have thus far achieved substantial success. In the last decade, a large number of common variants underlying complex diseases have been identified through GWAS. In most existing GWAS, the identified common variants are obtained by single marker‐based tests, that is, testing one single‐nucleotide polymorphism (SNP) at a time. Generally, the basic functional unit of inheritance is a gene, rather than a SNP. Thus, results from gene‐level association test can be more readily integrated with downstream functional and pathogenic investigation. In this paper, we propose a general gene‐based p‐value adaptive combination approach (GPA) which can integrate association evidence of multiple genetic variants using only GWAS summary statistics (either p‐value or other test statistics). The proposed method could be used to test genetic association for both continuous and binary traits through not only one study but also multiple studies, which would be helpful to overcome the limitation of existing methods that can only be applied to a specific type of data. We conducted thorough simulation studies to verify that the proposed method controls type I errors well, and performs favorably compared to single‐marker analysis and other existing methods. We demonstrated the utility of our proposed method through analysis of GWAS meta‐analysis results for fasting glucose and lipids from the international MAGIC consortium and Global Lipids Consortium, respectively. The proposed method identified some novel trait associated genes which can improve our understanding of the mechanisms involved in β ‐cell function, glucose homeostasis, and lipids traits.
Preterm Birth: A Narrative Review of the Current Evidence on Nutritional and Bioactive Solutions for Risk Reduction

Preterm birth (PTB) (<37 weeks of gestation) is the leading cause of newborn death and a risk factor for short and long-term adverse health outcomes. Most cases are of unknown cause. Although the mechanisms triggering PTB remain unclear, an inappropriate increase in net inflammatory load seems to be key. To date, interventions that reduce the risk of PTB are effective only in specific groups of women, probably due to the heterogeneity of its etiopathogenesis. Use of progesterone is the most effective, but only in singleton pregnancies with history of PTB. Thus, primary prevention is greatly needed and nutritional and bioactive solutions are a promising alternative. Among these, docosahexaenoic acid (DHA) is the most promising to reduce the risk for early PTB. Other potential nutrient interventions include the administration of zinc (possibly limited to populations with low nutritional status or poor zinc status) and vitamin D; additional preliminary evidence exists for vitamin A, calcium, iron, folic acid, combined iron-folate, magnesium, multiple micronutrients, and probiotics. Considering the public health relevance of PTB, promising interventions should be studied in large and well-designed clinical trials. The objective of this review is to describe, summarize, and discuss the existing evidence on nutritional and bioactive solutions for reducing the risk of PTB.
A comparison of the academic outcome of chiropractic students on full-time and full-time equivalent chiropractic education routes.

OBJECTIVE To compare the academic equivalence of full-time (FT) and full-time equivalent (FTE) delivery routes for chiropractic training and to assess nontraditional education delivery as a viable method for training chiropractors. METHODS A retrospective analysis of student summative assessment data was undertaken on a total of 196 FT and FTE students studying for the master's in chiropractic degree at a UK chiropractic college between 2009 and graduating by 2017. The analysis consisted of within-group comparison and between-group comparisons using the Kruskal-Wallis test and the Mann-Whitney U test. RESULTS The demographics of the 2 student groups varied in terms of gender and age distribution. The analysis of summative data indicated no differences between the 2 routes of delivery. There was also no difference in the distribution of final degree classification outcome between the 2 routes. CONCLUSIONS While it is possible that demographic differences influence the outcomes in each training route, this preliminary study indicates that, based only on analysis of overall achievement, there is no difference in either FT or FTE programs in training chiropractors, allowing them to register with the UK regulatory body. It suggests that a nontraditional mode of delivery is an achievable route to qualification as a chiropractor, enabling a greater number of students to consider chiropractic as a career choice while managing other life commitments.