Miracle-dz/UniFAR-FTUs huggingface dataset:
simGWAS: a fast method for simulation of large scale case–control GWAS summary statistics

Motivation Methods for analysis of GWAS summary statistics have encouraged data sharing and democratised the analysis of different diseases. Ideal validation for such methods is application to simulated data, where some “truth” is known. As GWAS increase in size, so does the computational complexity of such evaluations; standard practice repeatedly simulates and analyses genotype data for all individuals in an example study. Results We have developed a novel method based on an alternative approach, directly simulating GWAS summary data, without individual data as an intermediate step. We mathematically derive the expected statistics for any set of causal variants and their effect sizes, conditional upon control haplotype frequencies (available from public reference datasets). Simulation of GWAS summary output can be conducted independently of sample size by simulating random variates about these expected values. Across a range of scenarios, our method, produces very similar output to that from simulating individual genotypes with a substantial gain in speed even for modest sample sizes. Fast simulation of GWAS summary statistics will enable more complete and rapid evaluation of summary statistic methods as well as opening new potential avenues of research in fine mapping and gene set enrichment analysis. Availability and Implementation Our method is available under a GPL license as an R package from http://github.com/chr1swallace/simGWAS Contact cew54@cam.ac. uk Supplementary Information Supplementary Information is appended.
Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice

Isoliquiritigenin (ILG) is a flavonoid constituent of Glycyrrhizae plants. The current study investigated the effects of ILG on diet-induced obesity and metabolic diseases. C57BL/6J mice were fed a normal diet (AIN-76 purified diet), high-fat diet (40 kcal% fat), and high-fat diet +0.02% (w/w) ILG for 16 weeks. Supplementation of ILG resulted in decreased body fat mass and plasma cholesterol level. ILG ameliorated hepatic steatosis by suppressing the expression of hepatic lipogenesis genes and hepatic triglyceride and fatty acid contents, while enhancing β-oxidation in the liver. ILG improved insulin resistance by lowering plasma glucose and insulin levels. This was also demonstrated by the intraperitoneal glucose tolerance test (IPGTT). Additionally, ILG upregulated the expression of insulin signaling-related genes in the liver and muscle. Interestingly, ILG elevated energy expenditure by increasing the expression of thermogenesis genes, which is linked to stimulated mitochondrial biogenesis and uncoupled cellular respiration in brown adipose tissue. ILG also suppressed proinflammatory cytokine levels in the plasma. These results suggest that ILG supplemented at 0.02% in the diet can ameliorate body fat mass, plasma cholesterol, non-alcoholic fatty liver disease, and insulin resistance; these effects were partly mediated by increasing energy expenditure in high-fat fed mice.
Association Between Changes in Hemoglobin Concentration and Cardiovascular Risks and All‐Cause Mortality Among Young Women

Background Anemia is considered to increase the risk of mortality in high‐risk populations, but its effect has not been examined among young populations. This study aimed to determine the effect of hemoglobin (Hb) concentration and its changes on the risk of acute myocardial infarction (AMI), stroke, cerebrovascular disease and all‐cause mortality among young women. Methods and Results We analyzed data from the Korean National Health Information Database on 808 143 women aged 20 to 39 years without any cardiocerebrovascular disease. A 1‐time Hb concentration and changes in Hb over a 2‐year period were calculated as exposures. Participants were followed for a median of 10 years to determine the risk of AMI, stroke, cerebrovascular disease, and all‐cause mortality. There were U‐ or J‐shaped associations between Hb concentration or change in Hb and AMI, stroke, cerebrovascular disease, and all‐cause mortality. Increasing the Hb concentration from normal to high increased the risk for AMI (hazard ratio [95% confidence interval]: 1.49 [1.08‐2.04]). With regard to the risk for stroke, increasing the Hb concentration from a normal to a high range increased the risk (hazard ratio [95% confidence interval]: 1.10 [1.02‐1.35]), and decreasing the Hb concentration from a high to a normal range decreased this risk (hazard ratio [95% confidence interval]: 0.80 [0.60‐0.97]). Improving anemia to the normal Hb range decreased all‐cause mortality (hazard ratio [95% confidence interval]: 0.81 [0.69‐0.94]); however, overcorrection of Hb concentration (Hb≥14.0 g/dL) was not significant. Conclusions These findings suggest that regular Hb analysis may assist in identifying young women who are at risk of AMI, stroke, cerebrovascular disease, and all‐cause mortality.
Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Cyclosporine-A via Suppression of Mitochondrial DNA

Background Lipopolysaccharide (LPS) is generally associated with sepsis, which causes multiple system injuries and systemic inflammatory response. Mitochondrial DNA (mtDNA) is of great importance in mediation of inflammation. The aim of this study was to investigate the protective profiles of Cyclosporine-A (CsA) in LPS-induced acute lung injury (ALI) and systemic inflammation by the inhibition of mtDNA and Toll-like receptor. Material/Methods Twenty-four C57BL/6 mice were randomly assigned to 4 groups: a sham group (n=6); an experiment group (ALI induced through intraperitoneal injection of 10 mg/ml LPS, n=6); a low-CsA group (injection of 2.5 mg/kg of CsA 15 min after injection of LPS, n=6); and a high-CsA group (injection of 25 mg/kg of CsA 15 min after injection of LPS, n=6). Lung tissue, bronchoalveolar lavage fluid (BALF), and blood samples were collected at 6 h for further analyses. Results CsA treatment significantly attenuated LPS-induced lung histopathological changes (P<.05), myeloperoxidase (MPO) activity (P<.05) and lung wet-to-dry weight ratio (P<.05). In addition, injection of CsA decreased total cells (P<.05), neutrophils (P<.05), and total protein (P<.05) in BALF and inflammatory mediators, including tumor necrosis factor-α (TNF-α, P<.05) and interleukin-6 (IL-6, P<.05) in a dose-dependent manner. A significant decrease in mtDNA was observed in the CsA group when compared with controls (P<.05). Furthermore, we demonstrated that there was a significant difference between the high-CsA group and low-CsA group in lung injury score (P<.05), mtDNA (P<.05), and MPO (P<.05). Conclusions The evidence from this study suggests that CsA attenuated lung inflammation after LPS injection, and the protective mechanism may at least in part involve decreasing the release of inflammatory cytokines and mtDNA.
In-line Medicine Inspection by Carbon Nanotube Terahertz Scanners

We report on a real-time one-dimensional medicine inspection with a carbon nanotube (CNT) terahertz (THz) scanner. On the basis of different THz transmittance of medicines, we demonstrated in-line identification of different types of medicine pills. The bendable feature of the CNT scanner is expected to lead to multi-view examinations in the future, enabling more accurate whole surface imaging.
Tet methylcytosine dioxygenase 1 promotes hypoxic gene induction and cell migration in colon cancer

Ten‐eleven translocation 1 (TET1), a widely reported DNA demethylation protein, has been associated with tumorigenesis and metastasis. However, whether TET1 is an oncogene or tumor suppressor gene has been controversial; the mechanism of how TET1 affects cancer progression remains unclear. The current study aims to investigate how TET1 is changed in the tumor microenvironment and to explore the mechanisms of how TET1 affects colon cancer progression. Because hypoxia prevails on solid tumors, we established an important connection between hypoxia and DNA demethylation in tumorigenesis. By qPCR and RNA interference (RNAi) technology, we found that hypoxia increased TET1 expression with a hypoxia‐inducible factor‐1‐alpha (HIF‐1α)‐dependent manner. By CHIP‐qPCR and pyrosequencing technology, we demonstrated that TET1 regulated the target gene expression of HIF‐1α through HIF‐1α binding to hypoxia‐responsive elements (HREs), and HIF‐1α binding to HREs depended on CpG methylation levels. By Cell Counting Kit‐8 (CCK‐8) and transwell assay, we showed that loss of TET1 did not affect cell proliferation but inhibited migration. We also identified two novel gene mutants of TET1 in 120 paired tumor/normal tissue specimens by DNA sequencing and found that TET1 E2082K mutant blocked the TET1‐enhanced cell migration. Our results showed that the downregulation of TET1 rescued the abnormally high levels of gene expression resulting from hypoxia in tumors and reduced the migration activity of tumor cells, suggesting a therapeutic role by interference with TET1 in colon cancer treatment. By demonstrating that hypoxia upregulated TET1 and that TET1 drove HIF‐1α‐responsive genes, we showed that an epigenetic mechanism and tumor microenvironment‐driven models coexisted and mutually affected colon cancer.
Conceptual Model of Medication Adherence in Older Adults with High Blood Pressure-An Integrative Review of the Literature

Background: Medication adherence (MA) is the most important controlling factor of high blood pressure (HBP). There are a few MA models, but they have not been successful in predicting MA completely. Thus, this study aimed to ex-pand a conceptual model of MA based on an ecological approach. Methods: An integrative review of the literature based on theoretical and empirical studies was completed. Data source com-prised: Medline (including PubMed and Ovid), ISI, Embase, Google scholar, and internal databases such as Magiran, Google, SID, and internal magazines. Primary English and Persian language studies were collected from 1940 to 2018. The steps of study included: (a) problem identification, (b) literature review and extracting studies, (c) appraising study quality, (d) gathering data, (e) data analysis using the directed content analysis, (f) concluding. Results: Thirty-six articles were finally included and analyzed. After analysis, predictors of MA in older adults with hyper-tension were categorized into personal, interpersonal, organizational, and social factors. Although the personal factors have the most predictors in sub-categories of behavioral, biological, psychological, knowledge, disease, and medication agents, social, organizational and interpersonal factors can have indirect and important effects on elderly MA. Conclusion: There are many factors influencing MA of elderly with HBP. The personal factor has the most predictors. The designed model of MA because of covering all predictor factors, can be considered as a comprehensive MA model. It is sug-gested that future studies should select factors for study from all levels of the model.
The Effects of Transshipment Link on the Design of Spare Parts Network With Time-Window Based Service Level

We investigate the design problems of service parts network considering time-window-based service level and multiple operational flexibilities, which include no transshipment, unidirectional, and/or bidirectional transshipment, and the transshipment from support warehouse. We develop discrete event simulation models, a simulation optimization methodology and the measure indexes for system performance in order to analyze the effect of operational flexibility on system performance. Through a plenty of simulation experiments, we show that complete pooling policy is not necessarily appropriate for all spare parts networks, the performance of partial pooling policy may be close to or even outperform the one of full pooling policy in some cases. Besides, we also suggest some rough guidelines for the design of spare parts system.
Myocardial Perfusion Is Impaired and Relates to Cardiac Dysfunction in Patients With Atrial Fibrillation Both Before and After Successful Catheter Ablation

Background Atrial fibrillation (AF) is associated with myocardial infarction, and patients with AF and no obstructive coronary artery disease can present with symptoms and evidence of cardiac ischemia. We hypothesized that microvascular coronary dysfunction underlies these observations. Methods and Results Myocardial blood flow (MBF) at baseline and during adenosine stress and left ventricular and left atrial function were evaluated by magnetic resonance in 49 patients with AF (25 paroxysmal, 24 persistent) with no history of epicardial coronary artery disease or diabetes mellitus, before and 6 to 9 months after ablation. Findings were compared with those obtained in matched controls in sinus rhythm (n=25). Before ablation, patients with AF had impaired left atrial function and left ventricular ejection fraction and strain indices (all P<0.05 versus controls). MBF was impaired in patients both under baseline conditions (1.21±0.24 mL/min per g·[mm Hg·bpm/104]−1 versus 1.34±0.28 mL/min per g·[mm Hg·bpm/104]−1 in controls, P=0.044) and during adenosine stress (2.29±0.48 mL/min per g versus 2.73±0.37 mL/min per g in controls, P<0.001). Under baseline conditions, MBF correlated with left ventricular strain and left atrial function (all P≤0.001), so that cardiac function was most impaired in patients with the lowest MBF. Baseline and stress MBF remained unchanged postablation (both P=ns), and baseline MBF showed similar correlations with functional indices to those present preablation (all P≤0.001). Conclusions Baseline and stress MBF are significantly impaired in patients with AF but no epicardial coronary artery disease. Reduction in MBF is proportional to severity of left ventricular and left atrial dysfunction, even after successful ablation. Coronary microvascular dysfunction may be a relevant pathophysiological mechanism in patients with a history of AF.
The Association between Sense of Coherence and Dental Caries in Low Social Status Schoolchildren

The relationship between dental caries and sense of coherence (SOC) has not been substantiated in children and adolescents, particularly among those with a low socioeconomic status. The aim of this study was to investigate the association between SOC and dental caries in schoolchildren from a low socioeconomic background. A random sample of 356 8- to 14-year-old schoolchildren enrolled in public schools from the poorest region of Santa Maria, a southern city in Brazil, was selected. Dental examinations were performed to assess dental plaque and dental caries (DMF-S and dmf-s indexes). The children’s SOC was assessed using a validated Brazilian version of the SOC-13 scale. Socioeconomic, demographic, and behavioral data were collected from parents using a questionnaire. Multilevel Poisson regression analysis was used following a hierarchical approach to investigate the association between the SOC and DMF-T + dmf-t mean. Children whose mothers had studied for 8 years or less (RR 1.30; 95% CI 1.08–1.57) and children with dental plaque (RR 1.29; 95% CI 1.06–1.58) presented with higher DMF-T scores than their counterparts (p < 0.05). A higher household income (RR 0.66; 95% CI 0.51–0.84) and greater SOC scores (RR 0.71, 95% CI 0.56–0.90) were associated with lower DMF-T in children (p < 0.05). Children’s SOC seems to be a relevant protective psychosocial factor for dental caries experience in socially vulnerable children.
Information Encoding Methods for a Balance Assist Device Using Vibrotactile Feedback

This study investigates the applicability of information encoding methods for a balance assist device using vibrotactile feedback. In the device, two motors were employed to provide information on the model’s sway angle in each of the forward and backward directions. In the experiment involving ten healthy volunteers, two encoding modes with different vibration patterns were compared using an equivalent body model. The influence of proficiency level was also investigated. The results indicated that a simple encoding method outperformed a complex one even after the proficiency level was improved. Further analyses on the input and output of the model indicated the necessity of a time domain signal for encoding feedback information with the complex encoding methodology.
Multiple Empirical Kernel Mapping Based Broad Learning System for Classification of Parkinson’s Disease With Transcranial Sonography

Transcranial sonography (TCS) has become more popular for diagnosis of Parkinson’s disease (PD), and the TCS-based computer-aided diagnosis (CAD) for PD also attracts considerable attention, in which classifier is a critical component. Broad learning system (BLS) is a newly proposed single layer feedforward neural network for classification. In BLS, the original input features are mapped to several new feature representations to form the feature nodes, and then these mapped features are expanded to enhancement nodes by random mapping in a wide sense. However, random mapping performed for enhancement nodes is too simple and the generated features lack interpretability together with relative low representation. In this work, we propose a multiple empirical kernel mapping (MEKM) based BLS (MEKM-BLS) algorithm, which adopts MEKM to map the data of feature nodes to enhancement nodes. MEKM-BLS then has more meaningful enhancement layer in feedforward neural network. Moreover, the experiment for PD diagnosis with TCS shows that MEKM-BLS achieves superior performance to the original BLS algorithm.
IIT(BHU)–IIITH at CoNLL–SIGMORPHON 2018 Shared Task on Universal Morphological Reinflection

This paper describes the systems submitted by IIT (BHU), Varanasi/IIIT Hyderabad (IITBHU–IIITH) for Task 1 of CoNLL– SIGMORPHON 2018 Shared Task on Universal Morphological Reinﬂection (Cotterell et al., 2018). The task is to generate the in-ﬂected form given a lemma and set of morphological features. The systems are evaluated on over 100 distinct languages and three different resource settings (low, medium and high). We formulate the task as a sequence to sequence learning problem. As most of the characters in inﬂected form are copied from the lemma, we use Pointer-Generator Network (See et al., 2017) which makes it easier for the system to copy characters from the lemma. Pointer-Generator Network also helps in dealing with out-of-vocabulary characters during inference. Our best performing system stood 4th among 28 systems, 3rd among 23 systems and 4th among 23 systems for the low, medium and high resource setting respectively.
Manometric recordings bring out post-stimulus refractory states in the anal canal in neonates

Anorectal manometry is a diagnostic technique used to investigate the correct mechanical performance of the internal anal sphincter (IAS). By distending the rectal ampulla while recording changes in the luminal pressure, this method allows for characterizing the anorectal reflex. It can also provide, indirectly, information about the electrical activity of the IAS. In this study, seventeen neonates having 24-hour delayed passage of meconium or presenting distal intestinal obstruction symptoms underwent anorectal manometry to discard Hirschsprung’s disease. All patients had normal anorectal reflex. The time delay between stimulation of the rectal ampulla and the relaxation of the anal canal was studied. The average period of the pressure fluctuations was 5.44 ± 0.13s. The overall duration of the relaxation time was 9.71 ± 0.21s. The maximum lag between the onset of the stimulus and the relaxation of the IAS was 2.90 s, and was achieved when the stimulus was applied following a local maximum of the pressure wave. The existence of a refractory period during the suprathreshold depolarization of smooth muscle cells can explain the evidence of a temporal delay between the stimulus and the mechanical response. In occasions, relaxation appeared first distally. This phenomenon can be explained by the arrangement and morphology of bipolar cells, which may evidence the anisotropic propagation of the mechanical activity. These data may contribute to depict the alterations in excitability underlying the relaxation reflex by means of manometric recording of the anal canal.
Habitat-specific variation in gut microbial communities and pathogen prevalence in bumblebee queens (Bombus terrestris)

Gut microbial communities are critical for the health of many insect species. However, little is known about how gut microbial communities respond to anthropogenic changes and how such changes affect host-pathogen interactions. In this study, we used deep sequencing to investigate and compare the composition of gut microbial communities within the midgut and ileum (both bacteria and fungi) in Bombus terrestris queens collected from natural (forest) and urbanized habitats. Additionally, we investigated whether the variation in gut microbial communities under each habitat affected the prevalence of two important bumblebee pathogens that have recently been associated with Bombus declines (Crithidia bombi and Nosema bombi). Microbial community composition differed strongly among habitat types, both for fungi and bacteria. Fungi were almost exclusively associated with bumblebee queens from the forest habitats, and were not commonly detected in bumblebee queens from the urban sites. Further, gut bacterial communities of urban B. terrestris specimens were strongly dominated by bee-specific core bacteria like Snodgrassella (Betaproteobacteria) and Gilliamella (Gammaproteobacteria), whereas specimens from the forest sites contained a huge fraction of environmental bacteria. Pathogen infection was very low in urban populations and infection by Nosema was only observed in specimens collected from forest habitats. No significant relationship was found between pathogen prevalence and microbial gut diversity. However, there was a significant and negative relationship between prevalence of Nosema and relative abundance of the core resident Snodgrassella, supporting its role in pathogen defense. Overall, our results indicate that land-use change may lead to different microbial gut communities in bumblebees, which may have implications for bumblebee health, survival and overall fitness.