bluuebunny/crossref_metadata_2025_split huggingface dataset:
Family-based genome-wide association study of leprosy in Vietnam
Authors: Gzara Chaima , Dallmann-Sauer Monica , Orlova Marianna , Van Thuc Nguyen , Thai Vu Hong , Fava Vinicius M. , Bihoreau Marie-Thérèse , Boland Anne , Abel Laurent , Alcaïs Alexandre , Schurr Erwin , Cobat Aurélie 
Published: February 2020

AbstractLeprosy is a chronic infectious disease of the skin and peripheral nerves with a strong genetic predisposition. Recent genome-wide approaches have identified numerous common variants associated with leprosy, almost all in the Chinese population. We conducted the first family-based genome-wide association study of leprosy in 622 affected offspring from Vietnam, followed by replication in an independent sample of 1189 leprosy cases and 671 controls of the same ethnic origin. The most significant results were observed within the HLA region, in which six SNPs displayed genome-wide significant associations, all of which were replicated in the independent case/control sample. We investigated the signal in the HLA region in more detail, by conducting a multivariate analysis on the case/control sample of 319 GWAS-suggestive HLA hits for which evidence for replication was obtained. We identified three independently associated SNPs, two located in the HLA class I region (rs1265048: OR=0.69 [0.58-0.80], combined p-value = 5.53×10−11; and rs114598080: OR=1.47 [1.46-1.48], combined p-value = 8.77×10−13), and one located in the HLA class II region (rs3187964 (OR=1.67 [1.55-1.80], combined p-value = 8.35×10−16). We also validated two previously identified risk factors for leprosy: the missense variant rs3764147 in the LACC1 gene (OR=1.52 [1.41-1.63], combined p-value = 5.06×10−14), and the intergenic variant rs6871626 located close to the IL12B gene (OR=0.73 [0.61-0.84], combined p-value = 6.44×10−8). These results shed new light on the genetic control of leprosy, by dissecting the influence of HLA SNPs, and validating the independent role of two additional variants in a large Vietnamese sample.
Deep Learning for pericardial fat extraction and evaluation on a population study
Authors: Santini Gianmarco , Latta Daniele Della , Vatti Alessio , Ripoli Andrea , Chiappino Sara , Piagneri Valeria , Chiappino Dante , Martini Nicola 
Published: February 2020

AbstractObjectivesThe pericardial fat represents a powerful (promising) index which has been seen to correlate with several cardiovascular events. We propose a novel approach to automatically measure it from CT scans and we seek to explore how it is distributed in a study population.MethodsWe studied a population of 1528 patients where 47 (3%) showed a cardiac event. The fat segmentation model was based on a deep neural network to identify the heart and from it, the pericardial fat was extract by threshold. Statistical analysis was finally computed to stratify the population according the quantity of pericardial fat.ResultsThe high segmentation quality was reported with a Dice index (92.5%) and a Pearson coefficient (0.990, p<0.001). Notably, normalized pericardial fat volume was significantly higher in patients with cardiac event (73.46±30.84 vs 60.06±25.38 cm3/m2, p=0.005) with a AUC of 63,44% for discrimination of cardiac event.ConclusionsThe proposed approach reached accurate and fast performance for the evaluation of the pericardial fat making it reliable for a population analysis.
Quantitatively Evaluating the Cross-Sectoral and One Health Impact of Interventions: A Scoping Review and Application to Antibiotic Resistance
Authors: Naylor Nichola R. , Lines Jo , Waage Jeff , Wieland Barbara , Knight Gwenan M. 
Published: February 2020

AbstractCurrent published guidance on how to evaluate antibiotic resistance (ABR) from a One Health perspective has focussed on the evaluation of intervention design and of the intervention implementation process. For efficient resource allocation, it is also important to consider quantitative measures of intervention impact. In particular, there has been little discussion of how to practically evaluate ABR-related agri- and aquaculture interventions from a public health perspective. Lessons can be learned from other One Health and cross-sectoral intervention impact evaluations.WebofScience, EconLit, PubMed and grey literature were searched for literature quantitatively evaluating interventions across humans, animals and/or the environment. The review included 90 studies: 73 individual evaluations (from 72 papers) and 18 reviews, all including some measure of human impact, but only 29 papers covered all three One Health perspectives (human, animal and environmental). To provide decision makers with expected outcome estimates that are related to their objective functions, evaluations should provide outcome estimates from different perspectives. These include individual, microeconomic and/or macroeconomic perspectives across the One Health system. Based on the methods found in this review, a multi-level compartmental modelling approach for ABR-related intervention evaluation is proposed. The outcomes of such models can then feed into multi-criteria-decision analyses that weigh respective impact estimates alongside other chosen outcome estimates (for example equity or uncertainty). It is key that future quantitative evaluation models of ABR-related interventions are shared (for example through open source code sharing websites) to avoid duplication of effort and to enable more comprehensive estimates of intervention impact to be modelled in the future.
Genetically determined body mass index mediates the effect of smoking on type 2 diabetes risk, but not coronary artery disease risk
Authors: Thom Christopher S , Ding Zhuoran , Levin Michael G , Damrauer Scott M , Voight Benjamin F 
Published: February 2020

AbstractClinical observations have linked tobacco smoking with increased type 2 diabetes risk (1–5), a major public health concern (6). Mendelian randomization analysis has recently suggested smoking may be a causal risk factor for type 2 diabetes (7). However, this initial association could be mediated by additional causal risk factors correlated with smoking behavior, which have not been investigated to date. We hypothesized that body mass index (BMI) could explain the association between smoking and diabetes risk. First, we confirmed previous reports that genetically determined smoking behavior increased risk for both type 2 diabetes (OR=1.21, 95% CI: 1.15-1.27, P=1×10−12) and coronary artery disease (CAD; OR=1.21, 95% CI: 1.16-1.26, P=2×10−20). Additionally, a 2-fold increased smoking risk is positively associated with body mass index (BMI; ∼0.8 kg/m2, 95% CI: 0.54-0.98 kg/m2, P=1.8×10−11). In multivariable Mendelian randomization analysis, including BMI accounted for nearly all of the risk of smoking on type 2 diabetes (OR 1.06, 95% CI: 1.01-1.11, P=0.03). In contrast, the independent association between smoking and CAD persisted (OR 1.12, CI: 1.08-1.17, P=3×10−8) despite controlling for BMI. Causal mediation analyses agreed with these estimates. Our findings support a model whereby smoking initiation increases obesity, which in turn increases type 2 diabetes risk, with minimal if any direct effects from smoking on diabetes risk. Patients should be advised to stop smoking to limit both type 2 diabetes and CAD risk, and therapeutic efforts should consider pathophysiology relating smoking and obesity.
Oral, intestinal, and pancreatic microbiomes are correlated and exhibit co-abundance in patients with pancreatic cancer and other gastrointestinal diseases
Authors: Chung Mei , Zhao Naisi , Meier Richard , Koestler Devin C. , Del Castillo Erika , Wu Guojun , Paster Bruce J. , Charpentier Kevin , Izard Jacques , Kelsey Karl T. , Michaud Dominique S. 
Published: February 2020

AbstractOral microbiota are believed to play important roles in systemic diseases, including cancer. We collected oral swabs and at least one pancreatic tissue or intestinal samples from 52 subjects, and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing in a total 324 samples. We identified a total of 73 unique Amplicon Sequence Variants (ASVs) that were shared between oral and pancreatic or intestinal samples. Accounting for pairing and within-subject correlation, 7 ASVs showed significant concordance (Kappa statistics) and 5 ASVs exhibited significant or marginally significant Pairwise Stratified Association (PASTA) between oral samples and pancreatic tissue or intestinal samples. Of these, two specific bacterial species (Gemella morbillorum and Fusobacterium nucleatum subsp. vincentii) showed consistent presence or absence patterns between oral and intestinal or pancreatic samples. Lastly, our microbial co-abundance analyses showed several distinct ASVs clusters and complex correlation-networks between ASV clusters in buccal, saliva, duodenum, jejunum, and pancreatic tumor samples. Toghether, our findings suggest that oral, intestinal, and pancreatic microbiomes are correlated and bacteria of oral origin exhibit co-abundance relationships and demonstrate complex correlation patterns in the intestinal and pancreatic tumor samples. Future prospective studies should aim to uncover the co-abundance of specific microbial communities for studying etiology of microbiota-driven carcinogenesis.
Added Value and Clinical Significance of Nonlinear Variability Indices of Walking Stride Interval in Neurodegenerative Diseases
Authors: Frédéric Dierick , Charlotte Vandevoorde , Frédéric Chantraine , Olivier White , Fabien Buisseret 
Published: February 2020

AbstractThough self-paced walking is highly stereotyped, the stride interval fluctuates from one stride to the next around an average value with a measurable statistical variability. In clinical gait analysis, this variability is usually assessed with indices such the standard deviation or the coefficient of variation (CV). The aim of this study is to understand the added value that nonlinear indices of walking stride interval variability, such as Hurst exponent (H) and Minkowski fractal dimension (D), can provide in a clinical context and to suggest a clinical significance of these indices in the most common neurodegenerative diseases: Parkinson, Huntington, and amyotrophic lateral sclerosis. Although evidence have been accumulated that the stride interval organization at long range displays a more random, less autocorrelated, gait pattern in neurodegenerative diseases compared with young healthy individuals, it is today necessary to recompute CV, H, and D indices in a unified way and to take into account aging impact on these indices. In fact, computed nonlinear indices of variability are mainly dependent on stride interval time series length and algorithms used, making quantitative comparisons between different studies difficult or even impossible. Here, we recompute these indices from available stride interval time series, either coming from our lab or from online databases, or made available to us by the authors of previously conducted research. We confirm that both linear and nonlinear variability indices are relevant indicators of aging process and neurodegenerative diseases. CV is sensitive to aging process and pathology but does not allow to discriminate between specific neurodegenerative diseases. D shows no significative change in pathological groups. However, since H index is correlated with Hoehn & Yahr scores and significantly lowered in patients suffering from Huntington’s disease, we recommend it as a relevant supplement to CV.
Status of water sources, hygiene and sanitation and its impact on the health of households of Makwane Village, Limpopo Province, South Africa
Authors: Budeli P , Moropeng RC , Mpenyana-Monyatsi L , Kamika I , Momba MNB 
Published: February 2020

ABSTRACTThe key to reducing or even eradicating the burden of waterborne diseases is through appropriate sanitation facilities and piped water systems. Installation of centralised system may take decades to be established, especially in impoverished rural communities of African countries. A survey of 88 households representing Makwane, a scattered settlement in South Africa, Limpopo Province, was conducted to assess the status of basic services. A questionnaire was designed to obtain the required information, such as improved water sources, improved sanitation facilities, hygiene practices and incidence of diarrhoeal diseases in the community. A house-to-house survey was conducted from July to August in 2014 and data were collected from the heads of each household. Results of the survey revealed a complete absence of improved drinking water sources in the community (100%). People rely on any available water sources such stream water, or on rainwater harvesting. Safe hygiene practices were observed in most households with regards to water storage as they store water in 25 L plastic buckets (57%), vessels stored inside a room (76%), use storage containers covered with a lid (76%) and wash these containers at any time prior to storing water (39%). Results also indicated a high percentage of households not treating water (81%) prior to use, disposing wastewater in the yard (97%), lacking access to improved sanitation facilities (41%), and not allowing children under 12 years old to use the toilets (62%). As a result, they practise open defecation as an alternative sanitation facility (86%). The main water source for the community was found to be the stream (31%) and this source is used for adequate personal hygiene in terms of full body bath (94%). In terms of health outcomes, the most prevalent health problem was found to be diarrhoea (75%), which occurred mostly in children less than 5 years old and was found to persist up to 3 days (34%). The community generally visited the clinic (75%) in cases of health problems. The implementation of point-of-use household drinking water treatment in Makwane households for the production of safe drinking water is highly recommended. In addition to this, a special education with emphasis on drinking water storage, cleaning of water storage containers and safe disposal of wastewater should be offered. Open defecation should also be discouraged to mitigate the bacterial contamination of water sources and transmission of diseases.
Context matters: Contrasting behavioral and residential risk factors for Lyme disease between two high-incidence regions in the Northeastern and Midwestern U.S
Authors: Bron Gebbiena M. , Fernandez Maria del P. , Larson Scott R. , Maus Adam , Gustafson Dave , Tsao Jean I. , Diuk-Wasser Maria A. , Bartholomay Lyric C. , Paskewitz Susan M. 
Published: February 2020

AbstractThe dynamics of zoonotic vector-borne diseases are determined by a complex set of parameters including human behavior that may vary with socio-ecological contexts. Lyme disease is the most common vector-borne disease in the United States and the Northeast and upper Midwest are the regions most affected - two areas with differing levels of urbanization and sociocultural settings. The probability of being diagnosed with Lyme disease is related to the risk of encounters with an infected blacklegged tick, which reflects both the environmental tick hazard and human behaviors. Herein, we compare behavioral and peridomestic risk factors associated with human-tick encounters between high-incidence states in the Northeast (New York and New Jersey) and Midwest (Wisconsin) of the United States. We used a smartphone application, The Tick App, as a novel survey tool, during spring and summer of 2018. Adaptive human behavior was identified in the relationship between outdoor activities and the use of preventive methods. More frequent recreational outdoor activities and gardening (a peridomestic activity) were associated with an increased likelihood of using personal protective measures. Weekly participation in non-seasonal recreational and peridomestic outdoor activities in spring and summer was associated with an increased likelihood of finding a tick in the fall or winter. Most outdoor activities were more frequently reported by participants from the Midwest than the Northeast. Participants in the Northeast reported less use of personal protective measures, but they reported more interventions to reduce the presence of peridomestic deer and ticks (i.e. pesticide applications on their property) than participants in the Midwest. Participants from the Midwest were more likely to kill rodents on their property. Context mattered, and our study illustrates the need for the assessment of personal behavior and tick exposure in these two Lyme disease-endemic regions to aid in targeted public health messaging to reduce tick-borne diseases.Highlights-Use of personal tick prevention was associated with more frequent outdoor activity-Personal protective measure use was higher in the Midwest than Northeast-Interventions reducing peridomestic deer and ticks more common in the Northeast
The impact of brain lesion characteristics and the corticospinal tract wiring pattern on mirror movement characteristics in unilateral cerebral palsy
Authors: Simon-Martinez Cristina , Zielinski Ingar , Hoare Brian , Decraene Lisa , Williams Jacqueline , Mailleux Lisa , Steenbergen Bert , Ortibus Els , Feys Hilde , Klingels Katrijn 
Published: February 2020

ABSTRACTBackgroundMirror movements (MM) influence bimanual performance in children with unilateral cerebral palsy (uCP). Whilst MM are related to brain lesion characteristics and the corticospinal tract (CST) wiring pattern, the combined impact of these neurological factors remains unknown.ObjectiveTo investigate the combined impact of neurological factors on MM.MethodsForty-nine children with uCP (mean age 10y6mo) performed a repetitive squeezing task to quantify similarity between MM activity (MM-similarity) and strength of the MM activity (MM-intensity). We used MRI to evaluate lesion type (periventricular white matter, N=30) cortico-subcortical, N=19), the extent of ipsilesional damage and damage to basal ganglia, thalamus and corpus callosum. The CST wiring pattern (17 CSTcontralateral, 16 CSTipsilateral, 16 CSTbilateral) was assessed with Transcranial Magnetic Stimulation. Data was analyzed with simple and multiple regression analyses.ResultsMM-similarity in the more-affected hand was higher with more damage to the corpus callosum. MM-intensity was higher in children with CSTcontralateral with damage to the basal ganglia and thalamus. In the less-affected hand, MM-similarity was explained by the interaction between lesion type and CST wiring pattern, with higher MM-similarity in children with cortico-subcortical lesions in the CSTcontralateral group. MM-intensity was higher with larger damage to the corpus callosum and unilateral lesions.ConclusionsA complex combination of neurological factors influences MM characteristics and the mechanisms differ between hands.
Elucidation of novel miRNA candidates and their role in unraveling the pathology of Non-Alcoholic Fatty Liver Disease
Authors: Biju Bincy Mary , Chhabra Saheb Singh , Sarkar Chiradeep 
Published: February 2020

AbstractNon-Alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease which is observed in people who do not abuse alcohol. Main cause of NAFLD is Non-Alcoholic Steatohepatitis (NASH) where there is accumulation of fats such as triglyceride in liver and the disease progression ranges from simple steatosis to fibrosis and cirrhosis. MicroRNAs are critical players in post-transcriptional gene regulation of diseases with complex etiology. In this study, we have elucidated the role of microRNAs (miRNAs) in the pathophysiology of NAFLD/NASH and unravelled molecular markers for diagnosis of NAFLD. A subset of genes (n=10) responsible for NAFLD/NASH were selected and detailedin silicoanalysis carried out using multiple tools. miRDB and DIANA-microT were used to find putative miRNA binding sites followed by analysis using miRTarBase which is an experimentally validated database of miRNA-target interactions. The study elucidated a number of statistically significant predictions for both miRDB (scores >80) and DIANA-microT (values >0.90) and also strong experimental validation in miRTarBase. The analysis revealed that certain miRNAs like miR-7 & miR-548 family members are found in both the programmes, miRDB and DIANA-microT, targeting genes involved in liver function. They were also identified in the experimental validation database miRTarBase. These miRNAs probably play an important role in the pathophysiology of this disease. They can also be used as prognostic/diagnostic markers for assessment of NAFLD.
BiCoN: Network-constrained biclustering of patients and omics data
Authors: Lazareva Olga , Van Do Hoan , Canzar Stefan , Yuan Kevin , Baumbach Jan , Blumenthal David B. , Tieri Paolo , Kacprowski Tim , List Markus 
Published: February 2020

AbstractMotivationUnsupervised learning approaches are frequently employed to identify patient subgroups and biomarkers such as disease-associated genes. Thus, clustering and biclustering are powerful techniques often used with expression data, but are usually not suitable to unravel molecular mechanisms along with patient subgroups. To alleviate this, we developed the network-constrained biclustering approach BiCoN (Biclustering Constrained by Networks) which (i) restricts biclusters to functionally related genes connected in molecular interaction networks and (ii) maximizes the difference in gene expression between two subgroups of patients.ResultsOur analyses of non-small cell lung and breast cancer gene expression data demonstrate that BiCoN clusters patients in agreement with known cancer subtypes while discovering gene subnetworks pointing to functional differences between these subtypes. Furthermore, we show that BiCoN is robust to noise and batch effects and can distinguish between high and low load of tumor-infiltrating leukocytes while identifying subnetworks related to immune cell function. In summary, BiCoN is a powerful new systems medicine tool to stratify patients while elucidating the responsible disease mechanism.AvailabilityPyPI package:https://pypi.org/project/biconWeb interface:https://exbio.wzw.tum.de/biconContactolga.lazareva@tum.deSupplementary informationSupplementary data are available atBioinformaticsonline.