bluuebunny/crossref_metadata_2025_split huggingface dataset:
dbgap2x: an R package to explore and extract data from the database of Genotypes and Phenotypes (dbGaP)
Authors: Versmée Grégoire , Versmée Laura , Dusenne Mikaël , Jalali Niloofar , Avillach Paul 
Published: August 2019

Abstract

Summary
Based on the Genomic Data Sharing Policy issued in August 2007, the National Institutes of Health (NIH) has supported several repositories such as the database of Genotypes and Phenotypes (dbGaP). dbGaP is an online repository that provides access to large-scale genetic and phenotypic datasets with more than 1000 studies. However, navigating the website and understanding the relationship between the studies are not easy tasks. Moreover, the decryption of the files is a complex procedure. In this study we propose the dbgap2x R package that covers a broad range of functions for searching dbGaP studies, exploring the characteristics of a study and easily decrypting the files from dbGaP.

Availability and implementation
dbgap2x is an R package with the code available at https://github.com/gversmee/dbgap2x. A containerized version including the package, a Jupyter server and with a Notebook example is available at https://hub.docker.com/r/gversmee/dbgap2x.

Supplementary information
Supplementary data are available at Bioinformatics online.
Beta-defensin126 is correlated with sperm motility in fertile and infertile men†
Authors: Aram Raheleh , Chan Peter T K , Cyr Daniel G 
Published: August 2019

AbstractA crucial function of the epididymis is providing a surface glycocalyx that is important for sperm maturation and capacitation. Defensins are antimicrobial peptides expressed in the epididymis. In the macaque epididymis, defensin beta 126 (DEFB126) is important for sperm motility, however, it is not known whether this is the case in humans. The objectives were to determine: (1) if DEFB126 on human ejaculated sperm was correlated with sperm motility in fertile and infertile men, (2) that recombinant DEFB126 could induce immature sperm motility in vitro. Immunofluorescence staining indicated that the proportion of DEFB126-positive sperm was significantly higher in motile sperm. Furthermore, the proportion of DEFB126-labeled sperm was positively correlated with sperm motility and normal morphology. Additional studies indicated that the proportion of DEFB126-positive spermatozoa in fertile volunteers was significantly higher than in volunteers with varicocele, and in infertile volunteers with semen deficiencies. To determine the role of DEFB126 on sperm motility, the DEFB126 gene was cloned and used to generate recombinant DEFB126 in H9C2 cells (rat embryonic heart myoblast cells). Deletion mutations were created into two regions of the protein, which have been linked to male infertility. Immotile testicular spermatozoa were incubated with cells expressing the different forms of DEFB126. Full-length DEFB126 significantly increased motility of co-cultured spermatozoa. However, no increase in sperm motility was observed with the mutated forms of DEFB126. In conclusion, these results support the notion that DEFB126 is important in human sperm maturation and the potential use of DEFB126 for in vitro sperm maturation.
Applications of molecular networks in biomedicine
Authors: Chagoyen Monica , Ranea Juan A G , Pazos Florencio 
Published: August 2019

Abstract
Due to the large interdependence between the molecular components of living systems, many phenomena, including those related to pathologies, cannot be explained in terms of a single gene or a small number of genes. Molecular networks, representing different types of relationships between molecular entities, embody these large sets of interdependences in a framework that allow their mining from a systemic point of view to obtain information. These networks, often generated from high-throughput omics datasets, are used to study the complex phenomena of human pathologies from a systemic point of view. Complementing the reductionist approach of molecular biology, based on the detailed study of a small number of genes, systemic approaches to human diseases consider that these are better reflected in large and intricate networks of relationships between genes. These networks, and not the single genes, provide both better markers for diagnosing diseases and targets for treating them. Network approaches are being used to gain insight into the molecular basis of complex diseases and interpret the large datasets associated with them, such as genomic variants. Network formalism is also suitable for integrating large, heterogeneous and multilevel datasets associated with diseases from the molecular level to organismal and epidemiological scales. Many of these approaches are available to nonexpert users through standard software packages.
Geographical distribution and habitat characterization of Poa schizantha (Poaceae), a narrow endemic of the coastal sand dunes of the southern Pampas, Argentina
Authors: Celsi Cintia E , Giussani Liliana M 
Published: August 2019

AbstractPoa schizantha is a dioecious, psammophilous grass endemic to Atlantic coastal dunes in Argentina. We quantified the distribution area of this rare endemic species and characterized its habitat in the southern Pampas region. Convex hull and α-hull methods were used to estimate and map its overall geographical range. Ecological characterization was based on location, environmental variables, floristic composition and vegetation cover. In total, 117 quadrats were sampled in spring. The convex hull (7553 ha) was split, after excluding discontinuities, into two polygons: area 1 (968 ha; a novel area for the species) and area 2 (449 ha) separated by 36 km, indicating two geographically distinct population groups. In active coastal dune fields, P. schizantha occurs mainly in interdune slacks, associated with herbaceous, short, grassland-type vegetation and moist sandy soils with low vegetation cover, suggesting high habitat specificity. Based on TWINSPAN classification and ordination analysis, P. schizantha is related to two main vegetation groups with 100% constancy and c. 30% relative importance: subgroups E (dominated by pioneer dune species) and F (associated with hygrophilous and ubiquitous species). Given the extent of occurrence (restricted to <100 km2) and the severely fragmented habitat condition, we propose the species be categorized as Critically Endangered, following IUCN criteria. Actions aimed towards the survival of this species must prioritize population monitoring and conservation of its dune habitat.
Mutations in CREBBP and EP300 genes affect DNA repair of oxidative damage in Rubinstein-Taybi syndrome cells
Authors: Dutto Ilaria , Scalera Claudia , Tillhon Micol , Ticli Giulio , Passaniti Gianluca , Cazzalini Ornella , Savio Monica , Stivala Lucia A , Gervasini Cristina , Larizza Lidia , Prosperi Ennio 
Published: August 2019

AbstractRubinstein-Taybi syndrome (RSTS) is an autosomal-dominant disorder characterized by intellectual disability, skeletal abnormalities, growth deficiency and an increased risk of tumors. RSTS is predominantly caused by mutations in CREBBP or EP300 genes encoding for CBP and p300 proteins, two lysine acetyl-transferases (KAT) playing a key role in transcription, cell proliferation and DNA repair. However, the efficiency of these processes in RSTS cells is still largely unknown. Here, we have investigated whether pathways involved in the maintenance of genome stability are affected in lymphoblastoid cell lines (LCLs) obtained from RSTS patients with mutations in CREBBP or in EP300 genes. We report that RSTS LCLs with mutations affecting CBP or p300 protein levels or KAT activity, are more sensitive to oxidative DNA damage and exhibit defective base excision repair (BER). We have found reduced OGG1 DNA glycosylase activity in RSTS compared to control cell extracts, and concomitant lower OGG1 acetylation levels, thereby impairing the initiation of the BER process. In addition, we report reduced acetylation of other BER factors, such as DNA polymerase β and Proliferating Cell Nuclear Antigen (PCNA), together with acetylation of histone H3. We also show that complementation of CBP or p300 partially reversed RSTS cell sensitivity to DNA damage. These results disclose a mechanism of defective DNA repair as a source of genome instability in RSTS cells.
Cellular and Widefield Imaging of Sound Frequency Organization in Primary and Higher Order Fields of the Mouse Auditory Cortex
Authors: Romero Sandra , Hight Ariel E , Clayton Kameron K , Resnik Jennifer , Williamson Ross S , Hancock Kenneth E , Polley Daniel B 
Published: August 2019

Abstract
The mouse auditory cortex (ACtx) contains two core fields—primary auditory cortex (A1) and anterior auditory field (AAF)—arranged in a mirror reversal tonotopic gradient. The best frequency (BF) organization and naming scheme for additional higher order fields remain a matter of debate, as does the correspondence between smoothly varying global tonotopy and heterogeneity in local cellular tuning. Here, we performed chronic widefield and two-photon calcium imaging from the ACtx of awake Thy1-GCaMP6s reporter mice. Data-driven parcellation of widefield maps identified five fields, including a previously unidentified area at the ventral posterior extreme of the ACtx (VPAF) and a tonotopically organized suprarhinal auditory field (SRAF) that extended laterally as far as ectorhinal cortex. Widefield maps were stable over time, where single pixel BFs fluctuated by less than 0.5 octaves throughout a 1-month imaging period. After accounting for neuropil signal and frequency tuning strength, BF organization in neighboring layer 2/3 neurons was intermediate to the heterogeneous salt and pepper organization and the highly precise local organization that have each been described in prior studies. Multiscale imaging data suggest there is no ultrasonic field or secondary auditory cortex in the mouse. Instead, VPAF and a dorsal posterior (DP) field emerged as the strongest candidates for higher order auditory areas.
Using the Principles of Multisensory Integration to Reverse Hemianopia
Authors: Dakos Alexander S , Jiang Huai , Stein Barry E , Rowland Benjamin A 
Published: August 2019

Abstract
Hemianopia can be rehabilitated by an auditory-visual “training” procedure, which restores visual responsiveness in midbrain neurons indirectly compromised by the cortical lesion and reinstates vision in contralesional space. Presumably, these rehabilitative changes are induced via mechanisms of multisensory integration/plasticity. If so, the paradigm should fail if the stimulus configurations violate the spatiotemporal principles that govern these midbrain processes. To test this possibility, hemianopic cats were provided spatially or temporally noncongruent auditory-visual training. Rehabilitation failed in all cases even after approximately twice the number of training trials normally required for recovery, and even after animals learned to approach the location of the undetected visual stimulus. When training was repeated with these stimuli in spatiotemporal concordance, hemianopia was resolved. The results identify the conditions needed to engage changes in remaining neural circuits required to support vision in the absence of visual cortex, and have implications for rehabilitative strategies in human patients.
Maternal Dietary Intake of Omega-3 Fatty Acids Correlates Positively with Regional Brain Volumes in 1-Month-Old Term Infants
Authors: Morton Sarah U , Vyas Rutvi , Gagoski Borjan , Vu Catherine , Litt Jonathan , Larsen Ryan J , Kuchan Matthew J , Lasekan John B , Sutton Brad P , Grant P Ellen , Ou Yangming 
Published: August 2019

Abstract
Maternal nutrition is an important factor for infant neurodevelopment. However, prior magnetic resonance imaging (MRI) studies on maternal nutrients and infant brain have focused mostly on preterm infants or on few specific nutrients and few specific brain regions. We present a first study in term-born infants, comprehensively correlating 73 maternal nutrients with infant brain morphometry at the regional (61 regions) and voxel (over 300 000 voxel) levels. Both maternal nutrition intake diaries and infant MRI were collected at 1 month of life (0.9 ± 0.5 months) for 92 term-born infants (among them, 54 infants were purely breastfed and 19 were breastfed most of the time). Intake of nutrients was assessed via standardized food frequency questionnaire. No nutrient was significantly correlated with any of the volumes of the 61 autosegmented brain regions. However, increased volumes within subregions of the frontal cortex and corpus callosum at the voxel level were positively correlated with maternal intake of omega-3 fatty acids, retinol (vitamin A) and vitamin B12, both with and without correction for postmenstrual age and sex (P &lt; 0.05, q &lt; 0.05 after false discovery rate correction). Omega-3 fatty acids remained significantly correlated with infant brain volumes after subsetting to the 54 infants who were exclusively breastfed, but retinol and vitamin B12 did not. This provides an impetus for future larger studies to better characterize the effect size of dietary variation and correlation with neurodevelopmental outcomes, which can lead to improved nutritional guidance during pregnancy and lactation.
Environmental, Nutritional, and Socioeconomic Determinants of IBD Incidence: A Global Ecological Study
Authors: Piovani Daniele , Danese Silvio , Peyrin-Biroulet Laurent , Bonovas Stefanos 
Published: August 2019

AbstractBackground and AimsThe wide variation in inflammatory bowel disease [IBD] incidence across countries entails an opportunity to recognise global disease determinants and hypothesise preventive policies.MethodsWe fitted multivariable models to identify putative environmental, nutritional, and socioeconomic determinants associated with the incidence of IBD (i.e. ulcerative colitis [UC] and Crohn’s disease [CD]). We used the latest available country-specific incidence rates, and aggregate data for 20 determinants, from over 50 countries accounting for more than half of the global population. We presented the associations with exponentiated beta coefficients (exp[β]) indicating the relative increase of disease incidence per unit increase in the predictor variables.ResultsCountry-specific incidence estimates demonstrate wide variability across the world, with a median of 4.8 new UC cases (interquartile range [IQR] 2.4–9.3), and 3.5 new CD cases [IQR 0.8–5.7] per 100 000 population per year. Latitude (exp[β] 1.05, 95% confidence interval [CI] 1.04‒1.06, per degree increase), prevalence of obesity [1.05, 1.02‒1.07, per 1% increase], and of tobacco smoking [0.97, 0.95‒0.99, per 1% increase] explained 71.5% of UC incidence variation across countries in the adjusted analysis. The model for CD included latitude [1.04, 1.02‒1.06], expenditure for health (1.03, 1.01‒1.05, per 100 purchasing power parity [PPP]/year per capita increase), and physical inactivity prevalence [1.03, 1.00‒1.06, per 1% increase], explaining 58.3% of incidence variation across countries. Besides expenditure for health, these associations were consistent in low/middle- and high-income countries.ConclusionsOur analysis highlights factors able to explain a substantial portion of incidence variation across countries. Further high-quality research is warranted to develop global strategies for IBD prevention.
Deterioration of biventricular strain is an early marker of cardiac involvement in confirmed sarcoidosis
Authors: Kusunose Kenya , Fujiwara Mika , Yamada Hirotsugu , Nishio Susumu , Saijo Yoshihito , Yamada Nao , Hirata Yukina , Torii Yuta , Ise Takayuki , Yamaguchi Koji , Fukuda Daiju , Yagi Shusuke , Soeki Takeshi , Wakatsuki Tetsuzo , Sata Masataka 
Published: August 2019

Abstract

Aims
Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients.

Methods and results
LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: −18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P &lt; 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P &lt; 0.001).

Conclusion
Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.
Long-term outcomes of chronic coronary syndrome worldwide: insights from the international CLARIFY registry
Authors: Sorbets Emmanuel , Fox Kim M , Elbez Yedid , Danchin Nicolas , Dorian Paul , Ferrari Roberto , Ford Ian , Greenlaw Nicola , Kalra Paul R , Parma Zofia , Shalnova Svetlana , Tardif Jean-Claude , Tendera Michal , Zamorano José Luis , Vidal-Petiot Emmanuelle , Steg Philippe Gabriel ,   CLARIFY investigators
Published: August 2019

Abstract

Aims
Over the last decades, the profile of chronic coronary syndrome has changed substantially. We aimed to determine characteristics and management of patients with chronic coronary syndrome in the contemporary era, as well as outcomes and their determinants.

Methods and results
Data from 32 703 patients (45 countries) with chronic coronary syndrome enrolled in the prospective observational CLARIFY registry (November 2009 to June 2010) with a 5-year follow-up, were analysed. The primary outcome [cardiovascular death or non-fatal myocardial infarction (MI)] 5-year rate was 8.0% [95% confidence interval (CI) 7.7–8.3] overall [male 8.1% (7.8–8.5); female 7.6% (7.0–8.3)]. A cox proportional hazards model showed that the main independent predictors of the primary outcome were prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina, and peripheral artery disease. There was an interaction between angina and prior MI (P = 0.0016); among patients with prior MI, angina was associated with a higher primary event rate [11.8% (95% CI 10.9–12.9) vs. 8.2% (95% CI 7.8–8.7) in patients with no angina, P &lt; 0.001], whereas among patients without prior MI, event rates were similar for patients with [6.3% (95% CI 5.4–7.3)] or without angina [6.4% (95% CI 5.9–7.0)], P &gt; 0.99. Prescription rates of evidence-based secondary prevention therapies were high.

Conclusion
This description of the spectrum of chronic coronary syndrome patients shows that, despite high rates of prescription of evidence-based therapies, patients with both angina and prior MI are an easily identifiable high-risk group who may deserve intensive treatment.

Clinical registry
ISRCTN43070564
Catheter ablation of ventricular arrhythmias and in-hospital mortality: insights from the German-wide Helios hospital network of 5052 cases
Authors: König Sebastian , Ueberham Laura , Müller-Röthing René , Wiedemann Michael , Ulbrich Michael , Sause Armin , Tebbenjohanns Jürgen , Schade Anja , Shin Dong-In , Staudt Alexander , Andrié René , Neuser Hans , Kuhlen Ralf , Arya Arash , Hindricks Gerhard , Bollmann Andreas 
Published: August 2019

AbstractAimsCatheter ablation (CA) of ventricular arrhythmias is one of the most challenging electrophysiological interventions with an increasing use over the last years. Several benefits must be weighed against the risk of potentially life-threatening complications which necessitates a steady reevaluation of safety endpoints. Therefore, the aims of this study were (i) to investigate overall in-hospital mortality in patients undergoing such procedures and (ii) to identify variables associated with in-hospital mortality in a German-wide hospital network.Methods and resultsBetween January 2010 and September 2018, administrative data provided by 85 Helios hospitals were screened for patients with main or secondary discharge diagnosis of ventricular tachycardia (VT) or premature ventricular contractions (PVCs) in combination with an arrhythmia-related CA using ICD- and OPS codes. In 5052 cases (mean age 60.9 ± 14.3 years, 30.1% female) of 30 different hospitals, in-hospital mortality was 1.27% with a higher mortality in patients ablated for VT (1.99%, n = 2, 955) compared to PVC (0.24%, n = 2, 097, P < 0.01). Mortality rates were 2.06% in patients with ischaemic heart disease (IHD, n = 2, 137), 1.47% in patients with non-ischaemic structural heart disease (NIHD, n = 1, 224), and 0.12% in patients without structural heart disease (NSHD, n = 1, 691). Considering different types of hospital admission, mortality rates were 0.35% after elective (n = 2, 825), 1.60% after emergency admission/hospital transfer <24 h (n = 1, 314) and 3.72% following delayed hospital transfer >24 h after initial admission (n = 861, P < 0.01 vs. elective admission and emergency admission/hospital transfer <24 h). In multivariable analysis, a delayed hospital transfer >24 h [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.59–3.28, P < 0.01], the occurrence of procedure-related major adverse events (OR 6.81, 95% CI 2.90–16.0, P < 0.01), Charlson Comorbidity Index (CCI, OR 2.39, 95% CI 1.56–3.66, P < 0.01) and its components congestive heart failure (OR 8.04, 95% CI 1.71–37.8, P < 0.01), and diabetes mellitus (OR 1.59, 95% CI 1.13–2.22, P < 0.01) were significantly associated with in-hospital death.ConclusionsWe reported in-hospital mortality rates after CA of ventricular arrhythmias in the largest multicentre, administrative dataset in Germany which can be implemented in quality management programs. Aside from comorbidities, a delayed hospital transfer to a CA performing centre is associated with an increased in-hospital mortality. This deserves further studies to determine the optimal management strategy.