bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is living donor liver transplantation justified in high model for end-stage liver disease candidates (35+)?
Authors: Au Kin P. , Chan Albert C.Y. 
Published: August 2019

Purpose of review
Application of living donor liver transplantation (LDLT) in model for end-stage liver disease (MELD) 35+ patients has been regarded with skepticism. There is concern that a partial graft may not achieve favourable outcomes, and that a healthy donor is risked for a transplant which might turn out to be futile.

Recent findings
In practice, LDLT improves access to liver graft and allows timely transplantation. Long-term results from high-volume centres revealed that outcomes of LDLT in these patients have not been jeopardized by limited graft volumes. With unimpeded vascular outflow, a partial graft could provide sufficient function to overcome the stress of transplant operation. However, LDLT is a complex operation with immense technical demand. A steep learning curve is encountered before optimal outcomes could be produced. Meanwhile, donor safety remains the paramount concern. Donor should not be evaluated for futile candidates. MELD 35+ patients with refractory sepsis or cardiac event are unlikely to benefit from liver transplantation. Borderline donors, in terms of donor safety or graft quality, should not be accepted. As in recipient operation, accumulation of experience is crucial to reduce donor mortality and morbidity.

Summary
LDLT is justified for MELD 35+ in high-volume centres with vast experience. Satisfactory recipient outcomes can be produced with minimal donor morbidity.
Identifying Ashkenazi Jewish BRCA1/2 founder variants in individuals who do not self-report Jewish ancestry
Authors: Tennen Ruth I. , Laskey Sarah B. , Koelsch Bertram L. , McIntyre Matthew H. ,   The 23andMe Health Team, Tung Joyce Y. 
Published: August 2019

ABSTRACTCurrent guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants — 185delAG (c.68_69delAG), 5382insC (c.5266dupC), and 6174delT (c.5946delT) — are common in the Ashkenazi Jewish population. We characterized a cohort of more than 2,800 research participants in the 23andMe database who carry one or more of the three Ashkenazi Jewish founder variants, evaluating two characteristics that are typically used to recommend individuals for BRCA testing: self-reported Jewish ancestry and family history of breast, ovarian, prostate, or pancreatic cancer. Of the 1,967 carriers who provided self-reported ancestry information, 21% did not self-report any Jewish ancestry; of these individuals, more than half (62%) do have detectable Ashkenazi Jewish genetic ancestry. In addition, of the 343 carriers who provided both ancestry and family history information, 44% did not have a first-degree family history of a BRCA-related cancer and, in the absence of a personal history of cancer, would therefore be unlikely to qualify for clinical genetic testing. These findings provide support for the growing call for broader access to BRCA genetic testing.
Comparison of student perception and exam validity, reliability and items difficulty: cross-sectional study
Authors: Rezigalla Assad Ali , Eleragi Ali Mohammed Elhassan , Elkhalifa Masoud Ishag , Mohammed Ammar M A 
Published: August 2019

AbstractIntroductionStudent perception of an exam is a reflection of their feelings towards the exam items, while item analysis is a statistical analysis of students’ responses to exam items. The study was formulated to compare the student’s perception of the results of item analysis.Material and methodsType of the study is cross-sectional. The study was conducted in the college of medicine, in the duration from January to April 2019. The study uses a structured questionnaire and standardized item analysis of students’ exam. Participants are students registered for semester two level year (2018-2019). Exclusion criteria included all students who refused to participate in the study or do not fill the questionnaire.ResultThe response rate of the questionnaire was 88.9% (40/45). Students considered the exam as easy (70.4%). The average difficulty index of the exam is acceptable. KR-20 of the exam was 0.906. A significant correlation was reported between student perceptions towards exam difficulty and standard exam difficulty.DiscussionStudent perceptions support the evidances of exam vlaitdity. Students can estimate exam difficulty.
Host genetic variants near the PAX5 gene locus associate with susceptibility to invasive group A streptococcal disease
Authors: Parks Tom , Auckland Kathryn , Lamagni Theresa L. , Mentzer Alexander , Elliott Katherine , Guy Rebecca , Cartledge Doreen , Strakova Lenka , O’Connor Daniel , Pollard Andrew J , Chapman Stephen J. , Thomas Matthew , Brodlie Malcolm , Colot Julien , D’Ortenzio Eric , Baroux Noémie , Mirabel Mariana , Gilchrist James J. , Scott J. Anthony G. , Williams Thomas N. , Knight Julian , Steer Andrew C. , Hill Adrian V. S. , Sriskandan Shiranee 
Published: August 2019

AbstractWe undertook a genome-wide association study of susceptibility to invasive group A streptococcal (GAS) disease combining data from distinct clinical manifestations and ancestral populations. Amongst other signals, we identified a susceptibility locus located 18kb from PAX5, an essential B-cell gene, which conferred a nearly two-fold increased risk of disease (rs1176842, odds ratio 1.8, 95% confidence intervals 1.5-2.3, P=3.2×10−7). While further studies are needed, this locus could plausibly explain some inter-individual differences in antibody-mediated immunity to GAS, perhaps providing insight into the effects of intravenous immunoglobulin in streptococcal toxic shock.
Causal mediation analysis of Subclinical Hypothyroidism in children with obesity and Non-Alcoholic Fatty Liver Disease
Authors: Nichols Presley , Pan Yue , May Benjamin , Pavlicova Martina , Mencin Ali , Thaker Vidhu V 
Published: August 2019

AbstractContextNonalcoholic Fatty Liver Disease (NAFLD) is a common co-morbidity of obesity and a leading cause of liver disease in children. Subclinical hypothyroidism (SH) occurs with obesity and may contribute to dysmetabolic state that predisposes to NAFLD.ObjectiveTo assess the relationship between SH and NAFLD in children with biopsy-proven NAFLD compared to controls.Design and MethodsIn this retrospective study of cases from a registry of children with biopsy-proven NAFLD and age-matched controls, the association of SH with NAFLD and other cardiometabolic parameters was assessed followed by causal mediation analyses under the counter-factual framework.ResultsSixty-six cases and 4067 age-matched controls were included in the study. Children with NAFLD were more likely to be male (74.6 vs 39.4%, p < 0.001), have higher modified BMI-z scores (2.3 ±1.6 vs 1±1.6, p < 0.001), and abnormal metabolic parameters (TSH, ALT, HDL-C, non-HDL-C, LDL-C, and TG). Multivariate analyses controlling for age, sex and severity of obesity showed significant association between the 4thquartile of TSH and NAFLD. Causal mediation analysis demonstrates that TSH mediates 44% of the effect of modified BMI-z score on NAFLD. This comprises of 16.2% (OR = 1.1, p < 0.001) caused by the indirect effect of TSH and its interaction with modified BMI-z, and 26.5% (OR = 1.1, p = 0.01) as an autonomous effect of TSH on NAFLD regardless of the obesity.ConclusionsThe association of SH and biopsy-proven NAFLD is demonstrated in a predominately Latino population. Further, a causal mediation analysis implicates an effect of TSH on NAFLD, independent of obesity.
Elevated blood pressure in the emergency department – a risk factor for incident cardiovascular disease: An EHR-based cohort study
Authors: Oras P. , Häbel H. , Skoglund P. H. , Svensson P. 
Published: August 2019

ABSTRACTObjectivesIn the emergency department (ED), high blood pressure (BP) is commonly observed but mostly used to evaluate patients’ health in the short-term. We aimed to study whether ED-measured BP is associated with incident atherosclerotic cardiovascular disease (ASCVD), myocardial infarction (MI), or stroke in long-term, and to estimate the number needed to screen (NNS) to prevent ASCVD.DesignElectronic Health Records (EHR) and national register-based cohort study. The association between BP and incident ASCVD was studied with Cox-regression.SettingTwo university hospital emergency departments in Sweden.Data sourcesBP data were obtained from EDs EHR, and outcome information was acquired through the Swedish National Patient Register for all participants.ParticipantsAll patients ≥18 years old who visited the EDs between 2010 to 2016, with an obtained BP (n=300,193).Main outcome measuresIncident ASCVD, MI, and stroke during follow-up.ResultsThe subjects were followed for a median of 42 months. 8,999 incident ASCVD events occurred (MI: 4,847, stroke: 6,661). Both diastolic and systolic BP (SBP) was associated with incident ASCVD, MI, and stroke with a progressively increased risk for SBP within hypertension grade 1 (HR 1.15, 95% CI 1.06 to 1.24), 2 (HR 1.35, 95% CI 1.25 to 1.47), and 3 (HR 1.63, 95% CI 1.49 to 1.77). The six-year cumulative incidence of ASCVD was 12% for patients with SBP ≥180 mmHg compared to 2% for normal levels. To prevent one ASCVD event during the median follow-up, NNS was estimated to 151, whereas NNT to 71.ConclusionsBP in the ED is associated with incident ASCVD, MI, and stroke. High BP recordings in EDs should not be disregarded as isolated events, but an opportunity to detect and improve treatment of hypertension. ED-measured BP provides an important and under-used tool with great potential to reduce morbidity and mortality associated with hypertension.
Reclassification of Pterulaceae Corner (Basidiomycota: Agaricales) introducing the ant-associated genus Myrmecopterula gen. nov., Phaeopterula Henn. and the corticioid Radulomycetaceae fam. nov.
Authors: Leal-Dutra Caio A. , Griffith Gareth W. , Neves Maria Alice , McLaughlin David J. , McLaughlin Esther G. , Clasen Lina A. , Dentinger Bryn T. M. 
Published: August 2019

ABSTRACTPterulaceae was formally proposed to group six coralloid and dimitic genera [Actiniceps (=Dimorphocystis), Allantula, Deflexula, Parapterulicium, Pterula and Pterulicium]. Recent molecular studies have shown that some of the characters currently used in Pterulaceae Corner do not distinguish the genera. Actiniceps and Parapterulicium have been removed and a few other resupinate genera were added to the family. However, none of these studies intended to investigate the relationship between Pterulaceae genera. In this study, we generated 278 sequences from both newly collected and fungarium samples. Phylogenetic analyses support by morphological data allowed a reclassification of Pterulaceae where we propose the introduction of Myrmecopterula gen. nov. and Radulomycetaceae fam. nov., the reintroduction of Phaeopterula, the synonymisation of Deflexula in Pterulicium and 51 new combinations. Pterula is rendered polyphyletic requiring a reclassification; thus, it is split into Pterula, Myrmecopterula gen. nov., Pterulicium and Phaeopterula. Deflexula is recovered as paraphyletic alongside several Pterula species and Pterulicium, and is sunk into the latter genus. Phaeopterula is reintroduced to accommodate species with darker basidiomes. The neotropical Myrmecopterula gen. nov. forms a distinct clade adjacent to Pterula, and most members of this clade are associated with active or inactive attine ant nests. The resupinate genera Coronicium and Merulicium are recovered in a strongly supported clade close to Pterulicium. The other resupinate genera previously included in Pterulaceae, and which form basidiomes lacking cystidia and with monomitic hyphal structure (Radulomyces, Radulotubus and Aphanobasidium), are reclassified into Radulomycetaceae fam. nov. Allantula is still an enigmatic piece in this puzzle known only from the type specimen that requires molecular investigation. A key for the genera of Pterulaceae and Radulomycetaceae fam. nov. is provided here.
Proteome-wide characterization and biomarker identification of intracranial aneurysm
Authors: Sharma Tanavi , Datta Keshava K. , Kumar Munish , Dey Gourav , Khan Aafaque Ahmad , Mangalaparthi Kiran Kumar , Saharan Poonam , Shobia C. , Aggarwal Ashish , Singla Navneet , Ghosh Sujata , Rawat Amit , Dhandapani Sivashanmugam , Salunke Pravin , Chhabra Rajesh , Singh Dalbir , Takkar Aastha , Gupta Sunil K. , Keshava Prasad T. S. , Gowda Harsha , Pandey Akhilesh , Bhagat Hemant 
Published: August 2019

AbstractThe scientific basis of intracranial aneurysm (IA) formation, its rupture and further development of cerebral vasospasm remains incompletely understood. Deciphering the molecular mechanisms underlying these events will lead to identification of early detection biomarkers and in turn, improved treatment outcomes. Aberrant protein expression may drive structural alterations of vasculature found in IA. To unravel these aberrations, we performed untargeted, global, quantitative proteomic analysis of aneurysm tissue and serum from patients with IA. Samples were derived from patients of three clinical sub groups– 1) unruptured aneurysm 2) ruptured aneurysm without vasospasm 3) ruptured aneurysm who developed vasospasm. A total of 937 and 294 proteins were identified in aneurysm tissue and serum samples respectively. Several proteins that are known to maintain the structural integrity of vasculature were found to be dysregulated. ORM1, a glycoprotein, was significantly upregulated in both the aneurysm tissue and serum samples of unruptured IA patients. We employed a larger cohort of patients and validated ORM1 as a potential biomarker for screening of unruptured aneurysm using ELISA. Samples from ruptured aneurysm with vasospasm showed significant upregulation of MMP9 as compared to ruptured aneurysm without vasospasm. Using a cohort of ruptured aneurysm patients with and without vasospasm, we validated MMP9 as a potential biomarker for vasospasm. This study reveals pathophysiology underlying different clinical sub groups of IA and also suggests potential biomarkers.
xQTLImp: efficient and accurate xQTL summary statistics imputation
Authors: Wang Tao , Yin Quanwei , Liu Yongzhuang , Chen Jin , Wang Yadong , Peng Jiajie 
Published: August 2019

AbstractMotivationQuantitative trait locus (QTL) analysis of multiomic molecular traits, such as gene transcription (eQTL), DNA methylation (mQTL) and histone modification (haQTL), has been widely used to infer the effects of genomic variation on multiple levels of molecular activities. However, the power of xQTL (various types of QTLs) detection is largely limited by missing association statistics due to missing genotypes and limited effective sample size. Existing hidden Markov model (HMM)-based imputation approaches require individual-level genotypes and molecular traits, which are rarely available. No available implementation exists for the imputation of xQTL summary statistics when individual-level data are missed.ResultsWe present xQTLImp, a C++ software package specifically designed for efficient imputation of xQTL summary statistics based on multivariate Gaussian approximation. Experiments on a single-cell eQTL dataset demonstrates that a considerable amount of novel significant eQTL associations can be rediscovered by xQTLImp.AvailabilitySoftware is available at https://github.com/hitbc/xQTLimp.Contactydwang@hit.edu.cn or jiajiepeng@nwpu.edu.cnSupplementary informationSupplementary data are available at Bioinformatics online.
Meta-Analysis of Transcriptomic Variation in T cell Populations Reveals Novel Signatures of Gene Expression and Splicing
Authors: Radens Caleb M. , Blake Davia , Jewell Paul , Barash Yoseph , Lynch Kristen W. 
Published: August 2019

SummaryDistinct T cell subtypes are typically defined by the expression of distinct gene repertoires. However, there is variability between studies regarding the markers used to define each T cell subtype. Moreover, previous analysis of gene expression in T cell subsets has largely focused on gene expression rather than alternative splicing. Here we take a meta-analysis approach, comparing eleven independent RNA-Seq studies of human Th1, Th2, Th17 and/or Treg cells to identify transcriptomic features that correlate consistently with subtype. We find that known master-regulators are consistently enriched in the appropriate subtype, however, cytokines and other genes often used as markers are more variable. Importantly, we also identify previously unknown transcriptomic markers that consistently differentiate between subsets, including a few Treg-specific splicing patterns. Together this work highlights the heterogeneity in gene expression between isolates of the same subtype, but also suggests additional markers that can be used to define functional groupings.
MisMatch Negativity-study showing pre-lexical sensitivity to both primary Final Accent and secondary Initial Accent in French
Authors: te Rietmolen Noémie , El Yagoubi Radouane , Astésano Corine 
Published: August 2019

AbstractIn French, accentuation is not lexically distinctive and tightly intertwined with intonation. This has led to the language being described of as ‘a language without accent’ and to French listeners being alleged ‘deaf to stress’. However, if one considers Di Cristo’s model in which the metrical structure of speech plays a central role, it becomes possible to envision stress templates underlying the cognitive representation of words. This event-related potential (erp) study examined whether French listeners are sensitive to the French primary final accent (fa) and secondary initial accent (ia), and whether the accents are part of the French phonologically expected stress pattern. Two oddball studies were carried out. In the first study, in one condition, deviants were presented without (−fa) and standards with final accent (+fa), while in another condition, these positions were switched. We obtained asymmetricmmnwaveforms, such that deviants −faelicited a largermmnthan deviants +fa(which did not elicit anmmn), pointing toward a preference for stress patterns withfa. Additionally, the difference waveforms between identical stimuli in different positions within the oddball paradigms indicated −fastimuli to be disfavored whether they were the deviants or the standards. In the second study, standards were always presented with both the initial and final accent, while deviants were presented either without final accent (−fa) or without initial accent (−ia). Here, we obtainedmmns both to deviants −faand to deviants −ia, although −fadeviants elicited a more amplemmn. Nevertheless, the results show that French listeners are not deaf to the initial and final accents, pointing instead to an abstract phonological representation for both accents. In sum, the results argue against the notion of stress deafness for French and instead suggest accentuation to play a more important role in French speech comprehension than is currently acknowledged.
Post-EMT: Cadherin-11 mediates cancer hijacking fibroblasts
Authors: Kang Weirong , Fan Yibo , Du Yinxiao , Tonkova Elina A. , Hsu Yi-Hsin , Tan Kel Vin , Alexander Stephanie , Wong Bin Sheng , Yang Haocheng , Luo Jingyuan , Yao Kuo , Yang Jiayao , Hu Xin , Liu Tingting , Gan Yu , Zhang Jian , Zhao Jean J. , Konstantopoulos Konstantinos , Friedl Peter , Khong Pek Lan , Lu Aiping , Hung Mien-Chie , Brenner Michael B. , Segall Jeffrey E. , Gu Zhizhan 
Published: August 2019

AbstractCurrent prevailing knowledge on EMT (epithelial mesenchymal transition) deems epithelial cells acquire the characters of mesenchymal cells to be capable of invading and metastasizing on their own. One of the signature events of EMT is called “cadherin switch”, e.g. the epithelial E-cadherin switching to the mesenchymal Cadherin-11. Here, we report the critical events after EMT that cancer cells utilize cadherin-11 to hijack the endogenous cadherin-11 positive fibroblasts. Numerous 3-D cell invasion assays with high-content live cell imaging methods reveal that cadherin-11 positive cancer cells adhere to and migrate back and forth dynamically on the cell bodies of fibroblasts. By adhering to fibroblasts for co-invasion through 3-D matrices, cancer cells acquire higher invasion speed and velocity, as well as significantly elevated invasion persistence, which are exclusive characteristics of fibroblast invasion. Silencing cadherin-11 in cancer cells or in fibroblasts, or in both, significantly decouples such physical co-invasion. Additional bioinformatics studies and PDX (patient derived xenograft) studies link such cadherin-11 mediated cancer hijacking fibroblasts to the clinical cancer progression in human such as triple-negative breast cancer patients. Further animal studies confirm cadherin-11 mediates cancer hijacking fibroblasts in vivo and promotes significant solid tumor progression and distant metastasis. Moreover, overexpression of cadherin-11 strikingly protects 4T1-luc cells from implant rejection against firefly luciferase in immunocompetent mice. Overall, our findings report and characterize the critical post-EMT event of cancer hijacking fibroblasts in cancer progression and suggest cadherin-11 can be a therapeutic target for solid tumors with stroma. Our studies hence provide significant updates on the “EMT” theory that EMT cancer cells can hijack fibroblasts to achieve full mesenchymal behaviors in vivo for efficient homing, growth, metastasis and evasion of immune surveillance. Our studies also reveal that cadherin-11 is the key molecule that helps link cancer cells to stromal fibroblasts in the “Seed & Soil” theory.Graphical Abstract
Global transcriptomic profiling of the bone marrow stromal microenvironment during postnatal development, aging and inflammation
Authors: Helbling Patrick M. , Piñeiro-Yáñez Elena , Gerosa Rahel , Boettcher Steffen , Al-Shahrour Fátima , Manz Markus G. , Nombela-Arrieta César 
Published: August 2019

SummaryBone marrow (BM) stromal cells provide the structural and regulatory framework for hematopoiesis and contribute to developmental-stage specific niches, such as those preserving hematopoietic stem cell (HSCs). Despite recent advances in our understanding of stromal composition and function, little is known on the dynamic transcriptional remodeling that this compartment undergoes over time and during adaptation to stress. Similarly, how molecular changes in stroma are linked to age-related modulation of hematopoiesis is poorly understood. Using RNA-sequencing, we performed a longitudinal comparison of the transcriptional profile of four principal mesenchymal and endothelial stromal subsets, namely CXCL12-abundant reticular (CARc), PDGFR-α+Sca-1+, sinusoidal (SECs) and arterial endothelial cells (AECs), isolated from early postnatal, adult and aged mice. Our data i) provide molecular fingerprints defining novel, cell-specific anatomical and functional features ii) reveal radical reprogramming of pro-hematopoietic, immune and matrisomic transcriptional programs during the narrow temporal transition from juvenile to adult stages iii) demonstrate that homeostatic aging is characterized by a progressive and pronounced upregulation of pro-inflammatory gene-expression and loss of stromal cell fitness. By profilingin vivoresponses of stromal cells to infection-mimicking agents, we finally demonstrate that transcriptomic pathways elicited by sterile inflammation are largely recapitulated during aging, thereby supporting the inflammatory basis of aging-related adaptations of BM hematopoietic function.