bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2
Authors: Seyerle Amanda A , Lin Henry J , Gogarten Stephanie M , Stilp Adrienne , Méndez Giráldez Raul , Soliman Elsayed , Baldassari Antoine , Graff Mariaelisa , Heckbert Susan , Kerr Kathleen F , Kooperberg Charles , Rodriguez Carlos , Guo Xiuqing , Yao Jie , Sotoodehnia Nona , Taylor Kent D , Whitsel Eric A , Rotter Jerome I , Laurie Cathy C , Avery Christy L 
Published: November 2017

ObjectivePR interval (PR) is a heritable electrocardiographic measure of atrial and atrioventricular nodal conduction. Changes in PR duration may be associated with atrial fibrillation, heart failure and all-cause mortality. Hispanic/Latino populations have high burdens of cardiovascular morbidity and mortality, are highly admixed and represent exceptional opportunities for novel locus identification. However, they remain chronically understudied. We present the first genome-wide association study (GWAS) of PR in 14 756 participants of Hispanic/Latino ancestry from three studies.MethodsStudy-specific summary results of the association between 1000 Genomes Phase 1 imputed single-nucleotide polymorphisms (SNPs) and PR assumed an additive genetic model and were adjusted for global ancestry, study centre/region and clinical covariates. Results were combined using fixed-effects, inverse variance weighted meta-analysis. Sequential conditional analyses were used to identify independent signals. Replication of novel loci was performed in populations of Asian, African and European descent. ENCODE and RoadMap data were used to annotate results.ResultsWe identified a novel genome-wide association (P<5×10−8) with PR at ID2 (rs6730558), which replicated in Asian and European populations (P<0.017). Additionally, we generalised 10 previously identified PR loci to Hispanics/Latinos. Bioinformatics annotation provided evidence for regulatory function in cardiac tissue. Further, for six loci that generalised, the Hispanic/Latino index SNP was genome-wide significant and identical to (or in high linkage disequilibrium with) the previously identified GWAS lead SNP.ConclusionsOur results suggest that genetic determinants of PR are consistent across race/ethnicity, but extending studies to admixed populations can identify novel associations, underscoring the importance of conducting genetic studies in diverse populations.
Can reference images improve interobserver agreement in reporting liver fibrosis?
Authors: German Alyn L , Fleming Kenneth , Kaye Philip , Davies Susan , Goldin Robert , Hubscher Stefan G , Tiniakos Dina , McGregor Angus , Wyatt Judith I 
Published: November 2017

Staging of fibrosis in medical liver biopsies has inherent interobserver variability. There are a number of disease-specific scoring systems available. While recognising the importance of these scoring systems, there is scope to consider how concordance amongst histopathologists could be improved using a generic fibrosis staging system.Using virtual slides, we approached both specialist liver histopathologists and general histopathologists from the UK to assess the degree of fibrosis against a proposed four-tiered reporting system. Example reference images were then produced and distributed to the same responders who were asked to rate a second set of slides to assess if the use of reference images improved concordance between pathologists.The use of reference images eliminated spread across three categories (from 15% to 0%). Overall, agreement was already good; our study showed an improved agreement amongst all participants for percentage agreement (67.79% to 70.08%) and interobserver agreement improved (Fleiss’ Kappa 0.55 to 0.59).
Homozygous mutation inCEP19,a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly
Authors: Yıldız Bölükbaşı Esra , Mumtaz Sara , Afzal Muhammad , Woehlbier Ute , Malik Sajid , Tolun Aslıhan 
Published: November 2017

BackgroundBardet-Biedl syndrome (BBS) is a ciliopathy with extensive phenotypic variability and genetic heterogeneity. We aimed to discover the gene mutated in a consanguineous kindred with multiple cases of a BBS phenotype.MethodsSNP genotype data were used for linkage analysis and exome sequencing to identify mutations. Modelling and in silico analysis were performed to predict mutation severity.ResultsPatients had postaxial polydactyly plus variable other clinical features including rod-cone dystrophy, obesity, intellectual disability, renal malformation, developmental delay, dental anomalies, speech disorder and enlarged fatty liver. The 4.57 Mb disease locus harboured homozygous, truncatingCEP19c.194_195insA (p.Tyr65*) mutation. We also foundglioma-associated oncogene homolog1(GLI1) c.820G>C (p.Gly274Arg) in the homozygous state in most patients. In silico modelling strongly suggests that it is damaging. Also, different combinations of four possible modifier alleles in BBS-related genes were detected. Two are known modifier alleles for BBS, splicing variantCCDC28Bc.330C>T and missenseMKKS/BBS6p.Ile339Val, and the others areC8ORF37/BBS21p.Ala178Val andTMEM67/BBS14 modifierp.Asp799Asp. Some patients carry all those five known/possible modifier alleles. Such variants are highly significantly more abundant in our patients than in a control group.ConclusionCEP19encodes a centrosomal and ciliary protein, as all BBS genes do. Another truncating mutation p.Arg82* has been reported as responsible for morbid obesity in a family; however, in the family we present, not all homozygotes are obese, although some are severely obese. The variant inGLI1, encoding a transcription factor that localises to the primary cilium and nucleus and is a mediator of the sonic hedgehog pathway, possibly exacerbates disease severity when in the homozygous state.
Stability in quadratic torsion theories
Authors: Vasilev Teodor Borislavov , Cembranos Jose A. R. , Valcarcel Jorge Gigante , Martín-Moruno Prado 
Published: November 2017

AbstractWe revisit the definition and some of the characteristics of quadratic theories of gravity with torsion. We start from a Lagrangian density quadratic in the curvature and torsion tensors. By assuming that General Relativity should be recovered when the torsion vanishes and investigating the behaviour of the vector and pseudo-vector torsion fields in the weak-gravity regime, we present a set of necessary conditions for the stability of these theories. Moreover, we explicitly obtain the gravitational field equations using the Palatini variational principle with the metricity condition implemented via a Lagrange multiplier.
Geology and hydrocarbon potential of offshore SE Somalia
Authors: Davidson L. M. , Arthur T. J. , Smith G. F. , Tubb S. 
Published: November 2017

Interpretation of a 20 550 line km 2D seismic survey acquired in 2014 by Soma Oil and Gas in the deep water offshore area of SE Somalia has identified three previously undocumented sedimentary provinces – Jubba Deep, Mogadishu Deep and Mid Somalia High – all of which have distinctive geological characteristics. Well and stratigraphic controls are limited, with inferred lithologies largely based on seismic stratigraphic interpretation.
The Jubba Deep has a thick Late Cretaceous–Early Tertiary deltaic section deformed by major gravitational collapses in the Paleocene-age Kismaayo Thrust Belt (KTB) and the Pliocene-age Baraawe Thrust Belt (BTB). It is proposed that the KTB has significant hydrocarbon potential in deltaic and pro-delta sands trapped in thrust anticlines and sourced with oil from Mid-Cretaceous mobile shales.
The Mogadishu Deep Basin has a thick Mesozoic and Tertiary section but is missing the thick deltaics seen in the Jubba Basin. Volcanics are present in this basin.
The Mid Somalia High has a relatively thinner sedimentary section where Cretaceous and Jurassic reservoirs and potential source rocks are at moderate burial depths. An extensive post-rift Mid–Late Jurassic carbonate platform is developed here with potential hydrocarbon targets in interpreted reefs and shoal facies.

Supplementary material
: Additional seismic examples and map figures are available at
https://doi.org/10.6084/m9.figshare.c.3902650
Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer
Authors: Janjigian Yelena Y. , Sanchez-Vega Francisco , Jonsson Philip , Chatila Walid K. , Hechtman Jaclyn F. , Ku Geoffrey Y. , Riches Jamie C. , Tuvy Yaelle , Kundra Ritika , Bouvier Nancy , Vakiani Efsevia , Gao Jianjiong , Heins Zachary J. , Gross Benjamin E. , Kelsen David P. , Zhang Liying , Strong Vivian E. , Schattner Mark , Gerdes Hans , Coit Daniel G. , Bains Manjit , Stadler Zsofia K. , Rusch Valerie W. , Jones David R. , Molena Daniela , Shia Jinru , Robson Mark E. , Capanu Marinela , Middha Sumit , Zehir Ahmet , Hyman David M. , Scaltriti Maurizio , Ladanyi Marc , Rosen Neal , Ilson David H. , Berger Michael F. , Tang Laura , Taylor Barry S. , Solit David B. , Schultz Nikolaus 
Published: November 2017

Abstract
The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability–high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein–Barr virus–positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance.
Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49–58. ©2017 AACR.
See related commentary by Sundar and Tan, p. 14.
See related article by Pectasides et al., p. 37.
This article is highlighted in the In This Issue feature, p. 1
Soluble CD80 Protein Delays Tumor Growth and Promotes Tumor-Infiltrating Lymphocytes
Authors: Horn Lucas A. , Long Tiha M. , Atkinson Ryan , Clements Virginia , Ostrand-Rosenberg Suzanne 
Published: November 2017

Abstract
Tumor cells use various immune-suppressive strategies to overcome antitumor immunity. One such method is tumor expression of programmed death ligand-1 (PD-L1), which triggers apoptotic death or anergy upon binding programmed death-1 (PD-1) on T cells. Our previous in vitro cellular studies with human and mouse PD-L1+ tumor cells demonstrated that a soluble form of the costimulatory molecule CD80 prevented PD-L1–mediated immune suppression and restored T-cell activation by binding PD-L1 and blocking interaction with PD-1. We now report that in vivo treatment of established syngeneic PD-L1+ CT26 colon carcinoma and B16F10 melanoma tumors with CD80-Fc delays tumor growth and promotes tumor-infiltrating T cells. Studies with PD-1−/− and CD28−/− mice demonstrate that soluble CD80 acts in vivo by simultaneously neutralizing PD-1 suppression and activating through CD28. We also report that soluble CD80 mediates its effects by activating transcription factors EGR1-4, NF-κB, and MAPK, downstream signaling components of the CD28 and T-cell receptor pathways. Soluble CD80 binds to CTLA-4 on activated human peripheral blood mononuclear cells. However, increasing quantities of CTLA-4 antagonist antibodies do not increase T-cell activation. These results indicate that soluble CD80 does not suppress T-cell function through CTLA-4 and suggest that CTLA-4 acts as a decoy receptor for CD80, rather than functioning as a suppressive signaling receptor. Collectively, these studies demonstrate that soluble CD80 has therapeutic efficacy in vivo in mouse tumor systems and that its effects are due to its ability to inhibit PD-1–mediated suppression while concurrently activating T cells through CD28. Cancer Immunol Res; 6(1); 59–68. ©2017 AACR.
Low-Dose Tirofiban Improves Functional Outcome in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy
Authors: Zhao Wenbo , Che Ruiwen , Shang Shuyi , Wu Chuanjie , Li Chuanhui , Wu Longfei , Chen Jian , Duan Jiangang , Song Haiqing , Zhang Hongqi , Ling Feng , Wang Yuping , Liebeskind David , Feng Wuwei , Ji Xunming 
Published: November 2017

Background and Purpose—
Chinese patients largely experience acute ischemic stroke (AIS) because of large artery atherosclerosis rather than cardioembolism, and whether tirofiban is safe and effective in these patients treated with endovascular thrombectomy (ET) is unknown. This study evaluated the safety and efficacy of tirofiban in Chinese patients with AIS treated with ET.

Methods—
This observational study is based on a single-center prospective registry study. Patients with AIS undergoing ET with second-generation stent retrievers from January 2013 to February 2017 were treated with ET alone or ET plus low dose of tirofiban. The primary outcome was symptomatic intracerebral hemorrhage (sICH). The secondary outcomes included rate of early reocclusion, any ICH, fatal ICH, and 3-month and long-term functional outcomes.

Results—

One hundred eighty AIS subjects were included in the analysis, including 90 subjects treated with tirofiban and 90 subjects without tirofiban. Sixty-three subjects (35%) had any ICH, 19 of them (11%) were sICH, and 9 of them (5%) were fatal ICH. Ten subjects (11%) treated with tirofiban experienced sICH and 9 subjects (10%) not given tirofiban experienced sICH, not a significant difference (
P
=0.808). Early reocclusion happened in 4 of 90 subjects (4.4%) treated with tirofiban and 8 of 90 subjects (8.9%) not treated with tirofiban (
P
=0.370). One hundred sixty-one subjects (89%) completed long-term follow-up, subjects treated tirofiban were associated with lower odds of death (23% versus 44%,
P
=0.005) when compared with those who were not treated. Additionally, tirofiban was associated with better odds of long-term functional independence (adjusted odds ratio, 4.37; 95% confidence interval, 1.13–16.97;
P
=0.033).

Conclusions—
In patients with AIS undergoing ET, tirofiban is not associated with higher sICH, it seems to lead to lower odds of deaths and better odds of long-term functional independence. Further investigations are needed to determine the efficacy of tirofiban in preventing early reocclusion, the underlying mechanisms, and its optimal treatment protocol.
Sequence Organization of Requests among Australian English and Saudi Arabic Speakers: A Contrastive Study
Authors: Al-Gahtani Saad 
Published: November 2017

Abstract
Previous research on cross-cultural pragmatics has primarily focused on how native speakers of different languages perform speech acts in relation to politeness and directness. However, Gabriele Kasper (2006), among others, has called for adopting a more discursive approach rather than analyzing data according to the Cross-Cultural Speech Act Realization Project (ccsarp) coding scheme. Therefore, this paper used Conversation Analysis for Interlanguage Pragmatics to investigate sequence organization of requests in Australian English and Saudi Arabic using role-play scenarios. It specifically examined pre-expansions, pre-pres, accounts in request turn, insert-expansions, and post-expansions, and the extent to which the social variable power affects them. The results showed that both languages shared some regularities in aspects of sequence organization but differed in others. Power influenced the production of some regularities in both languages.
Is Collingwood a Historicist? Remarks on Leo Strauss’s Critique of Collingwood’s Philosophy of History
Authors: Chénard Sophie Marcotte 
Published: November 2017

Abstract
In this paper, I examine Strauss’s critique of Collingwood’s interpretive approach and argue that Strauss’s accusation of historicism partly misses its target. While Collingwood can be said to be a “historicist” thinker insofar as he pursues the project of the German historicist tradition and attempts to establish the autonomy and specificity of philosophy of history as a discipline, he does not endorse the premises of radical historicism according to which all thought is historically relative. Although many of Strauss’s arguments against interpretive historicism are valid, they do not apply to Collingwood’s enterprise. In creating a dialogue between the two thinkers, I demonstrate that their respective theories of interpretation are as a matter of fact closer than they appear at first sight. Both philosophers defend the possibility of understanding past authors as they understood themselves, they maintain the importance of the quest for philosophical truth in interpreting the past texts and make the case for the necessity of history for philosophy.
L. S. Klejn and R. G. Collingwood on History, Archaeology, and Detection
Authors: Leach Stephen 
Published: November 2017

Abstract
Collingwood is well-known for noting, in The Idea of History, similarities between the work of the historian and the work of the detective. In this essay I argue that it is not the historian who is similar to the detective but rather the archaeologist.
In presenting this argument I make use of the work of the Russian archaeologist L. S. Klejn, who has explored in detail both the similarities between archaeology and detection and the differences between archaeology and history.
Part of the interest in comparing the views of Klejn and Collingwood is that they are from radically different backgrounds. Collingwood’s views were formed in pre-war Britain whereas Klejn’s views were formed in the post-war Soviet Union. How they conceive of their work on theory is also different: Klejn sees himself not as a philosopher but as an archaeological theorist; whereas Collingwood saw himself as a philosopher of history. Yet there is common ground in their approaches and in some of their conclusions. It will be argued that Klejn is more accurate than Collingwood in comparing the archaeologist – rather than the historian – to the detective; but, once this concession is made, their views of history can then be reconciled.
Mesoscale Ensemble Weather Prediction at U.S. Army Dugway Proving Ground, Utah
Authors: Knievel Jason C. , Liu Yubao , Hopson Thomas M. , Shaw Justin S. , Halvorson Scott F. , Fisher Henry H. , Roux Gregory , Sheu Rong-Shyang , Pan Linlin , Wu Wanli , Hacker Joshua P. , Vernon Erik , Gallagher Frank W. , Pace John C. 
Published: November 2017

Abstract
Since 2007, meteorologists of the U.S. Army Test and Evaluation Command (ATEC) at Dugway Proving Ground (DPG), Utah, have relied on a mesoscale ensemble prediction system (EPS) known as the Ensemble Four-Dimensional Weather System (E-4DWX). This article describes E-4DWX and the innovative way in which it is calibrated, how it performs, why it was developed, and how meteorologists at DPG use it. E-4DWX has 30 operational members, each configured to produce forecasts of 48 h every 6 h on a 272-processor high performance computer (HPC) at DPG. The ensemble’s members differ from one another in initial-, lateral-, and lower-boundary conditions; in methods of data assimilation; and in physical parameterizations. The predictive core of all members is the Advanced Research core of the Weather Research and Forecasting (WRF) Model. Numerical predictions of the most useful near-surface variables are dynamically calibrated through algorithms that combine logistic regression and quantile regression, generating statistically realistic probabilistic depictions of the atmosphere’s future state at DPG’s observing sites. Army meteorologists view E-4DWX’s output via customized figures posted to a restricted website. Some of these figures summarize collective results—for example, through means, standard deviations, or fractions of the ensemble exceeding thresholds. Other figures show each forecast, individually or grouped—for example, through spaghetti diagrams and time series. This article presents examples of each type of figure.
Discrimination of Mature and Dissipating Severe-Wind-Producing MCSs with Layer-Lifting Indices
Authors: Alfaro Diego A. , Coniglio Michael C. 
Published: November 2017

Abstract
The environmental factors that drive the dissipation of linear severe-wind-producing mesoscale convective systems (MCSs) are investigated. Layer-lifting indices are emphasized, which measure convective instability in forward-propagating MCSs by considering that deep convective latent heating depends on 1) the potential latent heating within the atmospheric column, measured by the integrated CAPE (ICAPE), and 2) the dilution of buoyancy due to midtropospheric inflow, measured by the inflow fraction (IF) of convectively unstable air to total system-relative inflow. These elements are integrated to define the layer-lifting CAPE (CAPEll), which depends on environmental thermodynamics, kinematics, and the MCS’s movement vector. Radar reflectivity plots are used to subjectively identify and classify MCSs in terms of their stage (mature or dissipating) and degree of organization (highly or weakly organized). Nonparametric statistical inferences are performed on several metrics computed at maturity and dissipation from RUC/RAP analysis data, aiming to identify the most skillful indices for diagnosing three different aspects of MCS dissipation: 1) the transition from maturity to dissipation, 2) the stage of an MCS, and 3) the disorganization that characterizes the dissipating stage. In terms of MCS dissipation CAPEll is the best diagnostic. A close approximation to CAPEll is accomplished by estimating an MCS’s movement with Corfidi vectors, providing a potentially useful index in operational settings. ICAPE is the most skillful thermodynamic metric, while IF is the best kinematic discriminator of MCS stage and stage transition, suggesting the fundamental importance of layer-lifting convective instability for MCS maintenance. Layer-lifting indices are not particularly skillful at distinguishing the degree of MCS organization at maturity, which is best diagnosed by deep vertical wind shear.