bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial pulmonary arterial hypertension byKDRheterozygous loss of function
Authors: Eyries Mélanie , Montani David , Girerd Barbara , Favrolt Nicolas , Riou Marianne , Faivre Laurence , Manaud Grégoire , Perros Frédéric , Gräf Stefan , Morrell Nicholas W. , Humbert Marc , Soubrier Florent 
Published: January 2020

Beyond the major geneBMPR2, several new genes predisposing to PAH have been identified during the last decade. Recently, preliminary evidence of the involvement of theKDRgene was found in a large genetic association study.We prospectively analysed theKDRgene by targeted panel sequencing in a series of 311 PAH patients referred to a clinical molecular laboratory for genetic diagnosis of PAH.Two index cases with severe PAH from two different families were found to carry a loss-of-function mutation in theKDRgene. These two index cases were clinically characterised by low diffusing capacity for carbon monoxide adjusted for haemoglobin (DLCOc) and interstitial lung disease. In one family, segregation analysis revealed that variant carriers are either presenting with PAH associated with lowDLCOc, or have only decreasedDLCOc, whereas non-carrier relatives have normalDLCOc. In the second family, a single affected carrier was alive. His carrier mother was unaffected with normalDLCOc.We provided genetic evidence for consideringKDRas a newly identified PAH-causing gene by describing the segregation ofKDRmutations with PAH in two families. In our study,KDRmutations are associated with a particular form of PAH characterised by lowDLCOc and radiological evidence of parenchymal lung disease including interstitial lung disease and emphysema.
ZDHXB-101 (3′,5-Diallyl-2, 4′-dihydroxy-[1,1′-biphen-yl]-3,5′-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways
Authors: Jiang Jun-xia , Shen Hui-juan , Guan Yan , Jia Yong-liang , Shen Jian , Liu Qi , Xie Qiang-min , Yan Xiao-feng 
Published: January 2020

AbstractAirway remodeling consists of the structural changes of airway walls, which is often considered the result of longstanding airway inflammation, but it may be present to an equivalent degree in the airways of children with asthma, raising the need for early and specific therapeutic interventions. The arachidonic acid cytochrome P-450 (CYP) pathway has thus far received relatively little attention in its relation to asthma. In this study, we studied the inhibition of soluble epoxide hydrolase (sEH) on airway remodeling and hyperresponsiveness (AHR) in a chronic asthmatic model which long-term exposure to antigen over a period of 12 weeks. The expression of sEH and CYP2J2, the level of 14, 15-epoxyeicosatrienoic acids (EETs), airway remodeling, hyperresponsiveness and inflammation were analyzed to determine the inhibition of sEH. The intragastric administration of 3 or 10 mg/kg ZDHXB-101, which is a structural derivative of natural product honokiol and a novel soluble epoxide hydrolase (sEH) inhibitor, daily for 9 weeks significantly increased the level of 14, 15-EETs by inhibiting the expression of sEH and increasing the expression of CYP2J2 in lung tissues. ZDHXB-101 reduced the expression of remodeling-related markers such as interleukin (IL)-13, IL-17, MMP-9 N-cadherin, α-smooth muscle actin, S100A4, Twist, goblet cell metaplasia, and collagen deposition in the lung tissue or in bronchoalveolar lavage fluid. Moreover, ZDHXB-101 alleviated AHR, which is an indicator that is used to evaluate the airway remodeling function. The inhibitory effects of ZDHXB-101 were demonstrated to be related to its direct inhibition of the extracellular signal-regulated kinase (Erk1/2) phosphorylation, as well as inhibition of c-Jun N-terminal kinases (JNK) and the signal transducer and activator of transcription-3 (STAT3) signal transduction. These findings first revealed the anti-remodeling potential of ZDHXB-101 lead in chronic airway disease.
Fast photosynthesis measurements for phenotyping photosynthetic capacity of rice
Authors: Du Tingting , Meng Ping , Huang Jianliang , Peng Shaobing , Xiong Dongliang 
Published: January 2020

Abstract
Background
Over the past decades, the structural and functional genomics of rice have been deeply studied, and high density of molecular genetic markers have been developed. However, the genetic variation in leaf photosynthesis, the most important trait for rice yield improvement, was rarely studied. The lack of photosynthesis phenotyping tools is one of the bottlenecks, as traditional direct photosynthesis measurements are very low-throughput, and recently developed high-throughput methods are indirect measurements. Hence, there is an urgent need for a fast, accurate and direct measurement approach.

Result
We reported a fast photosynthesis measurement (FPM) method for phenotyping photosynthetic capacity of rice, which measures photosynthesis of excised tillers in environment-controlled lab conditions. The light response curves measured using FPM approach coped well with that the curves measured using traditional gas exchange approach. Importantly, the FPM technique achieved an average throughput of 5.4 light response curves per hour, which was 3 times faster than the 1.8 light response curves per hour using the traditional method. Tillers sampled at early morning had the highest photosynthesis, stomatal conductance and the lowest variability. In addition, even 12 h after sampling, there was no significant difference of photosynthesis rate between excised tillers and in situ. We finally investigated the genetic variations of photosynthetic traits across 568 F2 lines using the FPM technique and discussed the logistics of screening several hundred samples per day per instrumental unit using FPM to generate a wealth of photosynthetic phenotypic data, which might help to improve the selection power in large populations of rice with the ultimate aim of improving yield through improved photosynthesis.

Conclusions
Here we developed a high-throughput method that can measure the rice leaf photosynthetic capacity approximately 10 times faster than traditional gas exchange approaches. Importantly, this method can overcome measurement errors caused by environmental heterogeneity under field conditions, and it is possible to measure 12 or more hours per day under lab conditions.
The Italian ICD-11 field trial: clinical utility of diagnostic guidelines for schizophrenia and related disorders
Authors: Luciano Mario , Sampogna Gaia , Del Vecchio Valeria , Giallonardo Vincenzo , Palummo Carmela , Pocai Benedetta , Steardo Luca , Zinno Francesca , Rebello Tahilia , Reed Geoffrey M. , Fiorillo Andrea 
Published: January 2020

Abstract
Background
The 11th revision of the International Classification of Diseases and Related Disorders (ICD-11) has been released. In order to test the clinical consistency and the clinical utility of the proposed guidelines the World Health Organization (WHO) has carried out the Ecological Implementation Field Studies in various countries. In this paper the results of the Italian field trials on the clinical utility of the ICD-11 diagnostic guideline concerning schizophrenia and related disorders will be presented.

Methods
In Italy, field trials have been carried out at the Department of Psychiatry of the University of Campania “L. Vanvitelli”. All patients showing any psychotic symptom and referring to the outpatient and inpatient units have been recruited. Patients were interviewed by two clinicians with whom they had not had any prior clinical contact. At the end of each interview, clinicians were asked to complete 12 questions about the clinical utility of the diagnostic guidelines as applied to each patient.

Results
Fourteen clinicians and 100 patients have been involved. The ICD-11 clinical guidelines were perceived as easy to use, with an adequate goodness of fit, clear and understandable and with an adequate level of details and specificity to describe the essential features of the diagnoses. Clinicians rated very positively their usefulness in describing the threshold between patient’s disorder and normality. Despite still very positive, the guidelines have been perceived as less useful to select a treatment, to assess patients’ prognosis and to communicate with other mental health professionals.

Conclusions
The 11th revision of the chapter on Mental, Behavioural and Neurodevelopmental Disorders has made substantive changes to the conceptualization of mental disorders which could have impacted on their reliability and clinical utility. Results of the Italian field studies, in line with those reported by the international sample, highlight that ICD-11 has been rated as highly clinically useful by participating clinician, more than the ICD-10. This could be considered a good reason to be optimistic about the implementation of the ICD-11 among global clinicians.
Trial registration The study has been approved by the Ethical Review Board of the University of Campania “L. Vanvitelli” (N. 416, 2016)
Characterization of the plant homeodomain (PHD) reader family for their histone tail interactions
Authors: Jain Kanishk , Fraser Caroline S. , Marunde Matthew R. , Parker Madison M. , Sagum Cari , Burg Jonathan M. , Hall Nathan , Popova Irina K. , Rodriguez Keli L. , Vaidya Anup , Krajewski Krzysztof , Keogh Michael-Christopher , Bedford Mark T. , Strahl Brian D. 
Published: January 2020

Abstract
Background
Plant homeodomain (PHD) fingers are central “readers” of histone post-translational modifications (PTMs) with > 100 PHD finger-containing proteins encoded by the human genome. Many of the PHDs studied to date bind to unmodified or methylated states of histone H3 lysine 4 (H3K4). Additionally, many of these domains, and the proteins they are contained in, have crucial roles in the regulation of gene expression and cancer development. Despite this, the majority of PHD fingers have gone uncharacterized; thus, our understanding of how these domains contribute to chromatin biology remains incomplete.

Results
We expressed and screened 123 of the annotated human PHD fingers for their histone binding preferences using reader domain microarrays. A subset (31) of these domains showed strong preference for the H3 N-terminal tail either unmodified or methylated at H3K4. These H3 readers were further characterized by histone peptide microarrays and/or AlphaScreen to comprehensively define their H3 preferences and PTM cross-talk.

Conclusions
The high-throughput approaches utilized in this study establish a compendium of binding information for the PHD reader family with regard to how they engage histone PTMs and uncover several novel reader domain–histone PTM interactions (i.e., PHRF1 and TRIM66). This study highlights the usefulness of high-throughput analyses of histone reader proteins as a means of understanding how chromatin engagement occurs biochemically.
HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non–Insulin-Treated Type 2 Diabetes
Authors: Jacobi Thomas , Massier Lucas , Klöting Nora , Horn Katrin , Schuch Alexander , Ahnert Peter , Engel Christoph , Löffler Markus , Burkhardt Ralph , Thiery Joachim , Tönjes Anke , Stumvoll Michael , Blüher Matthias , Doxiadis Ilias , Scholz Markus , Kovacs Peter 
Published: January 2020

AbstractContextCommon genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes.Objectives and DesignThree cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted.ResultsIn a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non–insulin-treated diabetes (OR 1.37; P = 0.002).ConclusionsGenetic variation in the HLA class II locus exerts risk and protective effects on non–insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.
An Estimation Model for Cardiorespiratory Fitness in Adults with Rheumatoid Arthritis
Authors: LIFF MARTHE HALSAN , HOFF MARI , FREMO THOMAS , WISLØFF ULRIK , VIDEM VIBEKE 
Published: January 2020

ABSTRACTPurposeCardiopulmonary exercise testing of peak oxygen uptake (V˙O2peak) is the gold standard to measure cardiorespiratory fitness (CRF). For resource-intensive evaluation, equations estimating CRF (eCRF) may be used. The purpose was to investigate if an eCRF equation from a healthy population is useful in persons with rheumatoid arthritis (RA), and if necessary, develop new equations for eCRF in this group.MethodsV˙O2peakresults from 93 persons with RA were compared with eCRF calculated by an established equation for healthy individuals including age, sex, physical activity (PA index), resting HR (RHR), and waist circumference. Because of deviation from the observed V˙O2peak, new equations for eCRF in persons with RA were developed from regression analysis of variables associated with observed V˙O2peak.ResultsThe established equation overestimated CRF (R2= 0.48, root mean square error [RMSE] = 7.07). The new RA equation more accurately estimated CRF (R2= 0.81, RMSE = 4.44) (female = 0, male = 1; never smoked = 0, ever smoked = 1): eCRF = 77.961 + (sex × 28.791) − (age × 0.358) − (age–sex interaction × 0.326) − (body mass index [BMI] × 0.700) − (RHR × 0.125) − (smoking × 1.854) + (PA index × 0.211) − (patient global RA assessment × 0.071). Alternative new RA equation (R2= 0.79, RMSE = 4.63): eCRF = 77.851 + (sex × 25.460) − (age × 0.381) − (age–sex interaction × 0.254) − (BMI × 0.743) − (RHR × 0.115) − (smoking × 2.154) + (PA index × 0.209).ConclusionsThe new RA equations better predicted CRF in individuals with RA, preventing overestimation in low-fit persons. The new equation should be preferred when estimating CRF in individuals with RA. The alternative equation, without patient global assessment, is useful for individuals with RA in population-based studies.
Head Impact Exposure in College Football after a Reduction in Preseason Practices
Authors: STEMPER BRIAN D. , SHAH ALOK S. , MIHALIK JASON P. , HAREZLAK JAROSLAW , ROWSON STEVEN , DUMA STEFAN , RIGGEN LARRY D. , BROOKS ALISON , CAMERON KENNETH L. , GIZA CHRISTOPHER C. , GOLDMAN JOSHUA , HOUSTON MEGAN N. , JACKSON JONATHAN , MCGINTY GERALD , BROGLIO STEVEN P. , MCALLISTER THOMAS W. , MCCREA MICHAEL 
Published: January 2020

ABSTRACT

Introduction
Regulatory efforts toward reducing concussion risk have begun to focus on decreasing the number of head impacts (i.e., head impact burden) sustained by athletes in contact sports. To that end, in 2018, the NCAA decreased the number of preseason on-field team activities for Division I teams from 29 to 25. The objective of the current study was to quantify changes in practice schedule and head impact exposure between the 2017 and 2018 football preseasons.

Methods
Athletes from five NCAA Division I football teams (n = 426) were consented and enrolled.

Results
On average, athletes participated in 10% fewer contact practices in 2018. However, the effect of this ruling on preseason head impact burden was mixed. Across all athletes, the total preseason head impact burden was essentially the same from 2017 to 2018. However, this study revealed significant team-by-team differences in preseason head impact burden, with one team demonstrating a 35% increase in the average number of recorded head impacts from 2017 to 2018, despite a modest decrease in the number of contact practices. Other teams had similar or decreased head impact burden.

Conclusions
Team-based differences in total preseason head impact burden were attributable to changes in daily practice schedule, with longer practice durations and more intense contact practice sessions contributing to increases in daily head impact exposure that, in turn, led to greater preseason head impact burden. Results of this study have highlighted the difficulty in decreasing contact sport head impact exposure through rule changes targeted at limiting on-field team activities. Future efforts aimed specifically at contact practice duration, daily head impact exposure, or limiting time in specific drills may be more effective at reducing total preseason head impact burden.
Creating Platforms by Hosting Rivals
Authors: Hagiu Andrei , Jullien Bruno , Wright Julian 
Published: January 2020

We explore conditions under which a multiproduct firm can profitably turn itself into a platform by “hosting rivals,” that is, by inviting rivals to sell products or services on top of its core product. Hosting eliminates the additional shopping costs to consumers of buying a specialist rival’s competing version of the multiproduct firm’s noncore product. On the one hand, this makes it easier for the rival to compete on the noncore product. On the other hand, hosting turns the rival from a pure competitor into a complementor: the value added by its product now helps raise consumer demand for the multiproduct firm’s core product. As a result, hosting can be both unilaterally profitable for the multiproduct firm and jointly profitable for both firms. This paper was accepted by Joshua Gans, business strategy.
Why Do Option Prices Predict Stock Returns? The Role of Price Pressure in the Stock Market
Authors: Goncalves-Pinto Luis , Grundy Bruce D. , Hameed Allaudeen , van der Heijden Thijs , Zhu Yichao 
Published: January 2020

Stock and options markets can disagree about a stock’s value because of informed trading in options and/or price pressure in the stock. The predictability of stock returns based on this cross-market discrepancy in values is especially strong when accompanied by stock price pressure, and it does not depend on trading in options. We argue that option-implied prices provide an anchor for fundamental stock values that helps to distinguish stock price movements resulting from pressure versus news. Overall, our results are consistent with stock price pressure being the primary driver of the option price-based stock return predictability. This paper was accepted by Tyler Shumway, finance.
Survey-based Research on Science and Religion: A Review and Critique
Authors: Hill Jonathan P. 
Published: January 2020

This chapter evaluates survey measures, primarily from the USA, on science, religion and beliefs about human origins. The bulk of the chapter offers a compilation of measures used in high quality, representative surveys. This scope is limited to the two most central types of items: those measuring beliefs about the relationship between science and religion and those measuring beliefs about evolution and human origins. Measures are analysed for trends over time and disaggregated by key measures of religious identity, practice, and belief. The chapter concludes with several critiques and considerations for improving survey-based analysis of science and belief. These critiques include a call for measures to be more carefully calibrated to how the public reflects on these issues. They also encourage the development of new measures on morality, progress, teleology (for both religion and science). Likewise, they argue that measures of social context (friends, family, congregations), and group identity and dynamics are often missed by conventional measures. Finally, the conclusion calls for careful attention to domains of conflict outside of human origins along with the development of techniques to avoid unintentionally priming conflict between religion and science.
Metastatic Cutaneous Squamous Cell Carcinoma of the Colon Presenting as Transfusion-Dependent Hematochezia
Authors: Dornblaser David , Hajdu Cristina , Rosenberg Jonathan , Gurvits Grigoriy 
Published: January 2020

ABSTRACT
Squamous cell carcinoma (SCC) of the colon is an exceedingly rare clinical diagnosis with few cases reported in the literature. We report a case of a 61-year-old man with a medical history of cutaneous SCC of the penis who presented with hematochezia and was found to have metastatic SCC to the distal transverse colon. To our knowledge, this is the first case of colonic SCC presenting as a metastatic disease from a primary penile site.
Management of Early-Stage Esophageal Adenocarcinoma by Endoscopic Spray Cryotherapy in the Setting of Portal Hypertension With Varices
Authors: Coyle Walter J. , Pillsbury Elliott A. 
Published: January 2020

ABSTRACT
The use of endoscopic spray cryotherapy to manage pathological conditions of the esophagus has become increasingly common. This mucosal ablation technique is believed to carry a lower risk of bleeding than other modalities. A 71-year-old woman and a 64-year-old man with portal hypertension and varices were diagnosed with invasive esophageal adenocarcinoma during routine variceal surveillance. Staging by endoscopic ultrasound and computed tomography was uT1N0M0 in both patients. They each underwent mucosal ablation using liquid nitrogen cryosprays with no adverse events. Both cancers completely resolved with 2 treatments, and neither patient has shown recurrence of neoplasia during follow-up observations for up to 2 years.
Evaluation and Validation of the Modified Reflux Symptom Questionnaire–Electronic Diary in Patients With Persistent Gastroesophageal Reflux Disease
Authors: Andrae David A. , Hanlon Jennifer , Cala Mary Lynn , Scippa Kayla , Graham Christina , Witherspoon Brooke , Shao James Z. , Reasner David 
Published: January 2020

OBJECTIVES:
This study aimed to examine the validity of the modified Reflux Symptom Questionnaire–electronic Diary (mRESQ-eD) through patient input and psychometric testing of the questionnaire to support use in clinical trials in patients with persistent gastroesophageal reflux disease (GERD) and in accordance with Food and Drug Administration guidance on patient-reported outcome instruments.

METHODS:
Cognitive interviews were conducted with patients (n = 30) to evaluate the interpretability and content validity of draft mRESQ-eD items. Patient data from a phase 2b clinical study (ClinicalTrials.gov identifier: NCT02637557) on persistent GERD served to aid in the construction of weekly scores for heartburn severity, regurgitation severity, and total GERD severity. These scores' psychometric properties were also evaluated.

RESULTS:
Minor modifications were made to the draft mRESQ-eD based on patient feedback to improve interpretability and clarity of the instrument. Psychometric analysis suggested that an 8-item version of the mRESQ-eD was best suited to the clinical data. The internal consistency was found to be high (Coefficient ω = 0.95). Retest reliability and convergent validity were strong for a heartburn weekly severity score, regurgitation weekly severity score, and total GERD severity score.

DISCUSSION:
The final 8-item mRESQ-eD is a reliable and valid instrument with good psychometric properties for use in clinical trials in patients with persistent GERD. The mRESQ-eD may be considered for inclusion in clinical trials for persistent GERD and potentially positioned, in consultation with Food and Drug Administration, as endpoints to characterize treatment benefit.