bluuebunny/crossref_metadata_2025_split huggingface dataset:
CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis
Authors: Mougey Edward B. , Williams Andre , Coyne Ashlan J. Kunz , Gutiérrez‐Junquera Carolina , Fernández‐Fernández Sonia , Cilleruelo Maria Luz , Rayo Ana , Echeverría Luis , Román Enriqueta , González Lois Carmen , Chao Montserrat , Al‐Atrash Hadeel , Lima John J. , Franciosi James P. 
Published: September 2019

ABSTRACTObjective:Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI‐REE, PPI‐nonresponsive EoE).Methods:Genomic DNA was isolated from 92 esophageal tissue biopsies collected from participants of a prospective clinical trial of high‐dose PPI therapy for esophageal eosinophilia in children.Results:Of the 92 patients examined, 57 (62%) were PPI‐REE and 35 (38%) were PPI‐nonresponsive EoE. Forty‐six of the 92 patients were further characterized by pH probe monitoring; there was no association between reflux index and carriage of CYP2C19*17 (P = 0.35). In children who received a PPI dose between ≥1.54 and ⩽2.05 mg/kg/day, binary logistic regression modeling showed that carriage of CYP2C19*17 associated with PPI‐nonresponsive EoE (odds ratio (OR) [95% confidence interval (CI)] = 7.71 [1.21, 49.11], P = 0.031). Carriage of STAT6 allelic variant rs1059513 predicts PPI‐REE (OR [95% CI] = 6.16 [1.44, 26.4], P = 0.028), whereas carriage of STAT6 rs324011 synergizes with CYP2C19*17 to predict PPI‐nonresponsive EoE (rs324011 OR [95% CI] = 5.56 [1.33, 20.72], P = 0.022; CYP2C19*17 OR [95% CI] = 8.19[1.42, 50.57], P = 0.023).Conclusions:Common variants in CYP2C19 and STAT6 associate with a PPI‐nonresponsive EoE outcome of PPI therapy for esophageal eosinophilia suggesting that response rates may be improved by adopting a genotype‐guided approach to PPI dosing.
Gastric Hepatoid Adenocarcinoma: Differentiation From Gastric Adenocarcinoma With Dynamic Contrast-Enhanced Computed Tomographic Findings
Authors: Fu Yi , Zhu Hui , Peng Wei-jun 
Published: September 2019

Purpose
This study aimed to describe the computed tomographic (CT) findings of gastric hepatoid adenocarcinoma (GHA) and determine features distinguishing it from gastric adenocarcinoma (GA).

Methods
Computed tomographic images of pathologically verified GHA (n = 11) and GA (n = 38) were retrospectively reviewed. α-Fetoprotein (AFP), carcinoembryonic antigen (CEA), and CT findings were assessed in our study. Computed tomographic findings included the location, distribution, growth pattern, ulceration, thickness of gastric wall, enhancement pattern, and the ratio of lesion attenuation to aorta CT attenuation. Short diameter of the metastatic lymph nodes, mean short diameter of metastatic lymph nodes, and the ratio of the number of enlarged lymph node on CT to the number of metastatic lymph nodes pathologically were measured and calculated. Data were compared using the χ2 and Student t tests; significant CT criteria were identified using receiver operating characteristic curve.

Results
α-Fetoprotein, CEA, and CT findings, including the longest short diameter, the mean short diameter, the ratio of the number of enlarged lymph node on CT to the number of metastatic lymph nodes pathologically, the lesion in arterial phase minus portal venous phase, and the lesion/aorta ratio, were statistically significant predictors for the differentiation of GHA from GA (P < 0.05). When only the aforementioned CT findings were used as criteria, the sensitivity and specificity for diagnosing GHA were 82.86% and 90.91%, respectively. When AFP, CEA, and CT findings were used as criteria, sensitivity of 97.14% and specificity of 90.91% were achieved.

Conclusions
Elevated serum AFP level and CT findings could distinguish GHA and GA with a high degree of accuracy.
Use of a Virtual Reality Device for Basic Life Support Training
Authors: Bench Suzanne , Winter Colin , Francis Gary 
Published: September 2019

Introduction
Immediate initiation of cardiopulmonary resuscitation significantly increases the chances of survival after a cardiac arrest. Virtual reality devices allow the integration of features of real patients into training to facilitate interaction and feedback, thus improving performance. However, its use as a training tool remains underexplored. The aims of this study were to undertake initial testing of a virtual reality basic life support prototype and to explore users' views and experiences.

Methods
We recruited 23 adult staff members working at a Central London University in England and exposed them to a 5-minute virtual reality experience. Each participant completed a prequestionnaire and postquestionnaire and took part in a focus group discussion. Quantitative data were descriptively analyzed, whereas qualitative data underwent thematic analysis.

Results
Regardless of prior experience of using virtual reality and/or performing basic life support, most participants scored more than 90% for chest compressions and reported an increase in confidence and competence after the experience. Focus group discussions identified the following 4 key themes: experience and expectations; performance and feedback; interaction and immersion; and potential.

Conclusions
Our study suggests that virtual reality is an enjoyable method by which to teach basic life support. Although concerns over the accuracy of the tracking system and the small sample size weaken our conclusions regarding its ability to assess performance, our exploratory data are of value to educators, researchers, and policy makers. Future work needs to address our study limitations, consider how virtual reality fits into the broader context of training, and attend to accreditation and resource issues.
Return to Baseline Functional Status in Older Women Undergoing Surgery for Pelvic Organ Prolapse
Authors: Lee Daniel D. , Wasson Megan , Hallock Jennifer L. , Heredia-Melero Gerardo , Kinman Casey , Maldonado Pedro A. , Pilkinton Marjorie L. , Sammel Mary D. , Greer Joy A. , Arya Lily A. 
Published: September 2019

Objective
The aim of the study was to determine the rate of return to baseline functional status 3 months after surgery for pelvic organ prolapse (POP) in women 65 years or older.

Methods
This is a multicenter prospective cohort study of women older than 65 years undergoing POP surgery. Functional status was determined by the Activities Assessment Scale at the preoperative visit and 3 months after surgery. We compared a variety of clinical variables and preoperative functional status scores for women who worsened, improved, or returned to baseline functional status after surgery using univariable and multivariable analysis.

Results
A total of 192 women were enrolled in the study. Of 176 women who completed both sets of questionnaires, 59% improved, 35% returned, and 6% worsened from their baseline functional status. Variables significantly associated with postoperative functional status score were depression (P < 0.002) and preoperative functional status score (P < 0.001). The group that improved from baseline had the lowest (worst) preoperative functional status score (78.7 ± 16.4), whereas the group that worsened after surgery had the highest (best) preoperative functional status score (98.6 ± 2.2). After adjusting for age and depression, higher preoperative functional status score was predictive of failure to return to baseline functional status.

Conclusions
Most older women undergoing surgery for POP, including those with low preoperative functional status, return to or improve from their baseline functional status within 3 months of surgery. Women with higher functional status before surgery are less likely to report improvement in physical functioning after surgery.
Prevalence of Pelvic Floor Disorders in Female CrossFit Athletes
Authors: High Rachel , Thai Kim , Virani Hina , Kuehl Thomas , Danford Jill 
Published: September 2019

Objectives
This study aimed to estimate the prevalence of pelvic floor disorders by symptoms in female CrossFit athletes in the United States and characterize subjects reporting pelvic organ prolapse symptoms, urinary incontinence, and fecal incontinence.

Methods
A 27-question anonymous questionnaire was distributed to owners of CrossFit-affiliated gyms. Select questions from validated questionnaires were used to define symptoms. Positive responses with “moderate, or quite a bit” bother defined the presence of urinary incontinence (with stress or urgency). A response of “yes” to “having a bulge or something falling out” defined the presence of pelvic organ prolapse. A response of “yes” to “lose stool beyond your control” questions defined the presence of fecal incontinence.

Results
Three hundred fourteen respondents had mean age of 36 ± 10 years and a mean body mass index of 25.2 ± 4 kg/m2. Forty-four percent reported ≥1 vaginal delivery. For each workout, respondents reported lifting mean weights of 91 to 217 lb, and 90% reported participation in ≥3 CrossFit workouts per week. Pelvic floor disorder symptoms reported included the following: pelvic organ prolapse, 3.2% (10/314); urinary incontinence, 26.1% (82/314); and fecal incontinence, 6% (19/314). Higher age, parity, and number of vaginal deliveries were associated with urinary incontinence. Higher parity and number of vaginal deliveries were associated with prolapse. Fecal incontinence was not associated with age, body mass index, or obstetric history.

Conclusion
The prevalence of pelvic floor symptoms in female CrossFit athletes from the general population is likely similar to the general population; however, the prevalence of bothersome urinary incontinence is higher than the general population in women younger than 40 years.
CVRMS: Cross-validated Rank-based Marker Selection for Genome-wide Prediction of Low Heritability
Authors: Jeong Seongmun , Kim Jae-Yoon , Kim Namshin 
Published: September 2019

AbstractCVRMS is an R package designed to extract marker subsets from repeated rank-based marker datasets generated from genome-wide association studies or marker effects for genome-wide prediction (https://github.com/lovemun/CVRMS). CVRMS provides an optimized genome-wide biomarker set with the best predictability of phenotype by implemented ridge regression using genetic information. Applying our method to human, animal, and plant datasets with wide heritability (zero to one), we selected hundreds to thousands of biomarkers for precise prediction.
A precision virtual crossmatch decision support system for interpretation of ambiguous molecular HLA typing data
Authors: Kaur Navchetan , Pinelli David , Kransdorf Evan P. , Pando Marcelo J , Smith Geoffrey , Murphey Cathi L , Kamoun Malek , Bray Robert A , Tambur Anat , Gragert Loren 
Published: September 2019

ABSTRACTVirtual crossmatch (VXM) compares a transplant candidate’s unacceptable antigens to the HLA typing of the donor before an organ offer is accepted and, in selected cases, supplant a prospective physical crossmatch. However, deceased donor typing can be ambiguous, leading to uncertainty in compatibility prediction. We have developed a web application that utilizes ambiguous HLA molecular typing data to assist in VXM assessments. The application compares a candidate’s listed unacceptable antigens to computed probabilities of all possible two-field donor HLA alleles and UNOS antigens. The VIrtual CrossmaTch for mOleculaR HLA typing (VICTOR) tool can be accessed at http://www.transplanttoolbox.org/victor. We reanalyzed historical VXM cases where a transplant center’s manual interpretation of molecular typing results influenced offer evaluation. We found that VICTOR’s automated interpretation of ambiguous donor molecular typing data would influence VXM decisions. Standardized interpretation of molecular typing data, if applied to the match run, could also change which offers are made. HLA typing ambiguity has been an underappreciated source of immunological risk in organ transplantation. The VICTOR tool can serve as a testbed for development of allocation policies with the aim of decreasing offers refused due to HLA incompatibility.
Adaptive-Resolution Multi-Orientation Analysis of Complex Filamentous Network Images
Authors: Kittisopikul Mark , Vahabikashi Amir , Shimi Takeshi , Goldman Robert D. , Jaqaman Khuloud 
Published: September 2019

AbstractMicroscopy images of cytoskeletal, nucleoskeletal, and other filamentous structures contain complex junctions where multiple filaments with distinct orientations overlap, yet state-of-the-art software generally uses single orientation analysis to segment these structures. We describe an image analysis approach to simultaneously segment both filamentous structures and their intersections in microscopy images, based on analytically resolving coincident multiple orientations upon image filtering in a manner that balances orientation resolution and spatial localization.
Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization
Authors: Rosoff Daniel B. , Smith George Davey , Mehta Nehal , Clarke Toni-Kim , Lohoff Falk W. 
Published: September 2019

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.
Protein Design and Variant Prediction Using Autoregressive Generative Models
Authors: Shin Jung-Eun , Riesselman Adam J. , Kollasch Aaron W. , McMahon Conor , Simon Elana , Sander Chris , Manglik Aashish , Kruse Andrew C. , Marks Debora S. 
Published: September 2019

AbstractThe ability to design functional sequences and predict effects of variation is central to protein engineering and biotherapeutics. State-of-art computational methods rely on models that leverage evolutionary information but are inadequate for important applications where multiple sequence alignments are not robust. Such applications include the prediction of variant effects of indels, disordered proteins, and the design of proteins such as antibodies due to the highly variable complementarity determining regions. We introduce a deep generative model adapted from natural language processing for prediction and design of diverse functional sequences without the need for alignments. The model performs state-of-art prediction of missense and indel effects and we successfully design and test a diverse 105-nanobody library that shows better expression than a 1000-fold larger synthetic library. Our results demonstrate the power of the ‘alignment-free’ autoregressive model in generalizing to regions of sequence space traditionally considered beyond the reach of prediction and design.
The histone demethylase KDM6B fine-tunes the host response toStreptococcus pneumoniae
Authors: Connor Michael G. , Camarasa Tiphaine Marie-Noelle , Patey Emma , Rasid Orhan , Barrio Laura , Weight Caroline M. , Miller Daniel P. , Heyderman Robert S. , Lamont Richard J. , Enninga Jost , Hamon Melanie A. 
Published: September 2019

AbstractStreptococcus pneumoniaeis a natural colonizer of the human upper respiratory tract and an opportunistic pathogen. After colonization, bacteria either remain in the human upper respiratory tract, or may progress to cause pneumococcal disease. Although epithelial cells are among the first to encounter pneumococci, the cellular processes and contribution of epithelial cells to the host response are poorly understood. Here, we show aS. pneumoniaeserotype 6B ST90 strain, which does not cause disease in a murine infection model, induces a unique NF-κB signature response distinct from an invasive disease causing isolate of serotype 4 (TIGR4). This signature is characterized by activation of p65 (RelA) and requires a histone demethylase, KDM6B. At the molecular level, we show that interaction of the 6B strain with epithelial cells leads to chromatin remodeling within the IL-11 promoter in a KDM6B dependent manner, where KDM6B specifically demethylates histone H3 lysine 27 di-methyl. Chromatin remodeling of the IL-11 locus facilitates p65 access to three NF-κB sites, which are otherwise inaccessible when stimulated by IL-1β or TIGR4. Finally, we demonstrate through chemical inhibition of KDM6B, with GSK-J4 inhibitor, and through exogenous addition of IL-11 that the host responses to 6B ST90 and TIGR4 strains can be interchanged bothin vitroand in a murine model of infectionin vivo. Our studies hereby reveal how a chromatin modifier governs cellular responses during infection.
Neuroprotective effects of crocin I and II in an ischemia-reperfusion injury model
Authors: Lv Baowei , Yin Junyan , Feng Chunqing , Li Yanhui 
Published: September 2019

AbstractBackgroundCrocin I and II are derived from the medicinal plantCrocus sativusL. (Saffron), and their neuroprotective effects have been attracting more and more attention. However, their protective effect against cerebral apoplexy induced by hypoxia has not been reported. In this study, we aimed to clarify the roles of crocin I and II in protecting against ischemic injury.Materials/MethodsWe generated a rat cerebral ischemia-reperfusion injury model using a reversible cerebral artery occlusion suture method and found changes in amino acid neurotransmitters in the frontal cortex after drug administration. We also identified changes in mRNA expression ofBcl2, Bax, Casp3, P38, andNFkb1in the frontal cortex and changes in antioxidant indices in the brain.ResultsCrocin I and II both had protective effects on ischemic/anoxic injuryin vivoby downregulating the expression ofCasp3andNfkb1mRNA and the steady-state levels of excitatory amino acids/inhibitory amino acids during ischemia and reperfusion and by improving the total antioxidant capacity and total superoxide dismutase activities during ischemia. We also found that crocin I and II had synergistic effects when used together.ConclusionsThese findings displayed that crocin I and II could protect animal model against ischemic and anoxic injury and provided new evidence for both molecules’ potential medicinal value.
Evolution under pH stress and high population densities leads to increased density-dependent fitness in the protistTetrahymena thermophila
Authors: Moerman Felix , Arquint Angelina , Merkli Stefanie , Wagner Andreas , Altermatt Florian , Fronhofer Emanuel A. 
Published: September 2019

AbstractAbiotic stress is a major force of selection that organisms are constantly facing. While the evolutionary effects of various stressors have been broadly studied, it is only more recently that the relevance of interactions between evolution and underlying ecological conditions, that is, eco-evolutionary feedbacks, have been highlighted. Here, we experimentally investigated how populations adapt to pH-stress under high population densities. Using the protist speciesTetrahymena thermophila, we studied how four different genotypes evolved in response to stressfully low pH conditions and high population densities. We found that genotypes underwent evolutionary changes, some shifting up and others shifting down their intrinsic rates of increase (r0). Overall, evolution at low pH led to the convergence ofr0and intraspecific competitive ability (α) across the four genotypes. Given the strong correlation betweenr0andα, we argue that this convergence was a consequence of selection for increased density-dependent fitness at low pH under the experienced high density conditions. Increased density-dependent fitness was either attained through increase inr0, or decrease ofα, depending on the genetic background. In conclusion, we show that demography can influence the direction of evolution under abiotic stress.
Exploration of social spreading reveals behavior is prevalent amongPedobacterandP. fluorescensisolates, and shows variations in induction of phenotype
Authors: McCully Lucy M. , Graslie Jasmine , Bitzer Adam S. , Sigurbjörnsdóttir Auður M. , Vilhelmsson Oddur , Silby Mark W. 
Published: September 2019

AbstractWithin soil, bacteria are naturally found in multi-species communities, where interactions can lead to emergent community properties. It is critical that we study bacteria in a social context to investigate community-level functions. We previously showed that when co-cultured,Pseudomonas fluorescensPf0-1 andPedobactersp. V48 engage in interspecies social spreading on a hard agar surface, a behavior which required close contact and was dependent on the nutritional environment. In this study, we investigate whether the ability to participate in social spreading is widespread amongP. fluorescensandPedobacterisolates, and whether the requirements for interaction vary. We find that this phenotype is not restricted to the interaction betweenP. fluorescensPf0-1 andPedobactersp. V48, but is a more prevalent behavior found in one clade in theP. fluorescensgroup and two clades in thePedobactergenus. We also discovered that the interaction with certainPedobacterisolates occurred without close contact, indicating induction of spreading by a putative diffusible signal. As is the case for ISS by Pf0-1+V48, motility of all interacting pairs is influenced by the environment, with no spreading behaviors observed under high nutrient conditions. While Pf0-1+V48 require low nutrient but high NaCl conditions, in the broader range of interacting pairs this requirement for low nutrient and high salt was variable. The prevalence of motility phenotypes observed in this study and found within the literature indicates that community-induced locomotion in general, and social spreading in particular, is likely important within the environment. It is crucial that we continue to study microbial interactions and their emergent properties to gain a fuller understanding of the functions of microbial communities.