bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human urinary kallindinogenase therapy for acute ischemic stroke according to Chinese ischemic stroke subclassification: Clinical efficacy and risk factors
Authors: Chen Si‐Qia , Mao Dong‐Yang , Wei Dun‐Can , He Wen‐Zhen 
Published: December 2019

AbstractIntroductionTo evaluate effectiveness of human urinary kallindinogenase (HUK) in patients with acute ischemic stroke (AIS) according to Chinese ischemic stroke subclassification (CISS) and analyzed risk factors of clinical efficacy.MethodsIn this retrospective study, 134 patients received conventional therapy were enrolled to control group, and 132 patients received HUK treatment were enrolled to HUK group. National Institute of Health Stroke Scale (NIHSS) score was used to evaluate the clinical efficacy. Multivariate analysis of risk factors was performed by using logistic regression.ResultsAfter treatment, NIHSS score of HUK group was significant lower than that of control group (p = .009). Effectiveness rate was 71.2% in HUK group, and 53.7% in control group, respectively (p = .003). The NIHSS of patients with large artery atherosclerosis (LAA) subtype in HUK group was significantly lower than that in control group (p = .005). The absence of HUK (OR = 2.75), homocysteine (OR = 0.15), and CS subtype (OR = 0.18) were risk factors for HUK clinical efficacy.ConclusionsHuman urinary kallindinogenase is an effective therapeutic approach for treatment of patients with AIS, especially in patients with LAA subtype. The absence of HUK, elevated homocysteine, and cardiogenic stroke subtype were risk factor for clinical efficacy of HUK.
Genome‐wide screening of abberant methylated drivers combined with relative risk loci in bladder cancer
Authors: Zhang Chuanjie , Shen Kangjie , Zheng Yuxiao , Qi Feng , Luo Jun 
Published: December 2019

AbstractBackgroundTo explore important methylation‐driven genes (MDGs) and risk loci to construct risk model for prognosis of bladder cancer (BCa).MethodsWe utilized TCGA‐Assembler package to download 450K methylation data and corresponding transcriptome profiles. MethylMix package was used for identifying methylation‐driven genes and functional analysis was mainly performed based on ConsensusPathDB database. Then, Cox regression method was utilized to find prognostic MDGs, and we selected 17 hub genes via stepwise regression and multivariate Cox models. Kruskal‐Wallis test was implemented for comparisons between risk with other clinical variables. Moreover, we constructed the risk model and validated it in GSE13507. Gene set enrichment analysis was performed using the levels of risk score as the phenotype. Additionally, we further screened out the relative methylation sites associated with the 17 hub genes. Cox regression and Survival analysis were conducted to find the specifically prognostic sites.ResultsTwo hundred and twenty‐eight MDGs were chosen by ConsensusPathDB database. Results revealed that most conspicuous pathways were transcriptional mis‐regulation pathways in cancer and EMT. After Cox regression analysis, 17 hub epigenetic MDGs were identified. We calculated the risk score and found satisfactory predictive efficiency by ROC curve (AUC = 0.762). In the validation group from GSE13507, 17 hub genes remained higher predictive value with AUC = 0.723 and patients in high‐risk group. Meanwhile, Kruskal‐Wallis test revealed that higher risk score correlated with a higher level of TNM stage, tumor grade, and advanced pathological stages. Then, identified 38 risk methylated loci that highly associated with prognosis. Last, gene set enrichment analysis revealed that high‐risk level of MDGs may correlate with several important pathways, including MAPK signaling pathway and so on.ConclusionOur study indicated several hub‐MDGs, calculated novel risk score and explored the prognostic value in BCa, which provided a promising approach to BCA prognosis assessment.
Clinical outcomes of locally advanced esophageal neuroendocrine carcinoma treated with chemoradiotherapy
Authors: Honma Yoshitaka , Nagashima Kengo , Hirano Hidekazu , Shoji Hirokazu , Iwasa Satoru , Takashima Atsuo , Okita Natsuko , Kato Ken , Boku Narikazu , Murakami Naoya , Inaba Kouji , Ito Yoshinori , Itami Jun , Kanamori Jun , Oguma Junya , Daiko Hiroyuki 
Published: December 2019

AbstractBackgroundNeuroendocrine carcinoma (NEC) arising from the esophagus (EsoNEC) is extreme rare, accounting for approximately 1% of esophageal cancer. Even for localized NEC, multidisciplinary approach including chemotherapy is recommended in treatment guidelines because of its high rates of systemic recurrence. However, it is controversial whether adding surgery or radiotherapy is appropriate local treatment for EsoNEC. There have been few reports regarding the clinical outcomes of definitive chemoradiotherapy (dCRT) for EsoNEC. The purpose of this study was to clarify the survival outcome of patients with locally advanced EsoNEC treated with dCRT.MethodsClinical outcomes, feasibility, and prognostic factors of patients with locally advanced EsoNEC treated with radiotherapy (60 Gy/30 fraction) in combination with platinum plus etoposide (CE‐RT) or cisplatin plus 5‐fluorouracil (CF‐RT) at the National Cancer Center Hospital from 2001 to 2017 were retrospectively analyzed.ResultsA total of 22 patients were identified as the subjects of this study. The overall response rate and clinical complete remission rate in all patients were 86.4% and 77.3%, respectively. The median progression‐free survival and median survival time in all patients were 12.7 and 37.5 months, associated with a 5‐year survival rate of 45.4%. Patients treated with CE‐RT experienced more hematological adverse events, especially in neutropenia (≥grade 3) and febrile neutropenia(≥grade 3), but achieved more long‐term progression‐free survival than with CF‐RT.ConclusionsDefinitive chemoradiotherapy can be considered as an important treatment option for locally advanced esophageal neuroendocrine carcinoma.
Personalizing age‐specific survival prediction and risk stratification in intracranial grade II/III ependymoma
Authors: Deng Xiangyang , Zhang Xiaojia , Yang Liang , Lu Xiangqi , Fang Junhao , Yu Lisheng , Li Dandong , Sheng Hansong , Yin Bo , Zhang Nu , Lin Jian 
Published: December 2019

AbstractBackgroundModels for estimation of survival rates of patients with intracranial grade II/III ependymoma (EPN) are scarce. Considering the heterogeneity in prognostic factors between pediatric and adult patients, we aimed to develop age‐specific nomograms for predicting 3‐, 5‐, and 8‐year survival for these patients.MethodsA total of 1390 cases (667 children; 723 adults) of intracranial grade II/III EPNs diagnosed between 1988 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for our study. Univariable and multivariable Cox analyses were employed to identify independent prognostic predictors. Age‐specific nomograms were developed based on the results of multivariate Cox analyses. We also evaluated the performance of these predictive models by concordance index, calibration curves, time‐dependent receiver operating characteristic curves, and decision curve analyses.ResultsConsiderable heterogeneity in prognostic factors was highlighted between pediatric and adult patients. Age, sex, tumor grade, surgery treatment and radiotherapy were identified as significant predictors of overall survival for children, and age, tumor grade, tumor size, surgery treatment, and marital status for adult. Based on these factors, age‐specific nomogram models were established and internally validated. These models exhibited favorable discrimination and calibration characteristics. Nomogram‐based risk classification systems were also constructed to facilitate risk stratification in EPNs for optimization of clinical management.ConclusionsWe developed the first nomograms and corresponding risk classification systems for predicting survival in patients with intracranial grade II/III EPN. These easily used tools can assist oncologists in making accurate survival evaluation.
Can we predict who lives long with ovarian cancer?
Authors: Bookman Michael A. 
Published: December 2019

Women with ovarian cancer benefit from individualized management that incorporates advanced imaging technologies, sophisticated cytoreductive surgery integrated with combination chemotherapy, genetic risk assessment, and tumor molecular profiling. However, advanced ovarian cancer remains a highly lethal disease because of early peritoneal dissemination, rapid development of resistance to key therapeutic agents, and evasion of the host immune response. Over the last 15 years, several models and nomograms have been developed to predict surgical outcomes, progression‐free survival, or overall survival on the basis of clinical and pathologic data available at the primary diagnosis and recurrence. Each of these models has its strengths and limitations, and they provide a basis for future models that will incorporate functional imaging and molecular characteristics.
Phase 1 Pharmacokinetic Study of AZD5718 in Healthy Volunteers: Effects of Coadministration With Rosuvastatin, Formulation and Food on Oral Bioavailability
Authors: Ericsson Hans , Nelander Karin , Heijer Maria , Kjaer Magnus , Lindstedt Eva‐Lotte , Albayaty Muna , Forte Pablo , Lagerström‐Fermér Maria , Skrtic Stanko 
Published: December 2019

AbstractAZD5718 is a first‐in‐class small‐molecule anti‐inflammatory drug with the potential to reduce the residual risk of cardiovascular events after myocardial infarction in patients receiving lipid‐lowering statin therapy. Leukotrienes are potent proinflammatory and vasoactive mediators synthesized in leukocytes via 5‐lipoxygenase and 5‐lipoxygenase‐activating protein (FLAP). AZD5718 is a FLAP inhibitor that dose‐dependently reduced leukotriene biosynthesis in a first‐in‐human study. We enrolled 12 healthy men in a randomized, open‐label, crossover, single‐dose phase 1 pharmacokinetic study of AZD5718 to investigate a potential drug‐drug interaction with rosuvastatin, and the effects of formulation and food intake (ClinicalTrials.gov identifier: NCT02963116). Rosuvastatin (10 mg) were absorbed more rapidly when coadministered with AZD5718 (200 mg), probably owing to weak inhibition of hepatic statin uptake, but relative bioavailability was unaffected (geometric least‐squares mean ratio [GMR], 100%; 90% confidence interval [CI], 86%‐116%). AZD5718 pharmacokinetics were unaffected by coadministration of rosuvastatin. AZD5718 (200 mg) was absorbed less rapidly when formulated as tablets than oral suspension, with reduced relative bioavailability (GMR, 72%; 90%CI, 64%‐80%). AZD5718 absorption was slower when 200‐mg tablets were taken after a high‐fat breakfast than after fasting, but relative bioavailability was unaffected (GMR, 96%; 90%CI, 87%‐106%). In post hoc pharmacodynamic simulations, plasma leukotriene B4 levels were inhibited by >90% throughout the day following once‐daily AZD5718, regardless of formulation or administration with food. AZD5718 was well tolerated, with no severe or serious adverse events. These data supported the design of a phase 2a efficacy study of AZD5718 in patients with coronary artery disease.
Utilizing field collected insects for next generation sequencing: Effects of sampling, storage, and DNA extraction methods
Authors: Ballare Kimberly M. , Pope Nathaniel S. , Castilla Antonio R. , Cusser Sarah , Metz Richard P. , Jha Shalene 
Published: December 2019

AbstractDNA sequencing technologies continue to advance the biological sciences, expanding opportunities for genomic studies of non‐model organisms for basic and applied questions. Despite these opportunities, many next generation sequencing protocols have been developed assuming a substantial quantity of high molecular weight DNA (>100 ng), which can be difficult to obtain for many study systems. In particular, the ability to sequence field‐collected specimens that exhibit varying levels of DNA degradation remains largely unexplored. In this study we investigate the influence of five traditional insect capture and curation methods on Double‐Digest Restriction Enzyme Associated DNA (ddRAD) sequencing success for three wild bee species. We sequenced a total of 105 specimens (between 7–13 specimens per species and treatment). We additionally investigated how different DNA quality metrics (including pre‐sequence concentration and contamination) predicted downstream sequencing success, and also compared two DNA extraction methods. We report successful library preparation for all specimens, with all treatments and extraction methods producing enough highly reliable loci for population genetic analyses. Although results varied between species, we found that specimens collected by net sampling directly into 100% EtOH, or by passive trapping followed by 100% EtOH storage before pinning tended to produce higher quality ddRAD assemblies, likely as a result of rapid specimen desiccation. Surprisingly, we found that specimens preserved in propylene glycol during field sampling exhibited lower‐quality assemblies. We provide recommendations for each treatment, extraction method, and DNA quality assessment, and further encourage researchers to consider utilizing a wider variety of specimens for genomic analyses.
Teaching laboratory for large cohorts of undergraduates: Private and social information in fish
Authors: Borcherding Jost , Webster Mike M. , Heubel Katja 
Published: December 2019

AbstractA challenge in the Bachelor's studies in Biology is to strike a balance between reducing the teaching of practical scientific experiments to what is feasible in a short time, and teaching “real” science in undergraduate laboratories for high numbers of participants. We describe a laboratory in behavioral biology, with the primary focus on the student learning. However, also the underlying scientific question and the results of the experiment, namely the behavior of the three‐spined stickleback (Gasterosteus aculeatus) in a trade‐off situation during foraging, is without a doubt timely and sufficient for scientific studies on this subject, and this through the experiments conducted and data collected by the students. The students rated this laboratory well and learned at the end that social information is certainly important, but that self‐learning can be more important, and this not only in small fish, but also for the students themselves.
Hybridization between Felis silvestris silvestris and Felis silvestris catus in two contrasted environments in France
Authors: Beugin Marie‐Pauline , Salvador Olivier , Leblanc Guillaume , Queney Guillaume , Natoli Eugenia , Pontier Dominique 
Published: December 2019

AbstractEuropean wildcat (Felis silvestris silvestris) populations are fragmented throughout most of the whole range of the subspecies and may be threatened by hybridization with the domestic cat F.s. catus. The underlying ecological processes promoting hybridization remain largely unknown. In France, wildcats are mainly present in the northeast and signs of their presence in the Pyrenees have been recently provided. However, no studies have been carried out in the French Pyrenees to assess their exposure to hybridization. We compared two local populations of wildcats, one living in a continuous forest habitat in the French Pyrenees, the other living in a highly fragmented forest‐agricultural landscape in northeastern France to get insights into the variability of hybridization rates. Strong evidence of hybridization was detected in northeastern France and not in the Pyrenees. Close kin in the Pyrenees were not found in the same geographic location contrary to what was previously reported for females in the northeastern wildcat population. The two wildcat populations were significantly differentiated (FST = 0.072) to an extent close to what has been reported (FST = 0.103) between the Iberian population, from which the Pyrenean population may originate, and the German population, which is connected to the northeastern population. The genetic diversity of the Pyrenean wildcats was lower than that of northeastern wildcat populations in France and in other parts of Europe. The lower hybridization in the Pyrenees may result from the continuity of natural forest habitats. Further investigations should focus on linking landscape features to hybridization rates working on local populations.
Cardiovascular and non‐cardiovascular death distinction: the utility of troponin beyond N‐terminal pro‐B‐type natriuretic peptide. Findings from the BIOSTAT‐CHF study
Authors: Ferreira João Pedro , Ouwerkerk Wouter , Tromp Jasper , Ng Leong , Dickstein Kenneth , Anker Stefan , Filippatos Gerasimos , Cleland John G. , Metra Marco , van Veldhuisen Dirk J. , Voors Adriaan A. , Zannad Faiez 
Published: December 2019

AimsHeart failure (HF) patients are at high‐risk of cardiovascular (CV) events, including CV death. Nonetheless, a substantial proportion of these patients die from non‐CV causes. Identifying patients at higher risk for each individual event may help selecting patients for clinical trials and tailoring cardiovascular therapies. The aims of the present study are to: (i) characterize patients according to CV vs. non‐CV death; (ii) develop models for the prediction of the respective events; (iii) assess the models' performance to differentiate CV from non‐CV death.Methods and resultsThis study included 2309 patients with HF from the BIOSTAT‐CHF (a systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) study. Competing‐risk models were used to assess the best combination of variables associated with each cause‐specific death. Results were validated in an independent cohort of 1738 HF patients. The best model to predict CV death included low blood pressure, estimated glomerular filtration rate ≤ 60 mL/min, peripheral oedema, previous HF hospitalization, ischaemic HF, chronic obstructive pulmonary disease, elevated N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), and troponin (c‐index = 0.73). The non‐CV death model incorporated age > 75 years, anaemia and elevated NT‐proBNP (c‐index = 0.71). Both CV and non‐CV death rose by quintiles of the risk scores; yet these models allowed the identification of patients in whom absolute CV death rates clearly outweigh non‐CV death ones. These findings were externally replicated, but performed worse in a less severely diseased population.ConclusionsRisk models for predicting CV and non‐CV death allowed the identification of patients at higher absolute risk of dying from CV causes (vs. non‐CV ones). Troponin helped in predicting CV death only, whereas NT‐proBNP helped in the prediction of both CV and non‐CV death. These findings can be useful both for tailoring therapies and for patient selection in HF trials in order to attain CV event enrichment.
Mitral regurgitation, left atrial structural and functional remodelling and the effect on pulmonary haemodynamics
Authors: Inciardi Riccardo M. , Rossi Andrea , Bergamini Corinna , Benfari Giovanni , Maffeis Caterina , Greco Carmen , Drago Andrea , Guazzi Marco , Ribichini Flavio L. , Cicoira Mariantonietta 
Published: December 2019

AbstractAimsTo assess the association between mitral regurgitation (MR) and left atrial (LA) structural and functional remodelling and their effect on pulmonary haemodynamics.Methods and resultsConsecutive unselected patients undergoing comprehensive echocardiography were enrolled. Parameters of cardiac structure and function were obtained as well as mitral effective regurgitant orifice area (ERO) and estimation of pulmonary artery systolic pressure (PASP). Measures of LA structure [LA volume (LAV)] and function [peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS) and conduit strain (CS)] were also calculated. The study population included 102 patients (mean age 70 ± 14 years, 42% women), with a mean ejection fraction of 52 ± 13%. MR was classified as organic due to mitral valve prolapse in 14 patients (14%) and functional in 88 patients (86%). Mean ERO was 0.12 ± 0.12 cm2 and 86 patients (84%) had an ERO ≤0.2 cm2. ERO was significantly associated with worse measures of LA structure and function. Despite the low burden of MR, the association remained significant after adjusting for clinical and echocardiographic confounders (β: 3.7, P = 0.022 for LAV; β: −3.0, P = 0.003 for PALS; β: −1.8, P = 0.027 for PACS) and was significantly related with functional MR (P for interaction <0.001). ERO was also significantly associated with PASP, and measures of LA function (PALS and PACS) significantly modified this relationship (P for interaction <0.001).ConclusionsEven a mild degree of MR contributes to LA remodelling and this relationship plays an active role in pulmonary circulation, suggesting a potential mechanism by which these parameters contribute to the development of heart failure.
The impact of placing obstacles on the distribution of the airflow inside a solar chimney
Authors: Ayadi Ahmed , Driss Zied , Abid Mohamed Salah 
Published: December 2019

AbstractSolar energy sources are alternative solutions to creating energy by the use of solar radiation. The solar chimney power plants (SCPPs) are non‐concentrated thermal systems that use the solar radiation to produce green energy. The main components of an SCPP are a collector, an absorber, a chimney, and a turbine that is coupled with a generator. The feasibility study of these thermal devices is required. In this paper, a study of a solar chimney power plant is reported. In fact, a numerical investigation of the obstacle effect on the distributions of the airflow in a solar chimney is presented using the commercial CFD code Ansys Fluent. The comparison between numerical and experimental findings has shown good agreement for the considered instance. Accordingly, the presented numerical model is capable of estimating the airflow characteristics inside the solar device. Results showed that the placement of obstacles at the collector output favors the performance of an existing solar chimney. The generated power could be enhanced by 11.5% using one obstacle and 14.75% using two obstacles.
An age‐integrated approach to improve measurement of potential spatial accessibility to emergency medical services for urban areas
Authors: Hashtarkhani Soheil , Kiani Behzad , Bergquist Robert , Bagheri Nasser , VafaeiNejad Reza , Tara Mahmood 
Published: December 2019

SummaryObjective: This study aimed to develop an age‐included approach to measure the potential accessibility to Emergency medical services (EMS) across urban and suburban areas of Mashhad city in Iran.Methods: We used an improved version of two‐step floating catchment area (2SFCA) and enhanced 2SFCA (E2SFCA) methods to measure the potential accessibility to EMS services with inclusion of age factor. This enabled us to better model accessibility of the older population to the EMS. We used 22 800 records of EMS enquiries from July to September 2018 to evaluate and assess the potential improvement in access to the EMS with incorporating age in the model.Results: Suburb areas had less potential accessibility compared with central urban due to the high density of EMS stations in the city center areas. Our model showed slight improvement in potential accessibility measurement as a result of the proposed age‐integrated method.Conclusion: An age‐integrated index of accessibility method takes into account the age distribution of the population in service area is highly associated with actual measures of accessibility to EMS services. Identifying areas with poor access to EMS will help policymakers to design better policy planning to allocate resources and improve provision of EMS services.