bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 2 study of GVAX colon vaccine with cyclophosphamide and pembrolizumab in patients with mismatch repair proficient advanced colorectal cancer
Authors: Yarchoan Mark , Huang Chiung‐Yu , Zhu Qingfeng , Ferguson Anna K. , Durham Jennifer N. , Anders Robert A. , Thompson Elizabeth D. , Rozich Noah S. , Thomas Dwayne L. , Nauroth Julie M. , Rodriguez Christina , Osipov Arsen , De Jesus‐Acosta Ana , Le Dung T. , Murphy Adrian G. , Laheru Daniel , Donehower Ross C. , Jaffee Elizabeth M. , Zheng Lei , Azad Nilofer S. 
Published: December 2019

AbstractBackgroundMismatch repair proficient (MMRp) colorectal cancer (CRC) has been refractory to single‐agent programmed cell death protein 1 (PD1) inhibitor therapy. Colon GVAX is an allogeneic, whole‐cell, granulocyte‐macrophage colony‐stimulating factor ‐secreting cellular immunotherapy that induces T‐cell immunity against tumor‐associated antigens and has previously been studied in combination with low‐dose cyclophosphamide (Cy) to inhibit regulatory T cells.MethodsWe conducted a single‐arm study of GVAX/Cy in combination with the PD1 inhibitor pembrolizumab in patients with advanced MMRp CRC. Patients received pembrolizumab plus Cy on day 1, GVAX on day 2, of a 21‐day cycle. The primary endpoint was the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary objectives included safety, overall survival, progression‐free survival, changes in carcinoembryonic antigen (CEA) levels, and immune‐related correlates.ResultsSeventeen patients were enrolled. There were no objective responses, and the disease control rate was 18% by RECIST 1.1. The median progression‐free survival was 82 days (95% confidence interval [CI], 48‐97 days) and the median overall survival was 213 days (95% CI 179‐441 days). Biochemical responses (≥30% decline in CEA) were observed in 7/17 (41%) of patients. Grade ≥ 3 treatment‐related adverse events were observed in two patients (hemolytic anemia and corneal transplant rejection). Paired pre‐ and on‐treatment biopsy specimens showed increases in programmed death‐ligand 1 expression and tumor necrosis in a subset of patients.ConclusionsGVAX/Cy plus pembrolizumab failed to meet its primary objective in MMRp CRC. Biochemical responses were observed in a subset of patients and have not previously been observed with pembrolizumab monotherapy in MMRp CRC, indicating that GVAX may modulate the antitumor immune response.
Landscape of distant metastasis mode and current chemotherapy efficacy of the advanced biliary tract cancer in the United States, 2010‐2016
Authors: Wang Jie , Bo Xiaobo , Nan Lingxi , Wang Chang Cheng , Gao Zhihui , Suo Tao , Ni Xiaoling , Liu Han , Lu Pinxiang , Wang Yueqi , Liu Houbao 
Published: December 2019

AbstractBackgroundThe distant metastasis (DM) mode and treatment efficacies in the advanced biliary tract cancer (BTC) were obscure, and a credible evaluation is urgently needed.MethodA total of 6348 advanced BTC patients (ICC, intrahepatic cholangiocarcinoma, n = 1762; PHCC, perihilar cholangiocarcinoma, n = 1103; GBC, gallbladder cancer, n = 2580; DCC, distal cholangiocarcinoma, n = 538; AVC, carcinoma of Vater ampulla, n = 365) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) process was carried out for less bias.ResultThe proportion of M1 patients in each subtype at first diagnosis was 26.4% (ICC), 37.2% (PHCC), 41. 0% (GBC), 24.5% (DCC), and 12.7% (AVC), and the constitution of DM sites in different subtypes varied apparently. Moreover, the survival of metastasis sites was different (P < .05 in all the subtypes) where the multi‐metastasis and distant lymph node (dLN) only always indicated the worst and best prognosis, respectively. Chemotherapy presented the most significant survival impact with the lowest hazard ratio by multivariate cox model and still provided a survival improvement after PSM (all P < .001) in all subtypes. However, the median months manifested different between patients with and without chemotherapy among the subtypes (ICC, from 5 to 9; PHCC, from 6 to 10; AVC, from 4 to 9; GBC, from 6 to 7; DCC from 6 to 8).ConclusionWe provided a landscape about the detailed DM mode of the advanced BTC in a large population, found the survival differences among DM sites, and revealed the different chemotherapy efficacies in the BTC subtypes.
Here today, gone tomorrow: Outcomes of residual leak following secundum atrial septal defect closure with the GORE CARDIOFORM Septal Occluder
Authors: Gordon Brent M. , Abudayyeh Islam , Goble Jake , Collado Nancy A. , Paolillo Joseph 
Published: December 2019

AbstractObjectiveTo assess the outcomes and potential predictors of residual leak after implantation of the GORE CARDIOFORM Septal Occluder (GSO) in secundum atrial septal defects (ASDs).BackgroundThe non‐self‐centering design of the GSO could lead to residual leak at the edge of the device. Outcomes of residual leak are poorly understood.MethodsRetrospective, multicenter review of patients treated with the GSO for the pivotal and continued access study. Procedural, echocardiographic, and follow up data were reviewed. Multivariate analysis was performed to determine predictors of leak at implant and outcomes of these leaks.ResultsThere were 370 total ASD device closures with the GSO, 65 (17.56%) of which were found to have residual leak at implantation. Patients with residual leak had larger defects (10.33 ± 3.05 mm vs. 9.13 ± 2.89 mm, p = .006) and smaller aortic rims (4.87 ± 3.33 mm vs. 6.17 ± 3.78 mm, p = .019), as compared to those without leak. Larger devices were implanted (p = .008) and more devices per case (p = .007) were utilized in the residual leak cohort as compared to those without leak. Overall, among patients with residual leak, there was a significant decrease in leak size over 1 year, from 1.55 ± 0.75 mm to 0.25 ± 0.74 mm (p < .001), with the majority (87.6%) disappearing by 12‐month follow‐up.ConclusionsResidual leak at implantation can be seen after ASD device closure with the GSO, more commonly in larger defects with smaller retroaortic rims. The vast majority of these leaks completely resolve by 1 year follow up.
Long‐term outcomes of percutaneous closure of coronary artery fistulae in the adult: A single‐center experience
Authors: Shah Ashish H. , Osten Mark , Benson Lee , Alnasser Sami , Bach Yvonne , Meier Lukas , Horlick Eric 
Published: December 2019

AbstractCoronary artery fistulae (CAF) are rare congenital cardiac abnormalities. With increasing age, patients with moderate to large fistulae are likely to become symptomatic and encounter complications. Percutaneous closure has been accepted as a safe and effective alternative to surgery; however, information regarding long‐term outcomes in adult patients after transcatheter closure is limited.MethodsWe describe our 20‐year experience with percutaneous closure of CAF in adult patients, focusing on long‐term outcomes.ResultsFrom 1995 to 2015, 25 adult patients underwent 33 transcatheter interventions to close 26 CAF at our institution. Mean age was 51.4 ± 16.8 years, and 14 (56%) were female. All the patients were symptomatic with dyspnea (21/25, 84%) being the most common complaint followed by chest pain (17/25, 68%), palpitations (9/25, 36%), and heart failure (2/25, 8%). Two patients presented with acute coronary syndrome, whereas 10/25 (40%) also had inducible ischemia on stress test. These CAFs were classified as medium (12, 46.2%), large (5, 19.2%), and giant (9, 34.6%). Immediately postprocedure complete occlusion was achieved in 21 (21/26, 81%), and residual trace leak was observed in three fistulae, whereas we could not deliver coils/device in two cases. Periprocedural complications occurred in the form of coronary dissection (n = 1), myocardial infarction (n = 2), coil embolization (n = 1), transient ST elevation (n = 1); the majority of complications were observed in the early years of our experience. Patients reported marked improvement in symptoms after the intervention. During a mean follow‐up of 76 ± 69 (5–214 months) (n = 22), 15 patients were investigated by either conventional (n = 6) or CT angiography (n = 8) or both (n = 1) that demonstrated thrombotic occlusion of a proximal coronary artery where a distal fistula was treated. Another patient was noted to have thrombus proximal to a vascular plug in a distal giant fistula. Three patients were lost to follow‐up. None of the investigated patients had recanalization of their fistula. We did not observe remodeling of the native coronary artery that was feeding the fistula, even after successful complete closure.ConclusionPercutaneous device closure of CAF is a feasible and effective therapeutic intervention in adult patients; however, patients with distal fistulas represent a significant challenge and the outcomes of these procedures are in question. All patients should have long‐term angiographic follow‐up.
Integrating the residual SYNTAX score to improve the predictive ability of the age, creatinine, and ejection fraction (ACEF) score for cardiac mortality in percutaneous coronary intervention patients
Authors: Gao Guofeng , Zhang Dong , Song Chenxi , Xu Han , Yin Dong , Guan Changdong , Yang Yuejin , Xu Bo , Dou Kefei 
Published: December 2019

AbstractObjectivesTo improve the prognostic value of the age, creatinine, and ejection fraction (ACEF) score following percutaneous coronary intervention (PCI) by integrating the residual SYNTAX score (rSS).BackgroundACEF score was proposed for predicting the operative mortality risk in elective cardiac operations and has been validated in numerous studies. However, it does not incorporate coronary lesion‐based variables for risk assessment of patients who undergo PCI.MethodsOverall, 10,072 patients who underwent PCI at our hospital in 2013 were enrolled. The endpoint was 2‐year cardiac death after PCI, defined as death that was not attributed to a non‐cardiac cause. ACEF‐rSS was constructed with incremental weights attributed to the ACEF score and rSS according to their estimated coefficients.Results2‐year cardiac death occurred in 63 patients (0.63%). In multivariable analyses, the ACEF score and rSS > 8 were independently associated with the risk of cardiac death. ACEF‐rSS was computed as age (years)/ejection fraction (%) + 1 (if creatinine ≥2.0 mg/dl) + 1 (if rSS >8). The discrimination of ACEF‐rSS was significantly better than that of the ACEF score based on receiver operating characteristic (ROC) curve analysis and integrated discrimination improvement (IDI) (C‐statistics = 0.835 vs. 0.776 for ACEF‐rSS and ACEF score, respectively, p = .029; IDI = 0.014, p < .001). Compared with all other SYNTAX‐derived risk scores, ACEF‐rSS had significantly better discrimination ability based on ROC curve analysis, net reclassification improvement, and IDI.ConclusionsCombining the ACEF score with rSS to produce the ACEF‐rSS enhanced the predictive ability for long‐term cardiac mortality.
Improved methods for moment restriction models with data combination and an application to two‐sample instrumental variable estimation
Authors: Shu Heng , Tan Zhiqiang 
Published: December 2019

AbstractCombining‐100 information from multiple samples is often needed in biomedical and economic studies, but differences between these samples must be appropriately taken into account in the analysis of the combined data. We study the estimation for moment restriction models with data combined from two samples under an ignorability‐type assumption while allowing for different marginal distributions of variables common to both samples. Suppose that an outcome regression (OR) model and a propensity score (PS) model are specified. By leveraging semi‐parametric efficiency theory, we derive an augmented inverse probability‐weighted (AIPW) estimator that is locally efficient and doubly robust with respect to these models. Furthermore, we develop calibrated regression and likelihood estimators that are not only locally efficient and doubly robust but also intrinsically efficient in achieving smaller variances than the AIPW estimator when the PS model is correctly specified but the OR model may be mispecified. As an important application, we study the two‐sample instrumental variable problem and derive the corresponding estimators while allowing for incompatible distributions of variables common to the two samples. Finally, we provide a simulation study and an econometric application on public housing projects to demonstrate the superior performance of our improved estimators. The Canadian Journal of Statistics 48: 259–284; 2020 © 2019 Statistical Society of Canada
A Mass Balance Study of 14C‐Labeled JTZ‐951 (Enarodustat), a Novel Orally Available Erythropoiesis‐Stimulating Agent, in Patients With End‐Stage Renal Disease on Hemodialysis
Authors: Pai Sudhakar M. , Connaire Jeffrey , Yamada Hiroyuki , Enya Seiji , Gerhardt Barbara , Maekawa Michihide , Tanaka Hiromasa , Koretomo Ryosuke , Ishikawa Tomohiro 
Published: December 2019

AbstractThe mass balance, pharmacokinetics, and biotransformation of JTZ‐951 (enarodustat), a novel hypoxia‐inducible factor prolyl hydroxylase inhibitor, were characterized in patients (N = 6) with end‐stage renal disease on hemodialysis. Following a 10‐mg (100 µCi) oral dose of 14C‐JTZ‐951, whole blood, feces, dialysate, and, if feasible, urine were obtained for pharmacokinetic assessments and for metabolite profiling and identification in appropriate matrices. Fecal excretion was the major route of elimination of radioactivity, and urinary excretion a minor route, with mean (coefficient of variation [%CV]) recovery of 77.1 (16.2)% and 10.9 (92.0)% of the dose, respectively. Radioactivity was not detected in the dialysate, and mean (%CV) total recovery in excreta was 88.0 (14.9)%. For parent JTZ‐951 in plasma, the mean (%CV) effective half‐life was 8.96 (7.7)% hours, and area under the curve over 24 hours comprised the majority (>80%) of total exposure, with relatively low variability in these pharmacokinetic variables. Based on profiling of plasma radioactivity, parent JTZ‐951 was the predominant circulating component, accounting for 93.7% or more of radioactivity, and metabolite M2 (hydroxylated product) was the only detectable metabolite, but its exposure was minor (<5%) versus unchanged JTZ‐951. In urine and feces, the predominant analyte was JTZ‐951, and metabolite M2 was the predominant albeit minor metabolite, with small amounts of other metabolites. Thus, plasma exposure to drug‐derived radioactivity was primarily due to parent JTZ‐951, and the drug was cleared mainly by excretion of unchanged JTZ‐951. The study appropriately characterized the disposition of JTZ‐951 in patients with end‐stage renal disease.
Essentiality of managing the resource information in the coordinated fog‐to‐cloud paradigm
Authors: Sengupta Souvik , Garcia Jordi , Masip‐Bruin Xavi 
Published: December 2019

SummaryFog‐to‐cloud (F2C) computing is an emerging computational platform. By combing the cloud, fog, and IoT, it provides an excellent framework for managing and coordinating the resources in any smart computing domain. Efficient management of these kinds of diverse resources is one of the critical tasks in the F2C system. Also, it must be considered that different types of services are offered by any smart system. So, before managing these resources and enabling the various types of services, it is essential to have some comprehensive informational catalogue of resources and services. Hence, after identifying the resource and service‐task taxonomy, our main aim in this paper is finding out a solution for properly organizing this information over the F2C system. For that purpose, we are proposing a modified F2C framework where all the information is distributively stored near to the edge of the network. Finally, by presenting some experimental results, we evaluate and validate the performance of our proposing framework.
Segmental analysis of antidepressant and antipsychotic drugs in the hair of schizophrenic patients
Authors: Wang Xin , Zhuo Yue , Tang Xiaowei , Qiang Huosheng , Liu Wei , Wu Hejian , Xiang Ping , Duan Gengli , Shen Min 
Published: December 2019

AbstractHair analysis is useful for documenting long‐term exposure to drugs. The potential of hair analysis for therapeutic drug monitoring within the forensic field has been studied, but reference values for some antidepressants and antipsychotics in the hair of individuals undergoing chronic therapy are still lacking. In the present study, a method was developed and validated for the determination of 23 analytes, including antidepressants, antipsychotics, and related metabolites, in human hair by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Hair samples (10 mg) were extracted with a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8% acetonitrile, pH 5.3) utilizing cryogenic grinding. The present method demonstrated sufficient selectivity, robustness, and accuracy. Sixteen analytes in hair were reported in 46 psychiatric patients receiving fixed drug dosages. To the best of our knowledge, the hair concentrations of perphenazine and norolanzapine, as well as the concentrations of amisulpride, aripiprazole and its metabolite dehydroaripiprazole, olanzapine, and sulpiride, in hair from individuals receiving fixed dosages is reported for the first time. A significant relationship between the administered dose and the concentration in the proximal hair segment was found only for clozapine, norclozapine, and chlorpromazine. The results confirmed that the idea of using hair concentrations to monitor a daily dose is inapplicable.
Emotional distress: Specifying a neglected part of chronic pain
Authors: Barke Antonia , Koechlin Helen , Korwisi Beatrice , Locher Cosima 
Published: December 2019

AbstractWe argue that in all randomized controlled trials that investigate treatments for chronic pain emotional distress should be reported. In a majority of cases, pain intensity and pain‐related disability are measured, yet—despite guidelines to the contrary—pain‐related distress is not included. We suggest that the new extension code for chronic pain as incorporated in the ICD‐11 will be well suited to fill this gap at minute additional effort for the participants.
The evolution of the concepts of seizures and epilepsy: What’s in a name?
Authors: Patel Puja , Moshé Solomon L. 
Published: December 2019

AbstractThis review aims to highlight the historical hallmarks in the development of the concepts of seizures and epilepsy. It begins with a discussion of seizure semiology and terminology, followed by the pathophysiology of seizures. We then discuss the definition of epilepsy, its etiologies, and ultimately classification schemes. Each section starts with our current views and subsequently transports the reader back in time to understand how these views evolved and came to be what they are today. People living as early as in the prehistoric times may have been aware of the existence of seizures, and descriptions and terminology have been provided as early as 2500 BC. While names have been revised and updated through time, the meanings are seemingly unchanged. However, it is clearly evident that we have come a long way in understanding the pathophysiology and etiology of seizures and epilepsy, thus leading to our current classification schemes. No classification scheme will be perfect yet, until our understanding is advanced enough to create one based predominantly on scientific grounds. The goal is that it is relevant to clinical practice, leading to a more precise diagnosis to guide targeted treatments.
Effects of passenger blockage on smoke flow properties in longitudinally ventilated tunnel fires
Authors: Wang Yan , Wu Fan , Wu Peihong 
Published: December 2019

SummaryThis paper investigates the effects of passenger blockage on smoke flow properties in longitudinally ventilated tunnel fires. A series of numerical simulations were conducted in a 1/5 small‐scale tunnel with the different heat release rates (50‐100 kW), longitudinal ventilation velocities (0.5‐1 m/s), passenger blockage lengths (2‐6 m), and ratios (0.17‐0.267). The typical smoke flow properties in different tunnel fire scenarios are analyzed, and the results show that under the same heat release rate and longitudinal ventilation velocity, the smoke back‐layering length, maximum smoke temperature, and downstream smoke layer height decrease with increasing passenger blockage length or ratio. The Li correlations can well predict the smoke back‐layering length and maximum smoke temperature in tunnel fire scenarios without the passenger blockage. When the passenger blockage exists, the modified local ventilation velocity that takes the blockage length and ratio into account has been proposed to correct the Li correlations. The smoke back‐layering length and maximum smoke temperature with the different blockage lengths and ratios can be predicted by the modified correlations, which are shown to well reproduce the simulation results.
Can education transform?: Contradictions between the emerging future and the walled past
Authors: Inayatullah Sohail 
Published: December 2019

AbstractWhile many imagine education as far more flexible and student‐centered, creating a different system has been far more challenging. Why is this the case? What are the tensions between the imagined future and the weight of the past. This essay seeks to answer this question through insights gained from anticipatory action learning interventions in Australia, Malaysia, Norway, and the Philippines.
RETRACTED: Health lipid indices and physicochemical properties of dual fortified yogurt with extruded flaxseed omega fatty acids and fibers for hypercholesterolemic subjects
Authors: Ahmad Nazir , Manzoor Muhammad Faisal , Shabbir Umair , Ahmed Saeed , Ismail Tariq , Saeed Farhan , Nisa MahrUn , Anjum Faqir Muhammad , Hussain Shahzad 
Published: December 2019

AbstractThe aim of the present study was to prepare designer yogurt for the hypercholesterolemic subject. The yogurts were prepared from sheep and cow milk by fortifying omega fatty acids and dietary fibers of extruded flaxseed powder (EFSP). The EFSP, Streptococcus thermophilus, and Lactobacillus delbrueckii sub sp bulgaricus at 2% were added for yogurt formation. The water retention capacity, fat adsorption capacity, swelling, and solubility of EFSP were 14.38 ± 3.16 g/g, 5.31 ± 0.93 g oil/g, 25.57 ± 1.35 ml/g, and 30.53 ± 8.5%, respectively. The proximate value of protein content increased significantly from 4.12% to 5.12%. Total fat content increased from 3.50% to 4.28%. Total dietary fibers increased from 0% to 24.14%. Significant increase was observed in C18:1n9 and C18:2n6 fatty acid contents. The omega‐3 (18:3n3) was significantly increased higher as compared to other omega fatty acids in fortified yogurts. Atherogenicity index (IA: 2.23 ± 0.41 to 1.42 ± 0.23) and thrombogenicity index (IT: 1.68 ± 0.95 to 0.65 ± 0.01) were significantly decreased while the ratio of hypocholesterolemic and hypercholesteremic fatty acids (HH: 0.82 ± 0.05 to 1.29 ± 0.46) increased significantly in sheep milk yogurt. IA (2.74 ± 0.31 to 1.48 ± 0.08) and IT (1.84 ± 0.28 to 0.39 ± 0.04) were also decreased significantly while HH (0.54 ± 0.05to 1.12 ± 0.02) increased significantly in cow milk yogurt. Δ9‐desaturase (18) index was found highest (75.67 ± 8.04) in EFSP‐fortified sheep milk yogurt and lowest (62.27 ± 8.65) in cow milk yogurt while Δ9‐desaturase (16) index was maximum (6.21 ± 1.25) in cow milk yogurt and minimum (3.93 ± 1.38) in EFSP‐fortified sheep milk yogurt. Significant effect on consistency, firmness, viscosity index, and cohesiveness was also noticed in fortified yogurts. EFSP has also significant impact on colony formation of stains culture. The fortified product got good flavor and textural acceptance score. Thus; EFSP improved the health lipids quality and physicochemical characteristics. It can act as a good stabilizer and texturizer in yogurt formation and a healthy alternative for hazardous adulterants used in yogurt formation.