bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study
Authors: Wei Andrew H. , Strickland Stephen A. , Hou Jing-Zhou , Fiedler Walter , Lin Tara L. , Walter Roland B. , Enjeti Anoop , Tiong Ing Soo , Savona Michael , Lee Sangmin , Chyla Brenda , Popovic Relja , Salem Ahmed Hamed , Agarwal Suresh , Xu Tu , Fakouhi Kaffa M. , Humerickhouse Rod , Hong Wan-Jen , Hayslip John , Roboz Gail J. 
Published: March 2019

PURPOSE Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML. PATIENTS AND METHODS Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled. Prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), was permitted. Eighty-two patients were treated at the recommended phase II dose: venetoclax 600 mg per day orally in 28-day cycles, with LDAC (20 mg/m2 per day) administered subcutaneously on days 1 to 10. Key end points were tolerability, safety, response rates, duration of response (DOR), and overall survival (OS). RESULTS Median age was 74 years (range, 63 to 90 years), 49% had secondary AML, 29% had prior HMA treatment, and 32% had poor-risk cytogenetic features. Common grade 3 or greater adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and WBC count decreased (34%). Early (30-day) mortality was 6%. Fifty-four percent achieved complete remission (CR)/CR with incomplete blood count recovery (median time to first response, 1.4 months). The median OS was 10.1 months (95% CI, 5.7 to 14.2), and median DOR was 8.1 months (95% CI, 5.3 to 14.9 months). Among patients without prior HMA exposure, CR/CR with incomplete blood count recovery was achieved in 62%, median DOR was 14.8 months (95% CI, 5.5 months to not reached), and median OS was 13.5 months (95% CI, 7.0 to 18.4 months). CONCLUSION Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy. High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy.
Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E–Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study
Authors: Van Cutsem Eric , Huijberts Sanne , Grothey Axel , Yaeger Rona , Cuyle Pieter-Jan , Elez Elena , Fakih Marwan , Montagut Clara , Peeters Marc , Yoshino Takayuki , Wasan Harpreet , Desai Jayesh , Ciardiello Fortunato , Gollerkeri Ashwin , Christy-Bittel Janna , Maharry Kati , Sandor Victor , Schellens Jan H.M. , Kopetz Scott , Tabernero Josep 
Published: March 2019

PURPOSE To determine the safety and preliminary efficacy of selective combination targeted therapy for BRAF V600E–mutant metastatic colorectal cancer (mCRC) in the safety lead-in phase of the open-label, randomized, three-arm, phase III BEACON Colorectal Cancer trial ( ClinicalTrials.gov identifier: NCT02928224; European Union Clinical Trials Register identifier: EudraCT2015-005805-35). PATIENTS AND METHODS Before initiation of the randomized portion of the BEACON Colorectal Cancer trial, 30 patients with BRAF V600E–mutant mCRC who had experienced treatment failure with one or two prior regimens were to be recruited to a safety lead-in of encorafenib 300 mg daily, binimetinib 45 mg twice daily, plus standard weekly cetuximab. The primary end point was safety, including the incidence of dose-limiting toxicities. Efficacy end points included overall response rate, progression-free survival, and overall survival. RESULTS Among the 30 treated patients, dose-limiting toxicities occurred in five patients and included serous retinopathy (n = 2), reversible decreased left ventricular ejection fraction (n = 1), and cetuximab-related infusion reactions (n = 2). The most common grade 3 or 4 adverse events were fatigue (13%), anemia (10%), increased creatine phosphokinase (10%), increased AST (10%), and urinary tract infections (10%). In 29 patients with BRAF V600E–mutant tumors (one patient had a non– BRAF V600E–mutant tumor and was not included in the efficacy analysis), the confirmed overall response rate was 48% (95% CI, 29.4% to 67.5%), median progression-free survival was 8.0 months (95% CI, 5.6 to 9.3 months), and median overall survival was 15.3 months (95% CI, 9.6 months to not reached), with median duration of follow-up of 18.2 months (range, 16.6 to 19.8 months). CONCLUSION In the safety lead-in, the safety and tolerability of the encorafenib, binimetinib, and cetuximab regimen is manageable and acceptable for initiation of the randomized portion of the study. The observed efficacy is promising compared with available therapies and, if confirmed in the randomized portion of the trial, could establish this regimen as a new standard of care for previously treated BRAF V600E–mutant mCRC.
Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome
Authors: Simon Stacey L , McWhirter Laura , Diniz Behn Cecilia , Bubar Kate M , Kaar Jill L , Pyle Laura , Rahat Haseeb , Garcia-Reyes Yesenia , Carreau Anne-Marie , Wright Kenneth P , Nadeau Kristen J , Cree-Green Melanie 
Published: March 2019

Abstract

Context
To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed circadian timing of adolescence, which is an emerging link between circadian health and insulin sensitivity (SI), and decreased SI in PCOS.

Objective
To examine differences in the circadian melatonin rhythm between obese adolescent girls with PCOS and control subjects, and evaluate relationships between circadian variables and SI.

Design
Cross-sectional study.

Participants
Obese adolescent girls with PCOS (n = 59) or without PCOS (n = 33).

Outcome Measures
Estimated sleep duration and timing from home actigraphy monitoring, in-laboratory hourly sampled dim-light, salivary-melatonin and fasting hormone analysis.

Results
All participants obtained insufficient sleep. Girls with PCOS had later clock-hour of melatonin offset, later melatonin offset relative to sleep timing, and longer duration of melatonin secretion than control subjects. A later melatonin offset after wake time (i.e., morning wakefulness occurring during the biological night) was associated with higher serum free testosterone levels and worse SI regardless of group. Analyses remained significant after controlling for daytime sleepiness and sleep-disordered breathing.

Conclusion
Circadian misalignment in girls with PCOS is characterized by later melatonin offset relative to clock time and sleep timing. Morning circadian misalignment was associated with metabolic dysregulation in girls with PCOS and obesity. Clinical care of girls with PCOS and obesity would benefit from assessment of sleep and circadian health. Additional research is needed to understand mechanisms underlying the relationship between morning circadian misalignment and SI in this population.
Serum Uromodulin Is Associated With But Does Not Predict Type 2 Diabetes in Elderly KORA F4/FF4 Study Participants
Authors: Then Cornelia , Then Holger , Meisinger Christa , Heier Margit , Peters Annette , Koenig Wolfgang , Rathmann Wolfgang , Scherberich Jürgen , Seissler Jochen 
Published: March 2019

AbstractAimsSerum uromodulin has recently emerged as promising biomarker for kidney function and was suggested to be associated with type 2 diabetes (T2D) in patients with coronary heart disease. Here, we analyzed the association of serum uromodulin with T2D in the population-based KORA F4/FF4 study.MethodsIn 1119 participants of the KORA F4 study aged 62 to 81 years, serum uromodulin was measured, and the association of serum uromodulin with T2D was assessed using logistic and linear regression models stratified for sex. After a mean follow-up time of 6.5 years, 635 participants where re-evaluated. Glucose tolerance status was determined by oral glucose tolerance test at baseline and at the follow-up examination except in cases of known T2D.ResultsSerum uromodulin was inversely associated with T2D in the crude analysis and after adjustment for age and body mass index in men (P < 0.001) and in women (P < 0.05). After further adjustment for estimated glomerular filtration rate, serum uromodulin was significantly inversely associated with T2D in men (P < 0.001) but not in women. Serum uromodulin was not associated with prediabetes after multivariate adjustment and did not predict T2D in men or in women after the follow-up time of 6.5 ± 0.3 years.ConclusionsIn participants of the KORA F4 study, serum uromodulin is independently associated with T2D in men but is not a predictor of future development of T2D.
Recommendations for the packaging and containerizing of bioinformatics software
Authors: Gruening Bjorn , Sallou Olivier , Moreno Pablo , da Veiga Leprevost Felipe , Ménager Hervé , Søndergaard Dan , Röst Hannes , Sachsenberg Timo , O'Connor Brian , Madeira Fábio , Dominguez Del Angel Victoria , Crusoe Michael R. , Varma Susheel , Blankenberg Daniel , Jimenez Rafael C. ,   BioContainers Community, Perez-Riverol Yasset 
Published: March 2019

Software Containers are changing the way scientists and researchers develop, deploy and exchange scientific software. They allow labs of all sizes to easily install bioinformatics software, maintain multiple versions of the same software and combine tools into powerful analysis pipelines. However, containers and software packages should be produced under certain rules and standards in order to be reusable, compatible and easy to integrate into pipelines and analysis workflows. Here, we presented a set of recommendations developed by the BioContainers Community to produce standardized bioinformatics packages and containers. These recommendations provide practical guidelines to make bioinformatics software more discoverable, reusable and transparent. They are aimed to guide developers, organisations, journals and funders to increase the quality and sustainability of research software.
ПОВЫШЕНИЕ ИКТ-КОМПЕТЕНТНОСТИ РАБОТНИКОВ ОБРАЗОВАНИЯ КАК ПЕДАГОГИЧЕСКАЯ ПРОБЛЕМА
Authors: Gitman Elena Konstantinovna , Tokhtueva Tatiana Valerevna 
Published: March 2019

Цель. Статья посвящена актуальной проблеме подготовки высоко квалифицированных кадров, способных включать в образовательный процесс новые информационные технологии. Предметом анализа выступает готовность работников образования к повышению уровня ИКТ-компетентности. Авторы ставят своей целью выявить уровень ИКТ-компетентности педагогов разных возрастных категорий.Методология проведения работы. В основу исследования положены общетеоретические и эмпирические методы – сравнительный анализ и обобщения, наблюдение, анкетирование, эксперимент.Результаты. Авторами представлен анализ результатов констатирующего эксперимента. Авторы делают вывод о наличии проблемы неоднородности уровня владения ИКТ-компетентностью у педагогов разных поколений, поэтому возникает вопрос о необходимости выравнивания компетентностного фона работников образования.Область применения результатов. Результаты исследования выявляют необходимость качественного подхода к проблеме повышения ИКТ-компетентности современного педагога. Необходимы новые идеи в системе регулярной подготовки и переподготовки в сфере применения информационно-коммуникационных технологий в педагогической деятельности.
Diffuse Large B-Cell Lymphoma Mimicking an Ulcerative Colitis Flare
Authors: Mansour Ramy , Beattie Michael , Miller Justin , Haus Carolyn 
Published: March 2019

ABSTRACT
We present a case of non-Hodgkin lymphoma of the rectum in a 41-year-old African American male with a 1 year history of ulcerative colitis and no previous immunomodulatory therapy. The patient presented with a 10-day history of hematochezia, for which endoscopy was performed with gross findings indicative of ulcerative colitis flare. Tissue biopsy, however, demonstrated significant lymphoid infiltrating regions with histologic findings suggestive of a diffuse large B-cell lymphoma. Non-Hodgkin's lymphoma accounts for less than 1% of all cases of colorectal cancer. Associated risk factors have been previously reported but, were absent in the patient’s history. This suggests the possibility of distinct genetic abnormalities inherent to the tumor and/or an underlying germline mutation inherent to the patient that may have contributed to the premature development of diffuse large B-cell lymphoma.
Measurement of Drilling Fluid Rheology and Modeling of Thixotropic Behavior
Authors: Skadsem Hans Joakim , Leulseged Amare , Cayeux Eric 
Published: March 2019

AbstractDrilling fluids perform a number of important functions during a drilling operation, including that of lifting drilled cuttings to the surface and balancing formation pressures. Drilling fluids are usually designed to be structured fluids exhibiting shear thinning and yield stress behavior, and most drilling fluids also exhibit thixotropy. Accurate modeling of drilling fluid rheology is necessary for predicting friction pressure losses in the wellbore while circulating, the pump pressure needed to resume circulation after a static period, and how the fluid rheology evolves with time while in static or near-static conditions. Although modeling the flow of thixotropic fluids in realistic geometries is still a formidable future challenge to be solved, considerable insights can still be gained by studying the viscometric flows of such fluids. We report a detailed rheological characterization of a water-based drilling fluid and an invert emulsion oilbased drilling fluid. The micro structure responsible for thixotropy is different in these fluids which results in different thixotropic responses. Measurements are primarily focused at transient responses to step changes in shear rate, but cover also steady state flow curves and stress overshoots during start-up of flow. We analyze the shear rate step change measurements using a structural kinetics thixotropy model.
Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients – evidence for sex-specific differences
Authors: Artunc Ferruh , Haag Stefanie , Friedrich Björn , Mueller Christian , Häring Hans-Ulrich , Peter Andreas 
Published: March 2019

Abstract

Background
High sensitivity assays for the determination of cardiac troponin I (cTnI) are able to reliably measure cTnI far below the 99th percentile of healthy persons (hs-cTnI) and display sex-specific differences. There is uncertainty regarding the clinical utility of hs-cTnI in asymptomatic hemodialysis (HD) patients and if sex-specific differences also apply in this cohort.

Methods
In this multicenter study we measured hs-cTnI and sensitive cTnI (s-TnI) concentrations (both on Siemens Centaur) in 215 HD patients from a predialytic sample to determine the prevalence of elevated concentrations above the 99th percentile, the association with baseline characteristics, prognostic accuracy for death, and sex-specific differences.

Results
Hs-cTnI and s-cTnI concentrations were below the 99th percentile in 93% and 85% of patients with a median concentration of 12 ng/L (interquartile range 7–66) and 19 ng/L (12; 31, p < 0.0001). Hs-cTnI and s-cTnI concentrations were independently associated with age (p < 0.05) and ischemic cardiac disease (p < 0.05), but not with residual renal function. Both hs-cTnI and s-cTnI were predictors of death after median follow-up of 2.6 years with an AUC of 0.733 and 0.744, respectively (both p < 0.0001). Important sex-differences emerged for hs-cTnI, but not for s-cTnI: first, women had significantly lower hs-cTnI concentrations than men (p = 0.03); second, hs-cTnI had significantly higher prognostic accuracy for death in women than for men (AUC 0.824 vs. 0.674, p = 0.04).

Conclusions
The majority of HD patients have (h)s-cTnI concentrations below the 99th percentile. High normal values are predictive of death. Hs-cTnI allows to elucidate important sex-differences in HD patients with lower concentrations and higher prognostic accuracy in women.
Numerical Solution of Space and Time Fractional Telegraph Equation: A Meshless Approach
Authors: Bansu Hitesh , Kumar Sushil 
Published: March 2019

AbstractIn recent years, there has been an incredible enthusiasm towards fractional order partial differential equations because of their incessant presence alongside different fields. Fractional derivatives offer an in-depth and precise analysis of the models of the systems. Particularly, fractional order telegraph equations (FOTE) have been taken into consideration and solved by plenty of researchers, using different techniques. In this paper, we present a novel approach and technique to solve fractional telegraph equation by fusion of cubic radial basis function and Chebyshev polynomials with the aid of Kronecker product. The numerical examples have been considered to verify the accuracy and also to demonstrate the performance of the new approach.
The Multiplicity of Solutions for a Class of Nonlinear Fractional Dirichlet Boundary Value Problems with p-Laplacian Type via Variational Approach
Authors: Li Dongping , Chen Fangqi , An Yukun 
Published: March 2019

Abstract
In this paper, by using variational methods and a critical point theorem due to Bonanno and Marano, the existence of at least three weak solutions is obtained for a class of p-Laplacian type nonlinear fractional coupled systems depending on two parameters. Two examples are given to illustrate the applications of our main results.
Unfilled Training Positions in Germany – Regional and Establishment-Specific Determinants
Authors: Dummert Sandra , Leber Ute , Schwengler Barbara 
Published: March 2019

AbstractThe current situation in the German apprenticeship market is characterized by two contradictory developments. On the one hand, establishments are experiencing increasing problems filling the training positions they offer, and the number of vacant training positions is climbing. On the other hand, the transition into training is still difficult for many young people, and the number of unsuccessful vocational training applicants is rising. Hence, matching supply with demand is becoming increasingly difficult in the German job market for training positions. Using the Linked Employer-Employee dataset (LIAB) from the Institute for Employment Research (IAB), our paper provides a closer examination of the phenomenon of unfilled training positions. It presents an overview of the evolution of vacant training positions in eastern and western Germany and attempts to explain the number of vacancies by investigating the factors responsible for the establishments’ inability to fill their training positions. We assume that training position vacancies are due not only to internal company reasons such as firm size or the wage offer for apprentices but also to external conditions such as general regional factors. Therefore, our analysis also considers the situation on the demand side of the labor market within a region. The results of our multilevel mixed-effects estimations show that in addition to characteristics on the enterprise level, regional determinants also affect the share of vacant apprenticeships. With respect to establishment-related factors, mainly characteristics that describe the attractiveness of the firm prove to be important. With regard to regional-specific factors, we find that the availability of school leavers in a region in addition to the level of regional-sectoral competition impacts the recruiting success of establishments. Our analysis also shows that there are remarkable differences between eastern and western Germany concerning both the quantitative importance of unfilled training positions and the factors affecting them.
Language attitudes of young Romanians in Catalonia (Spain): The role of heritage language maintenance programs
Authors: Ianos Maria Adelina , Caballé Ester , Petreñas Cristina , Huguet Ángel 
Published: March 2019

Abstract
This article presents a mixed method analysis of the language attitudes held by secondary education students of Romanian origin, which are members of the second largest immigrant population living currently in Catalonia. The relevance of this data is based on the cardinal role played by attitudes in the success of any educational or linguistic policy (Lewis, E. Glyn. 1981. Bilingualism and bilingual education. Oxford, UK: Pergamon.) – a topic of special relevance in contexts with considerable migratory influxes, such as Catalonia, which aims to achieve social cohesiveness in a framework of interculturalism and multilingualism. The various initiatives implemented for this purpose include the heritage language maintenance programs, such as the “Romanian Language, Culture, and Civilization” (RLCC) program. The results showed that the young Romanians had the most favourable attitudes towards Spanish, followed closely by Romanian, and lastly Catalan, which was the least valued language. Furthermore, these attitudinal patterns were not determined by RLCC attendance. The insights provided by the in-depth interviews indicated various components and meanings associated with the attitudes towards the three languages. Namely, attitudes towards Spanish were primed by its international status and ease of learning, while attitudes towards Catalan were build on its integrative value and social status. Although esteemed for its emotional and symbolic bonds, Romanian seemed to be on a path towards invisibilization. Finally, the educational and social implications of these findings are discussed, emphasising the importance of involving and working with both the autochthonous and the Romanian immigrant population.
Enhancing functionalities of atomically thin semiconductors with plasmonic nanostructures
Authors: Cotrufo Michele , Sun Liuyang , Choi Junho , Alù Andrea , Li Xiaoqin 
Published: March 2019

Abstract
Atomically thin, two-dimensional, transition-metal dichalcogenide (TMD) monolayers have recently emerged as a versatile platform for optoelectronics. Their appeal stems from a tunable direct bandgap in the visible and near-infrared regions, the ability to enable strong coupling to light, and the unique opportunity to address the valley degree of freedom over atomically thin layers. Additionally, monolayer TMDs can host defect-bound localized excitons that behave as single-photon emitters, opening exciting avenues for highly integrated 2D quantum photonic circuitry. By introducing plasmonic nanostructures and metasurfaces, one may effectively enhance light harvesting, direct valley-polarized emission, and route valley index. This review article focuses on these critical aspects to develop integrated photonic and valleytronic applications by exploiting exciton–plasmon coupling over a new hybrid material platform.
Synthesis and characterization of size controlled bimetallic nanosponges
Authors: Wang Dong , Schaaf Peter 
Published: March 2019

AbstractMetallic and bimetallic nanosponges with well-defined size and form have attracted increasing attention due to their unique structural properties and their potential for many applications. In this chapter, the recently developed methods for the synthesis and preparation of metallic and bimetallic nanosponges are presented. These methods can be mainly cataloged in two groups: dealloying-based methods and reduction reaction-based methods. Different topographical reconstruction methods for the investigation of their structural properties are then reviewed briefly. The optical properties of the metallic nanosponges are clearly different from those of the solid counterparts due to the tailored disordered structure. The recent advances in the exploration of the distinct linear and non-linear optical properties of the nanosponges are summarized.Graphical Abstract: