bluuebunny/crossref_metadata_2025_split huggingface dataset:
European survey on national harmonization in clinical research
Authors: Magnin Annette , Iversen Valentina Cabral , Calvo Gonzalo , Čečetková Beata , Dale Ola , Demlová Regina , Blaskó György , Keane Fionnuala , Kovacs Gabor L. , Levy‐Marchal Claire , Monteiro Emilia C. , Palmisano Lucia , Pella Daniel , Portolés Antonio , Rascol Olivier , Schmid Caecilia , Tay Fabian , von der Leyen Heiko , Ohmann Christian 
Published: February 2020

AbstractBackgroundClinical trials remain key to the development of evidence‐based medical practice. However, they are becoming increasingly complex, mainly in a multinational setting. To address these challenges, the European Union (EU) adopted the Clinical Trial Regulation EU No. 536/2014 (CTR). Once in force, the CTR will lead to more consistent rules and simplification of procedures for conducting clinical trials throughout the EU. Existing harmonization initiatives and “research infrastructures” for clinical trials may facilitate this process. This publication offers a snapshot of the current level of harmonization activities in academic clinical research in Europe.MethodsA survey was performed among the member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardized questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the harmonization of academic clinical research processes at national level, to facilitate the exchange of expertise and experience among countries, and to identify new fields of action.ResultsMost scientific partners already have in place various working groups and harmonization activities at national level. Furthermore, they are involved in and open to sharing their know‐how and documents. Since harmonization was mainly a bottom‐up approach up until now, the extent and topics dealt with are diverse and there is only little cross‐networking and cross‐country exchange so far.ConclusionsCurrently, the ECRIN member countries offer a very solid base and collaborative spirit for further aligning processes and exchanging best practices for clinical research in Europe. They can support a smooth implementation of the EU CTR and may act as single contact with consolidated expertise in a country.
Advances in predicting patient exposure to medical device leachables
Authors: Saylor David M. , Chandrasekar Vaishnavi , Elder Robert M. , Hood Alan M. 
Published: February 2020

AbstractMedical device materials contain chemicals that may pose toxicological concern(s) if released in sufficient quantities. Toxicological risk assessment approaches are increasingly being used in lieu of animal testing to address these concerns. Currently, these approaches rely primarily on in vitro extraction testing to estimate the potential for patients to be exposed to chemicals that may possibly leach out of device materials, but the clinical relevance of the test results is often ambiguous. Recent developments suggest physics‐based models can be used to provide more clinically relevant exposure estimates. However, the lack of data available to parameterize and validate these models presents a barrier to routine use. Herein, we provide an overview of these approaches, including considerations in developing and parameterizing exposure models, strategies that can be used to address the challenges associated with limited data, and potential future directions and improvements.
Narrowing the Protein Deficit Gap in Critically Ill Patients Using a Very High‐Protein Enteral Formula
Authors: ApSimon Michele , Johnston Carrie , Winder Barb , Cohen Sarah S. , Hopkins Bethany 
Published: February 2020

AbstractBackgroundProtein deficits have been associated with longer intensive care unit (ICU) stays and increased mortality. Current view suggests if protein goals are met, meeting full energy targets may be less important and prevent deleterious effects of overfeeding. We proposed a very‐high protein (VHP) enteral nutrition (EN) formula could provide adequate protein, without overfeeding energy, in the first week of critical illness.MethodsThis was a retrospective study of medical/surgical ICU patients receiving EN exclusively for ≥5 days during the first week of ICU admission. Twenty participants received standard EN; 20 participants received the VHP‐EN formula (1 kcal/mL, 37% protein). Protein and energy prescribed/received, gastrointestinal tolerance, and feeding interruptions were examined.ResultsForty ICU patients [average Acute Physiology and Chronic Health Evaluation II score of 20.1] were included. Protein prescribed and received was significantly higher in the VHP group vs the standard EN group (135.5 g/d ± 22.9 vs 111.4 g/d ± 25; P = .003 and 112.2 g/d ± 27.8 vs 81.7 g/d ± 16.7, respectively; P = .002). Energy prescribed and received was similar between groups (1696 kcal/d ± 402 vs 1893 kcal/d ± 341, respectively; P = .101 and 1520 kcal/d ± 346 vs 1506 ± 380 kcal/d; P = .901). There were no differences in EN tolerance (P = .065) or feeding interruptions (P = .336).ConclusionsUse of a VHP formula in ICU patients resulted in higher protein intakes without overfeeding energy or use of modular protein in the first 5 days of exclusive EN.
The relationship between social comparison and submissive behaviors in people with social anxiety: Paranoid social cognition as the mediator
Authors: Zaffar Warisha , Arshad Tehreem 
Published: February 2020

AbstractBiased evaluation fears and paranoid thoughts lead to various safety behaviors that are the cardinal features and perpetuating factors of social anxiety. The present study aimed to emphasize evaluative and paranoid thoughts that predispose and maintain this growing psychological condition. A cross‐sectional research design was employed to explore the relationship between social comparison, paranoid social cognitions, and submissive behaviors in patients with social anxiety. Furthermore, predictive effects of social comparison and paranoid ideation on submissiveness, along with mediating factors, were assessed in a clinical sample. The study sample consisted of 100 treatment‐seeking female patients of social anxiety (M = 25.21 years), recruited through purposive sampling. The findings revealed significant correlations between social comparison, paranoid social cognitions, and submissive behaviors. Rank, a subscale of social comparison, and paranoid social cognitions turned out as predictive factors of submissive behaviors. A novel finding is that paranoid social cognitions mediate the relationship between social comparison and submissive behaviors in socially anxious individuals. Study results will assist clinicians to devise effective management plans for patients by comprehending possible causes of submissiveness and considering paranoid ideation as a manifestation of social anxiety.
A review of flow field forecasting: A high‐dimensional forecasting procedure
Authors: Caudle Kyle , Fleming Patrick S. , Hoover Randy C. 
Published: February 2020

AbstractForecasting, especially high‐dimensional forecasting, is becoming more and more sought after, particularly as computing resources increase in both size and speed. Flow field forecasting is a general purpose regression‐based forecasting method that has recently been expanded to high‐dimensional settings. In this article, we provide an overview of the flow field forecasting methodology, with a particular emphasis on environments where the number of candidate predictor variables is large, potentially larger than the number of observations.This article is categorized under:
Statistical Models > Time Series Models
Statistical Learning and Exploratory Methods of the Data Sciences > Classification and Regression Trees
Statistical and Graphical Methods of Data Analysis > Data Reduction, Smoothing, and Filtering
Glucose transporter 1 in rheumatoid arthritis and autoimmunity
Authors: Zezina Ekaterina , Sercan‐Alp Oezen , Herrmann Matthias , Biesemann Nadine 
Published: February 2020

AbstractKnowledge about metabolism of immune cells increased almost exponentially during the last two decades and thereby created the new area immunometabolism. Increased glucose uptake and glycolysis were identified as one of the major drivers in immune cells for rapid adaptation to changes in the microenvironment or external stimuli. These metabolic switches are crucial to generate macromolecules for immune cell proliferation and activation. Glucose transporter 1 (GLUT1), a ubiquitously expressed glucose transporter, is strongly upregulated after innate and adaptive immune cell activation. Deletion or inhibition of GLUT1 blocked T cell proliferation and effector function, antibody production from B cells and reduced inflammatory responses in macrophages. Increased glucose uptake and GLUT1 expression are not only observed in proinflammatory conditions, but also in murine models of autoimmunity as well as in human patients. Rheumatoid arthritis (RA), the most common autoimmune disease, is characterized by infiltration of immune cells, hyperproliferation of fibroblast‐like synoviocytes, and destruction of cartilage and bone. These processes create a hypoxic microenvironment in the synovium. Moreover, synovial samples including fibroblast‐like synoviocytes from RA patients showed increased lactate level and upregulate GLUT1. Similar upregulation of GLUT1 is observed in systemic lupus erythematosus and psoriasis patients as well as in murine autoimmune models. Inhibition of GLUT1 using either T cell specific knockouts or small molecule GLUT1/glycolysis inhibitors improved phenotypes of different murine autoimmune disease models like arthritis, lupus, and psoriasis. Thereby the therapeutic potential of immunometabolism and especially interference with glycolysis was proven.This article is categorized under:
Biological Mechanisms > Metabolism
Translational, Genomic, and Systems Medicine > Translational Medicine
Physiology > Mammalian Physiology in Health and Disease
Quantum elliptic Calogero-Moser systems from gauge origami
Authors: Chen Heng-Yu , Kimura Taro , Lee Norton 
Published: February 2020

Abstract
We systematically study the interesting relations between the quantum elliptic Calogero-Moser system (eCM) and its generalization, and their corresponding supersymmetric gauge theories. In particular, we construct the suitable characteristic polynomial for the eCM system by considering certain orbifolded instanton partition function of the corresponding gauge theory. This is equivalent to the introduction of certain co-dimension two defects. We next generalize our construction to the folded instanton partition function obtained through the so-called “gauge origami” construction and precisely obtain the corresponding characteristic polynomial for the doubled version, named the elliptic double Calogero-Moser (edCM) system.
Superfluids, vortices and spinning charged operators in 4d CFT
Authors: Cuomo Gabriel 
Published: February 2020

Abstract
We include vortices in the superfluid EFT for four dimensional CFTs at large global charge. Using the state-operator correspondence, vortices are mapped to charged operators with large spin and we compute their scaling dimensions. Different regimes are identified: phonons, vortex rings, Kelvin waves, and vortex crystals. We also compute correlators with a Noether current insertion in between vortex states. Results for the scaling dimensions of traceless symmetric operators are given in arbitrary spacetime dimensions.
IL6-receptor antibody tocilizumab as salvage therapy in severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a retrospective analysis
Authors: Kattner Anna-Sophia , Holler Ernst , Holler Barbara , Klobuch Sebastian , Weber Daniela , Martinovic Danilo , Edinger Matthias , Herr Wolfgang , Wolff Daniel 
Published: February 2020

AbstractChronic graft-versus-host disease (cGvHD) remains the most relevant factor affecting survival after allogeneic hematopoietic stem cell transplantation (alloHSCT). Besides corticosteroids (and ibrutinib in the USA), there is no established therapy for cGvHD. Tocilizumab, a humanized IgG1 IL6-receptor antibody, has shown efficacy in acute GvHD and cGvHD. We retrospectively analyzed the efficacy and safety of tocilizumab for the treatment of advanced cGvHD. Eleven patients with severe steroid refractory cGvHD (median age 49; range 21–62 years) that received at least two prior lines of therapy for cGvHD (range 2–8 regimens) were treated with tocilizumab (q4w, dosage 8 mg/kg IV) with a median number of 15 cycles (range 2–31). NIH consensus criteria grading for cGvHD were recorded prior to tocilizumab administration and after 3, 6, and 12 months of therapy. All patients received additional concomitant immunosuppression (IS) but no new IS within the last 4 weeks before start of tocilizumab and response assessment was terminated before start of any new IS. The median number of days between alloHSCT and initiation of tocilizumab therapy was 1033 days. Organs involved at initiation of tocilizumab therapy were skin (100%, all grade 3), eyes (82%), fascia (82%), mouth (64%), lungs (55%), and genitals (18%). Overall, 7/10 patients (70%) showed partial remission, 2/10 patients (20%) showed progressive cGvHD, 1/10 patient (10%) showed mixed response, and 1 patient died due to sepsis before first response assessment 1.5 months after initiation of treatment. Four patients required subsequent new immunosuppressive treatment. Two patients developed bacterial sepsis, one of whom died. The overall survival and relapse-free survival were 82% with an average follow-up of 22 months (range 1.5–52 months). Tocilizumab seems a promising treatment option in advanced cGvHD but further evaluation within a phase II trial is required.
Rechtsverträgliche und qualitätszentrierte Gestaltung für „KI made in Germany“
Authors: Knote Robin , Thies Laura Friederike , Söllner Matthias , Jandt Silke , Leimeister Jan Marco , Roßnagel Alexander 
Published: February 2020

ZusammenfassungKünstlich intelligente (KI) Systeme erfreuen sich immer größerer Beliebtheit. Insbesondere smarte persönliche Assistenten (SPAs) von Amazon, Google und vielen weiteren verzeichnen ein stetiges Marktwachstum. Den vielfältigen Potenzialen dieser KI-Systeme stehen jedoch auch zahlreiche Risiken gegenüber. Berichte von Datenpannen und -lecks häufen sich und haben bei Nutzern eine zunehmende Skepsis zur Folge, was zu einem gespaltenen Bild von KI in der Gesellschaft beiträgt. Diesem Problem stellt sich das Forschungsprojekt AnEkA mit einem interdisziplinären Gestaltungsansatz. Auf Basis von Rechts- und Qualitätszielen werden Anforderungen an rechtsverträgliche und qualitativ hochwertige SPAs abgeleitet. Zusätzlich werden Gestaltungsalternativen identifiziert, die diese Anforderungen unter Berücksichtigung möglicher Zielkonflikte umsetzen. Ergebnis des Projekts sind Entwurfsmuster, die Entwicklern von SPAs dabei helfen sollen, rechtsverträgliche und qualitativ hochwertige SPAs und KI-Systeme im Allgemeinen zu entwickeln. Dadurch soll das Alleinstellungsmerkmal einer „KI made in Germany“ entstehen, welche sowohl die Bedürfnisse von Nutzern berücksichtigt und sie ebenfalls bestmöglich vor Risiken der Systemnutzung schützt. Dieser Beitrag erläutert das interdisziplinäre Vorgehen anhand eines Szenarios zur Nutzung von SPAs.
Real-world use of denosumab and bisphosphonates in patients with solid tumours and bone metastases in Germany
Authors: Diel Ingo , Ansorge Sonja , Hohmann David , Giannopoulou Christina , Niepel Daniela , Intorcia Michele 
Published: February 2020

Abstract
Purpose
Bisphosphonates and denosumab prevent bone complications in patients with bone metastases from solid tumours. This retrospective, longitudinal, cohort study provides data on their real-world use in this setting in Germany.

Methods
Adults with bone metastases from breast, prostate or lung cancer who were newly initiated on a bisphosphonate or denosumab between 1 July 2011 and 31 December 2015 were identified from a German healthcare insurance claims database. Primary outcomes included persistence, compliance, discontinuation and switch rates at 12 months.

Results
This study included 1130 patients with bone metastases: 555 (49%) had breast cancer, 361 (32%) prostate cancer and 242 (21%) lung cancer. Mean age was 65 years for patients with breast or lung cancer and 74 years for those with prostate cancer. Across all tumour types, compared with any bisphosphonate, 12-month persistence was higher with denosumab (breast cancer 78% vs 54–58%, prostate cancer 58% vs 50%, lung cancer 68% vs 34–60%), median time to discontinuation was longer with denosumab and switch rates were lower for denosumab (breast cancer 5% vs 14–19%, prostate cancer 2% vs 11%, lung cancer 3% vs 7–12%). Compliance at 12 months was longer for denosumab than for any bisphosphonate in breast cancer (75% vs 42–48%) and in prostate cancer (47% vs 36%).

Conclusions
Patients initiated on denosumab following a diagnosis of bone metastases from breast, prostate or lung cancer had greater medication persistence, longer time to discontinuation, improved compliance and lower switch rates than those initiated on a bisphosphonate.
Small area estimation under a measurement error bivariate Fay–Herriot model
Authors: Burgard Jan Pablo , Esteban María Dolores , Morales Domingo , Pérez Agustín 
Published: February 2020

AbstractThe bivariate Fay–Herriot model is an area-level linear mixed model that can be used for estimating the domain means of two correlated target variables.
Under this model, the dependent variables are direct estimators calculated from survey data and the auxiliary variables are true domain means obtained from external data sources. Administrative registers do not always give good auxiliary variables, so that statisticians sometimes take them from alternative surveys and therefore they are measured with error.
We introduce a variant of the bivariate Fay–Herriot model that takes into account the measurement error of the auxiliary variables and we give fitting algorithms to estimate the model parameters. Based on the new model, we introduce empirical best predictors of domain means and we propose a parametric bootstrap procedure for estimating the mean squared error. We finally give an application to estimate poverty proportions and gaps in the Spanish Living Condition Survey, with auxiliary information from the Spanish Labour Force Survey.
Engineering a defined culture medium to grow Piscirickettsia salmonis for its use in vaccine formulations
Authors: Fuentealba Pablo , Latorre Yesenia , González Ernesto , Martínez Irene , Soto Carmen , Altamirano Claudia 
Published: February 2020

Abstract
Piscirickettsia salmonis is a facultative Gram-negative intracellular bacterium that produces piscirickettsiosis, disease that causes a high negative impact in salmonid cultures. The so-far-unidentified nutritional requirements have hindered its axenic culture at laboratory and industrial scales for the formulation of vaccines. The present study describes the development of a defined culture medium for P. salmonis. The culture medium was formulated through rational design involving auxotrophy test and statistical designs of experiments, considering the genome-scale metabolic reconstruction of P. salmonis reported by our group. The whole optimization process allowed for a twofold increase in biomass and a reduction of about 50% of the amino acids added to the culture medium. The final culture medium contains twelve amino acids, where glutamic acid, threonine and arginine were the main carbon and energy sources, supporting 1.65 g/L of biomass using 6.5 g/L of amino acids in the formulation. These results will contribute significantly to the development of new operational strategies to culture this bacterium for the production of vaccines.
Transnational Legal Communication: Towards Comprehensible and Consistent Law
Authors: Osiejewicz Joanna 
Published: February 2020

AbstractTransnational legal communication seeks to identify transnational legal regimes and attempts to establish channels and technics for comprehensible communication of the legal information to specified groups of recipients. It also strives to conclude about possible inconsistencies in law. The approach is based on the cooperation of scientists within the area of law and applied linguistics and the coordination of their efforts, in order to conduct research from various perspectives, share conclusions and develop more complete approaches as well as achieve and mutually use more multilateral research results. It strives to reconcile legal research and linguistics research despite of their very different paradigms. The paper aims to explain the nature of legal communication and to establish its general research questions and objectives. The study is going to find an answer to the question what methods are to be used to communicate law comprehensively to its recipients and to draw conclusions on the consistency of legal regimes to be communicated. It accentuates that the solidarity necessary to achieve the objective of comprehensible and consistent law goes beyond the particular interests of individual sciences and is the foundation of the existence of the transnational legal communication community, non-depending on the place of living and the scope of practical knowledge.
Evaluation of Fagopyrum esculentum Moench germplasm based on agro-morphological traits and the rutin and quercetin content of seeds under spring cultivation
Authors: Rauf Muhammad , Yoon Hyemyeong , Lee Sukyeung , Hyun Do Yoon , Lee Myung-Chul , Oh Sejong , Choi Yu -Mi 
Published: February 2020

AbstractBuckwheat is an important grain crop known for its nutritional value and content of bioactive compounds, particularly rutin. In this study, we characterized diverseFagopyrum esculentumMoench germplasm for the diversity of agro-morphological characteristics and the rutin and quercetin content in seeds under the spring cultivation. Of the 251 germplasm accessions assessed, 193 had red stems, 182 had a pale brown seed coat color, and 238 had ovate seeds. The times taken to reach 50% flowering and 80% maturity ranged from 38–45 to 73–95 days, respectively. The 1000-seed weight (TSW) varied from 21 to 42 g. Overall, the content of rutin and quercetin ranged from 7.22–47.86 to 0–1.22 mg/100 g DW, respectively. The number of days to flowering and maturity showed negative correlations with TSW and rutin and quercetin content. However, we found that at 73–80 days after sowing, early-maturing germplasm had significantly higher mean rutin content than either intermediate-or late-maturing germplasm. The TSW weight showed a positive correlation with the content of rutin and quercetin. We identified promising accessions based early maturity (< 80 days), higher seed weight (≥ 35 g) and higher content of rutin (≥ 35 mg/100 g DW) and quercetin (≥ 1 mg/100 g DW). These accessions will help to enhance grain yield and the rutin and quercetin content in existing buckwheat cultivars for spring cultivation.