bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming growth factor beta 1 levels in the blood of pediatric liver recipients: Clinical and biochemical correlations
Authors: Kurabekova Rivada , Tsirulnikova Olga , Pashkova Irina , Gichkun Olga , Mozheyko Natalia , Gautier Sergey , Shevchenko Olga 
Published: March 2020

AbstractTGF‐β1 is a cytokine with profibrogenic and immunosuppressive activities, which suggest the clinical significance of TGF‐β1 for the assessment of graft function after LT. We analyzed the dynamics of TGF‐β1 levels in the blood after LDLT in 135 pediatric liver recipients and examined the relationship between the cytokine levels and the laboratory and clinical variables. We found that TGF‐β1 levels in the blood of patients with ESLD were lower than that in healthy children of the same age, P = .001. Moreover, blood levels of TGF‐β1 were associated with liver disease etiology (r = .23) and hepatic fibrosis severity (r = .33). Before LDLT, TGF‐β1 levels were significantly higher in children with good outcomes than in recipients who developed graft dysfunction early in the post‐transplant period, P = .047. One month after LDLT, TGF‐β1 levels in blood plasma increased in pediatric recipients, P = .002. Cytokine levels were significantly correlated with gender (r = .21) and HLA (r = −.24) mismatches, as well as with TAC dosage (r = −.32) later in the post‐transplant period. One year after LDLT, TGF‐β1 plasma levels were higher (P = .01) than those before LDLT and did not correlate with most of the investigated biochemical and clinical variables. Conclusion: Blood levels of TGF‐β1 are associated with hepatic fibrosis severity, graft dysfunction development, and TAC dosage and can be regarded as a potential prognostic biomarker for the assessment of graft function and the optimization of immunosuppressant dosage in pediatric recipients after LDLT.
Vertical foreign direct investment: Make, buy, and sell
Authors: Milliou Chrysovalantou , Sandonis Joel 
Published: March 2020

AbstractAccording to conventional wisdom, multinational enterprises (MNEs) undertake vertical FDI to take advantage of cross‐border factor cost differences and source inputs from abroad at better terms. However, recent empirical studies document many instances in which intrafirm trade between parent firms and their vertically related foreign affiliates is absent. We provide theoretical support for these findings, demonstrating that a firm can engage in vertical FDI to exploit its intangible assets in another country and improve its input sourcing terms domestically by enhancing its cross‐threat. Furthermore, we show that the welfare implications of vertical FDI on the home and host country are neither always positive nor aligned.
Causes of Effects via a Bayesian Model Selection Procedure
Authors: Corradi Fabio , Musio Monica 
Published: March 2020

SummaryIn causal inference, and specifically in the causes-of-effects problem, one is interested in how to use statistical evidence to understand causation in an individual case, and in particular how to assess the so-called probability of causation. The answer involves the use of potential responses, which describe what would have happened to the outcome if we had observed a different value for the exposure. However, even given the best possible statistical evidence for the association between exposure and outcome, we can typically only provide bounds for the probability of causation. Dawid and his colleagues highlighted some fundamental conditions, namely exogeneity, comparability and sufficiency, that are required to obtain such bounds from experimental data. The aim of the present paper is to provide methods to find, in specific cases, the best subsample of the reference data set to satisfy these requirements. For this, we introduce a new variable, expressing the preference whether or not to be exposed, and we set the question up as a model selection problem. The best model is selected by using the marginal probability of the responses and a suitable prior over the model space. An application in the educational field is presented.
Discontinuous Galerkin Method and Dual-SLERP for Time Integration of Flexible Multibody Dynamics
Authors: Han Shilei , Bauchau Olivier A. 
Published: March 2020

Abstract
A novel time-discontinuous Galerkin (DG) method is introduced for the time integration of the differential-algebraic equations governing the dynamic response of flexible multibody systems. In contrast to traditional Galerkin methods, the rigid-body motion field is interpolated using the dual spherical linear scheme. Furthermore, the jumps inherent to time-DG methods are expressed in terms of a parameterization of the relative motion from one time-step to the next. The proposed scheme is third-order accurate for initial value problems of both rigid and flexible multibody dynamics.
Proglucagon peptide secretion profiles in type 2 diabetes before and after bariatric surgery: 1-year prospective study
Authors: Alexiadou Kleopatra , Cuenco Joyceline , Howard James , Wewer Albrechtsen Nicolai Jacob , Ilesanmi Ibiyemi , Kamocka Anna , Tharakan George , Behary Preeshila , Bech Paul R , Ahmed Ahmed R , Purkayastha Sanjay , Wheller Robert , Fleuret Matthieu , Holst Jens Juul , Bloom Stephen R , Khoo Bernard , Tan Tricia M-M 
Published: March 2020

IntroductionHyperglucagonemia is a key pathophysiological driver of type 2 diabetes. Although Roux-en-Y gastric bypass (RYGB) is a highly effective treatment for diabetes, it is presently unclear how surgery alters glucagon physiology. The aim of this study was to characterize the behavior of proglucagon-derived peptide (glucagon, glucagon-like peptide-1 (GLP-1), oxyntomodulin, glicentin) secretion after RYGB surgery.Research design and methodsProspective study of 19 patients with obesity and pre-diabetes/diabetes undergoing RYGB. We assessed the glucose, insulin, GLP-1, glucose-dependent insulinotropic peptide (GIP), oxyntomodulin, glicentin and glucagon responses to a mixed-meal test (MMT) before and 1, 3 and 12 months after surgery. Glucagon was measured using a Mercodia glucagon ELISA using the ‘Alternative’ improved specificity protocol, which was validated against a reference liquid chromatography combined with mass spectrometry method.ResultsAfter RYGB, there were early improvements in fasting glucose and glucose tolerance and the insulin response to MMT was accelerated and amplified, in parallel to significant increases in postprandial GLP-1, oxyntomodulin and glicentin secretion. There was a significant decrease in fasting glucagon levels at the later time points of 3 and 12 months after surgery. Glucagon was secreted in response to the MMT preoperatively and postoperatively in all patients and there was no significant change in this postprandial secretion. There was no significant change in GIP secretion.ConclusionsThere is a clear difference in the dynamics of secretion of proglucagon peptides after RYGB. The reduction in fasting glucagon secretion may be one of the mechanisms driving later improvements in glycemia after RYGB.Trial registration numberNCT01945840.
Association ofG6PDvariants with hemoglobin A1c and impact on diabetes diagnosis in East Asian individuals
Authors: Leong Aaron , Lim Victor Jun Yu , Wang Chaolong , Chai Jin-Fang , Dorajoo Rajkumar , Heng Chew-Kiat , van Dam Rob M , Koh Woon-Puay , Yuan Jian-Min , Jonas Jost B , Wang Ya Xing , Wei Wen-Bin , Liu Jianjun , Reilly Dermot F , Wong Tien-Yin , Cheng Ching-Yu , Sim Xueling 
Published: March 2020

ObjectiveHemoglobin A1c (HbA1c) accuracy is important for diabetes diagnosis and estimation of overall glycemia. TheG6PD-Asahi variant which causes glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to lower HbA1c independently of glycemia in African ancestry populations. As differentG6PDvariants occur in Asian ancestry, we sought to identify Asian-specificG6PDvariants associated with HbA1c.Research design and methodsIn eight Asian population-based cohorts, we performed imputation on the X chromosome using the 1000 Genomes reference panel and tested for association with HbA1c (10 005 East Asians and 2051 South Asians). Results were meta-analyzed across studies. We compared the proportion of individuals classified as having diabetes/pre-diabetes by fasting glucose ≥100 mg/dL or HbA1c ≥5.7% units among carriers and non-carriers of HbA1c-associated variants.ResultsThe strongest association was a missense variant (G6PD-Canton, rs72554665, minor allele frequency=2.2%, effect in men=−0.76% unit, 95% CI −0.88 to −0.64, p=1.25×10−27, n=2844). Conditional analyses identified a secondary distinct signal, missense variant (G6PD-Kaiping, rs72554664, minor allele frequency=1.6%, effect in men=−1.12 % unit, 95% CI −1.32 to −0.92, p=3.12×10−15, pconditional_Canton=7.57×10−11). Adjusting for glucose did not attenuate their effects. The proportion of individuals with fasting glucose ≥100 mg/dL did not differ by carrier status ofG6PD-Canton (p=0.21). Whereas the proportion of individuals with HbA1c ≥5.7% units was lower in carriers (5%) compared with non-carriers ofG6PD-Canton (30%, p=0.03).ConclusionsWe identified twoG6PDvariants in East Asian men associated with non-glycemic lowering of HbA1c. Carriers of these variants are more likely to be underdiagnosed for diabetes or pre-diabetes than non-carriers if screened by HbA1c without confirmation by direct glucose measurements.
Use of healthcare services and assistive devices among centenarians: results of the cross-sectional, international 5-COOP study
Authors: Dupraz Julien , Andersen-Ranberg Karen , Fors Stefan , Herr Marie , Herrmann Francois R , Wakui Tomoko , Jeune Bernard , Robine Jean-Marie , Saito Yasuhiko , Santos-Eggimann Brigitte 
Published: March 2020

ObjectivesTo measure the use of healthcare services and assistive devices by centenarians in five countries.DesignCross-sectional study using a survey questionnaire.SettingCommunity-dwelling and institutionalised centenarians living in Japan, France, Switzerland, Sweden and Denmark.Participants1253 participants aged 100 or in their 100th year of life, of whom 1004 (80.1%) were female and 596 (47.6%) lived in institutions.Main outcome measuresRecent use of medical visits, nursing care at home, home-delivered meals, acute care hospital stays overnight, professional assessments such as sight tests, mobility aids and other assistive devices. A set of national healthcare system indicators was collected to help interpret differences between countries.ResultsThere was considerable variability in the healthcare services and assistive devices used by centenarians depending on their country and whether they were community-dwelling or institutionalised. In contrast to the relatively homogeneous rates of hospitalisation in the past year (around 20%), community-dwelling centenarians reported widely ranging rates of medical visits in the past 3 months (at least one visit, from 32.2% in Japan to 86.6% in France). The proportion of community-dwellers using a mobility device to get around indoors (either a walking aid or a wheelchair) ranged from 48.3% in Japan to 79.2% in Sweden. Participants living in institutions and reporting the use of a mobility device ranged from 78.6% in Japan to 98.2% in Denmark.ConclusionsOur findings suggest major differences in care received by centenarians across countries. Some may result from the characteristics of national healthcare systems, especially types of healthcare insurance coverage and the amounts of specific resources available. However, unexplored factors also seem to be at stake and may be partly related to personal health and cultural differences.
What are potential barriers and enablers to patient and physician participation in Canadian cell therapy trials for stroke? A stakeholder interview study
Authors: Lalu Manoj M , Foster Madison , Presseau Justin , Dowlatshahi Dar , Castillo Gisell , Cardenas Analyssa , Tam Whitney , Zlepnig Jennifer , Timpson Deborah , Dong Yuan Yi , Juneau Pascale , Fergusson Dean A 
Published: March 2020

ObjectivesEarly phase cell therapy trials face many barriers to successful, timely completion. To optimise the conduct of a planned clinical trial of mesenchymal stem cell (MSC) therapy for chronic stroke, we sought patient and physician views on possible barriers and enablers that may influence their participation.DesignSemistructured interview study.SettingPatients were recruited from three rehabilitation centres in Ontario, Canada; physicians were recruited from across Canada through snowball sampling.ParticipantsThirteen chronic stroke patients (patients who had experienced a stroke at least 3 months prior; 10 male, 3 female) and 15 physicians (stroke physiatrists; 9 male, 6 female) participated in our interview study. Data adequacy was reached after 13 patient interviews and 13 physician interviews.MethodsInterview guides and directed content analysis were based on the Theoretical Domains Framework (TDF). Interviews were coded, and relevant themes were identified.ResultsMost patients were optimistic about participating in an MSC therapy clinical trial, and many expressed interest in participating, even if it was a randomised controlled trial with the possibility of being allocated to a placebo group. However, the method of administration of cells (intravascular preferred to intracerebral) and goal of the trial (efficacy preferred to safety) may influence their intention to participate. All physicians expressed interest in screening for the trial, though many stated they were less motivated to contribute to a safety trial. Physicians also identified several time-related barriers and the need for resources to ensure feasibility.ConclusionsThis novel application of the TDF helped identify key potential barriers and enablers prior to conducting a clinical trial of MSC therapy for stroke. This will be used to refine the design and conduct of our trial. A similar approach may be adopted by other investigators considering early phase cell therapy trials.
PREDICtors for health-related quality of life after elective sigmoidectomy for DIVerticular disease: the PREDIC-DIV study protocol of a prospective multicentric transnational observational study
Authors: Sohn Maximilian , Agha Ayman , Iesalnieks Igors , Bremer Susanne , Trum Stefanie , Di Cerbo Francesca , Nerlich Andreas , Lotz Natalie , Klieser Eckhard , Hochrein Alfred , Schredl Philipp , Kalcheva Dariya , Emmanuel Klaus , Presl Jaroslav 
Published: March 2020

IntroductionDiverticulitis is among the most common abdominal disorders. The best treatment strategy for this complicated disease as well as for recurrent stages is still under debate. Moreover, little knowledge exists regarding the effect of different therapeutic strategies on the health-related quality of life (HrQoL). Therefore, the PREDIC-DIV (PREDICtors for health-related quality of life after elective sigmoidectomy for DIVerticular disease) study aims to assess predictors of a change in HrQoL in patients after elective sigmoidectomy for diverticular disease.Methods and analysisA prospective multicentre transnational observational study was started in November 2017. Patients undergoing elective sigmoid resection for diverticular disease were included. Primary outcome includes HrQoL 6 months postoperatively, staged by the Gastrointestinal Quality of Life Index (GIQLI). Secondary outcomes include HrQoL 6 months after sigmoidectomy, assessed using the Short Form 36 Questionnaire and a custom-made Visual Analogue Scale-based inventory; HrQoL after 12 and 24 months; postoperative morbidity; mortality; influence of surgical technique (conventional laparoscopic multiport operation vs robotic approach); histological grading of inflammation and morphological characteristics of the bowel wall in the resected specimen; postoperative functional changes (faecal incontinence, faecal urge, completeness of emptying, urinary incontinence, sexual function); disease-specific healthcare costs; and changes in economic productivity, measured by the iMTA Productivity Cost Questionnaire. The total follow-up will be 2 years.Ethics and disseminationThe protocol was approved by the medical ethical committee of the Bavarian Medical Council (report identification number: 2017-177). The study was conducted in accordance with the Declaration of Helsinki. The findings of this study will be submitted to a peer-reviewed journal (BMJ Open,Annals of Surgery,British Journal of Surgery,Diseases of the Colon and the Rectum). Abstracts will be submitted to relevant national and international conferences.Trial registration numberThe study is registered with the ClinicalTrials.gov register asNCT03527706; Pre-results.
Physical activity and risk of behavioural and mental health disorders in kindergarten children: analysis of a series of cross-sectional complete enumeration (census) surveys
Authors: O'Brien Kathleen , Agostino Jason , Ciszek Karen , Douglas Kirsty A 
Published: March 2020

ObjectivesThere is mixed evidence on the relationship between physical activity and behavioural and mental health. We aimed to estimate the association between physical activity and risk of behavioural and mental health disorders in early school-aged children.DesignA series of cross-sectional complete enumeration (census) surveys.SettingsAll primary schools in the Australian Capital Territory, 2014–2016.ParticipantsAll children enrolled in their first year of full-time primary education (kindergarten) were invited to participate. Of the 16 662 eligible kindergarten children, 15 040 completed the survey for the first time.Outcome measuresAverage daily physical activity participation and prevalence of risk of behavioural and mental health disorders derived from parent-reported data and the Strengths and Difficulties Questionnaire (SDQ). Characteristics associated with SDQTotal difficultiesand subscales were estimated using logistic regression.Results8340 (61.7%) children met physical activity targets (60 min or more daily) and 709 (4.8%) were at clinically significant risk of behavioural and mental health disorders (Total difficulties).Known sociodemographic correlates were also those variables associated with high risk of behavioural and mental health disorders (Total difficulties): Aboriginal and Torres Strait Islander status (OR 2.72, 95% CI 1.78–4.16), relative socioeconomic disadvantage (most disadvantaged vs least disadvantaged, OR 1.86, 95% CI 1.38–2.50) and male sex (OR 1.80, 95% CI 1.49–2.17). Average daily physical activity was not significant, despite the highest levels of physical activity (90 min or more daily) being reported in boys, Aboriginal and Torres Strait Islander children and those from more disadvantaged areas.ConclusionsOur study provides comprehensive cross-sectional data on the relationship between physical activity participation and the risk of behavioural and mental health disorders in a large cohort of early school-aged Australian children. Aboriginal and Torres Strait Islander children, boys and those from the most disadvantaged socioeconomic group were at greatest risk of clinically significant behavioural and mental health disorders.
Patient perception of anticoagulant treatment for stroke prevention (RE-SONANCE study)
Authors: Vinereanu Dragos , Napalkov Dmitry , Bergler-Klein Jutta , Benczur Bela , Ciernik Martin , Gotcheva Nina , Medvedchikov Alexey , Põder Pentti , Simic Dragan , Skride Andris , Tang Wenbo , Trusz-Gluza Maria , Vesely Jiri , Vishnepolsky Tatiana , Vrabec Mirej 
Published: March 2020

ObjectiveWe evaluated atrial fibrillation (AF) patients’ perceptions of anticoagulation treatment with dabigatran or a vitamin K antagonist (VKA) for stroke prevention, according to accepted indications.MethodsThe RE-SONANCE observational, prospective, multicentre, international study used the validated Perception on Anticoagulant Treatment Questionnaire (PACT-Q) to assess patients with AF already taking a VKA who were switched to dabigatran (cohort A), and newly diagnosed patients initiated on either dabigatran or a VKA (cohort B). Visit 1 (V1) was at baseline, and visit 2 (V2) and visit 3 (V3) were at 30–45 and 150–210 days after baseline, respectively. Primary outcomes were treatment satisfaction and convenience in cohort A at V2 and V3 versus baseline, and in cohort B for dabigatran and a VKA at V2 and V3.ResultsThe main analysis set comprised 4100 patients in cohort A and 5365 in cohort B (dabigatran: 3179; VKA: 2186). In cohort A, PACT-Q2 improved significantly (p<0.001 for all) for treatment convenience (mean change V1 vs V2=20.72; SD=21.50; V1 vs V3=24.54; SD=22.85) and treatment satisfaction (mean change V1 vs V2=17.60; SD=18.76; V1 vs V3=21.04; SD=20.24). In cohort B, mean PACT-Q2 scores at V2 and V3 were significantly higher (p<0.001 for all) for dabigatran versus a VKA for treatment convenience (V2=18.38; SE =0.51; V3=23.34; SE=0.51) and satisfaction (V2=15.88; SE=0.39; V3=19.01; SE=0.41).ConclusionsSwitching to dabigatran from long-term VKA therapy or newly initiated dabigatran is associated with improved patient treatment convenience and satisfaction compared with VKA therapy.
Endonuclease FEN1 Coregulates ERα Activity and Provides a Novel Drug Interface in Tamoxifen-Resistant Breast Cancer
Authors: Flach Koen D. , Periyasamy Manikandan , Jadhav Ajit , Dorjsuren Dorjbal , Siefert Joseph C. , Hickey Theresa E. , Opdam Mark , Patel Hetal , Canisius Sander , Wilson David M. , Donaldson Collier Maria , Prekovic Stefan , Nieuwland Marja , Kluin Roelof J.C. , Zakharov Alexey V. , Wesseling Jelle , Wessels Lodewyk F.A. , Linn Sabine C. , Tilley Wayne D. , Simeonov Anton , Ali Simak , Zwart Wilbert 
Published: March 2020

Abstract

Estrogen receptor α (ERα) is a key transcriptional regulator in the majority of breast cancers. ERα-positive patients are frequently treated with tamoxifen, but resistance is common. In this study, we refined a previously identified 111-gene outcome prediction-classifier, revealing FEN1 as the strongest determining factor in ERα-positive patient prognostication. FEN1 levels were predictive of outcome in tamoxifen-treated patients, and FEN1 played a causal role in ERα-driven cell growth. FEN1 impacted the transcriptional activity of ERα by facilitating coactivator recruitment to the ERα transcriptional complex. FEN1 blockade induced proteasome-mediated degradation of activated ERα, resulting in loss of ERα-driven gene expression and eradicated tumor cell proliferation. Finally, a high-throughput 465,195 compound screen identified a novel FEN1 inhibitor, which effectively blocked ERα function and inhibited proliferation of tamoxifen-resistant cell lines as well as ex vivo–cultured ERα-positive breast tumors. Collectively, these results provide therapeutic proof of principle for FEN1 blockade in tamoxifen-resistant breast cancer.

Significance:
These findings show that pharmacologic inhibition of FEN1, which is predictive of outcome in tamoxifen-treated patients, effectively blocks ERα function and inhibits proliferation of tamoxifen-resistant tumor cells.