bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular models for beta‐cell function and diabetes gene therapy
Authors: Green A. D. , Vasu S. , Flatt P. R. 
Published: December 2017

AbstractDiabetes is characterized by the destruction and/or relative dysfunction of insulin‐secreting beta‐cells in the pancreatic islets of Langerhans. Consequently, considerable effort has been made to understand the physiological processes governing insulin production and secretion in these cells and to elucidate the mechanisms involved in their deterioration in the pathogenesis of diabetes. To date, considerable research has exploited clonal beta‐cell lines derived from rodent insulinomas. Such cell lines have proven to be a great asset in diabetes research, in vitro drug testing, and studies of beta‐cell physiology and provide a sustainable, and in many cases, more practical alternative to the use of animals or primary tissue. However, selection of the most appropriate rodent beta cell line is often challenging and no single cell line entirely recapitulates the properties of human beta‐cells. The generation of stable human beta‐cell lines would provide a much more suitable model for studies of human beta‐cell physiology and pathology and could potentially be used as a readily available source of implantable insulin‐releasing tissue for cell‐based therapies of diabetes. In this review, we discuss the history, development, functional characteristics and use of available clonal rodent beta‐cell lines, as well as reflecting on recent advances in the generation of human‐derived beta‐cell lines, their use in research studies and their potential for cell therapy of diabetes.
Letter: thiopurines ‐ is less really more? Authors’ reply
Authors: Roblin X. , Paul S. , Nancey S. , Flourie B. 
Published: December 2017

Linked ContentThis article is linked to Roblin et al papers. To view these articles visit https://doi.org/10.1111/apt.14106 and https://doi.org/10.1111/apt.14375.
Letter: biologics treatment in Crohn's disease and risk of bowel resection—what about the patients who stop anti‐TNF therapy? Authors’ reply
Authors: Eberhardson M. , Söderling J. K. , Olén O. 
Published: December 2017

Linked ContentThis article is linked to Eberhardson et al and Ribaldone papers. To view these articles visit https://doi.org/10.1111/apt.14224 and https://doi.org/10.1111/apt.14321.
Patients with chronic bipolar disorder exhibit widespread increases in extracellular free water
Authors: Tuozzo Carissa , Lyall Amanda E. , Pasternak Ofer , James Anthony C.D. , Crow Timothy J. , Kubicki Marek 
Published: December 2017

ObjectivesBipolar disorder (BP) is a debilitating psychiatric disease that is not well understood. Previous diffusion magnetic resonance imaging (dMRI) studies of BP patients found prominent microstructural white matter (WM) abnormalities of reduced fractional anisotropy (FA). Because FA is a nonspecific measure, relating these abnormalities to a specific pathology is difficult. Here, dMRI specificity was increased by free water (FW) imaging, which allows identification of changes in extracellular space (FW) from neuronal tissue (fractional anisotropy of tissue [FA‐t]). Previous studies identified increased FW in early schizophrenia (SZ) stages which was replaced by widespread decreased FA‐t in chronic stages. This is the first analysis utilizing this method to compare BP patients and controls.Methods3 Tesla diffusion weighted imaging (3T DWI) data were acquired for 17 chronic BP and 28 healthy control (HC) participants at Oxford University. Tract‐based spatial statistics was utilized to generate a WM skeleton. FW imaging deconstructed the diffusion signal into extracellular FW and tissue FA‐t maps. These maps were projected onto the skeleton and FA, FA‐t, and FW were compared between groups.ResultsWe found significantly lower FA in BP patients when compared to HC in areas that overlapped with extensive FW increases. There were no FA‐t differences.ConclusionsOur study suggests that chronic BP shows similar WM changes to early SZ, suggesting that extracellular FW increases could be a transient indication of recent psychotic episodes. Since FW increase in SZ has been suggested to be related to neuroinflammation, we theorize that neuroinflammation might be a shared pathology between chronic BP and early SZ.
New Semiparametric Method for Predicting High-Cost Patients
Authors: Maidman Adam , Wang Lan 
Published: December 2017

Summary
Motivated by the Medical Expenditure Panel Survey containing data from individuals’ medical providers and employers across the United States, we propose a new semiparametric procedure for predicting whether a patient will incur high medical expenditure. Problems of the same nature arise in many other important applications where one would like to predict if a future response occurs at the upper (or lower) tail of the response distribution. The common practice is to artificially dichotomize the response variable and then apply an existing classification method such as binomial regression or a classification tree. We propose a new semiparametric prediction rule to classify whether a future response occurs at the upper tail of the response distribution. The new method can be considered a semiparametric estimator of the Bayes rule for classification and enjoys some nice features. It does not require an artificially dichotomized response and better uses the information contained in the data. It does not require any parametric distributional assumptions and tends to be more robust. It incorporates nonlinear covariate effects and can be adapted to construct a prediction interval and hence provides more information about the future response. We provide an R package plaqr to implement the proposed procedure and demonstrate its performance in Monte Carlo simulations. We illustrate the application of the new method on a subset of the Medical Expenditure Panel Survey data.
Dynamic Borrowing Through Empirical Power Priors that Control Type I Error
Authors: Nikolakopoulos Stavros , van der Tweel Ingeborg , Roes Kit C. B. 
Published: December 2017

Summary
In order for historical data to be considered for inclusion in the design and analysis of clinical trials, prospective rules are essential. Incorporation of historical data may be of particular interest in the case of small populations where available data is scarce and heterogeneity is not as well understood, and thus conventional methods for evidence synthesis might fall short. The concept of power priors can be particularly useful for borrowing evidence from a single historical study. Power priors employ a parameter that quantifies the heterogeneity between the historical study and the new study. However, the possibility of borrowing data from a historical trial will usually be associated with an inflation of the type I error. We suggest a new, simple method of estimating the power parameter suitable for the case when only one historical dataset is available. The method is based on predictive distributions and parameterized in such a way that the type I error can be controlled by calibrating to the degree of similarity between the new and historical data. The method is demonstrated for normal responses in a one or two group setting. Generalization to other models is straightforward.
C-learning: A new Classification Framework to Estimate Optimal Dynamic Treatment Regimes
Authors: Zhang Baqun , Zhang Min 
Published: December 2017

Summary
A dynamic treatment regime is a sequence of decision rules, each corresponding to a decision point, that determine that next treatment based on each individual's own available characteristics and treatment history up to that point. We show that identifying the optimal dynamic treatment regime can be recast as a sequential optimization problem and propose a direct sequential optimization method to estimate the optimal treatment regimes. In particular, at each decision point, the optimization is equivalent to sequentially minimizing a weighted expected misclassification error. Based on this classification perspective, we propose a powerful and flexible C-learning algorithm to learn the optimal dynamic treatment regimes backward sequentially from the last stage until the first stage. C-learning is a direct optimization method that directly targets optimizing decision rules by exploiting powerful optimization/classification techniques and it allows incorporation of patient's characteristics and treatment history to improve performance, hence enjoying advantages of both the traditional outcome regression-based methods (Q- and A-learning) and the more recent direct optimization methods. The superior performance and flexibility of the proposed methods are illustrated through extensive simulation studies.
Left behind and left out: The impact of the school environment on young people with continence problems
Authors: Whale Katie , Cramer Helen , Joinson Carol 
Published: December 2017

ObjectivesTo explore the impact of the secondary school environment on young people with continence problems.DesignIn‐depth qualitative semi‐structured interviews.MethodsWe interviewed 20 young people aged 11–19 years (11 female and nine male) with continence problems (daytime wetting, bedwetting, and/or soiling). Interviews were conducted by Skype (n = 11) and telephone (n = 9). Transcripts were analysed using inductive thematic analysis.ResultsWe generated five main themes: (1) Boundaries of disclosure: friends and teachers; (2) Social consequences of avoidance and deceit; (3) Strict and oblivious gatekeepers; (4) Intimate actions in public spaces; and (5) Interrupted learning.ConclusionDisclosure of continence problems at school to both friends and teachers was rare, due to the perceived stigma and fears of bullying and social isolation. The lack of disclosure to teachers and other school staff, such as pastoral care staff, creates challenges in how best to support these young people. Young people with continence problems require unrestricted access to private and adequate toilet facilities during the school day. There is a need for inclusive toilet access policies and improved toilet standards in schools. Addressing the challenges faced by young people with continence problems at school could help to remove the barriers to successful self‐management of their symptoms. It is particularly concerning that young people with continence problems are at higher risk of academic underachievement. Increased support at school is needed to enable young people with continence problems to achieve their academic potential.
Statement of Contribution

What is already known on this subject?

Continence problems are among the most common paediatric health problems

Self‐management of continence problems requires a structured schedule of fluid intake and bladder emptying

Inadequate toilet facilities and restricted access make it difficult for young people to manage their incontinence

What does this study add?

Improvement is needed in teacher understanding of the needs of young people with continence problems

Young people are reluctant to disclose continence problems due to perceived stigma and fear of social isolation

Young people with continence problems may be at increased risk of academic underachievement
Physical activity and family‐based obesity treatment: a review of expert recommendations on physical activity in youth
Authors: Foster C. , Moore J. B. , Singletary C. R. , Skelton J. A. 
Published: December 2017

SummaryTargeting physical inactivity in children is pertinent to aiding in the decrease of childhood obesity rates. Only 33% of adolescents are obtaining the recommended goal of at least 60 min of physical activity per day. The objectives of this review are to summarize professional recommendations for physical activity and exercise in children and adolescents, and identify family‐centred strategies that can be implemented by weight management clinicians. Clinically oriented recommendations and policy statements from professional organizations were identified through literature and internet searches, summarized using rubrics of aerobic, muscle strengthening and bone strengthening exercise, then examined for details on family‐based focus, inclusion of child developmental stage and age, and application to the prevention and treatment of obesity. Current recommendations give guidelines for the amount of physical activity that children should acquire and how many days a week activities should occur. However, available guidelines need an improved approach to addressing the role of the parents and caregivers in targeting physical activity and weight management in youth. Efforts must be taken in order to make sure that the types of physical activity offered are both suitable and enjoyable. Sports, games, free play and other age appropriate activities are adequate ways to increase moderate to vigorous physical activity in children. Differentiating physical activities types in accordance with developmental stage, level of enjoyment, and family characteristics is needed to establish sustainable habits. One paediatric obesity program has developed approaches to teaching families fun and engaging ways to be active together.
Prevalence of comorbidities in patients with obstructive sleep apnea syndrome, overlap syndrome and obesity hypoventilation syndrome
Authors: Lacedonia Donato , Carpagnano Giovanna Elisiana , Patricelli Giulia , Carone Mauro , Gallo Crescenzio , Caccavo Incoronata , Sabato Roberto , Depalo Annarita , Aliani Maria , Capozzolo Alberto , Foschino Barbaro Maria Pia 
Published: December 2017

AbstractIntroductionSleep‐disordered breathing causes a burden to the sufferer, the health care system and the society. Most studies have focused on obstructive sleep apnea (OSA); however, the prevalence of comorbidities in patients affected by overlap syndrome (OS) and obesity hypoventilation syndrome (OHS) has not been carefully evaluated.Study objectivesThe principal aim of this study was to identify the presence of comorbidities in patients suffering from OSA, OS, OHS and the differences in three groups of patients. Another purpose was to verify if sleepiness is associated with a greater prevalence of comorbidities.MethodsA retrospective analysis in 989 adults referred for sleep diagnostic testing to our sleep center was performed. Patients were classified in OSA (721), OS (123) and OHS (145).ResultsThe prevalence of comorbidities was higher in patients affected by OS and was the highest in the OHS group, while the prevalence of arterial hypertension is the highest in patients affected by OS. The probability of having more than two comorbidities follows the same trend. Excessive daytime sleepiness was associated with an increased rate of arterial hypertension, diabetes mellitus and the presence of multimorbidity in each group of patients.ConclusionsThe presence and the association of comorbidities seem to be higher in patients suffering from OSA, OS and OHS. Subjects suffering of OHS present a high prevalence of main diseases despite their younger age compared with others patients with SDB. Sleepiness may have a role, at least in a subset of these patients, into the development of comorbidities.
Das infantile Hämangiom: Pathogenese und Wirkmechanismus von Propranolol
Authors: Rotter Anita , de Oliveira Zilda Najjar Prado 
Published: December 2017

ZusammenfassungDas infantile Hämangiom (IH) ist der häufigste gutartige Tumor im Kindesalter. Die Prävalenz beträgt 4 % bis 10 %. Es ist gekennzeichnet durch eine proliferative schnelle Wachstumsphase, die nach wenigen Lebenswochen beginnt, gefolgt von einer langsamen Regressionsphase. Bei den IH‐Fällen, bei denen eine Entstellung oder lebensbedrohlicher Verlauf zu befürchten ist (10 % bis 15 % aller Fälle), sollte unverzüglich eine systemische Therapie eingeleitet werden.DatenquelleDie vorliegende Studie gibt einen Überblick über die publizierten wissenschaftlichen Artikel in zuverlässigen elektronischen Datenbanken. Wir wählten alle Studien aus, welche die Pathogenese des IH und den Wirkmechanismus von Propranolol untersuchten.ErgebnisseDie Pathogenese des IH wurde noch nicht vollständig aufgeklärt. Wie Studien zeigen, liegt in der Proliferationsphase des IH ein Ungleichgewicht der angiogenen Faktoren vor. Darüber hinaus steigen die Spiegel des vaskulären endothelialen Wachstumsfaktors (VEGF) und der Matrix‐Metalloproteinasen 2 und 9 an. In der Regressionsphase nehmen die Konzentrationen dieser Faktoren ab, während die Spiegel der anti‐angiogenen Faktoren, darunter die der Gewebeinhibitoren der Matrix‐Metalloproteinasen, zunehmen. Seit 2008 stellt die Behandlung mit Propranolol das Mittel der ersten Wahl dar. Dieses Arzneimittel beeinflusst den Gefäßtonus, die Angiogenese und die Apoptose. Die derzeitigen Kenntnisse über die Pathogenese des IH ermöglicht die Entwicklung neuer therapeutischer Strategien.
Regionale fachärztliche Versorgung und demographischer Wandel in Deutschland – Szenarien zur dermatologischen Versorgung im Jahr 2035
Authors: Kis Anne , Augustin Matthias , Augustin Jobst 
Published: December 2017

ZusammenfassungHintergrundMithilfe der Bedarfsplanungsrichtlinie des Gemeinsamen Bundesausschusses soll die medizinische Versorgung in Deutschland flächendeckend sichergestellt werden. Kalkulatorische Größe zur Abbildung der räumlichen Versorgungssituation ist der „korrigierte Versorgungsgrad“. Vor dem Hintergrund des demographischen Wandels und bereits heute existenter Wiederbesetzungsschwierigkeiten steht die Frage, wie sich die dermatologische Versorgung kleinräumig entwickeln wird.MethodikMit bundesweiten Daten zu Hautarztstandorten sowie aktuellen und prognostizierten Bevölkerungszahlen auf Kreisebene wurde auf Basis der aktuellen Bedarfsplanungsrichtlinie der korrigierte Versorgungsgrad in drei Wiederbesetzungsszenarien (Szenario 1: 100%ige Wiederbesetzung, Szenario 2: Wegfall eines Arztsitzes je Planungsbereich, Szenario 3: Wegfall von zwei Arztsitzen in ländlichen Planungsbereichen) für das Prognosejahr 2035 exemplarisch berechnet.ErgebnisseWährend sich in Szenario 1 die Versorgungssituation von 2014 auf 2035 in einigen Teilräumen sogar verbessern würde (n = 3 nicht mehr unterversorgt), zeigen die wahrscheinlicheren Szenarien 2 und 3 mit dem Wegfall einzelner Arztstandorte und dem altersselektiven Wanderungsverhalten, dass ganze Regionen in die Unterversorgung gelangen könnten.SchlussfolgerungenEs ist davon auszugehen, dass die räumliche Heterogenität der dermatologischen Versorgung unter Berücksichtigung des demographischen Wandels zunehmen wird. Weitere Anstrengungen in der Bedarfsplanung, aber auch hinsichtlich kreativer Versorgungsmodelle und interkommunaler Kooperation sind erforderlich, um die Versorgung dem demographischen Wandel sowie veränderten Lebensentwürfen junger Mediziner anzupassen.
Das Interesse an Solarien und Sonnenschutz im deutschsprachigen Raum
Authors: Kirchberger Michael C. , Kirchberger Laura F. , Eigentler Thomas K. , Reinhard Raphael , Berking Carola , Schuler Gerold , Heinzerling Lucie , Heppt Markus V. 
Published: December 2017

ZusammenfassungHintergrundDie steigende Inzidenz nahezu aller Hautkrebsarten lässt sich durch eine zunehmende Exposition gegenüber natürlicher und künstlicher ultravioletter Strahlung (UV) erklären. Präventionsrelevante Statistiken über Risikoverhalten oder Sonnenschutz sind jedoch rar.MethodikWir analysierten das Suchverhalten mit der Suchmaschine Google® nach Solarium und Sonnencreme bzw. Sonnenschutz in Deutschland, Österreich und der Schweiz im weltweiten Vergleich von 2004 bis 2016. Dabei werden „Normalized Search Volumes“ (NSV) für die Suchanfragen berechnet und die zugehörigen Polynomfunktionen untereinander und im zeitlichen Verlauf verglichen.ErgebnisseGlobal nehmen die Suchanfragen nach Solarium seit 2011 deutlich ab und nach Sonnencreme stetig zu. Im deutschsprachigen Raum hingegen können seit Jahren durchgehend mehr Suchanfragen zu Solarium als zu Sonnencreme verzeichnet werden. Hier ist innerhalb eines Jahres ist eine Periodizität der Suchanfragen zu beobachten mit höchsten NSV für Solarium zwischen März und Mai und für Sonnencreme in den Sommermonaten um Juni. Innerhalb Deutschlands zeigen vor allem die Stadtstaaten Hamburg und Berlin besonders hohe NSV für Solarium.SchlussfolgerungenIn deutschsprachigen Ländern zeigt sich im weltweiten Vergleich ein auffallend ungünstiges Suchverhalten. Es besteht weiterhin ein hoher Aufklärungs‐ und Präventionsbedarf von Sonnenschutz und Karenz gegenüber künstlicher UV‐Exposition.
The impact of volume overload on right heart function in end‐stage renal disease patients on hemodialysis
Authors: Ünlü Serkan , Şahinarslan Asife , Gökalp Gökhan , Seçkin Özden , Arınsoy Selim Turgay , Boyacı Nuri Bülent , Çengel Atiye 
Published: December 2017

PurposeThe aim of this study was to evaluate the impact of volume overload on echocardiographic parameters used for the assessment of the right ventricle (RV) and right atrium (RA), to determine volume‐independent parameters and to noninvasively investigate the physio‐mechanics of RV and RA by examining end‐stage kidney patients before and after hemodialysis (HD).MethodsThe echocardiographic images were obtained from 67 patients (49.2 ± 17.3 years, 23 f) before and after HD. Changes in echocardiographic parameters with HD were examined. The average ultrafiltrated volume was 3088.1 ± 1103.7 mL.ResultsThe size of RV and RA and tricuspid annular plane systolic excursion (TAPSE) decreased after HD, whereas myocardial performance index increased. RV fractional area change and iso‐volumetric contraction acceleration time remained unchanged. RV global longitudinal strain (GLS) and RV early diastolic strain rate (SR) decreased after HD. Systolic and late diastolic SR of the RV showed no statistically significant difference after HD. Longitudinal strain and SR of RA contraction were not significantly different after HD. The changes in RV GLS (r = .641, P = .027), RV free wall longitudinal strain (r = .643, P < .001), RA reservoir phase strain (r = .60, P = .008), and TAPSE (r = .642, P = .001) significantly correlated with ultrafiltrated volume.ConclusionTwo‐dimensional speckle tracking echocardiography is an easy and noninvasive tool that could provide additional volume‐independent echocardiographic parameters and more information on RA physio‐mechanics. This might lead to a better evaluation of the cardiac pathophysiology and hemodynamics of patients. Moreover, providing novel volume‐independent parameters for the evaluation of right heart chambers would improve the clinical perspectives of patients.
Significance of thrombocytopenia in patients with primary and postessential thrombocythemia/polycythemia vera myelofibrosis
Authors: Masarova Lucia , Alhuraiji Ahmad , Bose Prithviraj , Daver Naval , Pemmaraju Naveen , Cortes Jorge , Pierce Sherry , Kantarjian Hagop , Verstovsek Srdan 
Published: December 2017

AbstractSevere thrombocytopenia (platelets <50 × 109/L) is associated with very poor outcome of patients with myelofibrosis (MF). As patients with primary myelofibrosis (PMF) differ from patients with postessential thrombocythemia (PET‐MF) and postpolycythemia vera myelofibrosis (PPV‐MF), we aimed to evaluate the significance of low platelets among these patients. We present clinical characteristics and outcome of patients with either PMF, PPV‐MF, or PET‐MF, and thrombocytopenia who presented to our institution between 1984 and 2015. Of 1269 patients (877 PMF, 212 PPV‐MF, 180 PET‐MF), 11% and 14% had platelets either <50 × 109/L or between 50‐100 × 109/L, respectively. Patients with platelets <50 × 109/L were most anemic and transfusion dependent, had highest blast count and unfavorable karyotype. In general, their overall and leukemia‐free survival was the shortest with median time of 15 and 13 months, respectively; with incidence of acute leukemia almost twice as high as in the remaining patients (6.9 vs 3.6 cases per 100 person‐years). Nevertheless, this observation remains mostly significant for patients with PMF, as those with PEV/PVT‐MF have already significantly inferior prognosis with platelets <100 × 109/L.