bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective long‐term follow‐up study of optic disc pit maculopathy treated with pars plana vitrectomy, drainage of subretinal fluid and peeling of internal limiting membrane
Authors: Makdoumi Karim , Crafoord Sven 
Published: May 2020

AbstractPurposeTo describe the long‐term results of surgical repair of patients with optic disc pit maculopathy (ODP‐M).MethodsProspective, consecutive, noncomparative follow‐up study including 12 patients with ODP‐M treated by pars plana vitrectomy (PPV), peeling of internal limiting membrane followed by gas tamponade. Subretinal fluid (SRF) was drained in 11 eyes through a retinotomy without laser photocoagulation. Preoperatively, macular detachment with retinoschisis was seen in 9 out of 12 eyes with three eyes having only subretinal fluid in the macular area. The median age at surgery was 20 years (range 9–60 years).ResultsFollow‐up time from initial surgery was 63 months (median). Eight eyes were anatomically reattached after one operation without remaining SRF in the macula. Two patients required a reoperation due to leakage from the retinotomy and another two underwent a second PPV procedure due to late recurrences. Successful healing was at follow‐up control observed in 11 of 12 eyes. There was no statistically significant difference in visual acuity between patients before and after surgery (p = 0.24). Central visual field defects with depressed mean deviation were detected in all treated eyes.ConclusionIn this long‐term study of ODP‐M final outcome regarding healing was relatively efficacious, however, a relatively large proportion had complications associated to retinotomies. We conclude that drainage of SRF should likely be avoided since it appears to contribute little to the resorption rate of SRF and seems to linked to unnecessary risks.
Muscle function and architecture in children with juvenile idiopathic arthritis
Authors: Bourdier Pierre , Birat Anthony , Rochette Emmanuelle , Doré Éric , Courteix Daniel , Dutheil Frédéric , Pereira Bruno , Ratel Sébastien , Merlin Etienne , Duché Pascale 
Published: May 2020

AbstractAimTo assess muscle function and functional abilities in children with juvenile idiopathic arthritis (JIA).MethodsFourteen children with JIA and 14 healthy controls matched for age and sex were included. Muscle characteristics, both structural (thickness, cross‐sectional area (CSA) and fascicle angle) and qualitative (intermuscular adipose tissue; IMAT), were assessed in thigh muscles using ultrasound and peripheral quantitative computed tomography (pQCT). Muscle function and functional abilities were determined from the assessment of maximal voluntary isometric contraction (MVIC) knee extensors force and vertical jump performance.ResultsNo significant difference in MVIC force was observed between the two groups. However, squat jump height was significantly reduced in children with JIA (18.3 ± 5.4 vs 24.3 ± 7.9 cm, P < .05). No differences in structural parameters were observed, but IMAT/CSA (0.22 ± 0.02 vs 0.25 ± 0.03; P = .01) was significantly lower in children with JIA than in healthy children.ConclusionKnee extensor muscle architecture and force were comparable between children with and without JIA, but functional abilities (vertical jump performance) were poorer in JIA. The lower IMAT area in JIA could result from a lower physical activity level compared with healthy children.
Review article: the signalling and functional role of the extracellular matrix in the development of liver fibrosis
Authors: Villesen Ida Falk , Daniels Samuel Joseph , Leeming Diana Julie , Karsdal Morten Asser , Nielsen Mette Juul 
Published: May 2020

SummaryBackgroundPatients with liver fibrosis show a large heterogeneity, and for that reason effective treatments are still lacking. Emerging data suggest that there is more to fibrosis than previously understood. Opposed to earlier belief of being a passive scaffold for cells to reside in, the extracellular matrix (ECM) is now known to hold both signalling and functional properties important for the development of fibrosis. The interaction between the ECM and the collagen‐producing cells determines the course of the disease but is still poorly understood. Exploring the dynamics of this interplay will aid in the development of effective treatments.AimTo summarise and discuss the latest advances in the pathogenesis of liver fibrosis as well as key mediators of early disease progression.MethodsThrough literature search using databases including PubMed and Google Scholar, manuscripts published between 1961 and 2019 were included to assess both well‐established and recent theories of fibrosis development. Both pre‐clinical and clinical studies were included.ResultsFibrosis alters the structure of the ECM releasing signalling fragments with the potential to escalate disease severity. In a diseased liver, hepatic stellate cells and other fibroblasts, together with hepatocytes and sinusoidal cells, produce an excessive amount of collagens. The cell‐to‐collagen interactions are unique in the different liver aetiologies, generating ECM profiles with considerable patient‐monitoring potential.ConclusionsThe local milieu in the injured area affects the course of fibrosis development in a site‐specific manner. Future research should focus on the dissimilarities in the ECM profile between different aetiologies of liver fibrosis.
Clopidogrel, a CYP2C8 inhibitor, causes a clinically relevant increase in the systemic exposure to the active metabolite of selexipag in healthy subjects
Authors: Axelsen Lene Nygaard , Poggesi Italo , Rasschaert Freya , Perez Ruixo Juan Jose , Bruderer Shirin 
Published: May 2020

AimsSelexipag is a prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension. Cytochrome P450 (CYP) 2C8 is involved in the metabolism of selexipag and its active metabolite, ACT‐333679. This study evaluated the interaction of selexipag and clopidogrel, a CYP2C8 inhibitor.MethodsThe study had a 2‐treatment, 1‐sequence, crossover design. Pharmacokinetics (PK) and CYP2C8 genotype were assessed in healthy male subjects administered selexipag (200 μg twice daily [b.i.d.]) alone or with clopidogrel (300 mg single dose or 75 mg once daily [o.d.]). PK modelling and simulation were conducted to support dosing recommendations.ResultsClopidogrel had a comparatively small effect on selexipag (<1.5‐fold difference in any PK variable). For ACT‐333679, the major contributor to the drug effect, the area under the plasma concentration–time curve during a dose interval and the maximum plasma concentration increased 2.25‐fold (90% confidence interval [CI] 2.06, 2.46) and 1.69‐fold (90% CI 1.55, 1.84), respectively with clopidogrel 300 mg and 2.70‐fold (90% CI 2.45, 2.96) and 1.90‐fold (90% CI 1.72, 2.11), respectively with clopidogrel 75 mg. The effect of clopidogrel on selexipag and ACT‐333679 exposure was comparable for all identified CYP2C8 genotypes. PK simulations predicted comparable exposure to ACT‐333679 following selexipag 400 μg b.i.d., 400 μg o.d. in combination with clopidogrel 75 mg o.d and 200 μg b.i.d. with clopidogrel 75 mg o.d.ConclusionResults suggest that ACT‐333679 exposure can be maintained within the therapeutic range by reducing selexipag dosing frequency to o.d. or dose to half, when selexipag is coadministered with clopidogrel.
Flexible link functions in a joint hierarchical Gaussian process model
Authors: Su Weiji , Wang Xia , Szczesniak Rhonda D. 
Published: May 2020

AbstractMany longitudinal studies often require jointly modeling a biomarker and an event outcome, in order to provide more accurate inference and dynamic prediction of disease progression. Cystic fibrosis (CF) studies have illustrated the benefits of these models, primarily examining the joint evolution of lung‐function decline and survival. We propose a novel joint model within the shared‐parameter framework that accommodates nonlinear lung‐function trajectories, in order to provide more accurate inference on lung‐function decline over time and to examine the association between evolution of lung function and risk of a pulmonary exacerbation (PE) event recurrence. Specifically, a two‐level Gaussian process (GP) is used to estimate the nonlinear longitudinal trajectories and a flexible link function is introduced for a more accurate depiction of the binary process on the event outcome. Bayesian model assessment is used to evaluate each component of the joint model in simulation studies and an application to longitudinal data on patients receiving care from a CF center. A nonlinear structure is suggested by both longitudinal continuous and binary evaluations. Including a flexible link function improves model fit to these data. The proposed hierarchical GP model with a flexible power link function where Laplace distribution is the baseline (spep) has the best fit of all joint models considered, characterizing how accelerated lung‐function decline corresponds to increased odds of experiencing another PE.
Estimating the burden of the opioid epidemic for adults and adolescents in Ohio counties
Authors: Kline David , Hepler Staci A. 
Published: May 2020

AbstractQuantifying the opioid epidemic at the local level is a challenging problem that has important consequences on resource allocation. Adults and adolescents may exhibit different spatial trends and require different interventions and resources so it is important to examine the problem for each age group. In Ohio, surveillance data are collected at the county level for each age group on measurable outcomes of the opioid epidemic, overdose deaths, and treatment admissions. However, our interest lies in quantifying the unmeasurable construct, representing the burden of the opioid epidemic, which drives rates of the outcomes. We propose jointly modeling adult and adolescent surveillance outcomes through a multivariate spatial factor model. A generalized spatial factor model within each age group quantifies a latent factor related to the number of opioid‐associated treatment admissions and deaths. By assuming a multivariate conditional autoregressive model for the spatial factors of adults and adolescents, we allow the adolescent model to borrow strength from the adult model (and vice versa), improving estimation. We also incorporate county‐level covariates to help explain spatial heterogeneity in each of the factors. We apply this approach to the state of Ohio and discuss the findings. Our framework provides a coherent approach for synthesizing information across multiple outcomes and age groups to better understand the spatial epidemiology of the opioid epidemic.
Episodic future thinking together with observational learning benefits prospective memory in high‐functioning Korsakoff’s syndrome patients
Authors: Lloyd Beth , Oudman Erik , Altgassen Mareike , Walvoort Serge J. W. , Kessels Roy P. C. , Postma Albert 
Published: May 2020

ObjectivePatients with Korsakoff’s syndrome (KS) have difficulty carrying out tasks which rely on prospective memory (PM). Since remembering to carry out an action in the future is crucial for living independently, it is of primary interest to develop strategies that improve PM performance in KS patients.DesignThe study employed a computer categorization task as an ongoing activity into which a PM task was embedded. We included episodic future thinking (EFT) and observational learning (Experiment 2) to boost PM.MethodsExperiment 1 evaluated the efficacy of EFT following written PM task instructions in ten KS patients. Due to floor‐level PM performance in Experiment 1, Experiment 2 included an instructional video demonstrating the PM intention. In Experiment 2, twenty‐six KS patients performed both conditions (EFT and no‐EFT) at least 1 week apart, while twelve controls with alcohol use disorder without KS performed the no‐EFT condition. In Experiment 2, the PM instructions were also shown through video (observational learning component). Mild cognitive impairment was assessed in a short test battery.ResultsExperiment 1 showed overall floor performance in both conditions. Experiment 2 showed that KS patients performed PM tasks less accurately than the control group in the no‐EFT condition. In Experiment 2, where the observational learning component was included, EFT improved PM performance in KS patients. This effect was driven by a sub‐group of high‐functioning KS patients.ConclusionsThis study showed the value of an observational learning component together with EFT in improving PM performance, in relatively high‐functioning KS patients.Practitioner points

KS patients performed the PM task less accurately than non‐KS controls with alcohol use disorder, confirming PM impairment in this patient population.

Controls with alcohol use disorder performed the PM task at ceiling level.

Showing an instructional video demonstrating the PM intention improved PM performance and later recall of PM task instructions in KS patients.

Episodic future thinking strategy improved PM performance in KS patients with relatively intact cognitive functioning.
New evidence for construct validity and interpretability of the German Quality of Life in Hand Eczema Questionnaire (QOLHEQ)
Authors: Ofenloch Robert F. , Weisshaar Elke , Apfelbacher Christian 
Published: May 2020

AbstractBackgroundThe Quality of Life in Hand Eczema Questionnaire (QOLHEQ) is a disease‐specific instrument used to assess health‐related quality of life (HRQoL) in patients with hand eczema according to the domains of (a) symptoms, (b) emotions, (c) functioning, and (d) treatment/prevention. Today it is not clear what a single score of the QOLHEQ in its German‐language version means to a patient.ObjectivesIt was the aim of this study to band the QOLHEQ score to an anchor question (AQ) in order to obtain meaningful categories of the QOLHEQ to aid its interpretation. In addition, we assessed the minimal important change (MIC) by using anchor‐ and distribution‐based methods.MethodsOverall n = 440 hand eczema patients were included in the study. Mean age was 47.5 years (SD 11.9); 38.4% of the sample were female.ResultsWith a weighted kappa of 0.62, the total QOLHEQ score showed the best agreement for the following band: QOLHEQ of <17 = no impairment; QOLHEQ of 18–28 = slight impairment; QOLHEQ of 29–41 = moderate impairment; QOLHEQ of 42–79 = severe impairment; and QOLHEQ of >79 = very severe impairment. The MIC for the total score was found to be 16.5 points.ConclusionThis banding represents a standardized means of interpreting the QOLHEQ total score. Our results indicate that a banding study should be performed for each language version of the QOLHEQ.
Interindividual Variability in Lymphocyte Stimulation and Transcriptomic Response Predicts Mycophenolic Acid Sensitivity in Healthy Volunteers
Authors: Collins Kimberly S. , Cheng Ying‐Hua , Ferreira Ricardo M. , Gao Hongyu , Dollins Matthew D. , Janosevic Danielle , Khan Nida A. , White Chloe , Dagher Pierre C. , Eadon Michael T. 
Published: May 2020

Mycophenolic acid (MPA) is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. MPA inhibits IMPDH2 within stimulated lymphocytes, reducing guanosine synthesis. Despite the widespread use of MPA, interindividual variability in response remains with rates of allograft rejection up to 15% and approximately half of individuals fail to achieve complete remission to lupus nephritis. We sought to identify contributors to interindividual variability in MPA response, hypothesizing that the HPRT1 salvage guanosine synthesis contributes to variability. MPA sensitivity was measured in 40 healthy individuals using an ex vivo lymphocyte viability assay. Measurement of candidate gene expression (n ± 40) and single‐cell RNA‐sequencing (n ± 6) in lymphocytes was performed at baseline, poststimulation, and post‐MPA treatment. After stimulation, HPRT1 expression was 2.1‐fold higher in resistant individuals compared with sensitive individuals (P ± 0.049). Knockdown of HPRT1 increased MPA sensitivity (12%; P ± 0.003), consistent with higher expression levels in resistant individuals. Sensitive individuals had higher IMPDH2 expression and 132% greater stimulation. In lymphocyte subpopulations, differentially expressed genes between sensitive and resistant individuals included KLF2 and LTB. Knockdown of KLF2 and LTB aligned with the predicted direction of effect on proliferation. In sensitive individuals, more frequent receptor‐ligand interactions were observed after stimulation (P ± 0.0004), but fewer interactions remained after MPA treatment (P ± 0.0014). These data identify a polygenic transcriptomic signature in lymphocyte subpopulations predictive of MPA response. The degree of lymphocyte stimulation, HPRT1, KLF2, and LTB expression may serve as markers of MPA efficacy.
Chronische Nierenerkrankung bei Psoriasis: eine Kohortenstudie
Authors: Conti Andrea , Giovannini Lisa , Mandel Victor Desmond , Odorici Giulia , Lasagni Claudia , Bigi Laura , Pellacani Giovanni , Cappelli Gianni 
Published: May 2020

ZusammenfassungHintergrundPsoriasis ist eine chronische, schubförmig verlaufende Erkrankung, die häufig mit Komorbiditäten einhergeht. Während die Wechselwirkungen mit kardiovaskulären und metabolischen Einflussfaktoren bereits untersucht wurden, ist über den Zusammenhang mit einer Beeinträchtigung der Nierenfunktion wenig bekannt.Materialien und MethodikWir führten eine Kohortenstudie mit 219 Psoriasis‐Patienten durch, in der wir die chronische Nierenerkrankung (CKD), die eGFR und die Albuminurie nach den Kriterien zur Risikostratifizierung in den KDIGO‐Leitlinien beurteilten. Des Weiteren untersuchten wir zirkulierende Immunglobuline (IgG, IgA, IgM), C3‐ und C4‐Spiegel und die Albumin‐Kreatinin‐Ratio im Urin (UACR). Wir teilten die Patienten in zwei Gruppen ein, je nach dem, ob bekannte und etablierte CKD‐Risikofaktoren vorlagen oder nicht.ErgebnisseIn unserer Patientenpopulation war das CKD‐Risiko bei 17,35 % der Patienten mäßig, bei 5,02 % stark und bei 3,66 % sehr stark erhöht. Die Prävalenz des CKD‐Risikos war in der Gruppe ohne etablierte Risikofaktoren gegenüber der in der NHANES 1999–2006 berichteten Risikoprävalenz leicht erhöht. Das Vorliegen einer Psoriasisarthritis, die Dauer der Psoriasis (≥ 21 Jahre) und die Höhe des PASI‐Scores zeigten eine positive Korrelation mit der Albumin‐Kreatinin‐Ratio im Urin.SchlussfolgerungenWir fanden eine Assoziation zwischen Mikroalbuminurie und Dauer der Psoriasis sowie Psoriasisarthritis. Darüber hinaus wiesen Patienten mit Mikroalbuminurie entsprechend der Risikostratifizierung in den KDIGO‐Leitlinien ein erhöhtes Risiko auf.
The cancer of corruption and World Bank project performance: Is there a connection?
Authors: Feil Hauke 
Published: May 2020

AbstractMotivationCorruption is often cited as a central reason why development projects fail. The article tests this claim by assessing whether World Bank projects perform worse in implementation environments with a higher corruption level. The article focuses specifically on bribery between public officials and firms during the procurement of needed goods and services.Approach and MethodsI use data from the World Bank’s Enterprise Surveys to avoid the often‐criticized corruption perception indices and to allow for an assessment of effects at the subnational level. The analysis builds on an assessment of the performance ratings of 1,228 World Bank projects and covers 87 different countries.FindingOverall, the article finds a small but statistically significant correlation between the corruption level and project performance. This result indicates that the corruption level of recipient countries should be considered during the design and implementation of projects.Policy ImplicationsNonetheless, the relatively small correlation and the low pseudo R‐squareds advise not overestimating the relevance of corruption for project performance. At least for the project level, the article finds no indication that corruption is a primary obstacle to aid effectiveness.
Left ventricular pseudoaneurysm complicating a ruptured isolated congenital diverticulum
Authors: Fang Liang , Xue Chao , Zhao Ying , Wen Zhaoying , Henein Michael 
Published: May 2020

AbstractWe report a case of 41‐year‐old woman who presented with chest tightness and shortness of breath. Transthoracic echocardiogram (TTE) showed left ventricular (LV) pseudoaneurysm of the inferior wall with preserved LV systolic function. Coronary angiogram was normal. Surgical repair of the pseudoaneurysm with a pericardial patch was performed, and pathological results confirmed rupture of an isolated congenital LV diverticulum, as the most likely etiology.
Response to technical comment ‘A cautionary note for users of linear diversification dependencies’
Authors: Morlon Hélène , Rolland Jonathan , Condamine Fabien L. 
Published: May 2020

AbstractThe comment by Gamisch (2020) draws the attention of users of the R‐package RPANDA (Methods Ecol. Evol., 7, 2016, 589) on situations when properly interpreting the results of linear diversification dependencies requires caution. Here we provide clarifications to help users interpreting their results when using any type of functional diversification dependencies with time or the environment.
Progressive supranuclear palsy often develops idiopathic normal pressure hydrocephalus‐like magnetic resonance imaging features
Authors: Ohara M. , Hattori T. , Yokota T. 
Published: May 2020

Background and purposeIdiopathic normal pressure hydrocephalus (iNPH) is a clinical entity without established pathological hallmarks. Previous autopsy studies reported that patients with an antemortem diagnosis of iNPH had a different postmortem diagnosis, commonly progressive supranuclear palsy (PSP). Disproportionately enlarged subarachnoid space hydrocephalus (DESH) has been reported as a characteristic feature of iNPH on magnetic resonance imaging (MRI). In addition, periventricular white matter hyperintensities (PVHs) are noted in most patients with iNPH; these PVHs are supposed to reflect transependymal movement of ventricular cerebrospinal fluid. It is hypothesized that PSP develops more iNPH‐like MRI features than other neurodegenerative disorders.MethodsThirty‐eight patients with a clinical diagnosis of PSP, 42 with Parkinson’s disease (PD) without dementia, 30 with PD with dementia (PDD) and 29 with Alzheimer’s disease (AD) were enrolled. The DESH score and PVH grade were measured using the conventional MRI sequence and were compared amongst the patient groups.ResultsDisproportionately enlarged subarachnoid space hydrocephalus score was significantly higher in patients with PSP than PD without dementia, and there was a trend that the DESH score was higher in patients with PSP than PDD or Alzheimer’s disease. PVH grade was significantly larger in patients with PSP than PD without dementia. In the components of the DESH score, callosal angle was significantly smaller in patients with PSP than in PD without dementia or PDD.ConclusionsThis study demonstrated that some PSP patients develop iNPH‐like MRI features, suggesting the presence of iNPH‐like features in the clinical spectrum of PSP. A clinical phenotype of PSP with hydrocephalus is proposed, which should be further investigated in future studies.