cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5124784
title: Supplementary Material for: Introduction of Hypothermia for Neonates with Perinatal Asphyxia in the Netherlands and Flanders

description: <b><i>Background:</i></b> Therapeutic hypothermia was introduced in the Netherlands and Flanders, Belgium, in 2008. Since then, an increasing number of patients has been treated - up to 166 in 2010. Complications and outcome were registered in an online database. <b><i>Objectives:</i></b> The aim of this study was to analyse complications and outcome after implementation. <b><i>Methods:</i></b> Data were retrieved from an online database to which all centres had contributed. <b><i>Results:</i></b> In 3 years, 332 patients were treated. Excluding 24 patients with congenital abnormalities or metabolic disorders, mortality was 31.8%. Of the 210 survivors without congenital malformations, 21 had cerebral palsy, another 19 a developmental delay of more than 3 months at the age of at least 24 months, and 2 had severe hearing loss. The total adverse outcome, combining death and adverse neurodevelopment, in 308 patients without congenital malformations is 45.5%, which is similar to that of the large trials. <b><i>Conclusions:</i></b> The introduction of therapeutic hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders has been rapid and successful, with results similar to findings in the randomised controlled trials.
DOI: 10.6084/m9.figshare.5124787.v1
title: Supplementary Material for: Two Novel GATA6 Mutations Cause Childhood-Onset Diabetes Mellitus, Pancreas Malformation and Congenital Heart Disease

description: <b><i>Background:</i></b><i>GATA6</i> mutations are the most frequent cause of pancreatic agenesis and diabetes in human sporadic cases. In families, dominantly inherited mutations show a variable phenotype also in terms of endocrine and exocrine pancreatic disease. We report two novel <i>GATA6</i> mutations in an independent cohort of 8 children with pancreas aplasia or hypoplasia and diabetes. <b><i>Methods:</i></b> We sequenced <i>GATA6</i> in 8 children with diabetes and inborn pancreas abnormalities, i.e. hypoplasia or aplasia in which other known candidate genes causing monogenic diabetes and pancreatic defects had been excluded. <b><i>Results:</i></b> We found two novel heterozygous <i>GATA6</i> mutations (c.951_954dup and c.754_904del) in 2 patients with sporadic pancreas hypoplasia, diabetes and severe cardiac defects (common truncus arteriosus and tetralogy of Fallot), but not in the remaining 6 patients. <i>GATA6</i> mutations in carriers exhibited hypoplastic pancreas with absent head in 1 patient and with increased echogenicity and decreasing exocrine function in the other patient. Additionally, hepatobiliary malformations and brain atrophy were found in 1 patient. <b><i>Conclusion:</i></b> Our 2 cases with novel <i>GATA6</i> mutations add more phenotype characteristics of <i>GATA6</i> haploinsufficiency. In agreement with an increasing number of published cases, the wide phenotypic spectrum of GATA6 diabetes syndrome should draw the attention of both pediatric endocrinologists and geneticists.
DOI: 10.6084/m9.figshare.5124784.v1
title: Supplementary Material for: Introduction of Hypothermia for Neonates with Perinatal Asphyxia in the Netherlands and Flanders

description: <b><i>Background:</i></b> Therapeutic hypothermia was introduced in the Netherlands and Flanders, Belgium, in 2008. Since then, an increasing number of patients has been treated - up to 166 in 2010. Complications and outcome were registered in an online database. <b><i>Objectives:</i></b> The aim of this study was to analyse complications and outcome after implementation. <b><i>Methods:</i></b> Data were retrieved from an online database to which all centres had contributed. <b><i>Results:</i></b> In 3 years, 332 patients were treated. Excluding 24 patients with congenital abnormalities or metabolic disorders, mortality was 31.8%. Of the 210 survivors without congenital malformations, 21 had cerebral palsy, another 19 a developmental delay of more than 3 months at the age of at least 24 months, and 2 had severe hearing loss. The total adverse outcome, combining death and adverse neurodevelopment, in 308 patients without congenital malformations is 45.5%, which is similar to that of the large trials. <b><i>Conclusions:</i></b> The introduction of therapeutic hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders has been rapid and successful, with results similar to findings in the randomised controlled trials.
DOI: 10.6084/m9.figshare.5124796.v1
title: Supplementary Material for: Sublingual Microvascular Glycocalyx Dimensions in Lacunar Stroke Patients

description: <b><i>Background:</i></b> Cerebral small vessel disease is thought to result from endothelial dysfunction. The glycocalyx, lining the endothelium, is a major determinant of endothelial function. The glycocalyx is partially accessible to flowing red blood cells at its luminal side, called the perfused boundary region (PBR). Glycocalyx damage results in increased PBR, which can be measured in the sublingual microvasculature. We tested whether PBR is increased in patients with cerebral small vessel disease, i.e. lacunar stroke patients, and further distinguished patients with presence of white matter lesions as a sign of extensive cerebral small vessel disease. <b><i>Methods: </i></b>We used sidestream dark field imaging of the sublingual microcirculation in 31 lacunar stroke patients (6 with and 25 without white matter lesions) and 19 healthy controls. In each subject, automatic image analyzing software analyzed PBR in more than 3,000 vessel segments and the average dimension of glycocalyx PBR was determined in vessel segments with a diameter of 5-25 μm. <b><i>Results:</i></b> PBR did not differ between lacunar stroke patients and healthy controls (2.10 ± 0.25 vs. 2.08 ± 0.24 μm, p = 0.8). However, lacunar stroke patients with white matter lesions had an increased PBR compared with both healthy controls (2.35 ± 0.23 vs. 2.08 ± 0.24 μm, p = 0.03) and patients without white matter lesions (2.04 ± 0.22 μm, p = 0.004). <b><i>Conclusions:</i></b> White matter lesions are associated with an increase in the red blood cell permeable part of the sublingual microvascular glycocalyx in lacunar stroke patients. This implicates compromised glycocalyx barrier properties, which is consistent with impaired endothelial function in lacunar stroke patients with white matter lesions.
DOI: 10.6084/m9.figshare.5124772
title: Supplementary Material for: Pulmonary Hypertension in Renal Disease: Epidemiology, Potential Mechanisms and Implications

description: Pulmonary hypertension (PH) is highly prevalent in end-stage renal disease. Several observational studies, based on an echocardiographic diagnosis of PH, have suggested a prevalence of 30-60% and an association with increased mortality and poorer outcome following renal transplantation. The pathogenesis of PH in this population remains poorly understood. Reported associations include arteriovenous fistulae, cardiac dysfunction, fluid overload, bone mineral disorder and non-biocompatible dialysis membranes. However, due to the small numbers, the cross-sectional nature of the majority of studies in this field, and the reliance on echocardiography for the diagnosis of PH, no consistent association with any individual risk factor has been demonstrated. There is no difference in prevalence between patients receiving different dialysis modalities and emerging evidence suggests that the onset of the condition may precede dialysis treatment in many patients. Furthermore, little is known about the impact of the ‘uraemic vasculopathy' on the pulmonary vasculature. Given the similarities between vascular changes in uraemia and those seen in pulmonary arterial hypertension, it is possible that a pulmonary vasculopathy may be present in a proportion of patients. There is a need for better understanding of the natural history and the pathogenesis of the condition which would help to individualise treatment of PH in end-stage renal disease. To enable such understanding, prospective adequately powered studies with an integrated investigational approach including right heart catheterisation are needed.
DOI: 10.6084/m9.figshare.5124778
title: Supplementary Material for: Ferric Citrate Hydrate, a New Phosphate Binder, Prevents the Complications of Secondary Hyperparathyroidism and Vascular Calcification

description: <b><i>Background/Aims:</i></b> Ferric citrate hydrate (JTT-751) is being developed as a treatment for hyperphosphatemia in chronic kidney disease patients, and shows serum phosphorus-reducing effects on hyperphosphatemia in hemodialysis patients. We examined whether JTT-751 could reduce phosphorus absorption in normal rats and prevent the progression of ectopic calcification, secondary hyperparathyroidism and bone abnormalities in chronic renal failure (CRF) rats. <b><i>Methods:</i></b> Normal rats were fed a diet containing 0.3, 1 or 3% JTT-751 for 7 days. The effects of JTT-751 on phosphorus absorption were evaluated with fecal and urinary phosphorus excretion. Next, a CRF model simulating hyperphosphatemia was induced by feeding rats a 0.75% adenine diet. After 21 days of starting the adenine diet feeding, 1 or 3% JTT-751 was administered for 35 days by dietary admixture. The serum phosphorus levels and mineral parameters were measured. Calcification in the aorta was examined biochemically and histopathologically. Hyperparathyroidism and bone abnormalities were evaluated by histopathological analysis of the parathyroid and femur, respectively. <b><i>Results:</i></b> In normal rats, JTT-751 increased fecal phosphorus excretion and reduced phosphorus absorption and urinary phosphorus excretion. In CRF rats, JTT-751 reduced serum phosphorus levels, the calcium-phosphorus product and calcium content in the aorta. Serum intact parathyroid hormone levels and the incidence and severity of parathyroid hyperplasia were also decreased. JTT-751 reduced femoral bone fibrosis, porosity and osteoid formation. <b><i>Conclusions:</i></b> JTT-751 could bind with phosphate in the gastrointestinal tract, increase fecal phosphorus excretion and reduce phosphorus absorption. JTT-751 could prevent the progression of ectopic calcification, secondary hyperparathyroidism and bone abnormalities in rats.
DOI: 10.6084/m9.figshare.5124790.v1
title: Supplementary Material for: Nonfocal Symptoms are More Frequent in Patients with Vertebral Artery than Carotid Artery Stenosis

description: <b><i>Introduction:</i></b> In patients with a transient ischemic attack (TIA) or ischemic stroke, the combination of focal and nonfocal symptoms has been associated with a higher risk of cardiovascular events. We hypothesized that nonfocal symptoms are more frequent in patients with symptomatic stenosis of a vertebral artery (VA) than of a carotid artery (CA). Therefore, we assessed the prevalence of nonfocal symptoms in patients with a recent TIA or nondisabling ischemic stroke and studied their relation with symptomatic CA or VA stenosis. <b><i>Methods:</i></b> We administered a standardized questionnaire on the occurrence of focal and nonfocal symptoms during the qualifying TIA or nondisabling ischemic stroke and in the preceding 6 months. We included 50 consecutive patients with a recently symptomatic CA stenosis ≥50%, 50 consecutive patients with a recently symptomatic VA stenosis ≥50%, 25 consecutive patients with an anterior circulation event without an ipsilateral CA stenosis ≥50%, and 25 consecutive patients with a posterior circulation event without a relevant VA stenosis ≥50%. Relative risks for the presence of nonfocal symptoms in relation to the presence of a symptomatic stenosis were calculated with univariate and multivariate Poisson regression. Adjustments were made for age, sex, stroke as the qualifying event, and cardiovascular risk factors. A subgroup analysis was performed for patients in whom the vascular territory of the event was confirmed on imaging. <b><i>Results:</i></b> During the qualifying ischemic event, focal symptoms were accompanied by nonfocal symptoms in 80 (53%) patients. Nonfocal symptoms occurred more frequently in patients with a VA stenosis (72%) than in patients with a CA stenosis [26%; adjusted relative risk (aRR), 2.9; 95% confidence interval (CI), 1.8-4.6]. A higher prevalence of nonfocal symptoms was found in patients with posterior circulation TIAs and strokes (73%) than in patients with anterior circulation TIAs and strokes (33%; aRR, 2.2; 95% CI, 1.6-3.1). During the preceding 6 months, 45% of patients with and 20% of patients without a symptomatic stenosis had had nonfocal symptoms (aRR, 2.4; 95% CI, 1.3-4.3). Subgroup analysis for the 89 (59%) patients with ischemia visible on imaging gave essentially the same results. <b><i>Conclusions:</i></b> More than half of the TIAs or nondisabling ischemic strokes were associated with nonfocal neurological symptoms. Nonfocal symptoms occurred more frequently in patients with a symptomatic VA stenosis than CA stenosis.
DOI: 10.6084/m9.figshare.5124766
title: Supplementary Material for: Efficient Simulation of Epistatic Interactions in Case-Parent Trios

description: Statistical approaches to evaluate interactions between single nucleotide polymorphisms (SNPs) and SNP-environment interactions are of great importance in genetic association studies, as susceptibility to complex disease might be related to the interaction of multiple SNPs and/or environmental factors. With these methods under active development, algorithms to simulate genomic data sets are needed to ensure proper type I error control of newly proposed methods and to compare power with existing methods. In this paper we propose an efficient method for a haplotype-based simulation of case-parent trios when the disease risk is thought to depend on possibly higher-order epistatic interactions or gene-environment interactions with binary exposures.
DOI: 10.6084/m9.figshare.5124751
title: Supplementary Material for: Brief Internet-Based Intervention Reduces Posttraumatic Stress and Prolonged Grief in Parents after the Loss of a Child during Pregnancy: A Randomized Controlled Trial

description: <b><i>Background:</i></b> The loss of a child during pregnancy causes significant psychological distress for many women and their partners, and may lead to long-lasting psychiatric disorders. Internet-based interventions using exposure techniques and cognitive restructuring have proved effective for posttraumatic stress disorder (PTSD) and prolonged grief. This study compared the effects of an Internet-based intervention for parents after prenatal loss with a waiting list condition (WLC). <b><i>Methods:</i></b> The Impact of Event Scale - Revised assessed symptoms of PTSD; the Inventory of Complicated Grief and the Brief Symptom Inventory assessed depression, anxiety, and general mental health. The 228 participants (92% female) were randomly allocated to a treatment group (TG; n = 115) or a WLC group (n = 113). The TG received a 5-week cognitive behavioral intervention including (1) self-confrontation, (2) cognitive restructuring, and (3) social sharing. <b><i>Results:</i></b> The TG showed significantly reduced symptoms of posttraumatic stress, prolonged grief, depression, and anxiety relative to the WLC control group. Intention-to-treat analysis revealed treatment effects of between d = 0.84 and d = 1.02 for posttraumatic stress and prolonged grief from pre- to posttreatment time points. Further significant improvement in all symptoms of PTSD and prolonged grief was found from the posttreatment evaluation to the 12-month follow-up. The attrition rate of 14% was relatively low. <b><i>Conclusions:</i></b> The Internet-based intervention proved to be a feasible and cost-effective treatment, reducing symptoms of posttraumatic stress, grief, depression, anxiety, and general mental health after pregnancy loss. Low-threshold e-health interventions should be further evaluated and implemented routinely to improve psychological support after pregnancy loss.
DOI: 10.6084/m9.figshare.5124757
title: Supplementary Material for: Sleep-Disordered Breathing and Periodic Limb Movements in Narcolepsy with Cataplexy: A Systematic Analysis of 35 Consecutive Patients

description: <b><i>Background:</i></b> Disturbed sleep is a core feature of narcolepsy with cataplexy (NC). Few studies have independently assessed sleep-disordered breathing (SDB) and periodic limb movements (PLMs) in non-homogeneous series of patients with and without cataplexy. We systematically assessed both SDB and PLMs in well-defined NC patients. <b><i>Methods:</i></b> We analyzed the clinical and polysomnographic features of 35 consecutive NC patients (mean age 40 ± 16 years, 51% males, 23/23 hypocretin-deficient) to assess the prevalence of SDB (apnea-hypopnea index &gt;5) and PLMs (periodic leg movements in sleep (PLMI) &gt;15) together with their impact on nocturnal sleep and daytime sleepiness using the multiple sleep latency test. <b><i>Results:</i></b> 11 (31%) and 14 (40%) patients had SDB and PLMs, respectively. SDB was associated with older age (49 ± 16 vs. 35 ± 13 years, p = 0.02), higher BMI (30 ± 5 vs. 27 ± 6, p = 0.05), and a trend towards higher PLMI (25 ± 20 vs. 12 ± 23, p = 0.052), whereas PLMs with older age (50 ± 16 vs. 33 ± 11 years, p = 0.002) and reduced and fragmented sleep (e.g. sleep efficiency of 82 ± 12% vs. 91 ± 6%, p = 0.015; sleep time of 353 ± 66 vs. 395 ± 28, p = 0.010). SDB and PLMs were also mutually associated (p = 0.007), but not correlated to daytime sleepiness. <b><i>Conclusions:</i></b> SDB and PLMs are highly prevalent and associated in NC. Nevertheless, SDB and PLMs are rarely severe, suggesting an overall limited effect on clinical manifestations.
DOI: 10.6084/m9.figshare.5124760
title: Supplementary Material for: Relating Centromeric Topography in Fixed Human Chromosomes to α-Satellite DNA and CENP-B Distribution

description: Despite extensive analyses on the centromere and its associated proteins, detailed studies of centromeric DNA structure have provided limited information about its topography in condensed chromatin. We have developed a method with correlative fluorescence light microscopy and atomic force microscopy that investigates the physical and structural organization of α-satellite DNA sequences in the context of its associated protein, CENP-B, on human metaphase chromosome topography. Comparison of centromeric DNA and protein distribution patterns in fixed homologous chromosomes indicates that CENP-B and α-satellite DNA are distributed distinctly from one another and relative to observed centromeric ridge topography. Our approach facilitates correlated studies of multiple chromatin components comprising higher-order structures of human metaphase chromosomes.
DOI: 10.6084/m9.figshare.5124754
title: Supplementary Material for: Selbstbezogenes Unvollständigkeitserleben bei Zwangsstörungen

description: <b><i>Hintergrund: </i></b>Unvollständigkeitserleben wird zunehmend als klinisch relevante Motivdimension der Zwangsstörung diskutiert. Hierbei wird primär der Aspekt des «Nicht-genau-richtig-Erlebens» betont, während selbstbezogenes Unvollständigkeitserleben (SU) als zwangsspezifische Ausprägungsform von Depersonalisationserleben bislang kaum untersucht wurde. Ziel dieser Studie ist es, ein ökonomisches Selbstbeurteilungsinstrument zur Messung der Schwere von SU zu entwickeln. <b><i>Methodik: </i></b>190 Patienten mit einer Zwangsstörung erhielten 24 Items, die inhaltlich SU abbilden, und zusätzlich eine Reihe weiterer Messinstrumente zur Untersuchung der Konstruktvalidität. <b><i>Ergebnisse: </i></b>Auf der Basis inhaltlicher und statistischer Überlegungen wurde der Fragebogen zum SU (FSU-12) entwickelt, der mit je 3 Items 4 Dimensionen des SU abbildet (Depersonalisationserleben, Derealisationserleben, Selbsterleben als automatenhaft, Fehlen lebendiger Gefühle). Ein lineares Strukturgleichungsmodell zeigt eine gute Passung der empirischen Daten und der Modellstruktur. Die innere Konsistenz der FSU-12-Gesamtskala und der einzelnen Subskalen ist hervorragend. SU und Nicht-genau-richtig-Erleben liefern voneinander unabhängige Beiträge zur Vorhersage der Schwere von Zwängen und zeigen unterschiedliche Zusammenhänge mit Depersonalisation/Derealisation und zwanghaften Persönlichkeitszügen. Sie stellen also voneinander abgrenzbare, gleichermaßen zwangsrelevante Aspekte von Unvollständigkeitserleben dar. <b><i>Schlussfolgerung: </i></b>Der FSU-12 ist ein reliables und valides Screening-Instrument zur Einschätzung des individuellen Ausprägungsgrads von SU bei Zwangsstörungen.
DOI: 10.6084/m9.figshare.5124766.v1
title: Supplementary Material for: Efficient Simulation of Epistatic Interactions in Case-Parent Trios

description: Statistical approaches to evaluate interactions between single nucleotide polymorphisms (SNPs) and SNP-environment interactions are of great importance in genetic association studies, as susceptibility to complex disease might be related to the interaction of multiple SNPs and/or environmental factors. With these methods under active development, algorithms to simulate genomic data sets are needed to ensure proper type I error control of newly proposed methods and to compare power with existing methods. In this paper we propose an efficient method for a haplotype-based simulation of case-parent trios when the disease risk is thought to depend on possibly higher-order epistatic interactions or gene-environment interactions with binary exposures.
DOI: 10.6084/m9.figshare.5124748
title: Supplementary Material for: Chronic Active Epstein-Barr Virus Infection-Associated Hydroa Vacciniforme-Like Eruption and Behçet's-Like Orogenital Ulcers

description: The cutaneous manifestations of chronic active Epstein-Barr virus (EBV) infection can be diverse. Among them, hydroa vacciniforme-like eruption is one of the best-known features. Although rare, mucosal ulcers have been reported to be associated with EBV as a result of primary infection or immune suppression. We describe a 65-year-old female with recurrent necrotic papulovesicles on the face and both arms for 2 years. She also complained of recurrent oral and genital mucosal ulcers developing simultaneously with skin eruptions. They appeared periodically during the spring and summer and were triggered or aggravated by sun exposure. Skin biopsies from the face and genitalia showed identical findings with dense lymphocytic infiltrations. In addition, in situ hybridization revealed EBV-positive lymphoid cells in both specimens. To our knowledge, this is the first case of serologically and pathologically proven chronic active EBV infection presenting hydroa vacciniforme-like eruption and orogenital ulcers at the same time in one patient.