cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127694.v1
title: Supplementary Material for: Prematurity, Opioid Exposure and Neonatal Pain: Do They Affect the Developing Brain?

description: <b><i>Background:</i></b> Traditionally, 10 years ago, children born preterm often routinely received morphine, especially during mechanical ventilation. Studies in neonatal rats, whose stage of brain development roughly corresponds to that of children born preterm, found negative long-term effects after pain and opioid exposure. <b><i>Objectives:</i></b> We studied possible effects of prematurity, procedural pain and opioids in humans 10 years later. We hypothesized that these factors would negatively influence neurobiological, neuropsychological and sensory development later in life. <b><i>Methods:</i></b> We included 19 children born preterm who as neonates participated in an RCT on the short-term effects of morphine administration and who previously participated in our follow-up studies at ages 5 and 8/9 years. We assessed associations between brain morphology (n = 11), neuropsychological functioning (n = 19) and thermal sensitivity (n = 17) and prematurity, opioid exposure and neonatal pain. <b><i>Results:</i></b> Significant correlations (coefficients 0.60-0.85) of gestational age, number of painful procedures and morphine exposure with brain volumes were observed. Significant correlations between these factors and thermal sensitivity were not established. Neuropsychological outcome was significantly moderately correlated with morphine exposure in only two subtests, and children performed in general ‘average' by Dutch norms. <b><i>Conclusions:</i></b> Although prematurity, opioid exposure and neonatal pain were significantly associated with brain volume, no major associations with neuropsychological functioning or thermal sensitivity were detected. Our findings suggest that morphine administration during neonatal life does not affect neurocognitive performance or thermal sensitivity during childhood in children born preterm without brain damage during early life. Future studies with larger sample sizes are needed to confirm these findings.
DOI: 10.6084/m9.figshare.5127679
title: Supplementary Material for: Acute Arteriovenous Access Failure: Long-Term Outcomes of Endovascular Salvage and Assessment of Co-Variates Affecting Patency

description: <b><i>Aims:</i></b> This study reports long-term outcomes after endovascular salvage (EVS) for acute dialysis fistula/graft dysfunction. <b><i>Methods:</i></b> All patients presenting with acute fistula or graft dysfunction, excluding primary failures, referred for endovascular salvage were included in this single-centre prospective study. <b><i>Results:</i></b> Altogether, 410 procedures were carried out in 232 patients. Overall, the incidence of thrombosis/occlusion (per patient-year) was 0.12 for fistulae and 0.9 for grafts. The anatomical success rate for EVS was 94% for fistulae and 92% for grafts. Primary patency rates for fistulae at 1, 6, 12, 24 and 36 months were 82, 64, 44, 34 and 26%, respectively, whereas secondary patency rates were 88, 84, 74, 69 and 61%, respectively. Primary patency rates for grafts at 1, 6 and 12 months were 50, 14 and 8%. The overall rate of complications was 6% with no incidence of symptomatic pulmonary embolism. In a Cox regression model, upper-arm location of fistula (HR 1.9, p = 0.04, n = 144) was associated with lower primary patency, whereas the presence of thrombosis was associated lower primary (HR 1.9, p = 0.004, n = 144) and secondary patency (HR 3.7, p &lt; 0.001, n = 144). Aspirin therapy was associated with longer primary patency (HR 0.6, p = 0.02, n = 144) and secondary patency (HR 0.58, p = 0.08, n = 144). <b><i>Conclusion:</i></b> EVS is effective but longer-term outcomes are poor. Presence of thrombosis portends poor fistula survival and strategies for prevention need attention. Balloon maceration, our preferred declotting technique, is safe and the most cost-effective method. Aspirin therapy for patients presenting with failure of fistulae deserves further investigation.
DOI: 10.6084/m9.figshare.5127688.v1
title: Supplementary Material for: Exome Sequencing Identification of <b><i>EP300</i></b> Mutation in a Proband with Coloboma and Imperforate Anus: Possible Expansion of the Phenotypic Spectrum of Rubinstein-Taybi Syndrome

description: Rubinstein-Taybi syndrome (RSTS) is a multisystem developmental disorder characterized by facial dysmorphisms, broad thumbs and halluces, growth retardation, and intellectual disability. In about 8% of RSTS cases, mutations are found in <i>EP300</i>. Previously, the <i>EP300</i> mutation has been shown to cause the highly variable RSTS phenotype. Using exome sequencing, we identified a de novo <i>EP300</i> frameshift mutation in a proband with coloboma, facial asymmetry and imperforate anus with minimal RSTS features. Previous molecular studies have demonstrated the importance of EP300 in oculogenesis, supporting the possibility that <i>EP300</i> mutation may cause ocular coloboma. Since a wide phenotypic spectrum is well known in <i>EP300</i>-associated RSTS cases, the atypical phenotype identified in our proband may be an example of rare manifestations of RSTS.
DOI: 10.6084/m9.figshare.5127676
title: Supplementary Material for: Nitric Oxide Pathway and Proliferation of Neural Progenitors in the Neonatal Rat

description: Several lines of evidence demonstrate that inhaled nitric oxide (iNO) not only acts locally on the pulmonary vasculature but also has remote effects on the mature and developing brain under basal or pathological conditions by modulating cerebral blood flow and microvascularization, white matter maturation, inflammation, and subsequent brain repair. Previously, consistent studies demonstrated that increased levels of guanosine 3′,5′ cyclic monophosphate (cGMP), the main effector of biological effect induced by nitric oxide (NO), significantly augment proliferation and neuronal differentiation of adult neural progenitor cells (NPCs). In the present study, we ask the question whether iNO could promote the proliferation of NPCs in the uninjured developing brain. We first reported that iNO exposure at a concentration of 20 ppm during the first 7 days of life was associated with a significant but transient elevation of brain cGMP concentration 2 h after the onset of iNO exposure and a subsequent increase in myelin content of the developing white matter at postnatal day (P) 10. Using BrDu labelling and colabelling with specific cell-type markers we found that iNO exposure of rat pups results in an increased NPC proliferation in several layers of the subventricular zone (SVZ) at both early (30 h) and late (P7) time points. These proliferating NPCs were found to be sustainably viable and subsequently differentiated into oligodendroglial cells in the developing white matter and cortex. We also found that NG2 immunoreactivity around vessel walls, labeling pericyte cells, was increased in NO-exposed rat pups in the periventricular SVZ. In conclusion, iNO appears to act on oligodendrocyte progenitor cells, leading to increased density of mature oligodendrocytes and myelin content in the immature rat brain.
DOI: 10.6084/m9.figshare.5127679.v1
title: Supplementary Material for: Acute Arteriovenous Access Failure: Long-Term Outcomes of Endovascular Salvage and Assessment of Co-Variates Affecting Patency

description: <b><i>Aims:</i></b> This study reports long-term outcomes after endovascular salvage (EVS) for acute dialysis fistula/graft dysfunction. <b><i>Methods:</i></b> All patients presenting with acute fistula or graft dysfunction, excluding primary failures, referred for endovascular salvage were included in this single-centre prospective study. <b><i>Results:</i></b> Altogether, 410 procedures were carried out in 232 patients. Overall, the incidence of thrombosis/occlusion (per patient-year) was 0.12 for fistulae and 0.9 for grafts. The anatomical success rate for EVS was 94% for fistulae and 92% for grafts. Primary patency rates for fistulae at 1, 6, 12, 24 and 36 months were 82, 64, 44, 34 and 26%, respectively, whereas secondary patency rates were 88, 84, 74, 69 and 61%, respectively. Primary patency rates for grafts at 1, 6 and 12 months were 50, 14 and 8%. The overall rate of complications was 6% with no incidence of symptomatic pulmonary embolism. In a Cox regression model, upper-arm location of fistula (HR 1.9, p = 0.04, n = 144) was associated with lower primary patency, whereas the presence of thrombosis was associated lower primary (HR 1.9, p = 0.004, n = 144) and secondary patency (HR 3.7, p &lt; 0.001, n = 144). Aspirin therapy was associated with longer primary patency (HR 0.6, p = 0.02, n = 144) and secondary patency (HR 0.58, p = 0.08, n = 144). <b><i>Conclusion:</i></b> EVS is effective but longer-term outcomes are poor. Presence of thrombosis portends poor fistula survival and strategies for prevention need attention. Balloon maceration, our preferred declotting technique, is safe and the most cost-effective method. Aspirin therapy for patients presenting with failure of fistulae deserves further investigation.
DOI: 10.6084/m9.figshare.5127667
title: Supplementary Material for: Effect Estimation of an Innovative Nursing Intervention to Improve Delirium among Home-Dwelling Older Adults: A Randomized Controlled Pilot Trial

description: <b><i>Aims:</i></b> Estimating the effect of a nursing intervention in home-dwelling older adults on the occurrence and course of delirium and concomitant cognitive and functional impairment. <b><i>Methods:</i></b> A randomized clinical pilot trial using a before/after design was conducted with older patients discharged from hospital who had a medical prescription to receive home care. A total of 51 patients were randomized into the experimental group (EG) and 52 patients into the control group (CG). Besides usual home care, nursing interventions were offered by a geriatric nurse specialist to the EG at 48 h, 72 h, 7 days, 14 days, and 21 days after discharge. All patients were monitored for symptoms of delirium using the Confusion Assessment Method. Cognitive and functional statuses were measured with the Mini-Mental State Examination and the Katz and Lawton Index. <b><i>Results:</i></b> No statistical differences with regard to symptoms of delirium (p = 0.085), cognitive impairment (p = 0.151), and functional status (p = 0.235) were found between the EG and CG at study entry and at 1 month. After adjustment, statistical differences were found in favor of the EG for symptoms of delirium (p = 0.046), cognitive impairment (p = 0.015), and functional status (p = 0.033). <b><i>Conclusion:</i></b> Nursing interventions to detect delirium at home are feasible and accepted. The nursing interventions produced a promising effect to improve delirium.
DOI: 10.6084/m9.figshare.5127673
title: Supplementary Material for: Public Perceptions of Disease Severity but Not Actionability Correlate with Interest in Receiving Genomic Results: Nonalignment with Current Trends in Practice

description: <b><i>Purpose:</i></b> Frameworks highlighting disease actionability and severity are evolving to address the need to organize results from genome-wide analyses. This approach represents a paradigm shift from consultations focused on one or more genes to multiple genes for multiple disorders. Empirical input from the general population is lacking, yet seems essential for understanding how to maximize patient autonomy and satisfaction in the decision-making process. <b><i>Methods:</i></b> We conducted a cross-sectional online survey with a representative sample of 900 US adults and assessed the participants' perceptions and attitudes toward disease actionability and severity, ranking hypothetical scenarios for these properties, and explored correlations with interest in learning test results. <b><i>Results:</i></b> Most respondents (&gt;85%) rated actionability and severity as useful concepts; 46.6% indicated actionability alone would be adequate for decision making. Over half of them (53.8%) reported being very/extremely confident in their ability to score for actionability and severity. The participants' scoring of medical scenarios varied significantly between individuals. Scores for severity but not actionability were correlated with interest in learning genetic results. Subsets of the respondents projected wanting all results (30%) or no results (16%). The use of expert-created lists was acceptable to 43%. <b><i>Conclusions:</i></b> The respondents from the general population were confident in making their own decisions. The responses suggested different priorities than current expert-driven approaches. The emphasis on binning genes may be missing a complementary, simplifying approach of grouping patients based upon their all/none interest in genomic results. This study illuminates important differences between the general public and genetic experts.
DOI: 10.6084/m9.figshare.5127676.v1
title: Supplementary Material for: Nitric Oxide Pathway and Proliferation of Neural Progenitors in the Neonatal Rat

description: Several lines of evidence demonstrate that inhaled nitric oxide (iNO) not only acts locally on the pulmonary vasculature but also has remote effects on the mature and developing brain under basal or pathological conditions by modulating cerebral blood flow and microvascularization, white matter maturation, inflammation, and subsequent brain repair. Previously, consistent studies demonstrated that increased levels of guanosine 3′,5′ cyclic monophosphate (cGMP), the main effector of biological effect induced by nitric oxide (NO), significantly augment proliferation and neuronal differentiation of adult neural progenitor cells (NPCs). In the present study, we ask the question whether iNO could promote the proliferation of NPCs in the uninjured developing brain. We first reported that iNO exposure at a concentration of 20 ppm during the first 7 days of life was associated with a significant but transient elevation of brain cGMP concentration 2 h after the onset of iNO exposure and a subsequent increase in myelin content of the developing white matter at postnatal day (P) 10. Using BrDu labelling and colabelling with specific cell-type markers we found that iNO exposure of rat pups results in an increased NPC proliferation in several layers of the subventricular zone (SVZ) at both early (30 h) and late (P7) time points. These proliferating NPCs were found to be sustainably viable and subsequently differentiated into oligodendroglial cells in the developing white matter and cortex. We also found that NG2 immunoreactivity around vessel walls, labeling pericyte cells, was increased in NO-exposed rat pups in the periventricular SVZ. In conclusion, iNO appears to act on oligodendrocyte progenitor cells, leading to increased density of mature oligodendrocytes and myelin content in the immature rat brain.
DOI: 10.6084/m9.figshare.5127685.v1
title: Supplementary Material for: The Cost Effectiveness of Erythropoietin-Stimulating Agents for Treating Anemia in Patients on Dialysis: A Systematic Review

description: <b><i>Background:</i></b> Anemia is a common complication associated with kidney failure and is marked by poor health and increased risk of morbidity and mortality. There are ongoing concerns with the use of Erythropoietin Stimulating Agents (ESAs) to treat anemia in patients with kidney failure on dialysis. Questions as to their benefits, harms and overall effect on quality of life are still relevant today. Our objective was to systematically review studies evaluating the cost-effectiveness of ESAs in patients with kidney failure on dialysis. <b><i>Methods:</i></b> We performed a systematic review of studies determining the cost-effectiveness of ESAs in adult patients on dialysis. Databases, including PubMed, EMBASE, and Cochrane Database of Systematic Reviews, were searched from their establishment until June 2013. Studies that reported an incremental cost-effectiveness ratio of hemoglobin correction strategies based on ESA treatments in comparison to red blood cell transfusions, lower hemoglobin targets, or no ESA treatment were included. <b><i>Results:</i></b> Seven studies met inclusion criteria. Reported cost/quality-adjusted life-year (QALY) ratios ranged from USD 931-677,749/QALY across five studies comparing ESAs to red blood cell transfusions. There was heterogeneity in results when considering higher hemoglobin targets, with studies finding higher targets to be both dominant and dominated. Mortality, hospitalization, and utility estimates were major drivers. <b><i>Conclusions:</i></b> There is substantial variability in the estimates of the cost-effectiveness of using ESAs in the dialysis population. New models incorporating recent meta-analyses for estimates of utility, mortality, and hospitalization changes would allow for a more comprehensive answer to this question.
DOI: 10.6084/m9.figshare.5127670
title: Supplementary Material for: Increased Cerebral Cannabinoid-1 Receptor Availability Is a Stable Feature of Functional Dyspepsia: A [<sup>18</sup>F]MK-9470 PET Study

description: <b><i>Background:</i></b> Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder (FGID) defined by chronic epigastric symptoms in the absence of organic abnormalities likely to explain them. Comorbidity with mood and anxiety disorders as well as with other FGIDs and functional somatic syndrome (FSS) is high. FD is characterized by abnormal regional cerebral activity in cognitive/affective pain modulatory circuits, but it is unknown which neurotransmitter systems are involved. The authors aimed to assess and compare in vivo cerebral cannabinoid-1 (CB<sub>1</sub>) receptor availability between FD patients and age-, gender- and BMI-matched healthy controls (HC). <b><i>Methods:</i></b> Twelve FD patients and 12 matched HC were investigated using positron emission tomography (PET) with the CB<sub>1</sub> receptor radioligand [<sup>18</sup>F]MK-9470. Nine of the patients received a second PET scan after a naturalistic follow-up period of 36 ± 9.6 months (range: 25.2-50.4 months). <b><i>Results:</i></b> FD patients had significantly higher CB<sub>1</sub> receptor availability in the cerebral regions involved in (visceral) nociception (brainstem, insula, anterior cingulate cortex) as well as in the homeostatic and hedonic regulation of food intake [hypothalamus, (ventral) striatum] (p &lt; 0.05 corrected for multiple testing, region of interest analysis), which persisted after a follow-up period of 36 ± 9.6 months. <b><i>Conclusions:</i></b> Although these findings need replication in larger samples, they suggest that the abnormal brain activity in several of these regions, previously demonstrated in FD, may be due to a sustained endocannabinoid system dysfunction, identifying it as a potential novel target for treatment and warranting further studies to elucidate whether it is also a feature of other FGIDs or FSSs.
DOI: 10.6084/m9.figshare.5127664
title: Supplementary Material for: A Sequence Kernel Association Test for Dichotomous Traits in Family Samples under a Generalized Linear Mixed Model

description: <b><i>Objective:</i></b> The existing methods for identifying multiple rare variants underlying complex diseases in family samples are underpowered. Therefore, we aim to develop a new set-based method for an association study of dichotomous traits in family samples. <b><i>Methods:</i></b> We introduce a framework for testing the association of genetic variants with diseases in family samples based on a generalized linear mixed model. Our proposed method is based on a kernel machine regression and can be viewed as an extension of the sequence kernel association test (SKAT and famSKAT) for application to family data with dichotomous traits (F-SKAT). <b><i>Results:</i></b> Our simulation studies show that the original SKAT has inflated type I error rates when applied directly to family data. By contrast, our proposed F-SKAT has the correct type I error rate. Furthermore, in all of the considered scenarios, F-SKAT, which uses all family data, has higher power than both SKAT, which uses only unrelated individuals from the family data, and another method, which uses all family data. <b><i>Conclusion:</i></b> We propose a set-based association test that can be used to analyze family data with dichotomous phenotypes while handling genetic variants with the same or opposite directions of effects as well as any types of family relationships.
DOI: 10.6084/m9.figshare.5127667.v1
title: Supplementary Material for: Effect Estimation of an Innovative Nursing Intervention to Improve Delirium among Home-Dwelling Older Adults: A Randomized Controlled Pilot Trial

description: <b><i>Aims:</i></b> Estimating the effect of a nursing intervention in home-dwelling older adults on the occurrence and course of delirium and concomitant cognitive and functional impairment. <b><i>Methods:</i></b> A randomized clinical pilot trial using a before/after design was conducted with older patients discharged from hospital who had a medical prescription to receive home care. A total of 51 patients were randomized into the experimental group (EG) and 52 patients into the control group (CG). Besides usual home care, nursing interventions were offered by a geriatric nurse specialist to the EG at 48 h, 72 h, 7 days, 14 days, and 21 days after discharge. All patients were monitored for symptoms of delirium using the Confusion Assessment Method. Cognitive and functional statuses were measured with the Mini-Mental State Examination and the Katz and Lawton Index. <b><i>Results:</i></b> No statistical differences with regard to symptoms of delirium (p = 0.085), cognitive impairment (p = 0.151), and functional status (p = 0.235) were found between the EG and CG at study entry and at 1 month. After adjustment, statistical differences were found in favor of the EG for symptoms of delirium (p = 0.046), cognitive impairment (p = 0.015), and functional status (p = 0.033). <b><i>Conclusion:</i></b> Nursing interventions to detect delirium at home are feasible and accepted. The nursing interventions produced a promising effect to improve delirium.