cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127904
title: Supplementary Material for: Improved Visual Perception in Very Low Birth Weight Infants on Enhanced Nutrient Supply

description: <b><i>Background:</i></b> Optimal nutrient supply to very low birth weight (VLBW: BW &lt;1,500 g) infants is important for growth and neurodevelopment. Growth restriction is common among these infants and may be associated with neurocognitive impairments. <b><i>Objectives:</i></b> To compare an enhanced nutrient supply to a routine supply given to VLBW infants and to evaluate the effects on visual perception of global form and motion measured by visual event-related potentials (VERP). <b><i>Methods:</i></b> A total of 50 VLBW infants were randomized to an intervention group that received an increased supply of energy, protein, fat, essential fatty acids, and vitamin A or a control group that received standard nutritional care. At 5 months' corrected age the infants were examined using VERP to investigate the responses to global form and motion. VERP were analysed at the first (f1) and third (f3) harmonics of the stimulus frequency. <b><i>Results:</i></b> Data from 31 subjects were eligible for analysis. The motion VERP responses for the f1 and f3 components were stronger in the area near the posterior midline region in the intervention group compared to the controls in the group analyses (p = 0.02 and p = 0.001, respectively). <b><i>Conclusion:</i></b> The results showed a more consistent response to global motion among infants receiving enhanced nutrition. The intervention may have improved visual perception of global motion.
DOI: 10.6084/m9.figshare.5127895
title: Supplementary Material for: New Insights into the Genetics of Fetal Megacystis: ACTG2 Mutations, Encoding γ-2 Smooth Muscle Actin in Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (Berdon Syndrome)

description: <b><i>Objective:</i></b> To identify the molecular basis for prenatally suspected cases of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) (MIM 249210) in 3 independent families with clinical and radiographic evidence of MMIHS. <b><i>Methods:</i></b> Whole-exome sequencing (WES) and Sanger sequencing of the ACTG2 gene. <b><i>Results:</i></b> We identified a novel heterozygous de novo missense variant in <i>ACTG2</i> c.770G&gt;A (p.Arg257His) encoding γ-2 smooth muscle actin (ACTG2) in 2 siblings with MMIHS, suggesting gonadal mosaicism of one of the parents. Two additional de novo missense variants (p.Arg257Cys and p.Arg178His) in ACTG2 were identified in 2 additional MMHIS patients. All of our patients had evidence of fetal megacystis and a normal or slightly increased amniotic fluid volume. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. <i>ACTG2</i> immunostaining of the intestinal tissue showed an altered muscularis propria, a markedly thinned longitudinal muscle layer, and a reduced amount and abnormal distribution of ACTG2. <b><i>Conclusion:</i></b> Our study demonstrates that de novo mutations in <i>ACTG2</i> are a cause of fetal megacystis in MMIHS and that gonadal mosaicism may be present in a subset of cases. These findings have implications for the counseling of families with a diagnosis of fetal megacystis with a preserved amniotic fluid volume and associated gastrointestinal findings.
DOI: 10.6084/m9.figshare.5127898
title: Supplementary Material for: Integrating Multiple Correlated Phenotypes for Genetic Association Analysis by Maximizing Heritability

description: Many correlated disease variables are analyzed jointly in genetic studies in the hope of increasing power to detect causal genetic variants. One approach involves assessing the relationship between each phenotype and each SNP individually and using a Bonferroni correction for the effective number of tests conducted. Alternatively, one can apply a multivariate regression or a dimension reduction technique, such as principal component analysis, and test for the association with the principal components of the phenotypes rather than the individual phenotypes. Inspired by the previous approaches of combining phenotypes to maximize heritability at individual SNPs, in this paper, we propose to construct a maximally heritable (MaxH) phenotype by taking advantage of the estimated total heritability and co-heritability. The heritability and co-heritability only need to be estimated once; therefore, our method is applicable to genome-wide scans. The MaxH phenotype is a linear combination of the individual phenotypes with increased heritability and power over the phenotypes being combined. Simulations show that the heritability and power achieved agree well with the theory for large samples and two phenotypes. We compare our approach with commonly used methods and assess both the heritability and the power of the MaxH phenotype. Moreover, we provide suggestions for how to choose the phenotypes for combination. An application of our approach to a GWAS on chronic obstructive pulmonary disease shows its practical relevance.
DOI: 10.6084/m9.figshare.5127901.v1
title: Supplementary Material for: Romiplostim Treatment in Adults with Immune Thrombocytopenia of Varying Duration and Severity

description: Romiplostim is recommended for the second- and third-line treatment of primary immune thrombocytopenia (ITP). We conducted a large, single-arm study (clinicaltrials.gov; NCT00508820) with broad entry criteria to evaluate the safety of romiplostim in adult ITP. Patients (n = 407) with ITP lasting 0.03-57.14 years and low platelet counts (median 14.0 × 10<sup>9</sup>/l) or uncontrolled bleeding received romiplostim for up to 4 years. The rates of treatment-related, serious adverse events, serious hemorrhage events, thromboembolic events and fatal events were similar to those reported in previous romiplostim trials (0.2, 0.4, 0.2 and 0.1/100 patient-weeks, respectively). Bone marrow reticulin was observed in 4 patients, but biopsies were not routinely performed so the true incidence of this event cannot be determined. Type I collagen (nonserious, unrelated) was reported in 1 patient who likely had myelodysplastic syndrome. No new class of adverse events was reported. Platelet responses were achieved by &gt;90% of the patients, typically within 1-2 weeks of the initiation of romiplostim treatment. From week 8, median platelet counts were &gt;100 × 10<sup>9</sup>/l; 47% of the patients received rescue medications (the use decreased over time). This study confirms and extends the tolerability/efficacy findings of previous romiplostim clinical studies. It was performed on a large ITP population, which is likely more representative of clinical practice.
DOI: 10.6084/m9.figshare.5127904.v1
title: Supplementary Material for: Improved Visual Perception in Very Low Birth Weight Infants on Enhanced Nutrient Supply

description: <b><i>Background:</i></b> Optimal nutrient supply to very low birth weight (VLBW: BW &lt;1,500 g) infants is important for growth and neurodevelopment. Growth restriction is common among these infants and may be associated with neurocognitive impairments. <b><i>Objectives:</i></b> To compare an enhanced nutrient supply to a routine supply given to VLBW infants and to evaluate the effects on visual perception of global form and motion measured by visual event-related potentials (VERP). <b><i>Methods:</i></b> A total of 50 VLBW infants were randomized to an intervention group that received an increased supply of energy, protein, fat, essential fatty acids, and vitamin A or a control group that received standard nutritional care. At 5 months' corrected age the infants were examined using VERP to investigate the responses to global form and motion. VERP were analysed at the first (f1) and third (f3) harmonics of the stimulus frequency. <b><i>Results:</i></b> Data from 31 subjects were eligible for analysis. The motion VERP responses for the f1 and f3 components were stronger in the area near the posterior midline region in the intervention group compared to the controls in the group analyses (p = 0.02 and p = 0.001, respectively). <b><i>Conclusion:</i></b> The results showed a more consistent response to global motion among infants receiving enhanced nutrition. The intervention may have improved visual perception of global motion.
DOI: 10.6084/m9.figshare.5127886
title: Supplementary Material for: The Influence of Bilateral Subthalamic Nucleus Deep Brain Stimulation on Impulsivity and Prepulse Inhibition in Parkinson's Disease Patients

description: <b><i>Background:</i></b> At least 14% of Parkinson disease (PD) patients develop impulse control disorders (ICDs). The pathophysiology behind these behaviors and the impact of deep brain stimulation in a real-life setting remain unclear. <b><i>Objectives:</i></b> We prospectively examined the impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on ICDs in PD patients, as well as the relationship between impaired sensorimotor gaiting and impulsivity. <b><i>Methods:</i></b> Patients undergoing bilateral STN-DBS were assessed for ICDs preoperatively and 1-year postoperatively using a validated questionnaire (QUIP-RS). A subset of patients completed the Balloon Analogue Risk Task (BART) and auditory prepulse inhibition (PPI) testing. <b><i>Results:</i></b> Analysis revealed 12 patients had an improvement in score assessing ICDs (‘good responders'; p = 0.006) while 4 had a worse or stable score (‘poor responders'; p &gt; 0.05). Good responders further exemplified a significant decrease in hypersexual behavior (p = 0.005) and binge eating (p = 0.01). Impaired PPI responses also significantly correlated with impulsivity in BART (<i>r</i> = -0.72, p = 0.044). <b><i>Discussion:</i></b> Following bilateral STN-DBS, 75% of our cohort had a reduction in ICDs, thus suggesting deep brain stimulation effectively manages ICDs in PD. The role of impaired PPI in predisposition to ICDs in PD warrants further investigation.
DOI: 10.6084/m9.figshare.5127889
title: Supplementary Material for: LRH-1 May Rescue SF-1 Deficiency for Steroidogenesis: An in vitro<b> </b>and in vivo<b> </b>Study

description: Steroidogenic factor 1 (<i>NR5A1</i>/SF-1) mutations usually manifest in 46,XY individuals with variable degrees of disordered sex development and in 46,XX women with ovarian insufficiency. So far, there is no genotype-phenotype correlation. The broad spectrum of phenotype with <i>NR5A1</i> mutations may be due to a second hit in a gene with similar function to <i>NR5A1</i>/SF-1. Liver receptor homologue-1 (LRH-1/<i>NR5A2</i>) might be a good candidate. We performed in vitro studies for the interplay between SF-1, LRH-1 and DAX-1, expression profiles in human steroidogenic tissues, and <i>NR5A2 </i>genetic studies in a cohort (11 patients, 8 relatives, 11 families) harboring heterozygote <i>NR5A1</i>/SF-1 mutations. LRH-1 isoforms transactivate the <i>CYP17A1 </i>and <i>HSD3B2</i> promoters similarly to SF-1 and compensate for SF-1 deficiency. DAX-1 inhibits SF-1- and LRH-1-mediated transactivation. LRH-1 is found expressed in human adult and fetal adrenals and testes. However, no <i>NR5A2</i>/LRH-1 mutations were detected in 14 individuals with heterozygote <i>NR5A1</i>/SF-1 mutations. These findings demonstrate that in vitro LRH-1 can act like SF-1 and compensate for its deficiency. Expression of LRH-1 in fetal testis suggests a role in male gonadal development. However, as we found no <i>NR5A2</i>/LRH-1 mutations, the ‘second genetic hit' in SF-1 patients explaining the broad phenotypic variability remains elusive.
DOI: 10.6084/m9.figshare.5127892
title: Supplementary Material for: Polymorphisms in Genes Coding for Cytokines, Mannose-Binding Lectin, Collagen Metabolism and Thrombophilia in Women with Cervical Insufficiency

description: <b><i>Objective:</i></b> To study the association between cervical insufficiency and single nucleotide polymorphisms in seven genes coding for pro- and anti-inflammatory cytokine-related factors, mannose-binding lectin 2 <i>(MBL2)</i>, collagen1α1 <i>(COL1A1)</i>, <i>factor II</i> and <i>factor V Leiden</i> genes. <b><i>Methods:</i></b> In a case-control study, potential maternal biomarkers for cervical insufficiency were investigated in 30 women with a history of second-trimester miscarriage or preterm birth due to cervical insufficiency and in 70 control women. <b><i>Results:</i></b> Homozygous carriers of the interleukin 6 <i>(IL6)</i> -174 genotype GG had an odds ratio (OR) of 3.1 [95% confidence interval (95% CI) 1.3-7.4, p = 0.01] and <i>MBL2</i> genotypes coding for low or intermediate levels of plasma MBL had an OR of 3.3 (95% CI 1.2-9.0, p = 0.01) for cervical insufficiency compared with controls. Serum MBL levels were lower in women with cervical insufficiency than in controls (median 408 and 1,985 ng/ml, respectively, p &lt; 0.01). <b><i>Conclusions:</i></b> Single nucleotide polymorphisms in the <i>IL6</i> gene and the <i>MBL2</i> gene and low MBL levels related to the latter polymorphism may increase the risk of preterm birth due to cervical insufficiency.
DOI: 10.6084/m9.figshare.5127898.v1
title: Supplementary Material for: Integrating Multiple Correlated Phenotypes for Genetic Association Analysis by Maximizing Heritability

description: Many correlated disease variables are analyzed jointly in genetic studies in the hope of increasing power to detect causal genetic variants. One approach involves assessing the relationship between each phenotype and each SNP individually and using a Bonferroni correction for the effective number of tests conducted. Alternatively, one can apply a multivariate regression or a dimension reduction technique, such as principal component analysis, and test for the association with the principal components of the phenotypes rather than the individual phenotypes. Inspired by the previous approaches of combining phenotypes to maximize heritability at individual SNPs, in this paper, we propose to construct a maximally heritable (MaxH) phenotype by taking advantage of the estimated total heritability and co-heritability. The heritability and co-heritability only need to be estimated once; therefore, our method is applicable to genome-wide scans. The MaxH phenotype is a linear combination of the individual phenotypes with increased heritability and power over the phenotypes being combined. Simulations show that the heritability and power achieved agree well with the theory for large samples and two phenotypes. We compare our approach with commonly used methods and assess both the heritability and the power of the MaxH phenotype. Moreover, we provide suggestions for how to choose the phenotypes for combination. An application of our approach to a GWAS on chronic obstructive pulmonary disease shows its practical relevance.
DOI: 10.6084/m9.figshare.5127883
title: Supplementary Material for: Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

description: <b><i>Background:</i></b> Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T<sub>3</sub>) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. <b><i>Methods:</i></b> Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T<sub>4</sub>) and T<sub>3</sub>, reverse (r)T<sub>3</sub>, 3-iodothyronamine (3-T<sub>1</sub>AM) and 3,5-diiodothyronine (3,5-T<sub>2</sub>) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. <b><i>Results:</i></b> Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T<sub>3</sub> and/or low T<sub>4</sub> syndrome), compared to 2 of 22 (p &lt; 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT<sub>3</sub> concentrations were significantly decreased, but still within their reference ranges. 3,5-T<sub>2</sub> concentrations directly correlated with rT<sub>3</sub> concentrations and inversely correlated with FT<sub>3</sub> concentrations. Furthermore, 3,5-T<sub>2</sub> concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT<sub>3</sub>, 3,5-T<sub>2</sub>, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. <b><i>Conclusion:</i></b> This study confirms reduced FT<sub>3</sub> concentrations in patients with POAF and is the first to report on elevated 3,5-T<sub>2</sub> concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms.
DOI: 10.6084/m9.figshare.5127886.v1
title: Supplementary Material for: The Influence of Bilateral Subthalamic Nucleus Deep Brain Stimulation on Impulsivity and Prepulse Inhibition in Parkinson's Disease Patients

description: <b><i>Background:</i></b> At least 14% of Parkinson disease (PD) patients develop impulse control disorders (ICDs). The pathophysiology behind these behaviors and the impact of deep brain stimulation in a real-life setting remain unclear. <b><i>Objectives:</i></b> We prospectively examined the impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on ICDs in PD patients, as well as the relationship between impaired sensorimotor gaiting and impulsivity. <b><i>Methods:</i></b> Patients undergoing bilateral STN-DBS were assessed for ICDs preoperatively and 1-year postoperatively using a validated questionnaire (QUIP-RS). A subset of patients completed the Balloon Analogue Risk Task (BART) and auditory prepulse inhibition (PPI) testing. <b><i>Results:</i></b> Analysis revealed 12 patients had an improvement in score assessing ICDs (‘good responders'; p = 0.006) while 4 had a worse or stable score (‘poor responders'; p &gt; 0.05). Good responders further exemplified a significant decrease in hypersexual behavior (p = 0.005) and binge eating (p = 0.01). Impaired PPI responses also significantly correlated with impulsivity in BART (<i>r</i> = -0.72, p = 0.044). <b><i>Discussion:</i></b> Following bilateral STN-DBS, 75% of our cohort had a reduction in ICDs, thus suggesting deep brain stimulation effectively manages ICDs in PD. The role of impaired PPI in predisposition to ICDs in PD warrants further investigation.
DOI: 10.6084/m9.figshare.5127895.v1
title: Supplementary Material for: New Insights into the Genetics of Fetal Megacystis: ACTG2 Mutations, Encoding γ-2 Smooth Muscle Actin in Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (Berdon Syndrome)

description: <b><i>Objective:</i></b> To identify the molecular basis for prenatally suspected cases of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) (MIM 249210) in 3 independent families with clinical and radiographic evidence of MMIHS. <b><i>Methods:</i></b> Whole-exome sequencing (WES) and Sanger sequencing of the ACTG2 gene. <b><i>Results:</i></b> We identified a novel heterozygous de novo missense variant in <i>ACTG2</i> c.770G&gt;A (p.Arg257His) encoding γ-2 smooth muscle actin (ACTG2) in 2 siblings with MMIHS, suggesting gonadal mosaicism of one of the parents. Two additional de novo missense variants (p.Arg257Cys and p.Arg178His) in ACTG2 were identified in 2 additional MMHIS patients. All of our patients had evidence of fetal megacystis and a normal or slightly increased amniotic fluid volume. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. <i>ACTG2</i> immunostaining of the intestinal tissue showed an altered muscularis propria, a markedly thinned longitudinal muscle layer, and a reduced amount and abnormal distribution of ACTG2. <b><i>Conclusion:</i></b> Our study demonstrates that de novo mutations in <i>ACTG2</i> are a cause of fetal megacystis in MMIHS and that gonadal mosaicism may be present in a subset of cases. These findings have implications for the counseling of families with a diagnosis of fetal megacystis with a preserved amniotic fluid volume and associated gastrointestinal findings.
DOI: 10.6084/m9.figshare.5127877
title: Supplementary Material for: Early Social Experience Affects Neural Activity to Affiliative Facial Gestures in Newborn Nonhuman Primates

description: A fundamental issue in cognitive neuroscience is how the brain encodes the actions and intentions of others. The discovery of an action-production-perception mechanism underpinning such a capacity advanced our knowledge of how these processes occur; however, no study has examined how the early postnatal environment may shape action-production-perception. Here, we examined the effects of social experience on action-production-perception in 3-day-old rhesus macaques that were raised either with or without their biological mothers. We measured the neonatal imitation skills and brain electrical activity responses, while infants produced and observed facial gestures. We hypothesized that early social experiences may shape brain activity, as assessed via electroencephalogram suppression in the α band (5-7 Hz in infants, known as the mu rhythm) during action observation, and lead to more proficient imitation skills. Consistent with this hypothesis, the infants reared by their mothers were more likely to imitate lipsmacking (LS) - a natural, affiliative gesture - and exhibited greater mu rhythm desynchronization while viewing LS gestures than the nursery-reared infants. These effects were not found in response to tongue protrusion, a meaningless gesture, or a nonsocial control. These data suggest that socially enriched early experiences in the first days after birth increase brain sensitivity to socially relevant actions.