cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127859
title: Supplementary Material for: Impact of Thyroid Hormones on Estrogen Receptor α-Dependent Transcriptional Mechanisms in Ventromedial Hypothalamus and Preoptic Area

description: Elevated levels of thyroid hormones (TH) reduce estradiol (E2)-dependent female sexual behavior. E2 stimulates progesterone receptor <i>(Pgr)</i> and oxytocin receptor <i>(Oxtr)</i> within the ventromedial hypothalamus and preoptic area, critical hypothalamic nuclei for sexual and maternal behavior, respectively. Here, we investigated the impact of TH on E2-dependent transcriptional mechanisms in female mice. First, we observed that triiodothyronine (T<sub>3</sub>) inhibited the E2 induction of <i>Pgr</i> and <i>Oxtr.</i> We hypothesized that differences in histone modifications and receptor recruitment could explain the influence of TH on E2-responsive <i>Pgr</i> and <i>Oxtr</i> expression. We observed that histone H3 acetylation (H3Ac) and methylation (H3K4me3) was gene and brain-region specific. We then analyzed the recruitment of estrogen receptor α (ERα) and TH receptor α (TRα) on the putative regulatory sequences of <i>Pgr</i> and <i>Oxtr</i>. Interestingly, T<sub>3</sub> inhibited E2-induced ERα binding to a specific <i>Pgr</i> enhancer site, whereas TRα binding was not affected, corroborating our theory that the competitive binding of TRα to an ERα binding site can inhibit ERα transactivation and the subsequent E2-responsive gene expression. On the <i>Oxtr</i> promoter, E2 and T<sub>3</sub> worked together to modulate ERα and TRα binding. Finally, the E2-dependent induction of cofactors was reduced by hypothyroidism and T<sub>3</sub>. Thus, we determined that the <i>Pgr</i> and <i>Oxtr</i> promoter regions are responsive to E2 and that T<sub>3</sub> interferes with the E2 regulation of <i>Pgr</i> and <i>Oxtr</i> expression by altering the recruitment of receptors to DNA and changing the availability of cofactors. Collectively, our findings provide insights into molecular mechanisms of response to E2 and TH interactions controlling sex behavior in the hypothalamus.
DOI: 10.6084/m9.figshare.5127850
title: Supplementary Material for: Cumulative Effects of Foraging Behavior and Social Dominance on Brain Development in a Facultatively Social Bee <b><i>(Ceratina australensis)</i></b>

description: In social insects, both task performance (foraging) and dominance are associated with increased brain investment, particularly in the mushroom bodies. Whether and how these factors interact is unknown. Here we present data on a system where task performance and social behavior can be analyzed simultaneously: the small carpenter bee <i>Ceratina australensis.</i> We show that foraging and dominance have separate and combined cumulative effects on mushroom body calyx investment. Female<i> C. australensis</i> nest solitarily and socially in the same populations at the same time. Social colonies comprise two sisters: the social primary, which monopolizes foraging and reproduction, and the social secondary, which is neither a forager nor reproductive but rather remains at the nest as a guard. We compare the brains of solitary females that forage and reproduce but do not engage in social interactions with those of social individuals while controlling for age, reproductive status, and foraging experience. Mushroom body calyx volume was positively correlated with wing wear, a proxy for foraging experience. We also found that, although total brain volume did not vary among reproductive strategies (solitary vs. social nesters), socially dominant primaries had larger mushroom body calyx volumes (corrected for both brain and body size variation) than solitary females; socially subordinate secondaries (that are neither dominant nor foragers) had the least-developed mushroom body calyces. These data demonstrate that sociality itself does not explain mushroom body volume; however, achieving and maintaining dominance status in a group was associated with mushroom body calyx enlargement. Dominance and foraging effects were cumulative; dominant social primary foragers had larger mushroom body volumes than solitary foragers, and solitary foragers had larger mushroom body volumes than nonforaging social secondary guards. This is the first evidence for cumulative effects on brain development by dominance and task performance.
DOI: 10.6084/m9.figshare.5127859.v1
title: Supplementary Material for: Impact of Thyroid Hormones on Estrogen Receptor α-Dependent Transcriptional Mechanisms in Ventromedial Hypothalamus and Preoptic Area

description: Elevated levels of thyroid hormones (TH) reduce estradiol (E2)-dependent female sexual behavior. E2 stimulates progesterone receptor <i>(Pgr)</i> and oxytocin receptor <i>(Oxtr)</i> within the ventromedial hypothalamus and preoptic area, critical hypothalamic nuclei for sexual and maternal behavior, respectively. Here, we investigated the impact of TH on E2-dependent transcriptional mechanisms in female mice. First, we observed that triiodothyronine (T<sub>3</sub>) inhibited the E2 induction of <i>Pgr</i> and <i>Oxtr.</i> We hypothesized that differences in histone modifications and receptor recruitment could explain the influence of TH on E2-responsive <i>Pgr</i> and <i>Oxtr</i> expression. We observed that histone H3 acetylation (H3Ac) and methylation (H3K4me3) was gene and brain-region specific. We then analyzed the recruitment of estrogen receptor α (ERα) and TH receptor α (TRα) on the putative regulatory sequences of <i>Pgr</i> and <i>Oxtr</i>. Interestingly, T<sub>3</sub> inhibited E2-induced ERα binding to a specific <i>Pgr</i> enhancer site, whereas TRα binding was not affected, corroborating our theory that the competitive binding of TRα to an ERα binding site can inhibit ERα transactivation and the subsequent E2-responsive gene expression. On the <i>Oxtr</i> promoter, E2 and T<sub>3</sub> worked together to modulate ERα and TRα binding. Finally, the E2-dependent induction of cofactors was reduced by hypothyroidism and T<sub>3</sub>. Thus, we determined that the <i>Pgr</i> and <i>Oxtr</i> promoter regions are responsive to E2 and that T<sub>3</sub> interferes with the E2 regulation of <i>Pgr</i> and <i>Oxtr</i> expression by altering the recruitment of receptors to DNA and changing the availability of cofactors. Collectively, our findings provide insights into molecular mechanisms of response to E2 and TH interactions controlling sex behavior in the hypothalamus.
DOI: 10.6084/m9.figshare.5127847
title: Supplementary Material for: The Histamine H4 Receptor Regulates Chemokine Production in Human Natural Killer Cells

description: <b><i>Background:</i></b> Natural killer (NK) cells have been detected in the lesional skin of patients with inflammatory skin diseases, where high levels of histamine are also present. Therefore, we investigated the effect of histamine, in particular via the histamine H4 receptor (H4R), on gene expression levels in human NK cells. <b><i>Methods:</i></b> Comprehensive microarray-based mRNA expression profiling was performed to assess the gene expression levels in human NK cells in response to H4R stimulation in an unbiased approach. The expression of selected cytokines and chemokines was quantified by real-time PCR and enzyme-linked immunosorbent assay. <b><i>Results:</i></b> The microarray analysis identified only few genes which were differentially regulated upon H4R stimulation. In follow-up studies, a significant upregulation of CCL3 and CCL4 at the mRNA level and in addition for CCL3 also at the protein level via the H4R was observed. <b><i>Conclusion: </i></b>The elevated expression levels of chemokines in response to H4R stimulation might foster the inflammation in allergic skin diseases and characterize the H4R as a promising therapeutic target.
DOI: 10.6084/m9.figshare.5127853.v1
title: Supplementary Material for: Different Techniques of Respiratory Support Do Not Significantly Affect Gas Exchange during Cardiopulmonary Resuscitation in a Newborn Piglet Model

description: <b><i>Background:</i></b> There are no evidence-based recommendations on the use of different techniques of respiratory support and chest compressions (CC) during neonatal cardiopulmonary resuscitation (CPR). <b><i>Objectives:</i></b> We studied the short-term effects of different ventilatory support strategies along with CC representing clinical practice on gas exchange [arterial oxygen saturation (SaO<sub>2</sub>), arterial partial pressure of oxygen (PaO<sub>2</sub>) and arterial partial pressure of carbon dioxide (PaCO<sub>2</sub>)], hemodynamics and cerebral oxygenation. We hypothesized that in newborn piglets with cardiac arrest, use of a T-piece resuscitator (TPR) providing positive end-expiratory pressure (PEEP) improves gas exchange as measured by SaO<sub>2</sub> during CPR as compared to using a self-inflating bag (SIB) without PEEP. Furthermore, we explored the effects of a mechanical ventilator without synchrony to CC. <b><i>Methods:</i></b> Thirty newborn piglets with asystole were randomized into three groups and resuscitated for 20 min [fraction of inspired oxygen (FiO<sub>2</sub>) = 0.21 for 10 min and 1.0 thereafter]. Group 1 received ventilation using a TPR [peak inspiratory pressure (PIP)/PEEP of 20/5 cm H<sub>2</sub>O, rate 30/min] with inflations interposed between CC (3:1 ratio). Group 2 received ventilation using a SIB (PIP of 20 cm H<sub>2</sub>O without PEEP, rate 30/min) with inflations interposed between CC (3:1 ratio). Group 3 received ventilation using a mechanical ventilator (PIP/PEEP of 20/5 cm H<sub>2</sub>O, rate 30/min). CC were applied with a rate of 120/min without synchrony to inflations. <b><i>Results:</i></b> We found no significant differences in SaO<sub>2</sub> between the three groups. However, there was a trend toward a higher SaO<sub>2</sub> [TPR: 28.0% (22.3-40.0); SIB: 23.7% (13.4-52.3); ventilator: 44.1% (39.2-54.3); median (interquartile range)] and a lower PaCO<sub>2</sub> [TPR: 95.6 mm Hg (82.1-113.6); SIB: 100.8 mm Hg (83.0-108.0); ventilator: 74.1 mm Hg (68.5-83.1); median (interquartile range)] in the mechanical ventilator group. <b><i>Conclusions:</i></b> We found no significant effect on gas exchange using different respiratory support strategies during CPR.
DOI: 10.6084/m9.figshare.5127841
title: Supplementary Material for: Visual Attention and Saccadic Oculomotor Control in Parkinson's Disease

description: <b><i>Background:</i></b> In patients with Parkinson's disease (PD) we aimed at differentiating the relation between selective visual attention, deficits of programming and dynamics of saccadic eye movements while searching for a target and hand-reaction time as well as hand-movement time. Visual attention is crucial for concentrating selectively on one aspect of the visual field while ignoring other aspects. Eye movements are anatomically and functionally related to mechanisms of visual attention. Saccadic dysfunction might confound selective visual attention in PD. <b><i>Methods:</i></b> We studied visual selective attention in 22 medicated PD patients (clinical ON status, mild to moderate disease severity) and 22 age matched controls. We looked for possible interferences through oculomotor deficits. Two tasks were compared: free viewing of photographs and time optimal visual search of a hidden target. Visual search times (VST), task related dynamics of saccades, and hand-reaction and hand-movement times were analyzed. <b><i>Results:</i></b> In the free viewing task mild to moderately affected PD patients did not differ statistically from healthy subjects with respect to saccade dynamics. However, patients differed significantly from healthy subjects in the time optimal visual search task with 25% lower rates of successful searches. Hand movement reaction time did not differ in both groups, whereas hand movement execution time was significantly prolonged in PD patients. <b><i>Conclusion:</i></b> Saccadic oculomotor control and hand movement reaction times were intact, whereas in our less severely affected treated PD patients, visual selective attention was not. The highly reduced successful search rate might be related to disturbed programming and delayed execution of saccades during time optimal visual search due to decreased execution of serial-order sequential generation of saccades.
DOI: 10.6084/m9.figshare.5127844
title: Supplementary Material for: Clinical Relevance of Cluster Analysis in Phenotyping Allergic Rhinitis in a Real-Life Study

description: <b><i>Background:</i></b> Disease stratification, using phenotypic characterization performed either by hypothesis- or data-driven methods, was developed to improve clinical decisions. However, cluster analysis has not been used for allergic rhinitis. <b><i>Objective:</i></b> To define clusters in allergic rhinitis and to compare them with ARIA (Allergic Rhinitis and Its Impact on Asthma), a hypothesis-driven approach. <b><i>Methods:</i></b> A French observational prospective multicenter study (EVEIL: Echelle visuelle analogique dans la rhinite allergique) was carried out on 990 patients consulting general practitioners for allergic rhinitis and treated as per clinical practice. In this study, changes in symptom scores, visual analogue scales and quality of life were measured at baseline and after 14 days of treatment. A post hoc analysis was performed to identify clusters of patients with allergic rhinitis - using Ward's hierarchical method - and to define their clinical relevance at baseline and after 14 days of treatment. The cluster approach was compared to the ARIA approach. <b><i>Results:</i></b> Patients were clustered into 4 phenotypes which partly followed the ARIA classes. These phenotypes differed in their disease severity including symptoms and quality of life. Physicians in real-life practice prescribed medication regardless of the phenotype and severity, with the exception of patients with ocular symptoms. Prescribed treatments were comparable in hypothesis- and data-driven analyses. The prevalence of uncontrolled patients during treatment was similar in the 4 clusters, but was significantly different according to the ARIA classes. <b><i>Conclusion:</i></b> Cluster analysis using demographic and clinical parameters only does not appear to add relevant information for disease stratification in allergic rhinitis.
DOI: 10.6084/m9.figshare.5127838
title: Supplementary Material for: Breast Cancer and Sarcoidosis: Case Series and Review of the Literature

description: <b><i>Background:</i></b> Sarcoidosis is a chronic inflammatory disease of unknown etiology, which can involve different organs and systems. Accordingly, sarcoidosis can mimic breast cancer, making the differential diagnosis very difficult. <b><i>Case Report:</i></b> 5 patients with a diagnosis of both sarcoidosis and breast cancer followed by the Rabin Medical Center between January 1993 and June 2012 were enrolled in this study. Additionally, a comprehensive literature review which identified 104 patients diagnosed with breast cancer and sarcoidosis was carried out. In both populations reviewed, the average age at diagnosis of sarcoidosis and breast cancer was 57 years. Among the 66 patients with both sarcoidosis and breast cancer, sarcoidosis preceded breast cancer in 31 cases, followed it in 23 cases, and appeared concurrently in 10 cases. <b><i>Conclusion:</i></b> Based on our clinical cases and literature review, a histological study is recommended over imaging if sarcoidosis or breast cancer may be present. Furthermore, breast cancer is rarely associated with sarcoidosis or sarcoidosis-like reaction.
DOI: 10.6084/m9.figshare.5127841.v1
title: Supplementary Material for: Visual Attention and Saccadic Oculomotor Control in Parkinson's Disease

description: <b><i>Background:</i></b> In patients with Parkinson's disease (PD) we aimed at differentiating the relation between selective visual attention, deficits of programming and dynamics of saccadic eye movements while searching for a target and hand-reaction time as well as hand-movement time. Visual attention is crucial for concentrating selectively on one aspect of the visual field while ignoring other aspects. Eye movements are anatomically and functionally related to mechanisms of visual attention. Saccadic dysfunction might confound selective visual attention in PD. <b><i>Methods:</i></b> We studied visual selective attention in 22 medicated PD patients (clinical ON status, mild to moderate disease severity) and 22 age matched controls. We looked for possible interferences through oculomotor deficits. Two tasks were compared: free viewing of photographs and time optimal visual search of a hidden target. Visual search times (VST), task related dynamics of saccades, and hand-reaction and hand-movement times were analyzed. <b><i>Results:</i></b> In the free viewing task mild to moderately affected PD patients did not differ statistically from healthy subjects with respect to saccade dynamics. However, patients differed significantly from healthy subjects in the time optimal visual search task with 25% lower rates of successful searches. Hand movement reaction time did not differ in both groups, whereas hand movement execution time was significantly prolonged in PD patients. <b><i>Conclusion:</i></b> Saccadic oculomotor control and hand movement reaction times were intact, whereas in our less severely affected treated PD patients, visual selective attention was not. The highly reduced successful search rate might be related to disturbed programming and delayed execution of saccades during time optimal visual search due to decreased execution of serial-order sequential generation of saccades.
DOI: 10.6084/m9.figshare.5127835
title: Supplementary Material for: Urine Metabolomics by <sup>1</sup>H-NMR Spectroscopy Indicates Associations between Serum 3,5-T<sub>2</sub> Concentrations and Intermediary Metabolism in Euthyroid Humans

description: <b><i>Context:</i></b> 3,5-Diiodo-L-thyronine (3,5-T<sub>2</sub>) is a thyroid hormone metabolite which exhibited versatile effects in rodent models, including the prevention of insulin resistance or hepatic steatosis typically forced by a high-fat diet. With respect to euthyroid humans, we recently observed a putative link between serum 3,5-T<sub>2</sub> and glucose but not lipid metabolism. <b><i>Objective:</i></b> The aim of the present study was to widely screen the urine metabolome for associations with serum 3,5-T<sub>2</sub> concentrations in healthy individuals. <b><i>Study Design and Methods:</i></b> Urine metabolites of 715 euthyroid participants of the population-based Study of Health in Pomerania (SHIP-TREND) were analyzed by <sup>1</sup>H-NMR spectroscopy. Multinomial logistic and multivariate linear regression models were used to detect associations between urine metabolites and serum 3,5-T<sub>2</sub> concentrations. <b><i>Results:</i></b> Serum 3,5-T<sub>2</sub> concentrations were positively associated with urinary levels of trigonelline, pyroglutamate, acetone and hippurate. In detail, the odds for intermediate or suppressed serum 3,5-T<sub>2</sub> concentrations doubled owing to a 1-standard deviation (SD) decrease in urine trigonelline levels, or increased by 29-50% in relation to a 1-SD decrease in urine pyroglutamate, acetone and hippurate levels. <b><i>Conclusion:</i></b> Our findings in humans confirmed the metabolic effects of circulating 3,5-T<sub>2</sub> on glucose and lipid metabolism, oxidative stress and enhanced drug metabolism as postulated before based on interventional pharmacological studies in rodents. Of note, 3,5-T<sub>2</sub> exhibited a unique urinary metabolic profile distinct from previously published results for the classical thyroid hormones.
DOI: 10.6084/m9.figshare.5127838.v1
title: Supplementary Material for: Breast Cancer and Sarcoidosis: Case Series and Review of the Literature

description: <b><i>Background:</i></b> Sarcoidosis is a chronic inflammatory disease of unknown etiology, which can involve different organs and systems. Accordingly, sarcoidosis can mimic breast cancer, making the differential diagnosis very difficult. <b><i>Case Report:</i></b> 5 patients with a diagnosis of both sarcoidosis and breast cancer followed by the Rabin Medical Center between January 1993 and June 2012 were enrolled in this study. Additionally, a comprehensive literature review which identified 104 patients diagnosed with breast cancer and sarcoidosis was carried out. In both populations reviewed, the average age at diagnosis of sarcoidosis and breast cancer was 57 years. Among the 66 patients with both sarcoidosis and breast cancer, sarcoidosis preceded breast cancer in 31 cases, followed it in 23 cases, and appeared concurrently in 10 cases. <b><i>Conclusion:</i></b> Based on our clinical cases and literature review, a histological study is recommended over imaging if sarcoidosis or breast cancer may be present. Furthermore, breast cancer is rarely associated with sarcoidosis or sarcoidosis-like reaction.
DOI: 10.6084/m9.figshare.5127856
title: Supplementary Material for: Increased Prevalence of Sleep Apnea in Children with Pseudohypoparathyroidism Type 1a

description: <b><i>Background/Aims:</i></b> Pseudohypoparathyroidism type 1a (PHP1a) is a rare genetic disorder. This study aimed to determine the prevalence of sleep apnea in children with PHP1a. <b><i>Methods:</i></b> Nineteen patients with PHP1a between the age of 2 and 21 years were enrolled prospectively using online advertisements. Parents completed a medical history and surveys to assess sleep behavior. Polysomnography records were obtained when available. In addition, 18 subjects were identified in a retrospective chart review of de-identified medical records with 2.3 million patient charts. <b><i>Results:</i></b> Parents reported sleep disturbance (94%) and daytime somnolence (81%) in their children with PHP1a. In the retrospective chart review, 39% had a history of sleep apnea versus 8.8% of a similarly obese control group. In the combined analysis (n = 31), 52% had a history of snoring and 45% had a diagnosis of sleep apnea. Patients were obese with a mean BMI z-score of 2.20 ± 0.59. Patients with sleep apnea were significantly younger than those without a diagnosis (8.1 ± 5.4 vs. 12.8 ± 5.0 years, p = 0.02). <b><i>Conclusions:</i></b> Children with PHP1a have a 4.4-fold greater relative risk of sleep apnea than similarly obese children. Screening for sleep apnea in this population may be warranted to prevent adverse health outcomes.
DOI: 10.6084/m9.figshare.5127865.v1
title: Supplementary Material for: A Generalized Sequential Bonferroni Procedure for GWAS in Admixed Populations Incorporating Admixture Mapping Information into Association Tests

description: <b><i>Objective:</i></b> To develop effective methods for GWAS in admixed populations such as African Americans. <b><i>Methods:</i></b> We show that, when testing the null hypothesis that the test SNP is not in background linkage disequilibrium with the causal variants, several existing methods cannot control well the family-wise error rate (FWER) in the strong sense in GWAS. These existing methods include association tests adjusting for global ancestry and joint association tests that combine statistics from admixture mapping tests and association tests that correct for local ancestry. Furthermore, we describe a generalized sequential Bonferroni (smooth-GSB) procedure for GWAS that incorporates smoothed weights calculated from admixture mapping tests into association tests that correct for local ancestry. We have applied the smooth-GSB procedure to analyses of GWAS data on American Africans from the Atherosclerosis Risk in Communities (ARIC) Study. <b><i>Results:</i></b> Our simulation studies indicate that the smooth-GSB procedure not only control the FWER, but also improves statistical power compared with association tests correcting for local ancestry. <b><i>Conclusion:</i></b> The smooth-GSB procedure can result in a better performance than several existing methods for GWAS in admixed populations.