cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126437.v1
title: Supplementary Material for: Dose of Hemodialysis and Survival: A Marginal Structural Model Analysis

description: <b><i>Background:</i></b> Observational studies have consistently demonstrated the survival benefits of a greater dialysis dose in maintenance hemodialysis (MHD) patients, whereas randomized controlled trials have shown conflicting results. The possible causal impact of dialysis dose on mortality needs to be investigated using rich cohort data analyzed with novel statistical methods such as marginal structural models (MSMs) that account for time-varying confounding and exposure. <b><i>Methods:</i></b> We quantified the effect of delivered dose of hemodialysis (HD) [single-pool Kt/V (spKt/V)] on mortality risk in a contemporary cohort of 68,110 patients undergoing HD 3 times weekly (7/2001-9/2005). We compared conventional Cox proportional hazard and MSM survival analyses, accounting for time-varying confounding by applying longitudinally modeled inverse-probability-of-dialysis-dose weights to each observation. <b><i>Results:</i></b> In conventional Cox models, baseline spKt/V showed a weak negative association with mortality, while higher time-averaged spKt/V was strongly associated with lower mortality risk. In MSM analyses, compared to a spKt/V range of 1.2-&lt;1.4, a spKt/V range of &lt;1.2 was associated with a higher risk of mortality [HR (95% CI) 1.67 (1.54-1.80)], whereas mortality risks were significantly lower with higher spKt/V [HRs (95% CI): 0.74 (0.70-0.78), 0.63 (0.59-0.66), 0.56 (0.52-0.60), and 0.56 (0.52-0.61) for spKt/V ranges of 1.4-&lt;1.6, 1.6-&lt;1.8, 1.8-&lt;2.0, and ≥2.0, respectively]. Thus, MSM analyses showed that the greatest survival advantage of a higher dialysis dose was observed for a spKt/V range of 1.8-&lt;2.0, and the dialysis dose-mortality relationship was robust in almost all subgroups of patients. <b><i>Conclusions:</i></b> Higher HD doses were robustly associated with greater survival in MSM analyses that more fully and appropriately accounted for time-varying confounding.
DOI: 10.6084/m9.figshare.5126422
title: Supplementary Material for: High Frequency of <b><i>DUOX2</i></b> Mutations in Transient or Permanent Congenital Hypothyroidism with Eutopic Thyroid Glands

description: <b><i>Background/Aims:</i></b> This study aimed to clarify the frequency, phenotypes, and molecular spectrum of <i>DUOX2</i>,<i> TPO</i>, <i>TSHR, </i>and <i>TG</i> mutations in patients with congenital hypothyroidism (CH) with enlarged or normal-sized eutopic thyroid glands. <b><i>Methods:</i></b> The study cohort included 43 subjects from 41 unrelated families who had CH with eutopic thyroid glands. Mutation analyses of <i>DUOX2</i>,<i> TPO</i>, and<i> TSHR</i> were performed. The functional capacities of novel missense variants of <i>DUOX2</i> were verified by measuring H<sub>2</sub>O<sub>2</sub> generation in vitro. <b><i>Results:</i></b> Of the 43 subjects, 23 (53.5%) had sequence variants in at least one gene. Twelve different <i>DUOX2</i> variants, including seven novel variants, were identified in 20 subjects. A functional analysis of the <i>DUOX2</i> variants revealed that most variants, other than p.G206V and p.H678R, caused a significant reduction in H<sub>2</sub>O<sub>2</sub> generation. Therefore, 15 subjects harbored functionally deleterious <i>DUOX2</i> variants. Of these, 5 subjects had transient CH, and 10 were found to have permanent CH. Sequence variants in <i>TSHR</i> were identified in 5 subjects. One of the 43 subjects (2.3%) had sequence variants in two different genes. <b><i>Conclusions:</i></b><i>DUOX2</i> variants are a relatively common cause of CH with normal-sized or enlarged eutopic thyroid glands. Variable phenotypes were associated with partial loss of the functional activity of <i>DUOX2</i> variants.
DOI: 10.6084/m9.figshare.5126434.v1
title: Supplementary Material for: An Alternative Transcription Start Site Yields Estrogen-Unresponsive <b><i>Kiss1</i></b> mRNA Transcripts in the Hypothalamus of Prepubertal Female Rats

description: The importance of the <i>Kiss1</i> gene in the control of reproductive development is well documented. However, much less is known about the transcriptional regulation of <i>Kiss1</i> expression in the hypothalamus. Critical for these studies is an accurate identification of the site(s) where <i>Kiss1</i> transcription is initiated. Employing 5′-RACE PCR, we detected a transcription start site (TSS1) used by the hypothalamus of rats, mice, nonhuman primates and humans to initiate <i>Kiss1</i> transcription. In rodents, an exon 1 encoding 5′-untranslated sequences is followed by an alternatively spliced second exon, which encodes 5′-untranslated regions of two different lengths and contains the translation initiation codon (ATG). In nonhuman primates and humans, exon 2 is not alternatively spliced. Surprisingly, in rat mediobasal hypothalamus (MBH), but not preoptic area (POA), an additional TSS (TSS2) located upstream from TSS1 generates an exon 1 longer (377 bp) than the TSS1-derived exon 1 (98 bp). The content of TSS1-derived transcripts increased at puberty in the POA and MBH of female rats. It also increased in the MBH after ovariectomy, and this change was prevented by estrogen. In contrast, no such changes in TSS2-derived transcript abundance were detected. Promoter assays showed that the proximal TSS1 promoter is much more active than the putative TSS2 promoter, and that only the TSS1 promoter is regulated by estrogen<i>. </i>These differences appear to be related to the presence of a TATA box and binding sites for transcription factors activating transcription and interacting with estrogen receptor-α in the TSS1, but not TSS2, promoter.
DOI: 10.6084/m9.figshare.5126419
title: Supplementary Material for: Natural History and Management of Congenital Hypothyroidism with in situ Thyroid Gland

description: <b><i>Background/Objective:</i></b> Normally sited glands account for increasing congenital hypothyroidism (CH). Mechanisms often remain unknown. To report the incidence of CH with in situ thyroid gland (ISTG) and describe the natural history of the disease without known etiology. <b><i>Method:</i></b> Clinical, biochemical and imaging data at diagnosis were retrospectively analyzed in 285 children positively screened for CH in Ile-de-France between 2005 and 2008. If treatment was discontinued, management of hormonal substitution and follow-up of biochemical thyroid function was performed.<b><i> Results:</i></b> 93 full-term CH neonates displayed ISTG (40.6%), including 50 with unexplained mechanism. Follow-up data were available in 32 of them. Therapy was withdrawn from 20 children at a median age of 23.5 months (6-66), among whom 18 remained still untreated over a median duration of 15.3 months (4.4-29.6). In 11 children, levothyroxine (L-T4) dosage was increased over time to maintain biochemical euthyroidism. No statistical differences in initial TSH or FT<sub>4</sub> levels, iodine status or birth weight were found between children with transient and permanent hypothyroidism.<b><i> Conclusion:</i></b> Withdrawal of L-T4 substitution was feasible in 56.2% of full-term children with CH with ISTG but unexplained mechanism, emphasizing the need for systematic therapy withdrawal. However, further studies are warranted to standardize withdrawal protocol.
DOI: 10.6084/m9.figshare.5126428.v1
title: Supplementary Material for: The Metabolic Syndrome and Cognitive Decline in the Atherosclerosis Risk in Communities Study (ARIC)

description: <b><i>Background:</i></b> Midlife metabolic syndrome (MetS) may impact cognitive health as a construct independently of hypertension, hyperlipidemia and other components. <b><i>Methods:</i></b> 10,866 participants aged 45-64 years at baseline were assessed for MetS and completed cognitive testing at two later time points (3 and 9 years from the baseline visit). <b><i>Results:</i></b> MetS is associated with increased odds of low cognitive performance in the domains of executive function and word fluency, but not with 6-year cognitive decline. Individual MetS components explained this association (hypertension, diabetes, low HDL, elevated triglycerides and increased waist circumference). <b><i>Conclusions:</i></b> A focus on the individual risk factors as opposed to MetS during midlife is important to reduce the incidence of cognitive impairment in later life.
DOI: 10.6084/m9.figshare.5126410
title: Supplementary Material for: Valves in the Heart of the Big Apple VIII: Evaluation and Management of Valvular Heart Diseases 2014. Fifth Annual Joint Scientific Session of the Heart Valve Society of America and Society of Heart Valve Diseases, New York City, N.Y., May 8-10, 2014: Abstracts

description: Medicine
DOI: 10.6084/m9.figshare.5126416
title: Supplementary Material for: Recombinant Human L-Ficolin Directly Neutralizes Hepatitis C Virus Entry

description: L-ficolin is a soluble pattern recognition molecule expressed by the liver that contributes to innate immune defense against microorganisms. It is well described that binding of L-ficolin to specific pathogen-associated molecular patterns activates the lectin complement pathway, resulting in opsonization and lysis of pathogens. In this study, we demonstrated that in addition to this indirect effect, L-ficolin has a direct neutralizing effect against hepatitis C virus (HCV) entry. Specific, dose-dependent binding of recombinant L-ficolin to HCV glycoproteins E1 and E2 was observed. This interaction was inhibited by soluble L-ficolin ligands. Interaction of L-ficolin with E1 and E2 potently inhibited entry of retroviral pseudoparticles bearing these glycoproteins. L-ficolin also inhibited entry of cell-cultured HCV in a calcium-dependent manner. Neutralizing concentrations of L-ficolin were found to be circulating in the serum of HCV-infected individuals. This is the first description of direct neutralization of HCV entry by a ficolin and highlights a novel role for L-ficolin as a virus entry inhibitor.
DOI: 10.6084/m9.figshare.5126407
title: Supplementary Material for: Regulator of G Protein Signaling Transcript Expression in Human Neural Progenitor Differentiation: R7 Subfamily Regulation by DNA Methylation

description: G protein-coupled receptors (GPCRs) and their ligands are critical regulators of neural progenitor differentiation, and GPCR signaling pathways are regulated by regulator of G protein signaling (RGS) proteins. RGS protein expression is dynamically regulated, and we have recently described the epigenetic regulation of RGS transcript expression. Given the potential of RGS proteins to regulate GPCR signaling and the established role of epigenetic regulation in progenitor differentiation, we explored the impact of epigenetic regulation of RGS transcripts during in vitro differentiation of human neural progenitors. Here, we demonstrate robust upregulation of the RGS transcripts RGS4, RGS5, RGS6, RGS7, and RGS11 during neuronal differentiation, while DNA methyltransferase (DNMT) and histone deacetylase enzyme expression is suppressed during differentiation. Transcripts encoding R7 subfamily RGS proteins and the R7-binding partners R7BP and R9AP showed the greatest upregulation. Further, we showed that direct pharmacological inhibition of DNMT activity enhances expression of RGS2, RGS4, RGS5, RGS6, RGS7, RGS8, RGS9L, RGS10, and RGS14 as well as R7BP and R9AP transcripts in progenitors, consistent with regulation by DNMTs. Our results reveal marked upregulation of RGS expression during neuronal differentiation and suggest that decreased expression of DNMT enzymes during differentiation contributes to upregulation. © 2014 S. Karger AG, Basel
DOI: 10.6084/m9.figshare.5126410.v1
title: Supplementary Material for: Valves in the Heart of the Big Apple VIII: Evaluation and Management of Valvular Heart Diseases 2014. Fifth Annual Joint Scientific Session of the Heart Valve Society of America and Society of Heart Valve Diseases, New York City, N.Y., May 8-10, 2014: Abstracts

description: Medicine
DOI: 10.6084/m9.figshare.5126413
title: Supplementary Material for: Postnatal Weight and Height Growth Modeling and Prediction of Body Mass Index as a Function of Time for the Study of Growth Determinants

description: Weight, height and body mass index (BMI) growth trajectories have been associated with several chronic diseases in later life. Our aim was to describe a method to model individual weight and height growth curves during infancy and to show how it can be used to study their determinants and relationships with later health outcomes as well as to predict BMI trajectories. In the EDEN mother-child cohort, we collected 17 measurements of weight and 16 of length/height per child between birth and 3 years of age in 1,900 infants from their health care booklet and during the study clinical examinations at 1 and 3 years; 1,436 (76%) had at least 1 measurement between 2 and 3 years. We fitted individual weight and height growth trajectories using the Jenss nonlinear model including random effects using the ‘SAEMIX' package (R software). We studied whether individual growth model parameters were associated with gender in one- and two-step approaches. We indirectly calculated BMI increase against time from both weight and height growth models combined and compared the fit with a direct multilevel spline model. By modeling observed growth data, we homogenized the data in terms of number and age of measurements and were able to calculate other specific parameters as growth velocities.
DOI: 10.6084/m9.figshare.5126401
title: Supplementary Material for: Treatment Policy rather than Patient Characteristics Determines Convection Volume in Online Post-Dilution Hemodiafiltration

description: <b><i>Background/Aims:</i></b> Sub-analyses of three large trials showed that hemodiafiltration (HDF) patients who achieved the highest convection volumes had the lowest mortality risk. The aims of this study were (1) to identify determinants of convection volume and (2) to assess whether differences exist between patients achieving high and low volumes. <b><i>Methods:</i></b> HDF patients from the CONvective TRAnsport STudy (CONTRAST) with a complete dataset at 6 months (314 out of a total of 358) were included in this post hoc analysis. Determinants of convection volume were identified by regression analysis. <b><i>Results:</i></b> Treatment time, blood flow rate, dialysis vintage, serum albumin and hematocrit were independently related. Neither vascular access nor dialyzer characteristics showed any relation with convection volume. Except for some variation in body size, patient characteristics did not differ across tertiles of convection volume. <b><i>Conclusion:</i></b> Treatment time and blood flow rate are major determinants of convection volume. Hence, its magnitude depends on center policy rather than individualized patient prescription.
DOI: 10.6084/m9.figshare.5126404
title: Supplementary Material for: Xeroderma Pigmentosum/De Sanctis-Cacchione Syndrome: Unusual Cause of Ataxia

description: <b><i>Introduction:</i></b> Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair, with a prevalence of 1 in 1 million. It may also be a cause of neurological symptoms including sensorineural hearing loss, peripheral neuropathy, ataxia, and chorea. Severe neurological symptoms including mental retardation, short stature, and hypogonadism invoke De Sanctis-Cacchione syndrome (DCS). <b><i>Case Report:</i></b> The patient was a 55-year-old woman with a history of mental retardation who developed chorea at age 32 and ataxia at age 37. She had numerous facial scars from 10 prior basal cell carcinoma excisions as well as diminished deep tendon reflexes, bilateral hearing loss, dysphagia, and skin freckling. Brain MRI revealed severe cortical, cerebellar, and brainstem atrophy. Supportive treatment and prevention of further damage from UV light is the mainstay of treatment in XP and DCS. <b><i>Conclusion:</i></b> XP and related disorders should be considered in the setting of neurological disorder and multiple cutaneous cancers.
DOI: 10.6084/m9.figshare.5126392
title: Supplementary Material for: Reduced Contralateral Cerebrovascular Reserve in Patients with Unilateral Steno-Occlusive Disease

description: The purpose of this study was to evaluate cerebrovascular reactivity (CVR) of major arterial vascular territories, particularly in the contralateral hemodynamically unaffected hemisphere, in patients with unilateral internal carotid artery (ICA) steno-occlusive disease compared to control subjects with risk factors for cerebrovascular disease. <b><i>Methods:</i></b> In this retrospective observational study, twenty-seven patients with right-sided unilateral ICA steno-occlusive disease (age range, 25 to 91 years; 17 males) and twenty-one patients with left-sided unilateral ICA steno-occlusive disease (age range, 24 to 83 years; 14 males) and 41 control subjects were studied. CVR was quantitated as the change in blood oxygen level dependent (BOLD) MRI signal (as a surrogate of cerebral blood flow), in response to a consistently applied step change in the arterial partial pressure of carbon dioxide (PaCO<sub>2</sub>). The CVR of each major arterial vascular territory was assessed in the ipsilateral hemodynamically affected hemisphere and compared to the corresponding territory in the contralateral hemisphere. <b><i>Results:</i></b> In patients, a significant reduction in CVR was observed in the ipsilateral anterior circulation compared to that of the corresponding territory on the contralateral side (0.027 ± 0.083 vs. 0.109 ± 0.066% BOLD change/​mm Hg, p &lt; 0.0001) and to controls (0.195 ± 0.054% BOLD change/mm Hg, p &lt; 0.0001). The CVR of the contralateral anterior circulation was reduced on average by 50% compared to controls (p &lt; 0.0001). <b><i>Conclusions:</i></b> The implication of these findings is that unilateral carotid stenosis affects the vascular reserve of both sides of the brain compared to control subjects. This indicates that the collateral blood flow support from the contralateral to the ipsilateral hemisphere comes at a cost of reduced reserve capacity in the contralateral hemisphere. The findings suggest that there may be a reduction in functional hyperemia associated with neuronal activation, not only affecting the hemisphere ipsilateral to an occlusion, but also the hemisphere contralateral to an occlusion. It remains to be determined if ‘stealing' from the ‘rich' to support the ‘poor' has clinical consequences over the long term.
DOI: 10.6084/m9.figshare.5126398
title: Supplementary Material for: Effects of Crit-Line® Monitor Use on Patient Outcomes and Epoetin Alfa Dosing following Onset of Hemodialysis: A Propensity Score-Matched Study

description: <b><i>Background:</i></b> The Crit-Line® monitor (CLM) is a device for monitoring hematocrit, oxygen saturation and change in intravascular blood volume during hemodialysis. Prior studies have evaluated CLM use in dialysis patients, but not specifically in those new to dialysis. <b><i>Methods:</i></b> In this retrospective analysis, 199 patients initiating dialysis at 8 facilities routinely using CLM were compared with 796 propensity score-matched non-CLM patients initiating dialysis at facilities not using CLM. Outcomes were considered over the first 180 days on dialysis. <b><i>Results:</i></b> Overall, the CLM group had higher StdKt/V (p = 0.06) and received lower doses of intravenous iron than the non-CLM group (p &lt; 0.001). Erythropoiesis-stimulating agent doses were lower in the CLM group in months 1-5. Serum iron and transferrin saturation levels were higher overall for the CLM group than the non-CLM group (p = 0.004 and 0.01, respectively). Hemoglobin levels and time to first hospitalization were similar for both groups. <b><i>Conclusion:</i></b> Use of CLM is associated with lower erythropoiesis-stimulating agent and iron use in incident hemodialysis patients.
DOI: 10.6084/m9.figshare.5126389
title: Supplementary Material for: In vitro and in vivo Characterization of a New Organic Nitrate Hybrid Drug Covalently Bound to Pioglitazone

description: <b><i>Background/Aims:</i></b> Organic nitrates represent a group of nitrovasodilators that are clinically used for the treatment of ischemic heart disease. The new compound CLC-3000 is an aminoethyl nitrate (AEN) derivative of pioglitazone, a thiazolidinedione antidiabetic agent combining the peroxisome proliferator-activated receptor γ agonist activity of pioglitazone with the NO-donating activity of the nitrate moiety. <b><i>Methods:</i></b> In vitro and in vivo characterization was performed by isometric tension recording, platelet function, bleeding time and detection of oxidative stress. <b><i>Results:</i></b> In vitro, CLC-3000 displayed more potent vasodilation than pioglitazone alone or classical nitrates. In vitro, some effects on oxidative stress parameters were observed. Authentic AEN or the AEN-containing linker CLC-1275 displayed antiaggregatory effects. In vivo treatment with CLC-3000 for 7 days did neither induce endothelial dysfunction nor nitrate tolerance nor oxidative stress. Acute or chronic administration of AEN increased the tail vein bleeding time in mice. <b><i>Conclusion:</i></b> In summary, the results of these studies demonstrate that CLC-3000 contains a vasodilative and antithrombotic activity that is not evident with pioglitazone alone, and that 7 days of exposure in vivo showed no typical signs of nitrate tolerance, endothelial dysfunction or other safety concerns in Wistar rats.
DOI: 10.6084/m9.figshare.5126392.v1
title: Supplementary Material for: Reduced Contralateral Cerebrovascular Reserve in Patients with Unilateral Steno-Occlusive Disease

description: The purpose of this study was to evaluate cerebrovascular reactivity (CVR) of major arterial vascular territories, particularly in the contralateral hemodynamically unaffected hemisphere, in patients with unilateral internal carotid artery (ICA) steno-occlusive disease compared to control subjects with risk factors for cerebrovascular disease. <b><i>Methods:</i></b> In this retrospective observational study, twenty-seven patients with right-sided unilateral ICA steno-occlusive disease (age range, 25 to 91 years; 17 males) and twenty-one patients with left-sided unilateral ICA steno-occlusive disease (age range, 24 to 83 years; 14 males) and 41 control subjects were studied. CVR was quantitated as the change in blood oxygen level dependent (BOLD) MRI signal (as a surrogate of cerebral blood flow), in response to a consistently applied step change in the arterial partial pressure of carbon dioxide (PaCO<sub>2</sub>). The CVR of each major arterial vascular territory was assessed in the ipsilateral hemodynamically affected hemisphere and compared to the corresponding territory in the contralateral hemisphere. <b><i>Results:</i></b> In patients, a significant reduction in CVR was observed in the ipsilateral anterior circulation compared to that of the corresponding territory on the contralateral side (0.027 ± 0.083 vs. 0.109 ± 0.066% BOLD change/​mm Hg, p &lt; 0.0001) and to controls (0.195 ± 0.054% BOLD change/mm Hg, p &lt; 0.0001). The CVR of the contralateral anterior circulation was reduced on average by 50% compared to controls (p &lt; 0.0001). <b><i>Conclusions:</i></b> The implication of these findings is that unilateral carotid stenosis affects the vascular reserve of both sides of the brain compared to control subjects. This indicates that the collateral blood flow support from the contralateral to the ipsilateral hemisphere comes at a cost of reduced reserve capacity in the contralateral hemisphere. The findings suggest that there may be a reduction in functional hyperemia associated with neuronal activation, not only affecting the hemisphere ipsilateral to an occlusion, but also the hemisphere contralateral to an occlusion. It remains to be determined if ‘stealing' from the ‘rich' to support the ‘poor' has clinical consequences over the long term.