cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127883.v1
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.5127892.v1
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.5127871
title: Supplementary Material for: Bipolar Patients' Quality of Life in Mixed States: A Preliminary Qualitative Study

description: <b><i>Background:</i></b> Approximately 20% of patients with bipolar disorder experience mixed states. Mixed states are associated with more comorbidity, poorer treatment response and prognosis, increased relapse rate, and decreased functioning. This study aimed to produce in-depth knowledge about bipolar patients' quality of life (QoL) and functioning related to mixed states. <b><i>Sampling and Methods:</i></b> This study used qualitative research methods. A semi-structured interview guide based on a literature study was applied in interviews with 6 remitted bipolar I patients having experienced mixed states. A medical anthropological approach was applied to analyse the data. <b><i>Results:</i></b> Participants described mixed states as worse than other bipolar disorder states and their residual symptoms were prolonged. Mixed states affected the functioning of patients in key life domains such as self-esteem, family, love and social life, physical well-being, and working capability. <b><i>Conclusions:</i></b> Mixed states may severely affect the QoL and functioning of bipolar patients. Our results indicate that improving these should be a main goal of patient treatment. With an aim of adequately identifying and treating mixed states, our findings highlight the need for knowledge about this particularly severe expression of bipolar disorder. These results should be confirmed in a larger sample of patients with varying socioeconomic status.
DOI: 10.6084/m9.figshare.5127874
title: Supplementary Material for: A Multidrug, Antiproteinuric Approach to Alport Syndrome: A Ten-Year Cohort Study

description: <b><i>Background/Aims:</i></b> Combined ACE inhibitor, angiotensin-receptor-blocker, non-dihydropyridine calcium-channel-blocker, and statin therapy (Remission Clinic) reduced proteinuria and halted progression in non-diabetic nephropathies, but their efficacy in Alport syndrome (AS) nephropathy is unknown. <b><i>Methods:</i></b> From February 2004 to September 2007, we included nine albuminuric AS adults with creatinine clearance &gt;20 ml/min/1.73 m<sup>2</sup> in a single-center, open-label, prospective, off-on-off academic study. After the 1-month wash-out from RAS inhibition (Run-in), patients entered the 4-month, add-on, treatment period with benazepril (10-20 mg/day), valsartan (80-160 mg/day), diltiazem (60-120 mg/day), and fluvastatin (40-80 mg/day) followed by the 1-month wash-out (Recovery). The primary outcome was albuminuria at month 4. After recovery, patients were kept on the Remission Clinic protocol and followed until July 2014 (Extension). <b><i>Results:</i></b> The median (IQR) albuminuria progressively declined from 657.7 (292.7-1,089.6) μg/min at baseline to 71.4 (21.7-504.9) μg/min at treatment end (p = 0.009) and raised to 404.3 (167.9-446.8) μg/min after recovery. Albumin and IgG fractional clearances significantly (p ≤ 0.005) decreased from 66.9 (53.6-80.8) to 9.4 (4.6-26.0) and from 5.1 (3.0-8.4) to 1.1 (0.6-3.2), and then recovered toward baseline. Blood pressure and lipids significantly decreased on treatment, without changes in inulin-measured GFR or para-aminohippuric-measured RPF. After recovery, one patient refused to enter the extension, one with severe renal insufficiency at baseline reached ESRD, and seven retained normal serum creatinine until the end of the study. At the final visit, three were microalbuminuric and one was normoalbuminuric. Treatment was well tolerated. <b><i>Conclusion:</i></b> The Remission Clinic approach safely ameliorated albuminuria, blood pressure, lipids, and glomerular selectivity in AS patients and halted long-term progression in those without renal insufficiency to start with.
DOI: 10.6084/m9.figshare.5127880
title: Supplementary Material for: Involvement of the L-Type Amino Acid Transporter Lat2 in the Transport of 3,3′-Diiodothyronine across the Plasma Membrane

description: Thyroid hormones are transported across cell membranes by transmembrane transporter proteins, for example by members of the monocarboxylate transporter (MCT) and the L-type amino acid transporter (LAT) families. LATs consist of a light chain (e.g. LAT2) and a heavy chain (CD98), which is essential for their cell surface expression and functionality. The specificity of Lat2 for thyroid hormones and their metabolites and its role in their transport was not fully clear. This fact motivated us to establish a cell system to elucidate the uptake of thyroid hormones and their metabolites by mouse Lat2. The coinjection of cRNA coding for Lat2 and CD98 into <i>Xenopus laevis</i> oocytes resulted in a markedly increased level of 3,3′-diiodo-L-thyronine (3,3′-T<sub>2</sub>) and to some extent also enhanced T<sub>3</sub> transport. To gain insight into properties of thyroid hormones and their metabolites transported by Lat2, we inhibited 3,3′-T<sub>2</sub> uptake by various iodothyronine derivatives. T<sub>1</sub> and T<sub>2</sub> derivatives as well as 2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid strongly competed with 3,3′-T<sub>2</sub> uptake. In addition, we performed T<sub>2</sub> uptake measurements with the thyroid hormone-specific transporter MCT8. For both Lat2 and MCT8, K<sub>m</sub> values in a low micromolar range were calculated. We demonstrated that oocytes are a suitable system for thyroid hormone transport studies mediated by Lat2. Our data indicates that Lat2 compared to other thyroid hormone transporters prefers 3,3′-T<sub>2</sub> as the substrate. Thus, Lat2 might contribute to the availability of thyroid hormone by importing and/or exporting 3,3′-T<sub>2</sub>, which is generated either by T<sub>3</sub> inactivation or by rapid deiodinase 1-mediated rT<sub>3</sub> degradation.
DOI: 10.6084/m9.figshare.5127889.v1
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.5127868
title: Supplementary Material for: Kidney Volume Estimations with Ellipsoid Equations by Magnetic Resonance Imaging in Autosomal Dominant Polycystic Kidney Disease

description: <b><i>Background:</i></b> Kidney volume (KV) becomes clinically relevant in autosomal dominant polycystic kidney disease (ADPKD) management. KV can be conveniently estimated (ceKV) using ellipsoid volume equations with three axes measurements; however, the accuracy and reliability are unknown. <b><i>Methods:</i></b> KVs of 347 kidneys in 177 consecutive ADPKD patients were determined with a volumetric method (standard-KV), and ceKV was calculated using six different ellipsoid equations with three axes measurements using magnetic resonance imaging. The inter- and intraobserver reliabilities were analyzed using intraclass correlation coefficients (ICCs). Ellipsoid-KVs were obtained by linear regression analysis between standard-KV and ceKVs, and six ellipsoid-KVs were validated with a bootstrap model. <b><i>Results:</i></b> The ICCs of intra- and interobserver reliabilities in standard-KV and axes measurements were highly reliable. All ceKVs underestimated standard-KV and % differences between ceKV and standard-KV were reduced by ellipsoid-KVs. Bootstrap analyses suggested that six ellipsoid-KVs reliably simulated standard-KV. <b><i>Conclusion:</i></b> Among six ellipsoid-KVs, ellipsoid-KV<sub>3</sub> = 84 + 1.01 x π/24 × Length × (sum of two width measurements)<sup>2</sup> relatively accurately simulated the standard-KV. Kidney volume estimation using ellipsoid equations is reliably applied to clinical management of ADPKD while recognizing wide scattering in the difference between estimated and volumetrically measured kidney volume.
DOI: 10.6084/m9.figshare.5127868.v1
title: Supplementary Material for: Kidney Volume Estimations with Ellipsoid Equations by Magnetic Resonance Imaging in Autosomal Dominant Polycystic Kidney Disease

description: <b><i>Background:</i></b> Kidney volume (KV) becomes clinically relevant in autosomal dominant polycystic kidney disease (ADPKD) management. KV can be conveniently estimated (ceKV) using ellipsoid volume equations with three axes measurements; however, the accuracy and reliability are unknown. <b><i>Methods:</i></b> KVs of 347 kidneys in 177 consecutive ADPKD patients were determined with a volumetric method (standard-KV), and ceKV was calculated using six different ellipsoid equations with three axes measurements using magnetic resonance imaging. The inter- and intraobserver reliabilities were analyzed using intraclass correlation coefficients (ICCs). Ellipsoid-KVs were obtained by linear regression analysis between standard-KV and ceKVs, and six ellipsoid-KVs were validated with a bootstrap model. <b><i>Results:</i></b> The ICCs of intra- and interobserver reliabilities in standard-KV and axes measurements were highly reliable. All ceKVs underestimated standard-KV and % differences between ceKV and standard-KV were reduced by ellipsoid-KVs. Bootstrap analyses suggested that six ellipsoid-KVs reliably simulated standard-KV. <b><i>Conclusion:</i></b> Among six ellipsoid-KVs, ellipsoid-KV<sub>3</sub> = 84 + 1.01 x π/24 × Length × (sum of two width measurements)<sup>2</sup> relatively accurately simulated the standard-KV. Kidney volume estimation using ellipsoid equations is reliably applied to clinical management of ADPKD while recognizing wide scattering in the difference between estimated and volumetrically measured kidney volume.
DOI: 10.6084/m9.figshare.5127871.v1
title: Supplementary Material for: Bipolar Patients' Quality of Life in Mixed States: A Preliminary Qualitative Study

description: <b><i>Background:</i></b> Approximately 20% of patients with bipolar disorder experience mixed states. Mixed states are associated with more comorbidity, poorer treatment response and prognosis, increased relapse rate, and decreased functioning. This study aimed to produce in-depth knowledge about bipolar patients' quality of life (QoL) and functioning related to mixed states. <b><i>Sampling and Methods:</i></b> This study used qualitative research methods. A semi-structured interview guide based on a literature study was applied in interviews with 6 remitted bipolar I patients having experienced mixed states. A medical anthropological approach was applied to analyse the data. <b><i>Results:</i></b> Participants described mixed states as worse than other bipolar disorder states and their residual symptoms were prolonged. Mixed states affected the functioning of patients in key life domains such as self-esteem, family, love and social life, physical well-being, and working capability. <b><i>Conclusions:</i></b> Mixed states may severely affect the QoL and functioning of bipolar patients. Our results indicate that improving these should be a main goal of patient treatment. With an aim of adequately identifying and treating mixed states, our findings highlight the need for knowledge about this particularly severe expression of bipolar disorder. These results should be confirmed in a larger sample of patients with varying socioeconomic status.
DOI: 10.6084/m9.figshare.5127853
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.5127862
title: Supplementary Material for: Localization of the Patency Capsule by Abdominal Tomosynthesis

description: <b><i>Background/Aims:</i></b> A patency capsule (PC) is used to assess intestinal patency in patients with known or suspected stricture, but PC localization by plain abdominal X-ray (AXR) is difficult in those patients in whom the PC is not detected in the feces. Tomosynthesis is a promising, cost-effective, and low-radiation digital tomographic technique. This prospective study evaluated its use for PC localization in the intestinal tract. <b><i>Methods:</i></b> The study subjects were 49 patients in whom the PC was not detected in the feces and was identified intra-abdominally on AXR films. PC localization in the small or large intestines by AXR alone or by tomosynthesis with AXR was compared with abdominal computed tomography (CT), which is the gold standard. <b><i>Results:</i></b> The PC was judged in the large and small intestines in 22 and 27 patients by AXR alone versus 34 and 15 patients, respectively, by tomosynthesis combined with AXR. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for PC detection by AXR alone were 52.9, 53.3, 56.2, 50.0, and 53.1%, respectively. The same parameters were 100, 100, 100, 100, and 100%, respectively, for tomosynthesis with AXR, which were identical to those of CT. <b><i>Conclusions:</i></b> Tomosynthesis with AXR is superior to AXR alone, though similar to CT, with respect to localization of the PC.
DOI: 10.6084/m9.figshare.5127862.v1
title: Supplementary Material for: Localization of the Patency Capsule by Abdominal Tomosynthesis

description: <b><i>Background/Aims:</i></b> A patency capsule (PC) is used to assess intestinal patency in patients with known or suspected stricture, but PC localization by plain abdominal X-ray (AXR) is difficult in those patients in whom the PC is not detected in the feces. Tomosynthesis is a promising, cost-effective, and low-radiation digital tomographic technique. This prospective study evaluated its use for PC localization in the intestinal tract. <b><i>Methods:</i></b> The study subjects were 49 patients in whom the PC was not detected in the feces and was identified intra-abdominally on AXR films. PC localization in the small or large intestines by AXR alone or by tomosynthesis with AXR was compared with abdominal computed tomography (CT), which is the gold standard. <b><i>Results:</i></b> The PC was judged in the large and small intestines in 22 and 27 patients by AXR alone versus 34 and 15 patients, respectively, by tomosynthesis combined with AXR. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for PC detection by AXR alone were 52.9, 53.3, 56.2, 50.0, and 53.1%, respectively. The same parameters were 100, 100, 100, 100, and 100%, respectively, for tomosynthesis with AXR, which were identical to those of CT. <b><i>Conclusions:</i></b> Tomosynthesis with AXR is superior to AXR alone, though similar to CT, with respect to localization of the PC.
DOI: 10.6084/m9.figshare.5127865
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.