cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127820.v1
title: Supplementary Material for: <b><i>VPS13D</i></b> Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock

description: <b><i>Background:</i></b> Genetic variations contribute to septic shock mortality. To discover a novel locus, we performed in vitro genome-wide association studies (GWAS) and further tested the result in a cohort of septic shock patients. <b><i>Methods:</i></b> Two in vitro GWAS using a quantitative trait locus analysis of stimulated IL-6 production in lymphoblastoid cells from 60 individuals of European ancestry were performed. <i>VPS13D</i> rs6685273 was genotyped in European ancestry patients (n = 498). The <i>VPS13D</i> gene was silenced in vitro. <b><i>Results:</i></b> Two GWAS using lymphoblastoid cells identified the locus of <i>VPS13D</i> rs6685273 that was significant in the same direction in both GWAS. The <i>VPS13D</i> rs6685273 C allele was associated with increased IL-6 production. Patients with septic shock who had the <i>VPS13D</i> rs6685273 CC genotype had an increased 28-day mortality (p = 0.023) and more organ failure (p &lt; 0.05) compared to the CT/TT genotypes. <i>VPS13D</i> in vitro gene silencing in the HeLa cell line increased IL-6 production. Furthermore, the rs6685273 genotype was associated with differential <i>VPS13D</i> splice variant expression. <b><i>Conclusions:</i></b> The <i>VPS13D </i>rs6685273 C allele was associated with increased IL-6 production in vitro. The patients with the <i>VPS13D </i>rs6685273 CC genotype had increased 28-day mortality and increased organ failure. <i>VPS13D</i> appears to regulate IL-6 production.
DOI: 10.6084/m9.figshare.5127805
title: Supplementary Material for: Association between Hypouricemia and Reduced Kidney Function: A Cross-Sectional Population-Based Study in Japan

description: <b><i>Background:</i></b> Hypouricemia, conventionally defined as a serum uric acid level of ≤2 mg/dl, is considered a biochemical disorder with no clinical significance. However, individuals with renal hypouricemia have a high risk of urolithiasis and exercise-induced acute kidney injury, both of which are risk factors for reduced kidney function. <b><i>Methods:</i></b> To test the hypothesis that individuals with hypouricemia would be at a higher risk of reduced kidney function, we conducted a population-based cross-sectional study using data from the Specific Health Checkups and Guidance System in Japan. Logistic analysis was used to examine the relationship between hypouricemia and reduced kidney function, defined as estimated glomerular filtration rate &lt;60 ml/min/1.73 m<sup>2</sup>. <b><i>Results:</i></b> Among 90,710 men (mean age, 63.8 years) and 136,935 women (63.7 years), 193 (0.2%) and 540 (0.4%) were identified as having hypouricemia, respectively. The prevalence of hypouricemia decreased with age in women (p for trend &lt;0.001), but not in men (p for trend = 0.24). Hypouricemia was associated with reduced kidney function in men (odds ratio, 1.83; 95% confidence interval, 1.23-2.74), but not in women (0.61; 0.43-0.86), relative to the reference category (i.e., serum uric acid levels of 4.1-5.0 mg/dl) after adjusting for age, drinking, smoking, diabetes, hypertension, hypercholesterolemia, obesity, and history of renal failure. Sensitivity analyses stratified by diabetic status yielded similar results. <b><i>Conclusions:</i></b> This study is the first to provide evidence that hypouricemia is associated with reduced kidney function in men. Further research will be needed to determine the long-term prognosis of individuals with hypouricemia.
DOI: 10.6084/m9.figshare.5127808
title: Supplementary Material for: Coexistence of Calcification, Intraplaque Hemorrhage and Lipid Core within the Asymptomatic Atherosclerotic Carotid Plaque: The Rotterdam Study

description: <b><i>Background:</i></b> There is a growing amount of evidence suggesting that the composition of carotid atherosclerotic plaques may be of clinical relevance. Yet, little is known on the coexistence of potentially vulnerable and stabilizing components within asymptomatic plaques. Therefore, in this study we set out to investigate the coexistence of intraplaque calcification, hemorrhage and lipid core within the carotid artery using a multi-modality imaging approach. <b><i>Methods:</i></b> In 329 subjects from the population-based Rotterdam Study, all with ultrasound-confirmed carotid wall thickening, we performed a multi-detector CT and a high-resolution MRI of the carotid artery bifurcation at both sides. On the CT examinations, we quantified the volume of intraplaque calcification, and using the MRI examinations we rated the presence of intraplaque hemorrhage and of lipid core. In total, we investigated 611 carotid arteries with plaques. With logistic regression models we investigated the relationship of calcification volume - as a potential stabilizing component - with the presence of potential vulnerable components (intraplaque hemorrhage and lipid core) within each carotid plaque. We adjusted all analyses for age, sex and maximal plaque thickness. Next, we stratified on degree of stenosis (≤ or &gt;30%) to evaluate effect modification by atherosclerotic burden. <b><i>Results:</i></b> We found that a larger calcification volume was associated with a higher prevalence of intraplaque hemorrhage, and a lower prevalence of lipid core (fully-adjusted odds ratio (OR) per standard deviation (SD) increase in calcification volume: 2.04 (95% confidence intervals (CI): 1.49; 2.78) and 0.72 (95% CI: 0.58; 0.90), respectively). Stratification on the degree of stenosis showed no difference in the association between calcification volume and hemorrhage over strata, while the relationship between a larger calcification volume and a lower prevalence of lipid seemed more pronounced in persons with a high degree of stenosis. <b><i>Conclusions:</i></b> In this population-based setting, we found that there is a complex relationship between calcification, intraplaque hemorrhage and lipid core within the carotid atherosclerotic plaque. Plaques with a higher load of calcification contain more often hemorrhagic components, but less often lipid core. Our results suggest that both in small and large plaques, intraplaque calcification may not be a stabilizing factor per se. These findings create an urge for conducting prospective studies investigating the interrelation of these different plaque components with regard to future cerebrovascular events.
DOI: 10.6084/m9.figshare.5127811.v1
title: Supplementary Material for: Serum Sodium Levels and Patient Outcomes in an Ambulatory Clinic-Based Chronic Kidney Disease Cohort

description: <b><i>Background: </i></b>Chronic kidney disease (CKD) patients are prone to both hypo- and hypernatremia. Little has been published on the epidemiology of hypo- and hypernatremia in ambulatory patients with non-dialysis CKD. <b><i>Methods:</i></b> Data collected in two contemporaneous CKD cohort studies, the Renal Research Institute (RRI)-CKD study (n = 834) and the Study of Treatment of Renal Insufficiency: Data and Evaluation (STRIDE) (n = 1,348) were combined and analyzed to study the association between serum sodium (Na<sup>+</sup>) and clinical outcomes. <b><i>Results:</i></b> Baseline estimated glomerular filtration rate (eGFR) and Na<sup>+</sup> were 26 ± 11 ml/min/1.73 m<sup>2</sup> and 140.2 ± 3.4 mEq/l, respectively. The prevalence of Na<sup>+</sup> ≤135 mEq/l and ≥144 mEq/l was 6 and 16%, respectively. Higher baseline Na<sup>+</sup> was significantly associated with male sex, older age, systolic blood pressure, BMI, serum albumin, presence of heart failure, and lower eGFR. The risk of end-stage renal disease (ESRD) was marginally significantly higher among patients with Na<sup>+</sup> ≤135 mEq/l, compared with 140&lt; Na<sup>+</sup> &lt;144 mEq/l (referent), in time-dependent models (adjusted hazard ratio, HR = 1.52, p = 0.06). Mortality risk was significantly greater at 135&lt; Na<sup>+</sup> ≤140 mEq/l (adjusted HR = 1.68, p = 0.02) and Na<sup>+</sup> ≥144 mEq/l (adjusted HR = 2.01, p = 0.01). <b><i>Conclusion:</i></b> CKD patients with Na<sup>+</sup> ≤135 mEq/l were at a higher risk for progression to ESRD, whereas both lower and higher Na<sup>+</sup> levels were associated with a higher risk of mortality. While caring for CKD patients, greater attention to serum sodium levels by clinicians is warranted and could potentially help improve patient outcomes.
DOI: 10.6084/m9.figshare.5127814.v1
title: Supplementary Material for: Effects of Moderate Hyperbilirubinemia on Nutritive Swallowing and Swallowing-Breathing Coordination in Preterm Lambs

description: <b><i>Background:</i></b> Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. HB induces acute neurological disorders (somnolence, abnormal tone, feeding difficulties, auditory dysfunction) and alterations in respiratory control. These findings suggest brainstem neurotoxicity that could also affect swallowing centers. <b><i>Objective:</i></b> To test the hypothesis that HB impairs nutritive swallowing (NS) and swallowing-breathing coordination. <b><i>Methods:</i></b> Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. On day 5 of life (D0), moderate HB (150-250 µmol/l) was induced during 17 h in the HB group. Swallowing was assessed via recording of pharyngeal pressure and respiration by respiratory inductance plethysmography and pulse oximetry. The effect of HB on NS was assessed during standardized bottle-feeding. A second recording was performed 48 h after recovery from HB (D3). <b><i>Results:</i></b> Swallows were less frequent (p = 0.003) and of smaller volume (p = 0.01) in HB lambs while swallowing frequency was decreased (p = 0.004). These differences disappeared after HB normalization. Swallowing-breathing coordination was impaired in HB lambs, with a decrease in percent time with NS burst-related apneas/hypopneas at D0 and D3. Simultaneously, HB lambs tended to experience more severe desaturations (&lt;80%) during bottle-feeding. Finally, following bottle-feeding, the respiratory rate was significantly lower, along with an increased apnea duration in HB lambs. <b><i>Conclusions:</i></b> Swallowing and swallowing-breathing coordination are altered by acute moderate HB in preterm lambs. Decreased efficiency at bottle-feeding is accompanied by continuation of breathing during swallow bursts, which may promote lung aspiration.
DOI: 10.6084/m9.figshare.5127799
title: Supplementary Material for: Expression of Somatostatin Receptors 1-5 and Dopamine Receptor 2 in Lung Carcinoids: Implications for a Therapeutic Role

description: <b><i>Objective:</i></b> The expression of somatostatin receptors (SSTRs) and dopamine receptor 2 (DR2) in neuroendocrine tumors is of clinical importance as somatostatin analogues and dopamine agonists can be used for their localization and/or treatment. The objective of this study is to examine the expression of the five SSTR subtypes and DR2 in lung carcinoids (LCs). <b><i>Methods:</i></b> We conducted a retrospective study of 119 LCs from 106 patients [typical carcinoids (TCs): n = 100, and atypical carcinoids (ACs): n = 19]. The expression of all five SSTR subtypes and DR2 was evaluated immunohistochemically and correlated to clinicopathological data. In a subgroup of cases, receptor expression was further analyzed using semiquantitative RT-PCR. <b><i>Results:</i></b> SSTR2A was the SSTR subtype most frequently expressed immunohistochemically (72%), followed by SSTR1 (63%), SSTR5 (40%), and SSTR3 (20%), whereas SSTR4 was negative. DR2 was expressed in 74% and co-expressed with SSTR1 in 56%, with SSTR2A in 59%, with SSTR3 in 19%, and with SSTR5 in 37% of the tumors. Receptor expression was not related to the histological subtype, tumor aggressiveness (disease extent/grading) or functionality; however, DR2 was expressed more frequently in ACs than TCs (95 vs. 70%, p = 0.017). In a subset of patients, RT-PCR findings highly suggested that the expression of SSTR2A, SSTR3, DR2, and to a lesser extent that of SSTR1 and SSTR5 is the outcome of increased gene transcription. <b><i>Conclusions:</i></b> The high and variable immunohistochemical expression of the majority of SSTRs along with their co-expression with DR2 in LCs provides a rationale for their possible treatment with agents that target these receptors.
DOI: 10.6084/m9.figshare.5127802
title: Supplementary Material for: Multitask Imaging Monitor for Surgical Navigation: Combination of Touchless Interface and Head-Mounted Display

description: As a result of the dramatic improvements in the resolution, wearability, and weight of head-mounted displays (HMDs), they have become increasingly applied in the medical field as personal imaging monitors. The combined use of a multiplexer with an HMD allows the wearer to simultaneously and seamlessly monitor multiple streams of imaging information through the HMD. We developed a multitask imaging monitor for surgical navigation by combining a touchless surgical imaging control system with an HMD. This system is composed of a standard color digital video camera mounted on the HMD and computer software that enables the identification of the number of pictured fingertips from the video camera image. The HMD wearer uses this information as a touchless interface for the operating multiplexer, which can control the arrays and types of imaging information displayed on the HMD. We used this system in an experimental demonstration during a single-port gasless partial nephrectomy. The use of this multitask imaging monitor using a touchless interface would refine the surgical workflow, especially during surgical navigation.
DOI: 10.6084/m9.figshare.5127796
title: Supplementary Material for: Pre-Sleep and Sleeping Platform Construction Behavior in Captive Orangutans (<b><i>Pongo </i></b>spp<b><i>.</i></b>): Implications for Ape Health and Welfare

description: The nightly construction of a ‘nest' or sleeping platform is a behavior that has been observed in every wild great ape population studied, yet in captivity, few analyses have been performed on sleep related behavior. Here, we report on such behavior in three female and two male captive orangutans (<i>Pongo</i> spp.), in a natural light setting, at the Indianapolis Zoo. Behavioral samples were generated, using infrared cameras for a total of 47 nights (136.25 h), in summer (n = 25) and winter (n = 22) periods. To characterize sleep behaviors, we used all-occurrence sampling to generate platform construction episodes (n = 217). Orangutans used a total of 2.4 (SD = 1.2) techniques and 7.5 (SD = 6.3) actions to construct a sleeping platform; they spent 10.1 min (SD - 9.9 min) making the platform and showed a 77% preference for ground (vs. elevated) sleep sites. Comparisons between summer and winter platform construction showed winter start times (17:12 h) to be significantly earlier and longer in duration than summer start times (17:56 h). Orangutans should be provisioned with seasonally appropriate, high quality materials suitable for construction of sleeping platforms to increase sleep quality and improve animal health and welfare.
DOI: 10.6084/m9.figshare.5127787
title: Supplementary Material for: Initiation of Renal Replacement Therapy in the Intensive Care Unit in Vicenza (IRRIV) Score

description: <b><i>Introduction:</i></b> One of the top research priorities in acute kidney injury is related to the timing of renal replacement therapy (RRT) initiation. The purpose was to develop an index that might serve as a standardized concept of timing of initiation of RRT. <b><i>Methods:</i></b> A previously described database was used. We applied a multivariable Cox regression model with backward selection to characterize parameters present in those patients who received RRT compared with those who did not receive RRT. <b><i>Results:</i></b> We studied 590 patients. We identified independent risk factors for RRT and a risk score was devised. The Area Under the Curve of the receiver operating characteristic curve was 0.81 (95% CI 0.74-0.86) for predicting the need for RRT. <b><i>Conclusions:</i></b> We have developed a simple Score (IRRIV Score) to identify patients at high risk of requiring RRT. This score may serve as a standardized definition of the timing of initiation of RRT.
DOI: 10.6084/m9.figshare.5127793
title: Supplementary Material for: Differences in Mouse Hepatic Thyroid Hormone Transporter Expression with Age and Hyperthyroidism

description: <b><i>Background:</i></b> Clinical features of thyroid dysfunction vary with age, and an oligosymptomatic presentation of hyperthyroidism is frequently observed in the elderly. This suggests age modulation of thyroid hormone (TH) action, which may occur, for example, by alterations in TH production, metabolism and/or TH action in target organs. <b><i>Objectives:</i></b> In this paper, we address possible changes in TH transporter expression in liver tissues as a mechanism of age-dependent variation in TH action. <b><i>Methods:</i></b> Chronic hyperthyroidism was induced in 4- and 20-month-old C57BL6/NTac male mice (n = 8-10) by intraperitoneal injections of 1 µg/g body weight L-thyroxine (T<sub>4</sub>) every 48 h over 7 weeks. Control animals were injected with PBS. Total RNA was isolated from liver samples for analysis of the TH transporter and TH-responsive gene expression. TH concentrations were determined in mice sera. <b><i>Results:</i></b> Baseline serum free T<sub>4</sub> (fT<sub>4</sub>) concentrations were significantly higher in euthyroid young compared to old mice. T<sub>4</sub> treatment increased total T<sub>4</sub>, fT<sub>4</sub> and free triiodothyronine to comparable concentrations in young and old mice. In the euthyroid state, TH transporter expression was significantly higher in old than in young mice, except for <i>Mct8</i> and <i>Oatp1a1 </i>expression levels<i>.</i> Hyperthyroidism resulted in upregulation of <i>Mct10</i>, <i>Lat1</i> and <i>Lat2</i> in liver tissue, while <i>Oatp1a1</i>, <i>Oatp1b2</i> and <i>Oatp1a4 </i>expression was downregulated. This effect was preserved in old animals. <b><i>Conclusion:</i></b> Here, we show age-dependent differences in TH transporter mRNA expression in the euthyroid and hyperthyroid state of mice focusing on the liver as a classical TH target organ.
DOI: 10.6084/m9.figshare.5127790
title: Supplementary Material for: Tissue Transglutaminase, Not Lysyl Oxidase, Dominates Early Calcium-Dependent Remodeling of Fibroblast-Populated Collagen Lattices

description: Cell-populated collagen gels have provided significant insight into the cellular contractile mechanisms and cell-matrix interactions that are necessary for compacting and remodeling extant matrix. Nevertheless, little research has been devoted towards determining how cells entrench these deformations that contribute to establishing a preferred mechanical state. To this end, we examined the roles of two covalent matrix cross-linkers, i.e. tissue transglutaminase and lysyl oxidase, during global remodeling of the free-floating fibroblast-populated collagen lattice. Inhibition of tissue transglutaminase resulted in a reduced rate of compaction compared to controls during early remodeling (up to 2 days). In contrast, inhibition of lysyl oxidase did not alter the early compaction of these lattices, but it reduced the compaction after 2 days of culture. Acute inhibition of different contractile mechanisms suggested further that calcium-dependent contractility may have dominated during the initial remodeling of the collagen lattice before giving way to calcium-independent contractility at later times. In summary, these findings suggest that early remodeling of the free-floating collagen lattice is facilitated by calcium-dependent cell contraction while entrenchment is dominated by a tissue transglutaminase-mediated cross-linking of the extant matrix. As remodeling continues, however, lysyl oxidase increases its contribution, perhaps by consolidating de novo collagen fibrils into fibers to continue the remodeling while the cells transition to a more sustained, calcium-independent contractility. These results promise to influence future tissue engineering studies as well as computational simulations aimed at understanding matrix remodeling in complex in vivo situations.
DOI: 10.6084/m9.figshare.5127799.v1
title: Supplementary Material for: Expression of Somatostatin Receptors 1-5 and Dopamine Receptor 2 in Lung Carcinoids: Implications for a Therapeutic Role

description: <b><i>Objective:</i></b> The expression of somatostatin receptors (SSTRs) and dopamine receptor 2 (DR2) in neuroendocrine tumors is of clinical importance as somatostatin analogues and dopamine agonists can be used for their localization and/or treatment. The objective of this study is to examine the expression of the five SSTR subtypes and DR2 in lung carcinoids (LCs). <b><i>Methods:</i></b> We conducted a retrospective study of 119 LCs from 106 patients [typical carcinoids (TCs): n = 100, and atypical carcinoids (ACs): n = 19]. The expression of all five SSTR subtypes and DR2 was evaluated immunohistochemically and correlated to clinicopathological data. In a subgroup of cases, receptor expression was further analyzed using semiquantitative RT-PCR. <b><i>Results:</i></b> SSTR2A was the SSTR subtype most frequently expressed immunohistochemically (72%), followed by SSTR1 (63%), SSTR5 (40%), and SSTR3 (20%), whereas SSTR4 was negative. DR2 was expressed in 74% and co-expressed with SSTR1 in 56%, with SSTR2A in 59%, with SSTR3 in 19%, and with SSTR5 in 37% of the tumors. Receptor expression was not related to the histological subtype, tumor aggressiveness (disease extent/grading) or functionality; however, DR2 was expressed more frequently in ACs than TCs (95 vs. 70%, p = 0.017). In a subset of patients, RT-PCR findings highly suggested that the expression of SSTR2A, SSTR3, DR2, and to a lesser extent that of SSTR1 and SSTR5 is the outcome of increased gene transcription. <b><i>Conclusions:</i></b> The high and variable immunohistochemical expression of the majority of SSTRs along with their co-expression with DR2 in LCs provides a rationale for their possible treatment with agents that target these receptors.