cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5129764
title: Supplementary Material for: Increased Levels of Total <b><i>p</i></b>-Cresylsulfate Are Associated with Pruritus in Patients with Chronic Kidney Disease

description: <b><i>Background:</i></b> Pruritus is a common and distressing symptom that affects patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and<i> p</i>-cresylsulfate (PCS) are uremic toxins with similar protein binding, dialytic clearance, and proinflammatory features. Pruritus in CKD may correlate better with uremic toxins than the glomerular filtration rate (GFR), suggesting that uremic toxins either in the central nervous system or peripherally may play an important role in the pathophysiology. <b><i>Objective:</i></b> We sought to investigate the potential contribution of serum total IS and PCS to the pathogenesis of pruritus. <b><i>Methods:</i></b> The serum levels of total IS and PCS concentrations were measured in all patients by using the Ultra Performance LC System. The characteristics of pruritus were assessed using a visual analog scale score and an interview questionnaire. <b><i>Results:</i></b> Among the 320 CKD patients, 35% had pruritus. The patients with pruritus were older and had a higher frequency of diabetes mellitus, higher uric acid, calcium, phosphorus, creatinine, high-sensitivity C-reactive protein, and total IS and PCS levels, and lower albumin concentrations and estimated GFR (eGFR) than those without pruritus. Increasing concentrations of total PCS were independently and significantly associated with pruritus. Multiple logistic regression analysis revealed total PCS as an independent association factor for pruritus, even after full adjustment of known biomarkers. Furthermore, serum total PCS levels were positively associated with calcium, phosphorus, blood urea nitrogen, creatinine, and white blood cell count, and negatively associated with eGFR, hemoglobin, and hematocrit. <b><i>Conclusion:</i></b> Our results indicate that total PCS may play a role in the pathogenesis of pruritus.
DOI: 10.6084/m9.figshare.5129755
title: Supplementary Material for: A CpG-SNP Located within the <b><i>ARPC3</i></b> Gene Promoter Is Associated with Hypertriglyceridemia in Severely Obese Patients

description: <b><i>Aims:</i></b> To test the potential association of cytosine-phosphate-guanine dinucleotides (CpG)-single-nucleotide polymorphisms (SNPs) located within actin-related protein 2/3 complex subunit 3 (<i>ARPC3</i>), a gene recently linked to adipogenesis and lipid accumulation, with metabolic syndrome (MetS) features in severely obese patients. <b><i>Methods:</i></b> Prioritized SNPs within the <i>ARPC3</i> locus were genotyped and tested for associations with MetS features in a cohort of 1,749 obese patients with and without MetS. Association testing with CpG methylation levels was performed in a methylation sub-cohort of 16 obese men. <b><i>Results:</i></b> A significant association was found between the CpG-SNP rs3759384 (C&gt;T) and plasma triglyceride (TG) levels (false discovery rate-corrected p = 3.5 × 10<sup>-2</sup>), with 0.6% of the phenotypic variance explained by the CpG-SNP, and with TT homozygotes showing the highest plasma TG levels (1.89 mmol/l). The carriers of the rs3759384 T allele also showed a significant decrease in methylation levels of the <i>ARPC3</i> promoter-associated CpG site cg10738648 in both visceral adipose tissue and blood. <i>ARPC3</i> expression levels showed a strong correlation with plasma TG levels (r = 0.70; p = 0.02). <b><i>Conclusions:</i></b> The increased plasma TG levels found in homozygous rs3759384 T allele carriers argue for a relevant role of this CpG-SNP in lipid management among obese individuals, which may be driven by an epigenetic-mediated mechanism.
DOI: 10.6084/m9.figshare.5129761
title: Supplementary Material for: Using ROADMAP Data to Identify Enhancers Associated with Disorders of Sex Development

description: Despite recent advances in our understanding, most cases of disorders of sex development (DSD) cannot be explained by mutations in known genes. In genome-wide screens of DSD patients, we and others detected duplications or deletions of potential regulatory regions of known or suspected DSD genes. It is therefore likely that a significant proportion of DSD cases may be explained by disrupted transcriptional regulation of gonad genes. Despite many recent technological advances, limited availability of relevant tissues - especially human embryonic material - can make the identification of long-range regulatory elements extremely difficult. In an attempt to overcome this limitation, we evaluated the usefulness of publicly available DNaseI hypersensitivity data from the Roadmap Epigenomics Project. For this feasibility study we used the ‘gene desert' around the <i>SOX9</i> gene and a genomic locus downstream of <i>GATA4</i>. Over 60% of our selected candidate regions had significant enhancer activity in luciferase assays. We show that this approach facilitates the detection of strong enhancer candidates worthy of further analysis.
DOI: 10.6084/m9.figshare.5129758
title: Supplementary Material for: Prescription Rates of Cardiovascular Medications in a Large UK Primary Care Chronic Kidney Disease Cohort

description: <b><i>Background and Aims:</i></b> Chronic kidney disease (CKD) is associated with increased cardiovascular (CV) risk. Guidelines have suggested the universal use of statins in CKD but aspirin's role is less well defined. The aim of this study was to determine prescription rates for statins and aspirin in a UK-based CKD cohort and to establish factors that influenced prescription rates. <b><i>Methods:</i></b> We used data from a UK primary care CKD cohort to study rates of prescription of statins and aspirin. Simple rates were initially calculated. Binary logistic regression was utilized with either statin or aspirin prescription as the outcome variable and covariates including demographic details and comorbidities. <b><i>Results:</i></b> There were 31,056 individuals in the cohort with at least one estimated glomerular filtration rate (eGFR) of &lt;60 ml/min/1.73 m<sup>2</sup>, and 65.1% individuals had 2 eGFR results &lt;60 ml/min/1.73 m<sup>2</sup> more than 3 months apart. Mean eGFR at baseline was 51.1 ml/min/1.73 m<sup>2</sup> (SD 9.1), and 64.9% had a diagnosis of hypertension (HTN), 18.8% had diabetes mellitus (DM) and 29.8% a history of CV disease. Statins were prescribed to 14,972 (48.2%) and aspirin to 11,023 (35.5%). The regression model suggested that CV disease, HTN and DM influenced the prescriptions of statins and aspirin but overall CKD stage, calculated by either eGFR or proteinuria, did not. <b><i>Conclusions:</i></b> Prescriptions of statins and aspirin in CKD is based more on the presence of comorbidities than the CKD severity. Further physician and patient education of the increased CV risk associated with CKD and its suitability for CV medication intervention is required.
DOI: 10.6084/m9.figshare.12815204.v1
title: Dataset for the paper "Increasing constraints of neighbourhood competition on tree growth at eastern Tibetan treelines"

description: This dataset include the main data and the R code for the paper "Increasing constraints of neighbourhood competition on tree growth at eastern Tibetan treelines".
DOI: 10.6084/m9.figshare.5129752
title: Supplementary Material for: Determinants of Basal Collaterals in Moyamoya Disease: Clinical and Genetic Factors

description: <b><i>Background/Aims:</i></b> To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD. <b><i>Methods:</i></b> We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed. <b><i>Results:</i></b> The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p &lt; 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (&gt;18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs. <b><i>Conclusion:</i></b> Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD.
DOI: 10.6084/m9.figshare.5129758.v1
title: Supplementary Material for: Prescription Rates of Cardiovascular Medications in a Large UK Primary Care Chronic Kidney Disease Cohort

description: <b><i>Background and Aims:</i></b> Chronic kidney disease (CKD) is associated with increased cardiovascular (CV) risk. Guidelines have suggested the universal use of statins in CKD but aspirin's role is less well defined. The aim of this study was to determine prescription rates for statins and aspirin in a UK-based CKD cohort and to establish factors that influenced prescription rates. <b><i>Methods:</i></b> We used data from a UK primary care CKD cohort to study rates of prescription of statins and aspirin. Simple rates were initially calculated. Binary logistic regression was utilized with either statin or aspirin prescription as the outcome variable and covariates including demographic details and comorbidities. <b><i>Results:</i></b> There were 31,056 individuals in the cohort with at least one estimated glomerular filtration rate (eGFR) of &lt;60 ml/min/1.73 m<sup>2</sup>, and 65.1% individuals had 2 eGFR results &lt;60 ml/min/1.73 m<sup>2</sup> more than 3 months apart. Mean eGFR at baseline was 51.1 ml/min/1.73 m<sup>2</sup> (SD 9.1), and 64.9% had a diagnosis of hypertension (HTN), 18.8% had diabetes mellitus (DM) and 29.8% a history of CV disease. Statins were prescribed to 14,972 (48.2%) and aspirin to 11,023 (35.5%). The regression model suggested that CV disease, HTN and DM influenced the prescriptions of statins and aspirin but overall CKD stage, calculated by either eGFR or proteinuria, did not. <b><i>Conclusions:</i></b> Prescriptions of statins and aspirin in CKD is based more on the presence of comorbidities than the CKD severity. Further physician and patient education of the increased CV risk associated with CKD and its suitability for CV medication intervention is required.
DOI: 10.6084/m9.figshare.5129764.v1
title: Supplementary Material for: Increased Levels of Total <b><i>p</i></b>-Cresylsulfate Are Associated with Pruritus in Patients with Chronic Kidney Disease

description: <b><i>Background:</i></b> Pruritus is a common and distressing symptom that affects patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and<i> p</i>-cresylsulfate (PCS) are uremic toxins with similar protein binding, dialytic clearance, and proinflammatory features. Pruritus in CKD may correlate better with uremic toxins than the glomerular filtration rate (GFR), suggesting that uremic toxins either in the central nervous system or peripherally may play an important role in the pathophysiology. <b><i>Objective:</i></b> We sought to investigate the potential contribution of serum total IS and PCS to the pathogenesis of pruritus. <b><i>Methods:</i></b> The serum levels of total IS and PCS concentrations were measured in all patients by using the Ultra Performance LC System. The characteristics of pruritus were assessed using a visual analog scale score and an interview questionnaire. <b><i>Results:</i></b> Among the 320 CKD patients, 35% had pruritus. The patients with pruritus were older and had a higher frequency of diabetes mellitus, higher uric acid, calcium, phosphorus, creatinine, high-sensitivity C-reactive protein, and total IS and PCS levels, and lower albumin concentrations and estimated GFR (eGFR) than those without pruritus. Increasing concentrations of total PCS were independently and significantly associated with pruritus. Multiple logistic regression analysis revealed total PCS as an independent association factor for pruritus, even after full adjustment of known biomarkers. Furthermore, serum total PCS levels were positively associated with calcium, phosphorus, blood urea nitrogen, creatinine, and white blood cell count, and negatively associated with eGFR, hemoglobin, and hematocrit. <b><i>Conclusion:</i></b> Our results indicate that total PCS may play a role in the pathogenesis of pruritus.
DOI: 10.6084/m9.figshare.5129749
title: Supplementary Material for: Checkpoint Inhibitors and Their Application in Breast Cancer

description: Immune checkpoints are crucial for the maintenance of self-tolerance and for the modulation of immune responses in order to minimize tissue damage. Tumor cells take advantage of these mechanisms to evade immune recognition. A significant proportion of tumors, including breast cancers, can express co-inhibitory molecules that are important formediating the escape from T cell-mediated immune surveillance. The interaction of inhibitory receptors with their ligands can be blocked by specific molecules. Monoclonal antibodies (mAbs) directed against the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and, more recently, against the programmed cell death protein 1 (PD1), have been approved for the therapy of melanoma (anti-CTLA4 and anti-PD1 mAbs) and non-small cell lung cancer (anti-PD1 mAbs). Moreover, inhibition of PD1 signaling has shown extremely promising signs of activity in breast cancer. An increasing number of molecules directed against other immune checkpoints are currently under clinical development. In this review, we summarize the evidence supporting the implementation of checkpoint inhibition in breast cancer by reviewing in detail data on PD-L1 expression and its regulation. In addition, opportunities to boost anti-tumor immunity in breast cancer with checkpoint inhibitor-based immunotherapies alone and in combination with other treatment options will be discussed.
DOI: 10.6084/m9.figshare.5129752.v1
title: Supplementary Material for: Determinants of Basal Collaterals in Moyamoya Disease: Clinical and Genetic Factors

description: <b><i>Background/Aims:</i></b> To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD. <b><i>Methods:</i></b> We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed. <b><i>Results:</i></b> The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p &lt; 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (&gt;18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs. <b><i>Conclusion:</i></b> Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD.
DOI: 10.6084/m9.figshare.5129761.v1
title: Supplementary Material for: Using ROADMAP Data to Identify Enhancers Associated with Disorders of Sex Development

description: Despite recent advances in our understanding, most cases of disorders of sex development (DSD) cannot be explained by mutations in known genes. In genome-wide screens of DSD patients, we and others detected duplications or deletions of potential regulatory regions of known or suspected DSD genes. It is therefore likely that a significant proportion of DSD cases may be explained by disrupted transcriptional regulation of gonad genes. Despite many recent technological advances, limited availability of relevant tissues - especially human embryonic material - can make the identification of long-range regulatory elements extremely difficult. In an attempt to overcome this limitation, we evaluated the usefulness of publicly available DNaseI hypersensitivity data from the Roadmap Epigenomics Project. For this feasibility study we used the ‘gene desert' around the <i>SOX9</i> gene and a genomic locus downstream of <i>GATA4</i>. Over 60% of our selected candidate regions had significant enhancer activity in luciferase assays. We show that this approach facilitates the detection of strong enhancer candidates worthy of further analysis.
DOI: 10.6084/m9.figshare.5129740
title: Supplementary Material for: Visceral Fat Is an Independent Predictor of Cerebral Microbleeds in Neurologically Healthy People

description: <b><i>Background:</i></b> Obesity has a significant contribution to the risk of intracerebral hemorrhage (ICH). However, little is known about the association between central obesity and the presence of cerebral microbleeds (CMBs), a precursor of ICH. We sought to assess whether visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are associated with the presence of CMB. <b><i>Methods:</i></b> We conducted a cross-sectional study of 1,737 neurologically healthy people (mean age 55.9 ± 9.1; 790 men), who underwent brain MRI and abdominal CT. Risk factors, anthropometric parameters and clinical information were obtained. CMBs were evaluated through T2*-weighted gradient-recalled echo MRI. The cross-sectional surface areas of the abdominal fat compartments were calculated. Study subjects were stratified into quartiles according to the distribution of VAT/SAT ratio. <b><i>Results:</i></b> A total of 75 (4.3%) subjects were found to have CMBs. Subjects with a greater quartile of VAT/SAT ratio were more likely to have higher numbers of CMBs (0 to ≥2; p = 0.001). In multivariable analysis, age and history of hypertension were associated with the presence of CMB (OR 1.09, 95% CI 1.06-1.13, p &lt; 0.001; OR 1.70, 95% CI 1.01-2.84, p = 0.046, respectively). A dose-response relationship was observed between the extent of VAT/SAT quartile and CMB: compared to the lowest VAT/SAT quartile, OR 2.14 (95% CI 0.86-5.35) for second VAT/SAT quartile; OR 2.26 (95% CI 0.86-5.92) for third VAT/SAT quartile; and OR 2.91 (95% CI 1.04-8.12) for the highest VAT/SAT quartile (p for trend 0.03). <b><i>Conclusion:</i></b> In our study, higher VAT/SAT ratios were found to be independent predictors of CMBs in neurologically healthy people. This finding strengthens previous data, suggesting that visceral fat distribution is an important contributor to cerebral small vessel disease.
DOI: 10.6084/m9.figshare.5129743
title: Supplementary Material for: Downregulation of SIRT4 Expression Is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma

description: <b><i>Objective:</i></b> SIRT4, a mitochondria-localized sirtuin, represses glutamine metabolism by inhibiting glutamate dehydrogenase (GDH). The current study aimed to evaluate the clinical and biological significance of SIRT4 in esophageal squamous cell carcinoma (ESCC). <b><i>Methods:</i></b> The study comprised 172 patients with surgically resected ESCC in two independent cohorts. <i>SIRT4</i> mRNA expression was analyzed in Cohort 1 (n = 79) and SIRT4 protein expression in Cohort 2 (n = 93). The association of SIRT4 expression with clinicopathological parameters and prognosis was assessed. Furthermore, the biological role of SIRT4 in ESCC cell lines was examined. <b><i>Results:</i></b> SIRT4 expression was not correlated with any clinicopathological parameters in both cohorts. In Cohort 1, low-<i>SIRT4</i>-expression cases had poorer overall survival than high-<i>SIRT4</i>-expression cases (p = 0.016). In Cohort 2, SIRT4-negative cases had poorer overall survival and disease-free survival than SIRT4-positive cases (p = 0.011 and 0.0026). Multivariate analysis revealed that SIRT4 expression was an independent prognostic factor for overall survival (HR = 2.06, p = 0.038). The rate of distant recurrence was significantly higher in SIRT4-negative cases than in SIRT4-positive cases (39.4 vs. 7.4%; p = 0.0023). In vitro, <i>SIRT4</i> knockdown significantly increased GDH activity and promoted cell proliferation and migration. <b><i>Conclusion:</i></b> SIRT4 is a potential prognostic biomarker in ESCC.
DOI: 10.6084/m9.figshare.5129746
title: Supplementary Material for: Rivaroxaban in Chronic Hemodialysis Patients

description: Medicine
DOI: 10.6084/m9.figshare.5129737
title: Supplementary Material for: Acceptance and Continuation of Contraceptive Methods Immediate Postabortion

description: <b><i>Background/Aims:</i></b> Providing preabortion contraceptive counseling for the method of contraception may reduce the incidence of repeat abortions. This study aimed to compare the acceptance and continuation rates of intrauterine devices (IUDs), combined oral contraceptives (COCs), and condom use after abortion in women who received preabortion contraceptive counseling. <b><i>Methods:</i></b> Women seeking a first-trimester abortion prospectively received preabortion contraceptive counseling and the choice of method of contraception was based on the counseling and not related to prior methods of birth control. Outcomes included continuation of postabortion contraceptive use and repeat abortions over a 6-month follow-up period. <b><i>Results:</i></b> Four hundred and fifty-five women (IUD group: n = 161; COC group: n = 149; condom group: n = 135) completed 6-month follow-up after the abortions. At the sixth month follow-up, patients continued using the IUD, COC, and condoms for contraception were 64.2, 10, and 51.5%, respectively. Higher age, being married, parity ≥1, and previous abortion were factors that were associated with more frequent selection of an IUD, while a higher education level was associated with a more frequent selection of COC and condoms. <b><i>Conclusion:</i></b> The continued use of COCs after abortion is low even with preabortion contraceptive counseling. The IUD offers reliable birth control with a lower discontinuation rate than COCs or condoms.
DOI: 10.6084/m9.figshare.5129746.v1
title: Supplementary Material for: Rivaroxaban in Chronic Hemodialysis Patients

description: Medicine