cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5128849.v1
title: Supplementary Material for: Estimated and Measured GFR Associate Differently with Retinal Vasculopathy in the General Population

description: <b><i>Background/Aims:</i></b> Estimated glomerular filtration rate (eGFR) is used extensively in epidemiological research. Validations of eGFR have demonstrated acceptable performance, but the dependence of creatinine and cystatin C on non-GFR factors could confound associations with disease. Few studies have investigated this issue in direct comparison with measured GFR (mGFR). We compared the associations between eGFR and mGFR and retinal vasculopathy, a marker of systemic microvasculopathy. <b><i>Methods:</i></b> Iohexol clearance and retinal photography were examined in the Renal Iohexol Clearance Survey in Tromsø 6, which consists of a representative sample of middle-aged persons from the general population. A total of 1,553 persons without self-reported kidney disease, cardiovascular disease or diabetes were investigated. Three eGFR equations based on creatinine and/or cystatin C from the Chronic Kidney Disease Epidemiology Collaboration were studied. Differences between eGFR and mGFR were analyzed with seemingly unrelated regression methods. <b><i>Results:</i></b> mGFR in the lowest quartile was associated with an increased multivariable-adjusted odds ratio of retinopathy (OR 1.86, 95% CI 1.16-2.97), but not with retinal artery or vein diameters. eGFR based on cystatin C (eGFR<sub>cys</sub>) was consistently biased relative to mGFR in its associations with retinal vessel diameters across different models. eGFR based on creatinine (eGFR<sub>crea</sub>) and eGFR based on both creatinine and cystatin C were also biased in several of these models (p &lt; 0.05). For retinopathy, the differences between the 3 eGFR and mGFR measurements were not statistically significant. <b><i>Conclusions:</i></b> Low mGFR is associated with retinopathy in the general population. eGFR based on creatinine and/or cystatin C are not valid substitutes for mGFR in studies of the relationship between the retina and kidney function in healthy persons.
DOI: 10.6084/m9.figshare.5128831
title: Supplementary Material for: Kicking Back Cognitive Ageing: Leg Power Predicts Cognitive Ageing after Ten Years in Older Female Twins

description: <b><i>Background:</i></b> Many observational studies have shown a protective effect of physical activity on cognitive ageing, but interventional studies have been less convincing. This may be due to short time scales of interventions, suboptimal interventional regimes or lack of lasting effect. Confounding through common genetic and developmental causes is also possible. <b><i>Objectives:</i></b> We aimed to test whether muscle fitness (measured by leg power) could predict cognitive change in a healthy older population over a 10-year time interval, how this performed alongside other predictors of cognitive ageing, and whether this effect was confounded by factors shared by twins. In addition, we investigated whether differences in leg power were predictive of differences in brain structure and function after 12 years of follow-up in identical twin pairs. <b><i>Methods:</i></b> A total of 324 healthy female twins (average age at baseline 55, range 43-73) performed the Cambridge Neuropsychological Test Automated Battery (CANTAB) at two time points 10 years apart. Linear regression modelling was used to assess the relationships between baseline leg power, physical activity and subsequent cognitive change, adjusting comprehensively for baseline covariates (including heart disease, diabetes, blood pressure, fasting blood glucose, lipids, diet, body habitus, smoking and alcohol habits, reading IQ, socioeconomic status and birthweight). A discordant twin approach was used to adjust for factors shared by twins. A subset of monozygotic pairs then underwent magnetic resonance imaging. The relationship between muscle fitness and brain structure and function was assessed using linear regression modelling and paired t tests. <b><i>Results:</i></b> A striking protective relationship was found between muscle fitness (leg power) and both 10-year cognitive change [fully adjusted model standardised β-coefficient (Stdβ) = 0.174, p = 0.002] and subsequent total grey matter (Stdβ = 0.362, p = 0.005). These effects were robust in discordant twin analyses, where within-pair difference in physical fitness was also predictive of within-pair difference in lateral ventricle size. There was a weak independent effect of self-reported physical activity. <b><i>Conclusion:</i></b> Leg power predicts both cognitive ageing and global brain structure, despite controlling for common genetics and early life environment shared by twins. Interventions targeted to improve leg power in the long term may help reach a universal goal of healthy cognitive ageing.
DOI: 10.6084/m9.figshare.5128834
title: Supplementary Material for: Intracranial Procedures and Expected Frequency of Creutzfeldt-Jakob Disease

description: <b><i>Background/Aims:</i></b> To assess the frequency and characteristics of intracranial procedures (ICPs) performed and the number of US residents living with a history of ICP. These data are used to calculate the expected annual number of sporadic Creutzfeldt-Jakob disease (CJD) cases among US residents with a history of ICP. <b><i>Methods:</i></b> The Nationwide Inpatient Sample provided data on the frequency and types of ICPs, and data from the National Center for Health Statistics was used to produce age-adjusted mortality rates. A model was constructed, which estimated long-term survival and sporadic CJD rates among ICP patients based on procedure type and age. <b><i>Results:</i></b> There were an estimated 2,070,488 ICPs in the United States from 1998 to 2007, an average of over 200,000 per year. There were an estimated 2,023,726 US residents in 2013 with a history of ICP in the previous 30 years. In 2013, there was expected to be 4.1 sporadic CJD cases (95% CI 1-8) among people with a history of ICP in the past 30 years. <b><i>Conclusions:</i></b> The considerable proportion of US residents living with a history of ICP is important information for retrospective assessments of CJD or any other suspected long-term outcome of ICPs.
DOI: 10.6084/m9.figshare.5128837.v1
title: Supplementary Material for: Neuroanatomical, Clinical and Cognitive Correlates of Post-Stroke Dysphagia

description: <b><i>Background and Purpose:</i></b> About half of the dysphagic stroke patients have persistent swallowing dysfunction after 7 days from symptom onset. The aim of the study was to evaluate incidence, prognosis, clinical and neuroradiological correlates of post-stroke dysphagia. <b><i>Methods:</i></b> We prospectively examined consecutive patients with acute ischemic or hemorrhagic stroke. Patients' clinical and neuroradiological data were collected. Swallowing function was assessed by the water swallow test upon admission and after 14 days; patients were then classified as persistent dysphagic, non-persistent dysphagic or non-dysphagic. <b><i>Results:</i></b> We recruited 275 patients, 121 of whom were dysphagic upon admission and 254 patients attended follow-up at 14 days; 141 never presented dysphagia, 21 had a non-persistent pattern of dysphagia and 92 had a persistent one. Stroke type, leukoaraiosis degree, previous cognitive impairment and stroke severity upon admission independently predicted the occurrence of dysphagia after stroke and its persistence as well. At receiver operating characteristic (ROC) analysis, the National Institutes of Health Stroke Scale (NIHSS) score of 11.5 was the best predictive value of persistent dysphagia, with a specificity of 90.1% and a sensitivity of 72.4%. <b><i>Conclusion:</i></b> Stroke severity is an important predictor of a persistent pattern of dysphagia, with a suggested NIHSS cutoff value of ≥12. An independent correlation was observed with leukoaraiosis and with previous cognitive impairment.
DOI: 10.6084/m9.figshare.5128840.v1
title: Supplementary Material for: Behavioural and Glucocorticoid Responses of a Captive Group of Spider Monkeys to Short-Term Variation in Food Presentation

description: The presentation of food may affect feeding competition and the well-being of captive social species. We hypothesized that feeding competition in a captive group of 5 black-handed spider monkeys <i>(Ateles geoffroyi)</i> should increase in response to certain food presentations in terms of size, distribution and quality of food, and that higher feeding competition should lead to an increase in agonism and physiological stress (measured by faecal glucocorticoid metabolites, FGCM) as well as to a decrease in affiliation, proximity among individuals and feeding activity. We used 5 experimental treatments representing different combinations of size, distribution and quality of food. We observed social interactions for 100 h, collected 6,500 proximity and feeding activity records, and gathered 226 faecal samples. When food was clumped, individuals spent less time feeding, and there was also significant individual variation in feeding activity within treatments. FGCM levels were higher when food was clumped. These results are probably linked to an increase in feeding competition when food is concentrated. At least in small groups of spider monkeys, dispersing food in two feeding stations may be sufficient to decrease differences among individuals in priority of access to food resources, hence reducing physiological stress and interindividual differences in feeding activity.
DOI: 10.6084/m9.figshare.5128843.v1
title: Supplementary Material for: Methods for Estimating the Global Burden of Cerebrovascular Diseases

description: The Global Burden of Disease (GBD) study is a long-standing effort to report consistent and comprehensive measures of disease burden for the world. In this paper, we describe the methods used to estimate the global burden of stroke for the GBD 2013 study. Pathologic subtypes of stroke are modeled separately for two mutually exclusive and exhaustive categories: (1) ischemic stroke and (2) hemorrhagic and other non-ischemic strokes. Acute and chronic strokes are estimated separately. The GBD 2013 study has incorporated large amounts of new data on stroke death rates, incidence and case fatality. Disease modeling methods have been updated to better integrate mortality and incidence data. Future efforts will focus on incorporating data on the regional variation in severity of disability. Stroke remains a new area for disease modeling. A better understanding of stroke incidence, mortality and severity, and how it varies among countries, can help guide priority setting and improve health policy related to this important condition.
DOI: 10.6084/m9.figshare.5128825
title: Supplementary Material for: Metformin-Derived Growth Inhibition in Renal Cell Carcinoma Depends on miR-21-Mediated <b><i>PTEN</i></b> Expression

description: <b><i>Purpose:</i></b> Metformin (MF) acts as a tumour-suppressor in renal cell carcinoma (RCC) by inhibiting the <i>AKT</i>/<i>mTOR</i> pathway via <i>AMPK </i>activation. Here, we explore the influence of miR-21 and its target gene <i>PTEN</i> on MF effects in CAKI-1 and CAKI-2 cells. <b><i>Methods:</i></b> Proliferation assays (MTS) and qRT-PCR after transient transfection with pre- and anti-miR-21 and MF treatment were conducted. <i>AMPK</i>-dependency was assessed via transfection of siAMPK. The expression of <i>PTEN</i>, <i>AKT</i> and miR-21 after transient pre-miR-21 transfection and MF treatment was analysed. <b><i>Results:</i></b> We demonstrate that CAKI-1 cells, which were found to be less sensitive towards MF, showed a significant higher miR-21 and lower PTEN expression than CAKI-2. This was confirmed in a primary RCC collective (n = 28): miR-21 and <i>PTEN </i>expression correlated negatively. MF treatment lowered miR-21 <i>AMPK</i>-dependently and increased <i>PTEN</i> expression in the cell lines. Ectopic miR-21 regulation modulated MF sensitivity. Western blot analysis showed that pre-miR-21 transfection and MF treatment regulated <i>PTEN</i> expression with impact on <i>pAKT</i> levels in the cells. <b><i>Conclusions:</i></b> We show that differing MF sensitivity in RCC cells is associated with and mediated through the regulation of miR-21/<i>PTEN </i>expression with an impact on subsequent <i>AKT</i> signalling. This provides imaginable clinical implications regarding MF therapy of RCC patients for the future.
DOI: 10.6084/m9.figshare.5128828
title: Supplementary Material for: Inhibitory Effects of Zinc Ions on Enamel Demineralisation Kinetics in vitro

description: Metal ions including zinc have the ability to influence enamel demineralisation. However, there is a paucity of data regarding reductions in demineralisation effected by zinc ions (Zn<sup>2+</sup>) in the literature. Therefore the aim was to measure the effects of zinc ion concentration ([Zn<sup>2+</sup>]) on the real-time in vitro demineralisation of enamel, during exposure to caries-simulating conditions, using scanning microradiography (SMR). Human enamel blocks were fixed in SMR environmental cells, through which acidic solutions (0.1 M acetic acid, pH 4.0) were circulated for periods of 50 h. SMR was used to quantitatively measure continuous mineral mass loss. Subsequently, the effects of sequentially increasing [Zn<sup>2+</sup>] (0.1-3,565 ppm) in the acidic solutions were measured on the rate of enamel demineralisation. This study demonstrated that Zn<sup>2+</sup> even at low concentrations significantly reduces enamel demineralisation. There was a log-linear relationship between the mean percentage reduction in demineralisation and increasing [Zn<sup>2+</sup>] up to 3,565 ppm, i.e. the change in the overall percentage reduction in demineralisation was greater at lower concentrations than at higher concentrations, with 60% reduction at 36 ppm increasing to 90% at 3,565 ppm. In conclusion, SMR demonstrated the ability of Zn<sup>2+</sup> to reduce the rate of enamel demineralisation under real-time in vitro acid conditions simulating dental caries. The results suggest that Zn<sup>2+</sup> in the oral fluids could protect against enamel demineralisation during an acidic challenge. The log-linear relationship between [Zn<sup>2+</sup>] and demineralisation suggests that the reduction in enamel dissolution is limited by the saturation of surface sites on the enamel surface.
DOI: 10.6084/m9.figshare.5128831.v1
title: Supplementary Material for: Kicking Back Cognitive Ageing: Leg Power Predicts Cognitive Ageing after Ten Years in Older Female Twins

description: <b><i>Background:</i></b> Many observational studies have shown a protective effect of physical activity on cognitive ageing, but interventional studies have been less convincing. This may be due to short time scales of interventions, suboptimal interventional regimes or lack of lasting effect. Confounding through common genetic and developmental causes is also possible. <b><i>Objectives:</i></b> We aimed to test whether muscle fitness (measured by leg power) could predict cognitive change in a healthy older population over a 10-year time interval, how this performed alongside other predictors of cognitive ageing, and whether this effect was confounded by factors shared by twins. In addition, we investigated whether differences in leg power were predictive of differences in brain structure and function after 12 years of follow-up in identical twin pairs. <b><i>Methods:</i></b> A total of 324 healthy female twins (average age at baseline 55, range 43-73) performed the Cambridge Neuropsychological Test Automated Battery (CANTAB) at two time points 10 years apart. Linear regression modelling was used to assess the relationships between baseline leg power, physical activity and subsequent cognitive change, adjusting comprehensively for baseline covariates (including heart disease, diabetes, blood pressure, fasting blood glucose, lipids, diet, body habitus, smoking and alcohol habits, reading IQ, socioeconomic status and birthweight). A discordant twin approach was used to adjust for factors shared by twins. A subset of monozygotic pairs then underwent magnetic resonance imaging. The relationship between muscle fitness and brain structure and function was assessed using linear regression modelling and paired t tests. <b><i>Results:</i></b> A striking protective relationship was found between muscle fitness (leg power) and both 10-year cognitive change [fully adjusted model standardised β-coefficient (Stdβ) = 0.174, p = 0.002] and subsequent total grey matter (Stdβ = 0.362, p = 0.005). These effects were robust in discordant twin analyses, where within-pair difference in physical fitness was also predictive of within-pair difference in lateral ventricle size. There was a weak independent effect of self-reported physical activity. <b><i>Conclusion:</i></b> Leg power predicts both cognitive ageing and global brain structure, despite controlling for common genetics and early life environment shared by twins. Interventions targeted to improve leg power in the long term may help reach a universal goal of healthy cognitive ageing.
DOI: 10.6084/m9.figshare.5128834.v1
title: Supplementary Material for: Intracranial Procedures and Expected Frequency of Creutzfeldt-Jakob Disease

description: <b><i>Background/Aims:</i></b> To assess the frequency and characteristics of intracranial procedures (ICPs) performed and the number of US residents living with a history of ICP. These data are used to calculate the expected annual number of sporadic Creutzfeldt-Jakob disease (CJD) cases among US residents with a history of ICP. <b><i>Methods:</i></b> The Nationwide Inpatient Sample provided data on the frequency and types of ICPs, and data from the National Center for Health Statistics was used to produce age-adjusted mortality rates. A model was constructed, which estimated long-term survival and sporadic CJD rates among ICP patients based on procedure type and age. <b><i>Results:</i></b> There were an estimated 2,070,488 ICPs in the United States from 1998 to 2007, an average of over 200,000 per year. There were an estimated 2,023,726 US residents in 2013 with a history of ICP in the previous 30 years. In 2013, there was expected to be 4.1 sporadic CJD cases (95% CI 1-8) among people with a history of ICP in the past 30 years. <b><i>Conclusions:</i></b> The considerable proportion of US residents living with a history of ICP is important information for retrospective assessments of CJD or any other suspected long-term outcome of ICPs.
DOI: 10.6084/m9.figshare.5128819
title: Supplementary Material for: Phase I Dose-Escalation and Pharmacokinetic Study of Intravenous Aflibercept in Combination with Docetaxel, Cisplatin, and 5-Fluorouracil in Patients with Advanced Solid Malignancies

description: <b><i>Purpose:</i></b> This phase I study (EudraCT No. 2006-001177-25) investigated aflibercept, a vascular endothelial growth factor decoy receptor protein (VEGF Trap), in combination with docetaxel, cisplatin, and 5-fluorouracil in patients with advanced solid tumors. <b><i>Patients and Methods:</i></b> Patients received 2, 4, or 6 mg/kg of intravenous aflibercept with docetaxel 75 mg/m<sup>2</sup>, cisplatin 75 mg/m<sup>2</sup>, and 5-fluorouracil 750 mg/m<sup>2</sup> in 3-week cycles until disease progression or unacceptable toxicity. Primary objectives were to evaluate dose-limiting toxicities (DLTs) during cycle 1 and to determine the recommended phase II dose. Pharmacokinetics, tolerability, and antitumor activity were also investigated. <b><i>Results:</i></b> Forty-four patients were enrolled and treated (29 patients in a dose-escalation phase and 15 patients in an expansion cohort). Following three cases of febrile neutropenia in patients receiving aflibercept at 4 mg/kg, the protocol was amended to allow earlier granulocyte colony-stimulating factor support (from day 6) and prophylactic use of ciprofloxacin. Subsequently, there were two DLTs: febrile neutropenia (2 mg/kg) and grade 4 pulmonary embolism (6 mg/kg). An excess of free over VEGF-bound aflibercept was observed at 6 mg/kg. The most frequent grade 3/4 adverse events (AEs) were neutropenia (54.5%), lymphopenia (47.7%), and stomatitis (38.6%). AEs associated with VEGF blockade (any grade) included epistaxis (61.4%), dysphonia (40.9%), hypertension (38.6%), and proteinuria (11.4%). There were 15 partial responses, including 9 in patients with gastroesophageal cancers. Thirteen patients had stable disease. <b><i>Conclusion:</i></b> Aflibercept 6 mg/kg administered every 3 weeks in combination with docetaxel, cisplatin, and 5- fluorouracil is the recommended dose for further clinical development based on tolerability, pharmacokinetics, and antitumor activity.
DOI: 10.6084/m9.figshare.5128822
title: Supplementary Material for: Neural Correlates of Schizophrenia Negative Symptoms: Distinct Subtypes Impact Dissociable Brain Circuits

description: <b><i>Background:</i></b> The negative symptoms of schizophrenia include deficits in emotional expression and motivation. These deficits are stable over the course of illness and respond poorly to current medications. Previous studies have focused on negative symptoms as a single category; however, individual symptoms might be related to separate neurological disturbances. We analyzed data from the Functional Biomedical Informatics Research Network dataset to explore the relationship between individual negative symptoms and functional brain activity during an auditory oddball task. <b><i>Methods:</i></b> Functional magnetic resonance imaging was conducted on 89 schizophrenia patients and 106 healthy controls during a two-tone auditory oddball task. Blood oxygenation level-dependent (BOLD) signal during the target tone was correlated with severity of five negative symptom domains from the Scale for the Assessment of Negative Symptoms. <b><i>Results:</i></b> The severity of alogia, avolition/apathy and anhedonia/asociality was negatively correlated with BOLD activity in distinct sets of brain regions associated with processing of the target tone, including basal ganglia, thalamus, insular cortex, prefrontal cortex, posterior cingulate and parietal cortex. <b><i>Conclusions:</i></b> Individual symptoms were related to different patterns of functional activation during the oddball task, suggesting that individual symptoms might arise from distinct neural mechanisms. This work has potential to inform interventions that target these symptom-related neural disruptions.
DOI: 10.6084/m9.figshare.5128810
title: Supplementary Material for: Evaluation of Computed Tomography for Lymph Node Staging in Bladder Cancer Prior to Radical Cystectomy

description: <b><i>Objectives:</i></b> To retrospectively evaluate the value of CT for lymph node (LN) staging in bladder cancer. <b><i>Methods:</i></b> Two uroradiologists reviewed CT scans of 231 patients who underwent radical cystectomy and pelvic lymphadenectomy according to a predefined 12-field template. A 5-step model was used to grade the radiological likelihood of a LN to represent malignant spread based on size, configuration and structure as well as regional clustering. Statistical analyses were performed both on patient- and field-based levels. <b><i>Results:</i></b> LN metastases were found in 59 of 231 patients (25.5%). On a patient-based level, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 52.6, 93.6, 73.2, 85.6 and 83.4%, respectively. Using the field-based approach, a total of 1,649 anatomical fields were evaluable, of which 114 fields showed malignancy (6.9%). On a field basis, sensitivity, specificity, PPV, NPV and accuracy were 30.2, 98, 51.5, 94.5 and 93.3%, respectively. Concerning local staging (pT category), the overall accuracy was 78%; overstaging occurred in 6% and understaging in 16%. <b><i>Conclusions:</i></b> In line with prior studies, the sensitivity of CT imaging for the detection of LN metastases was low, while high values for specificity were achieved. This was further underlined by analyzing standardized anatomical fields. Concerning local staging, postoperative changes after TURB-T rarely led to overstaging.