cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5125033.v1
title: Supplementary Material for: Clevidipine Rapidly and Safely Reduces Blood Pressure in Acute Intracerebral Hemorrhage: The ACCELERATE Trial

description: <b><i>Background:</i></b> Intracerebral hemorrhage (ICH) causes 10-15% of primary strokes, with mortality related to hematoma volume. Blood pressure (BP) reduction may attenuate hematoma expansion. ACCELERATE (the Evaluation of Patients with Acute Hypertension and Intracerebral Hemorrhage with Intravenous Clevidipine Treatment) is a pilot study representing the first evaluation of safety and efficacy of intravenous clevidipine for the rapid treatment of hypertension in ICH patients. <b><i>Methods:</i></b> ICH patients with a systolic BP (SBP) &gt;160 mm Hg who present within 6 h (n = 27) or 12 h (n = 10) of symptoms were prospectively enrolled, treated with open-label clevidipine until SBP ≤160 mm Hg was achieved and then titrated to keep target SBP between 140-160 mm Hg. <b><i>Results:</i></b> A total of 35 patients with baseline median Glasgow Coma Scale score of 12, median NIH Stroke Scale score of 14, mean SBP of 186 mm Hg and a mean time from onset of symptoms of 5.5 h received clevidipine. Median time to achieve SBP target range was 5.5 min. All patients achieved target SBP within 30 min; 96.9% achieved target SBP with clevidipine monotherapy. CT scans showed minimal hematoma volume change for the overall population (median change 0.01 ml, -2.9%). Mild/moderate hypotension was reported in 3 patients and resolved with dose reduction or drug discontinuation. <b><i>Conclusion:</i></b> Clevidipine monotherapy was effective and safe for rapid BP reduction in this cohort of critically ill ICH patients. Overall, patients showed minimal hematoma expansion with BP reduction, suggesting that rapid BP control with clevidipine may have a beneficial impact on hematoma expansion and warrants further investigation.
DOI: 10.6084/m9.figshare.5125024.v1
title: Supplementary Material for: Methyl Sulfone Manifests Anticancer Activity in a Metastatic Murine Breast Cancer Cell Line and in Human Breast Cancer Tissue - Part 2: Human Breast Cancer Tissue

description: <b><i>Background:</i></b> Methyl sulfone is a small molecule that reverses cancerous phenotypes of a melanoma cell line. Here, we sought to determine whether methyl sulfone was effective against human breast cancer tissue. <b><i>Methods:</i></b> We studied normal and cancerous breast tissue obtained from 17 patients. <b><i>Results:</i></b> Methyl sulfone introduced structural order, with cancer tissue taking on the morphology of normal in vivo breast tissue; this structural order was sustainable over long-term culture. Methyl sulfone promoted proper wound healing, including migration of cells into wounded areas and establishment of stable contact inhibition once wounds were covered. Methyl sulfone decreased expression of two breast stem cell marker proteins, HCAM and OCT3/4, which are associated with aberrantly rapid migration of metastatic cells. Finally, normal and cancerous primary breast cells remained viable and healthy in methyl sulfone culture for at least 90 days. <b><i>Conclusion:</i></b> Methyl sulfone reintroduced a normal structural phenotype to human breast cancer tissues.
DOI: 10.6084/m9.figshare.5125087.v3
title: Raw data

description: This folder consists of existing dataset from the container volume experiment which was carried out at the Hawkesbury Forest Experiment site (33°37'S 150°44'E) in Richmond, NSW, Australia. The site and experimental setup have been explained in detail by Campany et al. (2017).
DOI: 10.6084/m9.figshare.5125015
title: Supplementary Material for: Hypoxia Induces Mesenchymal Gene Expression in Renal Tubular Epithelial Cells: An in vitro Model of Kidney Transplant Fibrosis

description: <b><i>Background:</i></b> The development of interstitial fibrosis and tubular atrophy is a common complication after kidney transplantation and is associated with reduced long-term outcome. The hallmark of tubulointerstitial fibrosis is an increase in extracellular matrix resulting from exaggerated activation of fibroblasts/myofibroblasts, and tubular atrophy is characterized by a decrease in tubular diameter and loss of function. Atrophic epithelial cells may undergo epithelial-to-mesenchymal transition (EMT) with potential differentiation into interstitial fibroblasts. One potential driver of EMT in developing interstitial fibrosis and tubular atrophy is chronic hypoxia. <b><i>Methods:</i></b> The expression of 46 EMT-related genes was analyzed in an in vitro hypoxia model in renal proximal tubular epithelial cells (RPTEC). Furthermore, the expression of 342 microRNAs (miR) was evaluated in hypoxic culture conditions. <b><i>Results:</i></b> Hypoxic RPTEC expressed markers of a more mesenchymal phenotype and showed an increased expression of matrix metalloproteinase-2 (MMP2). MMP2 expression in RPTEC correlated inversely with a decreased expression of miR-124, which was found to have a putative binding site for the MMP2 transcript. Overexpression of miR-124 inhibited MMP2 protein translation. Hypoxia was associated with increased migration/proliferation of RPTEC which was reversed by miR-124. <b><i>Conclusions:</i></b> These results indicate that hypoxia promotes a mesenchymal and migratory phenotype in renal epithelial cells, which is associated with increased MMP2 expression. Hypoxia-dependent MMP2 expression is regulated via a reduced transcription of miR-124. Overexpression of miR-124 antagonizes hypoxia-induced cell migration. Further research is needed to elucidate the functional role of miR-124 and MMP2 in the development of fibrosis in renal transplant degeneration.
DOI: 10.6084/m9.figshare.5125018
title: Supplementary Material for: Gene <b>×</b> Environment Interactions in Obesity: The State of the Evidence

description: <b><i>Background/Aims:</i></b> Obesity is a pervasive and highly prevalent disease that poses substantial health risks to those it affects. The rapid emergence of obesity as a global epidemic and the patterns and distributions of the condition within and between populations suggest that interactions between inherited biological factors (e.g. genes) and relevant environmental factors (e.g. diet and physical activity) may underlie the current obesity epidemic. <b><i>Methods:</i></b> We discuss the rationale for the assertion that gene × lifestyle interactions cause obesity, systematically appraise relevant literature, and consider knowledge gaps future studies might seek to bridge. <b><i>Results:</i></b> We identified &gt;200 relevant studies, of which most are relatively small scale and few provide replication data. <b><i>Conclusion:</i></b> Although studies on gene × lifestyle interactions in obesity point toward the presence of such interactions, improved data standardization, appropriate pooling of data and resources, innovative study designs, and the application of powerful statistical methods will be required if translatable examples of gene × lifestyle interactions in obesity are to be identified. Future studies, of which most will be observational, should ideally be accompanied by appropriate replication data and, where possible, by analogous findings from experimental settings where clinically relevant traits (e.g. weight regain and weight cycling) are outcomes.
DOI: 10.6084/m9.figshare.5125021
title: Supplementary Material for: Maintenance of Ancestral Sex Chromosomes in Palearctic Tree Frogs: Direct Evidence from <b><i>Hyla orientalis</i></b>

description: Contrasting with the situation found in birds and mammals, sex chromosomes are generally homomorphic in poikilothermic vertebrates. This homomorphy was recently shown to result from occasional X-Y recombinations (not from turnovers) in several European species of tree frogs <i>(Hyla arborea</i>, <i>H. intermedia</i> and <i>H. molleri)</i>. Because of recombination, however, alleles at sex-linked loci were rarely diagnostic at the population level; support for sex linkage had to rely on multilocus associations, combined with occasional sex differences in allelic frequencies. Here, we use direct evidence, obtained from anatomical and histological analyses of offspring with known pedigrees, to show that the Eastern tree frog <i>(H. orientalis)</i> shares the same pair of sex chromosomes, with identical patterns of male heterogamety and complete absence of X-Y recombination in males. Conservation of an ancestral pair of sex chromosomes, regularly rejuvenated via occasional X-Y recombination, seems thus a widespread pattern among <i>Hyla </i>species. Sibship analyses also identified discrepancies between genotypic and phenotypic sex among offspring, associated with abnormal gonadal development, suggesting a role for sexually antagonistic genes on the sex chromosomes.
DOI: 10.6084/m9.figshare.5125030.v1
title: Supplementary Material for: Proof of Concept Study: Relating Infarct Location to Stroke Disability in the NINDS rt-PA Trial

description: <b><i>Background:</i></b> The summed Alberta Stroke Program Early CT Score (ASPECTS) for noncontrast head CT scan represents the extent of early brain ischemia and has been shown to be useful for predicting stroke outcome. The ASPECTS template contains information on anatomical location which so far has not been used in analysis. This may not have been done because adjacent brain regions have related functions and share vascular territory. The task of relating neurological deficit to infarct localization requires brain imaging analysis tools which deal with this issue of relatedness or collinearity. We have previously used partial least squares with penalized logistic regression (PLR) to handle this problem of collinearity. A disadvantage of this method is that it cannot be performed at the bedside and requires processing and analysis in the imaging laboratory. PLR is a simpler analytic tool compared to partial least squares with PLR for dealing with this issue of relatedness (collinearity). It provides results in terms of β coefficients related to specific infarct locations in a manner that is intuitively understood by clinicians. In this exploratory analysis, we hypothesized that infarct location as represented by the individual ASPECTS region may be independently related to disability. <b><i>Methods:</i></b> ASPECTS from CT scans of patients in the National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rt-PA) Study were obtained. Due to the collinearity between the ASPECTS regions, we used PLR to determine the independent associations of exposures (rt-PA), demographic variables (age and sex), and imaging (ASPECTS location) with poor outcome as defined by a modified Rankin Scale score of &gt;2. <b><i>Results:</i></b> In 607/624 subjects with ASPECTS readings, variables significantly associated with poor outcome included: interactions between ASPECTS M6 region (primary motor cortex/parietal lobe) and age (p = 0.004), lentiform nucleus and age (p = 0.007), and blood sugar level and age (p = 0.01). The model suggested that older age or involvement of either M6 or lentiform nucleus slightly increased the odds of disability. However, the predominant effect was driven by rt-PA which reduced the odds of poor disability (OR 0.597, 95% CI 0.425-0.838, p = 0.003). This may potentially explain why certain patients have smaller gains from rt-PA treatments. <b><i>Conclusion:</i></b> At an older age, specific infarct locations may be associated with a poorer outcome in this exploratory re-analysis of the NINDS rt-PA Study.
DOI: 10.6084/m9.figshare.5125012
title: Supplementary Material for: Neurological Soft Signs and Brainstem Morphology in First-Episode Schizophrenia

description: <b><i>Background:</i></b> Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported in patients with schizophrenia at any stage of their illness. NSS have been demonstrated to correlate with neuroanatomical abnormalities in various brain regions. Despite its important role in the integration and coordination of automatic motor actions, the brainstem has so far rather been ignored in previous neuroimaging studies on NSS in schizophrenia. <b><i>Method:</i></b> We investigated 21 right-handed first-episode schizophrenia patients using high-resolution magnetic resonance imaging at 3 T. The severity of NSS was measured with the Heidelberg Scale. Associations between NSS and both brainstem volume and shape changes were examined. <b><i>Results:</i></b> Higher NSS scores were significantly associated with structural alterations in the brainstem. According to volume measurements higher NSS scores correlated with global changes of the brainstem. Using shape analyses these associations referred to regionally specific morphometric alterations predominantly in the midbrain and pons. <b><i>Conclusion:</i></b> The findings suggest that brainstem morphometric alterations are associated with the severity of NSS in patients with first-episode schizophrenia. They further indicate the involvement of the brainstem in the pathogenesis of schizophrenia.
DOI: 10.6084/m9.figshare.5125015.v1
title: Supplementary Material for: Hypoxia Induces Mesenchymal Gene Expression in Renal Tubular Epithelial Cells: An in vitro Model of Kidney Transplant Fibrosis

description: <b><i>Background:</i></b> The development of interstitial fibrosis and tubular atrophy is a common complication after kidney transplantation and is associated with reduced long-term outcome. The hallmark of tubulointerstitial fibrosis is an increase in extracellular matrix resulting from exaggerated activation of fibroblasts/myofibroblasts, and tubular atrophy is characterized by a decrease in tubular diameter and loss of function. Atrophic epithelial cells may undergo epithelial-to-mesenchymal transition (EMT) with potential differentiation into interstitial fibroblasts. One potential driver of EMT in developing interstitial fibrosis and tubular atrophy is chronic hypoxia. <b><i>Methods:</i></b> The expression of 46 EMT-related genes was analyzed in an in vitro hypoxia model in renal proximal tubular epithelial cells (RPTEC). Furthermore, the expression of 342 microRNAs (miR) was evaluated in hypoxic culture conditions. <b><i>Results:</i></b> Hypoxic RPTEC expressed markers of a more mesenchymal phenotype and showed an increased expression of matrix metalloproteinase-2 (MMP2). MMP2 expression in RPTEC correlated inversely with a decreased expression of miR-124, which was found to have a putative binding site for the MMP2 transcript. Overexpression of miR-124 inhibited MMP2 protein translation. Hypoxia was associated with increased migration/proliferation of RPTEC which was reversed by miR-124. <b><i>Conclusions:</i></b> These results indicate that hypoxia promotes a mesenchymal and migratory phenotype in renal epithelial cells, which is associated with increased MMP2 expression. Hypoxia-dependent MMP2 expression is regulated via a reduced transcription of miR-124. Overexpression of miR-124 antagonizes hypoxia-induced cell migration. Further research is needed to elucidate the functional role of miR-124 and MMP2 in the development of fibrosis in renal transplant degeneration.
DOI: 10.6084/m9.figshare.5125087.v4
title: Inferring the effects of sink strength on plant carbon balance processes from experimental measurements

description: This folder consists of existing dataset from the container volume experiment which was carried out at the Hawkesbury Forest Experiment site (33°37'S 150°44'E) in Richmond, NSW, Australia. The site and experimental setup have been explained in detail by Campany et al. (2017). <br>In brief, 20 weeks old Eucalyptus tereticornis seedlings in tube stock were chosen from a single local Cumberland plain cohort. Ten additional seedlings of similar age and growth were harvested to measure initial leaf area and dry mass of leaves, stems and roots. A total of 49 Eucalyptus tereticornis seedlings were grown in a range of container sizes (5 L to 35 L) in field conditions, using freely-rooted seedlings as a control for the container size treatments, with the goal to examine how the C balance of the plants are affected to belowground sink limitations. Six container sizes were used with each container experiment had a complete replicate set of six container volumes along with a free seedling. Similar notations are used here as Campany et al. (2017) for the treatments in different pots as 5 L, 10 L, 15 L, 20 L, 25 L and 35 L in respect of their pot sizes. The experiment tracked leaf-level gas exchange, leaf carbohydrate accumulation and seedling allometry over the course of 4 months for all 7 treatments.
DOI: 10.6084/m9.figshare.5125006
title: Supplementary Material for: Comparison of Exhaled Endogenous Particles from Smokers and Non-Smokers Using Multivariate Analysis

description: <b><i>Background:</i></b> Smoking, along with many respiratory diseases, has been shown to induce airway inflammation and alter the composition of the respiratory tract lining fluid (RTLF). We have previously shown that the phospholipid and protein composition of particles in exhaled air (PEx) reflects that of RTLF. In this study, we hypothesized that the composition of PEx differs between smokers and non-smokers, reflecting inflammation in the airways. <b><i>Objective:</i></b> It was the aim of this study to identify differences in the phospholipid composition of PEx from smokers and non-smokers. <b><i>Methods:</i></b> PEx from 12 smokers and 13 non-smokers was collected using a system developed in-house. PEx was analysed using time-of-flight secondary ion mass spectrometry, and the mass spectral data were evaluated using multivariate analysis. Orthogonal partial least squares (OPLS) was used to relate smoking status, lung function and pack years to the chemical composition of RTLF. The discriminating ions identified by OPLS were then used as explanatory variables in traditional regression analysis. <b><i>Results:</i></b> There was a clear discrimination between smokers and non-smokers according to the chemical composition, where phospholipids from smokers were protonated and sodiated to a larger extent. Poor lung function showed a strong association with higher response from all molecular phosphatidylcholine species in the samples. Furthermore, the accumulated amount of tobacco consumed was associated with variations in mass spectra, indicating a dose-response relationship. <b><i>Conclusion:</i></b> The chemical composition of PEx differs between smokers and non-smokers, reflecting differences in the RTLF. The results from this study may suggest that the composition of RTLF is affected by smoking and may be of importance for lung function.
DOI: 10.6084/m9.figshare.5125009
title: Supplementary Material for: The Use of Haplotypes in the Identification of Interaction between SNPs

description: Although haplotypes can provide great insight into the complex relationships between functional polymorphisms at a locus, their use in modern association studies has been limited. This is due to our inability to directly observe haplotypes in studies of unrelated individuals, but also to the extra complexity involved in their analysis and the difficulty in identifying which is the truly informative haplotype. Using a series of simulations, we tested a number of different models of a haplotype carrying two functional single nucleotide polymorphisms (SNPs) to assess the ability of haplotypic analysis to identify functional interactions between SNPs at the same locus. We found that, when phase is known, analysis of the haplotype is more powerful than analysis of the individual SNPs. The difference between the two approaches becomes less either as an increasing number of non-informative SNPs are included, or when the haplotypic phase is unknown, while in both cases the SNP association becomes progressively better at identifying the association. Our results suggest that when novel genotyping and bioinformatics methods are available to reconstruct haplotypic phase, this will permit the emergence of a new wave of haplotypic analysis able to consider interactions between SNPs with increased statistical power.
DOI: 10.6084/m9.figshare.5125012.v1
title: Supplementary Material for: Neurological Soft Signs and Brainstem Morphology in First-Episode Schizophrenia

description: <b><i>Background:</i></b> Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported in patients with schizophrenia at any stage of their illness. NSS have been demonstrated to correlate with neuroanatomical abnormalities in various brain regions. Despite its important role in the integration and coordination of automatic motor actions, the brainstem has so far rather been ignored in previous neuroimaging studies on NSS in schizophrenia. <b><i>Method:</i></b> We investigated 21 right-handed first-episode schizophrenia patients using high-resolution magnetic resonance imaging at 3 T. The severity of NSS was measured with the Heidelberg Scale. Associations between NSS and both brainstem volume and shape changes were examined. <b><i>Results:</i></b> Higher NSS scores were significantly associated with structural alterations in the brainstem. According to volume measurements higher NSS scores correlated with global changes of the brainstem. Using shape analyses these associations referred to regionally specific morphometric alterations predominantly in the midbrain and pons. <b><i>Conclusion:</i></b> The findings suggest that brainstem morphometric alterations are associated with the severity of NSS in patients with first-episode schizophrenia. They further indicate the involvement of the brainstem in the pathogenesis of schizophrenia.
DOI: 10.6084/m9.figshare.5125003
title: Supplementary Material for: A Systematic Review of the Association between Pulmonary Tuberculosis and the Development of Chronic Airflow Obstruction in Adults

description: <b><i>Background:</i></b> Chronic obstructive pulmonary disease (COPD) is a major public health concern, accounting for 3 million deaths annually, 90% of which occur in low- and middle-income countries. Pulmonary tuberculosis (PTB) as a contributory factor in the aetiology of COPD is under debate, with most epidemiologic evidence suggesting a positive association. <b><i>Objectives:</i></b> To compile a systematic review of evidence for an association between PTB and the development of chronic airflow obstruction (CAO). <b><i>Methods:</i></b> We performed a systematic review of original English-language, peer-reviewed literature using the PubMed/MEDLINE database. CAO was defined by spirometry [FEV<sub>1</sub>:FVC ratio &lt;0.70 or <i>Results:</i> Nineteen studies (1 case series, 3 case-control studies, 4 cohort studies, 8 single-centre cross-sectional studies and 3 multi-centre cross-sectional studies) met the eligibility criteria. All but 2 reported a positive association between PTB and CAO. Three of 4 large population-based surveys (n = 4,291-8,066) confirmed a significant association between PTB and CAO (OR 1.37 - 2.94). A formal meta-analysis was not possible owing to marked heterogeneity between studies. <b><i>Conclusions: </i></b>This systematic review confirms evidence for a positive association between a past history of tuberculosis and the presence of CAO. The association is independent of cigarette smoking. Causality is likely but cannot be assumed.