cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5124157
title: Supplementary Material for: Critical Role of the Matricellular Protein SPARC in Mediating Erythroid Progenitor Cell Development in Zebrafish

description: Sparc (osteonectin) is a multifunctional matricellular glycoprotein expressed by many differentiated cells. Members of this family mediate cell-matrix interactions rather than acting as structural components of the extracellular matrix (ECM); therefore, they can influence many remodelling events, including haematopoiesis. We have investigated the role of <i>sparc</i> in embryonic haematopoiesis using a morpholino antisense oligonucleotide-based knockdown approach. Knockdown of <i>sparc</i> function resulted in specific erythroid progenitor cell differentiation defects that were highlighted by changes in gene expression and morphology, which could be rescued by injection of <i>sparc</i> mRNA. Furthermore, a comparison of blood phenotypes of <i>sparc</i> and <i>fgfs</i> knockdowns with similar defects and the <i>sparc</i> rescue of the<i> fgf21</i> blood phenotype places <i>sparc</i> downstream of <i>fgf21</i> in the genetic network regulating haematopoiesis in zebrafish. These results establish a role for an ECM protein (Sparc) as an important regulator of embryonic haematopoiesis during early development in zebrafish.
DOI: 10.6084/m9.figshare.5124160
title: Supplementary Material for: Genistein Ameliorates Adverse Cardiac Effects Induced by Arsenic Trioxide Through Preventing Cardiomyocytes Apoptosis

description: <b><i>Background/Aims: </i></b>Arsenic trioxide (As<sub>2</sub>O<sub>3</sub>) is a highly effective agent for treatment of acute promyelocytic leukemia (APL). However, consecutively administered As<sub>2</sub>O<sub>3</sub> induces serious adverse cardiac effects, including long QT syndrome (LQTs) and even sudden cardiac death. Previous studies have shown that genistein (Gen) exerts anti-oxidant, anti-inflammatory, and anti-apoptotic effects. The present study aimed to explore the potential protective effects of Gen on As<sub>2</sub>O<sub>3</sub>-induced adverse cardiac effects, and to elucidate the underlying molecular mechanisms. <b><i>Methods: </i></b>A rat model of As<sub>2</sub>O<sub>3</sub>-induced QT prolongation was generated by intravenous injection with As<sub>2</sub>O<sub>3</sub>. Surface electrocardiogram (ECG) and hemodynamics were employed to assess the LQTs and cardiac function. Intracellular calcium concentration ([Ca<sup>2+</sup>]<sub>i</sub>) and mitochondrial membrane potential (Δψm) were measured by confocal microscopy, and cardiomyocytes apoptosis were assessed by TUNEL assay. Western blot was applied to determine protein levels. <b><i>Results: </i></b>We found for the first time that treatment with Gen significantly reversed LQTs and dose-dependently improved As<sub>2</sub>O<sub>3</sub>-induced impairment of cardiac function. As<sub>2</sub>O<sub>3</sub> elevated [Ca<sup>2+</sup>]<sub>i</sub> and Gen mitigated this effect. Meanwhile, Gen significantly reversed As<sub>2</sub>O<sub>3</sub>-mediated cardiomyocytes apoptosis. Furthermore, Gen dose-dependently inhibited the phosphorylated JNK and p38-MAPK (pp38-MAPK), and blocked Δψm collapse, and further decreased cleaved caspase-3. <b><i>Conclusion: </i></b>Gen protects against the adverse cardiac effects of As<sub>2</sub>O<sub>3</sub> partly by mitigating cardiomyocytes apoptosis induced by As<sub>2</sub>O<sub>3</sub> through attenuating intracellular calcium overload and downregulating protein expression of p-JNK and pp38-MAPK to ameliorate the damage of Δψm leading to suppression of caspase-3 activation. Gen might be used as an adjunction therapy in APL patients receiving As<sub>2</sub>O<sub>3</sub> treatment to avoid, at least to minimize, the adverse cardiac effects of As<sub>2</sub>O<sub>3</sub>.
DOI: 10.6084/m9.figshare.5124151
title: Supplementary Material for: CD4+ T Lymphocytes, Especially Th2 Cells, Contribute to the Progress of Renal Fibrosis

description: <b><i>Background:</i></b> Renal tubulointerstitial fibrosis is the final common stage of renal failure. CD4+ T lymphocyte recruitment and activation after injury could be the very important early event that mediates the onset of renal fibrogenesis. But the role of CD4+ T lymphocytes in renal fibrosis is controversial and its cellular mechanism needs to be further investigated. <b><i>Methods:</i></b> Biopsy specimens were from patients with minimal-change or IgA nephropathy. Mouse renal fibrosis was induced by unilateral ureteral obstruction (UUO). CD4+ T lymphocytes of wild BALB/c mice were depleted with anti-CD4 antibody. BALB/c Nu/Nu mice were reconstituted with polarized Th1 or Th2 cells by tail vein injection. <b><i>Results:</i></b> Our study demonstrated that massive CD4+ T lymphocytes infiltrated fibrotic kidneys of patients. The depletion of CD4+ T lymphocytes inhibited UUO-induced mouse renal fibrosis. In the process of UUO-induced renal fibrosis, the ratios of Th2/Th1 increased with time. Results have also shown that Th2-reconstituted mice developed renal fibrosis more easily than Th1-reconstituted mice, which manifested by interstitial expansion and collagen deposition, higher expression of α-SMA and vimentin and increased expression of fibronectin, TGF-β and collagen I. We also found that CD4+ T cells from Th1-reconstitued mice tended to secrete IL-4 and IL-13 Th2-like cytokines. <b><i>Conclusion:</i></b> In conclusion, our study demonstrated the importance of CD4+ T lymphocytes in renal fibrosis and gave the first direct evidence that Th2 cells play a pivotal role in UUO-induced renal fibrosis. Inhibition of CD4+ T lymphocyte differentiation to Th2 would be a potential therapeutic intervention to prevent renal fibrosis.
DOI: 10.6084/m9.figshare.5124154
title: Supplementary Material for: Changes in N-Terminal Pro-Brain Natriuretic Peptide Correlate with Fluid Volume Changes Assessed by Bioimpedance in Peritoneal Dialysis Patients

description: <b><i>Background/Aims:</i></b> Both brain natriuretic peptide (BNP) and volume overload are reported to be powerful predictors of survival for peritoneal dialysis patients. The usefulness of single BNP determinations in helping determine volume status in peritoneal dialysis patients remains controversial, so we reviewed serial BNP and multifrequency bioimpedance measurements to determine whether changes in BNP reflected changes in volume status. <b><i>Methods:</i></b> Prospective measurements of fluid volume by multifrequency bioimpedance and serum N-terminal pro-BNP (NTproBNP) were conducted in stable adult peritoneal dialysis outpatients attending for routine assessments of peritoneal dialysis adequacy and transport status. <b><i>Results:</i></b> A total of 189 serial measurements were made in 92 patients, and NTproBNP increased from a median of 162.5 pmol/l (interquartile range 82–385.4) to 195 pmol/l (interquartile range 101.9–348.6; p &lt; 0.05). Changes in NTproBNP correlated with changes in extracellular water (ECW), total body water (TBW) and ECW/TBW (r = 0.38, 0.31 and 0.45, respectively; all p &lt; 0.0001). Patients were divided into quartiles depending upon NTproBNP changes; those with the greatest fall in NTproBNP had significant falls in ECW (p &lt; 0.001), TBW (p = 0.001) and ECW/TBW (p &lt; 0.001) compared to the quartile with the greatest increase in NTproBNP, who also had an increase in systolic blood pressure from 133.5 ± 22.7 to 142.7 ± 28.8 mm Hg (p = 0.0078), whereas it fell in the quartile with the greatest fall in NTproBNP (143.8 ± 24.6 vs. 136.5 ± 18.7 mm Hg). <b><i>Conclusions:</i></b> Serial measurements of NTproBNP correlated with changes in volume assessments made by multifrequency bioimpedance in peritoneal dialysis outpatients. As multifrequency bioimpedance measures total ECW, rather than effective plasma volume, serial NTproBNP determinations may prove an adjunct to the clinical assessment of volume status in peritoneal dialysis patients.
DOI: 10.6084/m9.figshare.5124148
title: Supplementary Material for: Interleukin-24 Suppresses the Growth of Vascular Smooth Muscle Cells by Inhibiting H<sub>2</sub>O<sub>2</sub>-Induced Reactive Oxygen Species Production

description: <b><i>Background/Aim:</i></b> The abnormal growth of vascular smooth muscle cells (VSMCs) induced by reactive oxygen species (ROS) is considered a major pathogenic process in vascular diseases. Interleukin (IL)-24 specifically inhibits cancer cell growth through the induction of cell cycle arrest and apoptosis. However, the role of IL-24 in ROS-induced VSMC growth has not yet been investigated. <b><i>Methods:</i></b> An MTT assay, gene expression analysis, flow cytometry and a scratch wound healing assay were performed to determine the anti-growth effects of IL-24 in H<sub>2</sub>O<sub>2</sub>-treated mouse vascular aortic smooth muscle (MOVAS) cells. To elucidate the effect of IL-24 on ROS-induced signaling, Western blot analysis was employed. <b><i>Results:</i></b> IL-24 inhibited the growth of normal MOVAS cells treated with H<sub>2</sub>O<sub>2</sub> by inducing a cell cycle arrest at the G₀/G<sub>1</sub> phase through the regulation of p21 and cyclin D1. Furthermore, IL-24 suppressed mRNA expression of vascular endothelial growth factor and platelet-derived growth factor and subsequently decreased the level of cell migration in response to H<sub>2</sub>O<sub>2</sub>. Interestingly, IL-24 attenuated the H<sub>2</sub>O<sub>2</sub>-induced ROS production by reducing the mitochondrial H<sub>2</sub>O<sub>2</sub> production and enhancing the expression of antioxidant enzymes. We also showed that the ability of H<sub>2</sub>O<sub>2</sub> to induce the PI3K/Akt and Erk signaling pathways was blocked by IL-24. <b><i>Conclusion:</i></b> These findings suggest a novel mechanism in which IL-24 suppresses the growth of normal VSMCs by inhibiting H<sub>2</sub>O<sub>2</sub>-induced ROS production through the regulation of mitochondrial ROS production and expression of antioxidant enzymes.
DOI: 10.6084/m9.figshare.5124148.v1
title: Supplementary Material for: Interleukin-24 Suppresses the Growth of Vascular Smooth Muscle Cells by Inhibiting H<sub>2</sub>O<sub>2</sub>-Induced Reactive Oxygen Species Production

description: <b><i>Background/Aim:</i></b> The abnormal growth of vascular smooth muscle cells (VSMCs) induced by reactive oxygen species (ROS) is considered a major pathogenic process in vascular diseases. Interleukin (IL)-24 specifically inhibits cancer cell growth through the induction of cell cycle arrest and apoptosis. However, the role of IL-24 in ROS-induced VSMC growth has not yet been investigated. <b><i>Methods:</i></b> An MTT assay, gene expression analysis, flow cytometry and a scratch wound healing assay were performed to determine the anti-growth effects of IL-24 in H<sub>2</sub>O<sub>2</sub>-treated mouse vascular aortic smooth muscle (MOVAS) cells. To elucidate the effect of IL-24 on ROS-induced signaling, Western blot analysis was employed. <b><i>Results:</i></b> IL-24 inhibited the growth of normal MOVAS cells treated with H<sub>2</sub>O<sub>2</sub> by inducing a cell cycle arrest at the G₀/G<sub>1</sub> phase through the regulation of p21 and cyclin D1. Furthermore, IL-24 suppressed mRNA expression of vascular endothelial growth factor and platelet-derived growth factor and subsequently decreased the level of cell migration in response to H<sub>2</sub>O<sub>2</sub>. Interestingly, IL-24 attenuated the H<sub>2</sub>O<sub>2</sub>-induced ROS production by reducing the mitochondrial H<sub>2</sub>O<sub>2</sub> production and enhancing the expression of antioxidant enzymes. We also showed that the ability of H<sub>2</sub>O<sub>2</sub> to induce the PI3K/Akt and Erk signaling pathways was blocked by IL-24. <b><i>Conclusion:</i></b> These findings suggest a novel mechanism in which IL-24 suppresses the growth of normal VSMCs by inhibiting H<sub>2</sub>O<sub>2</sub>-induced ROS production through the regulation of mitochondrial ROS production and expression of antioxidant enzymes.
DOI: 10.6084/m9.figshare.5124136
title: Supplementary Material for: Childhood Obesity Is Associated with Changes in the Serum Metabolite Profile

description: <b><i>Objective: </i></b>The human serum metabolite profile is reflective of metabolic processes, including pathophysiological changes characteristic of diseases. Therefore, investigation of serum metabolite concentrations in obese children might give new insights into biological mechanisms associated with childhood obesity. <b><i>Methods: </i></b>Serum samples of 80 obese and 40 normal-weight children between 6 and 15 years of age were analyzed using a mass spectrometry-based metabolomics approach targeting 163 metabolites. Metabolite concentrations and metabolite ratios were compared between obese and normal-weight children as well as between children of different pubertal stages. <b><i>Results: </i></b>Metabolite concentration profiles of obese children could be distinguished from those of normal-weight children. After correction for multiple testing, we observed 14 metabolites (glutamine, methionine, proline, nine phospholipids, and two acylcarnitines, <i>p </i>&lt; 3.8 × 10<sup>–4</sup>) and 69 metabolite ratios (<i>p</i> &lt; 6.0 × 10<sup>–6</sup>) to be significantly altered in obese children. The identified metabolite markers are indicative of oxidative stress and of changes in sphingomyelin metabolism, in β-oxidation, and in pathways associated with energy expenditure. In contrast, pubertal stage was not associated with metabolite concentration differences. <b><i>Conclusion: </i></b>Our study shows that childhood obesity influences the composition of the serum metabolome. If replicated in larger studies, the altered metabolites might be considered as potential biomarkers in the generation of new hypotheses on the biological mechanisms behind obesity.
DOI: 10.6084/m9.figshare.5124139
title: Supplementary Material for: An International Survey of Deep Brain Stimulation Procedural Steps

description: <b><i>Background:</i></b> Deep brain stimulation (DBS) surgery is standard of care for the treatment of certain movement disorders. <b><i>Objective:</i></b> We sought to characterize the spectrum of steps performed in DBS surgery, at centers around the world where this surgery is performed. <b><i>Methods:</i></b> We identified the main steps in DBS surgery workflow and grouped these 19 steps into 3 phases (preoperative, operative, and postoperative). A survey tool, informed by a pilot survey, was administered internationally by trained study personnel at high- and low-volume DBS centers. Procedural components, duration, and surgeon motivational factors were assessed. Cluster analysis was used to identify procedural and behavioral clusters. <b><i>Results:</i></b> One hundred eighty-five procedure workflow surveys (143 DBS centers) and 65 online surveys of surgeon motivational drivers were completed (45% response rate). Significant heterogeneity in technique, operative time, and surgeon motivational drivers was reported across centers. <b><i>Conclusions:</i></b> We provide a description of the procedural steps involved in DBS surgery and the duration of these steps, based on an international survey. These data will enable individual surgeons and centers to examine their own experience relative to colleagues at other centers and in other countries. Such information could also be useful in comparing efficiencies and identifying workflow obstacles between different hospital environments.
DOI: 10.6084/m9.figshare.5124142
title: Supplementary Material for: Topical Treatment with Basic Fibroblast Growth Factor Promotes Wound Healing and Barrier Recovery Induced by Skin Abrasion

description: It has been reported that basic fibroblast growth factor (bFGF) promotes the healing of skin ulceration by inducing fibroblast proliferation, yet the role of bFGF on epidermal barrier function, especially from the perspective of scratch-induced skin abrasion, remains unknown. To this end, we initially developed an epidermal abrasion mouse model induced by scratching with a stainless-steel wire brush, and examined the effects of bFGF on the wound healing induced by skin abrasion. This procedure induced a significant elevation of transepidermal water loss (TEWL) in a scratch-count-dependent manner. This elevated TEWL was significantly decreased following topical application of bFGF to the skin. In addition, bFGF increased the expression of Ki67 in keratinocytes following mechanical scratching. These results suggest that bFGF enhances keratinocyte proliferation, which, in turn, repairs the skin barrier disruption and wounds caused by scratching in mice. Consistently, bFGF stimulated proliferation of normal human epidermal keratinocytes (NHEK). Intriguingly, the effect of bFGF and other growth factors on NHEK proliferation was additive. However, high cell density diminished the effect of bFGF on NHEK proliferation. This particular result can be explained by our observation that FGF receptor mRNA expression in NHEK was low under conditions of high cell density. Our findings suggest that bFGF stimulates keratinocyte proliferation, especially in a lower cell density environment, to repair skin wound in accord with skin barrier recovery.
DOI: 10.6084/m9.figshare.5124133
title: Supplementary Material for: The Utility of Administrative Data for Surveillance of Comorbidity in Multiple Sclerosis: A Validation Study

description: <b><i>Background:</i></b> Although comorbidity is important in multiple sclerosis (MS), few validated methods for its assessment exist. We validated and applied administrative case definitions for several comorbidities in MS. <b><i>Methods:</i></b> Using provincial administrative data we identified persons with MS and a matched general population cohort. Case definitions for chronic lung disease (CLD), epilepsy, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and migraine were developed using administrative data, and validated against medical records. We applied these definitions to estimate the age-standardized prevalence of these comorbidities in the MS and matched cohorts. <b><i>Results:</i></b> Versus medical records, administrative case definitions showed moderate agreement for CLD (ĸ = 0.41), migraine (ĸ = 0.51), and epilepsy (ĸ = 0.44), fair agreement for IBS (ĸ = 0.36) and could not be calculated for IBD (small sample size). The 2005 prevalence of CLD was similar in the MS (15.6%) and general populations (14.4%). The prevalence of the remaining comorbidities was higher in the MS than the general populations: epilepsy (4.12 vs. 1.12%), IBD (0.78 vs. 0.65%), IBS (12.2 vs. 6.80%) and migraine (23.0 vs. 16.5%). <b><i>Conclusions:</i></b> Administrative data are valid for tracking CLD, epilepsy, and migraine in MS. The prevalence of epilepsy, IBD, IBS and migraine is increased in MS versus the general population.
DOI: 10.6084/m9.figshare.5124127
title: Supplementary Material for: Writing Therapy for Posttraumatic Stress: A Meta-Analysis

description: <b><i>Background:</i></b> Face-to-face psychological treatments have difficulty meeting today’s growing mental health needs. For the highly prevalent posttraumatic stress (PTS) conditions, accumulating evidence suggests that writing therapy may constitute an efficient treatment modality, especially when administered through the Internet. We therefore conducted a meta-analysis to investigate the efficacy of writing therapies for PTS and comorbid depressive symptoms. <b><i>Methods:</i></b> The literature was searched using several structured and unstructured strategies, including key word searches of the PubMed, Web of Science, PsycINFO, and PILOTS databases. Six studies met eligibility criteria and were included in the analyses. These studies included a total of 633 participants, of which 304 were assigned to writing therapy. <b><i>Results:</i></b> Across 5 direct comparisons of writing therapy to waiting-list control, writing therapy resulted in significant and substantial short-term reductions in PTS and comorbid depressive symptoms. There was no difference in efficacy between writing therapy and trauma-focused cognitive behavioral therapy, but we caution that this finding was based on only 2 direct comparisons. <b><i>Conclusions:</i></b> Writing therapy is an evidence-based treatment for PTS, and constitutes a useful treatment alternative for patients who do not respond to other evidence-based treatments. Internet adaptations of writing therapy for PTS may be especially useful for reaching trauma survivors in need of evidence-based mental health care who live in remote areas or who prefer to retain their anonymity.
DOI: 10.6084/m9.figshare.5124130
title: Supplementary Material for: Insular Ischemic Stroke: Clinical Presentation and Outcome

description: <b><i>Background:</i></b> The insula is a small but complex structure located in the depth of the sylvian fissure, covered by the frontal, parietal and temporal operculum. Ischemic strokes limited to the insula are rare and have not been well studied. Our objective is to better define the clinical presentation and outcome of insular ischemic strokes (IIS). <b><i>Methods:</i></b> We reviewed the institutional prospective, consecutive stroke database from two centers to identify patients with IIS seen between 2008 and 2010. We also searched the Medline database using the keywords insula(r), infarction and stroke to identify previously published IIS cases confirmed by MRI. Minimal extension to an adjacent operculum or subinsular area was accepted. Clinicoradiological correlation was performed by distinguishing IIS involving the anterior (AIC) or posterior insular cortex (PIC). We collected clinical, demographic and radiological data. The outcome was determined using the modified Rankin Scale (mRS). <b><i>Results:</i></b> We identified 7 patients from our institutions and 16 previously published cases of IIS. Infarcts were limited to the AIC (n = 4) or the PIC (n = 12) or affected both (n = 7). The five most frequent symptoms were somatosensory deficits (n = 10), aphasia (n = 10), dysarthria (n = 10), a vestibular-like syndrome (n = 8) and motor deficits (n = 6). A significant correlation was found between involvement of the PIC and somatosensory manifestations (p = 0.04). No other statistically significant associations were found. IIS presentation resembled a partial anterior circulation infarct (n = 9), a lacunar infarct (n = 2) or a posterior circulation infarct (n = 2). However, most cases presented findings that did not fit with these classical patterns (n = 10). At the 6 month follow up, mRS was 0 in 8/23 (35%) patients, 1–2 in 7/23 (30%) and unknown in 8/23 (35%). <b><i>Conclusions:</i></b> IIS presentation is variable. Due to the confluence of functions in a restricted region, it results in multimodal deficits. It should be suspected when vestibular-like or motor but especially somatosensory, speech or language disturbances are combined in the same patient. The outcome of IIS is often favorable. Larger prospective studies are needed to better define the clinical presentation and outcome of IIS.