cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127397
title: Supplementary Material for: Second-Generation Antipsychotic Drugs in Anorexia Nervosa: A Meta-Analysis of Randomized Controlled Trials

description: <b><i>Background:</i></b> Second-generation antipsychotic drugs (SGAs) are increasingly administered to achieve weight gain in anorexia nervosa. In this meta-analysis, we aimed to determine if any evidence for this treatment option can be derived from randomized controlled trials (RCTs). <b><i>Methods:</i></b> Based on the ‘World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Eating Disorders', a systematic update literature search was applied to identify all RCTs investigating the efficacy, acceptability, and tolerability of SGAs in anorexia nervosa in comparison to placebo/no treatment. The primary outcome was weight gain measured by mean change in body mass index (BMI). Secondary outcomes were mean changes in Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS) total score and Eating Disorders Inventory (EDI) total score and premature discontinuation of treatment. Employing a random-effects model standardized mean differences based on Hedges's g and Mantel-Haenszel risk ratios were calculated. <b><i>Results:</i></b> Seven RCTs (n = 201) investigating olanzapine (N = 4), quetiapine (N = 2), and risperidone (N = 1) were included. We found no statistically significant between-group differences for mean BMI change when pooling the SGAs (N = 7, n = 161; Hedges's g = 0.13, 95% CI: -0.17 to 0.43; p = 0.4) and when examining the individual drugs. Furthermore, the SGAs failed to differentiate statistically significantly from placebo/no treatment for all secondary outcomes. <b><i>Conclusions:</i></b> Based on the current evidence, pharmacological treatment of anorexia nervosa with SGAs cannot be generally recommended although some individuals or subgroups of patients might benefit from an antipsychotic medication. Further research is required to identify which patients will likely benefit from such a treatment option.
DOI: 10.6084/m9.figshare.5127400
title: Supplementary Material for: A Continuous Metabolic Syndrome Score Is Associated with Specific Biomarkers of Inflammation and CVD Risk in Prepubertal Children

description: <b><i>Background/Aims:</i></b> We aimed to evaluate the use of a continuous metabolic syndrome (MetS) score and to assess the associations of this score with risk biomarkers of inflammation, endothelial damage and cardiovascular disease (CVD) in prepubertal children. <b><i>Methods:</i></b> A total of 677 prepubertal children (295 obese, 146 overweight, and 236 normal-weight) were recruited. MetS traits, markers of inflammation, endothelial damage and CVD risk were measured, and a continuous MetS score was calculated, consisting of the sum/5 of the standardised scores of the MetS components. <b><i>Results:</i></b> The continuous MetS score was significantly associated with active plasminogen activator inhibitor-1 (r = 0.406, p &lt; 0.001), adiponectin (r = -0.212, p &lt; 0.001), resistin (r = 0.263, p &lt; 0.001), C-reactive protein (r = 0.254, p &lt; 0.001), tumour necrosis factor alpha (r = 0.120, p = 0.003), myeloperoxidase (r = 0.188, p &lt; 0.001) and sE-selectin (r = 0.278, p &lt; 0.001). Children in the normal-weight, overweight and obese groups with MetS totalled 0 (0%), 1 (0.7%) and 24 (8.7%), respectively, whereas the at-risk children identified using the continuous MetS score in each group totalled 2 (0.85%), 17 (11.6%) and 167 (56.6%), respectively. <b><i>Conclusions:</i></b> The association of the continuous MetS score with specific risk biomarkers of inflammation, endothelial damage and CVD supports its use in the early identification of children at increased risk of metabolic dysfunction.
DOI: 10.6084/m9.figshare.5127394
title: Supplementary Material for: The Gut Microbiome of Wild Lemurs: A Comparison of Sympatric <b><i>Lemur catta </i></b>and <b><i>Propithecus verreauxi</i></b>

description: Mammalian gut microbes are invaluable to the host's metabolism, but few researchers have examined gut microbial dynamics under natural conditions in wild mammals. This study aims to help fill this knowledge gap with a survey of the natural variation of the gut microbiome in 2 wild lemur species, <i>Lemur catta</i> and <i>Propithecus verreauxi</i>. The wild <i>L. catta </i>were also compared to a captive population to discern the effect of habitat within a species. Gut microbial DNA was extracted from fecal samples collected in Madagascar and the Vienna Zoo and sequenced. The wild and captive <i>L. catta</i> had distinct microbial communities, likely due to differences in diet and development between their populations. The wild <i>L. catta</i> and <i>P. verreauxi</i> also had distinct gut microbiomes, due to a change in microbial abundance, not composition. Within each lemur species, there was abundant variation between individuals and from the dry to the wet season. The intraspecific and temporal microbial variation requires more investigation, with changes in diet a likely contributor.
DOI: 10.6084/m9.figshare.5127400.v1
title: Supplementary Material for: A Continuous Metabolic Syndrome Score Is Associated with Specific Biomarkers of Inflammation and CVD Risk in Prepubertal Children

description: <b><i>Background/Aims:</i></b> We aimed to evaluate the use of a continuous metabolic syndrome (MetS) score and to assess the associations of this score with risk biomarkers of inflammation, endothelial damage and cardiovascular disease (CVD) in prepubertal children. <b><i>Methods:</i></b> A total of 677 prepubertal children (295 obese, 146 overweight, and 236 normal-weight) were recruited. MetS traits, markers of inflammation, endothelial damage and CVD risk were measured, and a continuous MetS score was calculated, consisting of the sum/5 of the standardised scores of the MetS components. <b><i>Results:</i></b> The continuous MetS score was significantly associated with active plasminogen activator inhibitor-1 (r = 0.406, p &lt; 0.001), adiponectin (r = -0.212, p &lt; 0.001), resistin (r = 0.263, p &lt; 0.001), C-reactive protein (r = 0.254, p &lt; 0.001), tumour necrosis factor alpha (r = 0.120, p = 0.003), myeloperoxidase (r = 0.188, p &lt; 0.001) and sE-selectin (r = 0.278, p &lt; 0.001). Children in the normal-weight, overweight and obese groups with MetS totalled 0 (0%), 1 (0.7%) and 24 (8.7%), respectively, whereas the at-risk children identified using the continuous MetS score in each group totalled 2 (0.85%), 17 (11.6%) and 167 (56.6%), respectively. <b><i>Conclusions:</i></b> The association of the continuous MetS score with specific risk biomarkers of inflammation, endothelial damage and CVD supports its use in the early identification of children at increased risk of metabolic dysfunction.
DOI: 10.6084/m9.figshare.5127391
title: Supplementary Material for: VEGF-A Inhibition Ameliorates Podocyte Apoptosis via Repression of Activating Protein 1 in Diabetes

description: <b><i>Background/Aims:</i></b> Vascular endothelial growth factor-A (VEGF-A) upregulation and podocyte apoptosis have been documented in diabetes. This study was designed to investigate whether inhibiting VEGF-A could ameliorate podocyte apoptosis in diabetes and the underlying mechanisms. <b><i>Methods:</i></b> In vitro, small interfering RNAs (siRNAs) of VEGF-A and activator protein 1 (AP-1, c-fos and c-jun), bevacizumab (VEGF-A inhibitor) and SP600125 (AP-1 inhibitor) were added to high glucose (30 mM) induced podocytes. Luciferase reporter assay was used to investigate whether AP-1 was a direct target of VEGF-A. In vivo, bevacizumab and SP600125 were administered to 12-week-old streptozotocin-induced male Sprague Dawley rats. The level of VEGF-A, c-fos, c-jun and bcl-2 were examined using immunostaining and Western blot analysis. Podocyte apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay, electron microscopy and flow cytometry. <b><i>Results:</i></b> Silencing VEGF-A or AP-1 upregulated bcl-2 and ameliorated podocyte apoptosis. Silencing VEGF-A decreased the level of c-fos and c-jun and bevacizumab and SP600125 treatment attenuated podocyte apoptosis. Luciferase reporter activity of VEGF-A-3′-UTR constructs was significantly provoked when stimulated with TGF-β1. In diabetic rat kidneys, VEGF-A co-localized with bcl-2 in podocytes. With bevacizumab and SP600125 treatment, the level of VEGF-A and AP-1 decreased while bcl-2 increased. Podocyte apoptotic rate was reduced with condensed podocyte nuclei less frequently observed. The urine albumin excretion rate (UAER) and albumin/creatinine were improved. <b><i>Conclusion:</i></b> This study demonstrates VEGF-A inhibition ameliorates podocyte apoptosis by regulating AP-1 and bcl-2 signaling. AP-1 is a direct target of VEGF-A and a novel player in podocyte apoptosis.
DOI: 10.6084/m9.figshare.5127403.v1
title: Supplementary Material for: Rare Disease Registries Classification and Characterization: A Data Mining Approach

description: <b><i>Background:</i></b> The European Commission and Patients Organizations identify rare disease registries (RDRs) as strategic instruments to develop research and improve knowledge in the field of rare diseases. Interoperability between RDRs is needed for research activities, validation of therapeutic treatments, and public health actions. Sharing and comparing information requires a uniform and standardized way of data collection, so levels of interconnection between RDRs with similar aims and/or nature of data should be identified. The objective of this study is to define a classification and characterization of RDRs in order to identify different profiles and informative needs. <b><i>Methods:</i></b> Exploratory statistical analyses (cluster analysis and random forest) were applied to data derived from the EPIRARE project (‘Building Consensus and Synergies for the EU Rare Disease Patient Registration') survey on the activities and needs of RDRs. <b><i>Results:</i></b> The cluster analysis identified 3 main typologies of RDRs: public health, clinical and genetic research, and treatment registries. The analysis of the most informative variables, identified by the random forest method, led to the characterization of 3 types of RDRs and the definition of different profiles and informative needs. <b><i>Conclusions:</i></b> These results represent a useful source of information to facilitate the harmonization and interconnection of RDRs in accordance with the different profiles identified. It could help sharing the information between RDRs with similar profiles and, whenever possible, interconnections between registries with different profiles.
DOI: 10.6084/m9.figshare.5127388
title: Supplementary Material for: Beneficial Effects of a Semi-Intensive Stroke Unit are Beyond the Monitor

description: <b><i>Background and Purpose:</i></b> Precise mechanisms underlying the effectiveness of the stroke unit (SU) are not fully established. Studies that compare monitored stroke units (semi-intensive type, SI-SU) versus an intensive care unit (ICU)-based mobile stroke team (MST-ICU) are lacking. Although inequalities in access to stroke unit care are globally improving, acute stroke patients may be admitted to Intensive Care Units for monitoring and followed by a mobile stroke team in hospital's lacking an SU with continuous cardiovascular monitoring. We aimed at comparing the stroke outcome between SI-SU and MST-ICU and hypothesized that the benefits of SI-SU are driven by additional elements other than cardiovascular monitoring, which is equally offered in both care systems. <b><i>Methods:</i></b> In a single-center setting, we compared the unfavorable outcomes (dependency and mortality) at 3 months in consecutive patients with ischemic stroke or spontaneous intracerebral hemorrhage admitted to a stroke unit with semi-intensive monitoring (SI-SU) to a cohort of stroke patients hospitalized in an ICU and followed by a mobile stroke team (MST-ICU) during an equal observation period of 27 months. Secondary objectives included comparing mortality and the proportion of patients with excellent outcomes (modified Rankin Score (mRS) 0-1). Equal cardiovascular monitoring was offered in patients admitted in both SI-SU and MST-ICU. <b><i>Results:</i></b> 458 patients were treated in the SI-SU and compared to the MST-ICU (n = 370) cohort. The proportion of death and dependency after 3 months was significantly improved for patients in the SI-SU compared to MST-ICU (p &lt; 0.001; aOR = 0.45; 95% CI: 0.31-0.65). The shift analysis of the mRS distribution showed significant shift to the lower mRS in the SI-SU group, p &lt; 0.001. The proportion of mortality in patients after 3 months also differed between the MST-ICU and the SI-SU (p &lt; 0.05), but after adjusting for confounders this association was not significant (aOR = 0.59; 95% CI: 0.31-1.13). The proportion of patients with excellent outcome was higher in the SI-SU (59.4 vs. 44.9%, p &lt; 0.001) but the relationship was no more significant after adjustment (aOR = 1.17; 95% CI: 0.87-1.5). <b><i>Conclusions:</i></b> Our study shows that moving from a stroke team in a monitored setting (ICU) to an organized stroke unit leads to a significant reduction in the 3 months unfavorable outcome in patients with an acute ischemic or hemorrhagic stroke. Cardiovascular monitoring is indispensable, but benefits of a semi-intensive Stroke Unit are driven by additional elements beyond intensive cardiovascular monitoring. This observation supports the ongoing development of Stroke Centers for efficient stroke care.
DOI: 10.6084/m9.figshare.5127394.v1
title: Supplementary Material for: The Gut Microbiome of Wild Lemurs: A Comparison of Sympatric <b><i>Lemur catta </i></b>and <b><i>Propithecus verreauxi</i></b>

description: Mammalian gut microbes are invaluable to the host's metabolism, but few researchers have examined gut microbial dynamics under natural conditions in wild mammals. This study aims to help fill this knowledge gap with a survey of the natural variation of the gut microbiome in 2 wild lemur species, <i>Lemur catta</i> and <i>Propithecus verreauxi</i>. The wild <i>L. catta </i>were also compared to a captive population to discern the effect of habitat within a species. Gut microbial DNA was extracted from fecal samples collected in Madagascar and the Vienna Zoo and sequenced. The wild and captive <i>L. catta</i> had distinct microbial communities, likely due to differences in diet and development between their populations. The wild <i>L. catta</i> and <i>P. verreauxi</i> also had distinct gut microbiomes, due to a change in microbial abundance, not composition. Within each lemur species, there was abundant variation between individuals and from the dry to the wet season. The intraspecific and temporal microbial variation requires more investigation, with changes in diet a likely contributor.
DOI: 10.6084/m9.figshare.5127379
title: Supplementary Material for: The Prevalence of Depressive Symptoms in Frontotemporal Dementia: A Meta-Analysis

description: <b><i>Background:</i></b> Depression is common in Alzheimer's and vascular dementia and is associated with poorer outcomes; however, less is known about the impact of depression on frontotemporal dementia (FTD). Here, we conducted a meta-analysis of diagnostic methods and the prevalence of depressive symptoms in FTD. <b><i>Methods:</i></b> PubMed, EMBASE and PsychINFO were queried for ‘depression' and/or ‘depressive mood' in behavioral- and language-variant FTD. The prevalence and diagnosis of depressive symptoms were extracted from relevant studies and the results pooled using a random-effects model. <b><i>Results:</i></b> We included 29 studies in this meta-analysis, with sample sizes ranging from 3 to 73 (n = 870). The omnibus estimated event rate of depressed mood was 0.334 (33%; 95% CI: 0.268-0.407). Symptoms were most commonly assessed via standardized neuropsychiatric rating scales, with other methods including subjective caregiver reports and chart reviews. The study results were heterogeneous due to the variability in diagnostic methods. <b><i>Conclusions:</i></b> Depressive symptoms similar to those in other dementias are commonly detected in FTD. However, the diagnostic methods are heterogeneous, and symptoms of depression often overlap with manifestations of FTD. Having a standardized diagnostic approach to depression in FTD will greatly facilitate future research in this area.
DOI: 10.6084/m9.figshare.5127385
title: Supplementary Material for: Augmented Pentose Phosphate Pathway Plays Critical Roles in Colorectal Carcinomas

description: Glycolysis and the pentose phosphate pathway (PPP) are preferentially activated in cancer cells. Accumulating evidence indicated the significance of the altered glucose metabolism in cancer, but the implication for oncotherapy remains unclear. Here we report that the synthesis of glycolytic and PPP enzymes is almost ubiquitously augmented in colorectal carcinoma (CRC) specimens. The mammalian target of rapamycin (mTOR) inhibitor INK128 (300 nM) and phytochemical Avemar (1 mg/ml) inhibited the synthesis of PPP enzymes in CRC cell lines. INK128 (150-600 nM) and resveratrol (75-300 μM) inhibited aerobic glycolysis in the cell lines. INK128 (300 nM) and Avemar (1 mg/ml) decreased the NADPH/NADP<sup>+</sup> ratio as well as the GSH/GSSG ratio in the cell lines. Finally, per os administration of INK128 (0.8 mg/kg) or Avemar (1 g/kg) suppressed tumor growth and delayed tumor formation by transplantable CRC specimens derived from patients. Taken together, pharmacological inhibition of the mTOR-PPP axis is a promising therapeutic strategy against CRCs.
DOI: 10.6084/m9.figshare.5127391.v1
title: Supplementary Material for: VEGF-A Inhibition Ameliorates Podocyte Apoptosis via Repression of Activating Protein 1 in Diabetes

description: <b><i>Background/Aims:</i></b> Vascular endothelial growth factor-A (VEGF-A) upregulation and podocyte apoptosis have been documented in diabetes. This study was designed to investigate whether inhibiting VEGF-A could ameliorate podocyte apoptosis in diabetes and the underlying mechanisms. <b><i>Methods:</i></b> In vitro, small interfering RNAs (siRNAs) of VEGF-A and activator protein 1 (AP-1, c-fos and c-jun), bevacizumab (VEGF-A inhibitor) and SP600125 (AP-1 inhibitor) were added to high glucose (30 mM) induced podocytes. Luciferase reporter assay was used to investigate whether AP-1 was a direct target of VEGF-A. In vivo, bevacizumab and SP600125 were administered to 12-week-old streptozotocin-induced male Sprague Dawley rats. The level of VEGF-A, c-fos, c-jun and bcl-2 were examined using immunostaining and Western blot analysis. Podocyte apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay, electron microscopy and flow cytometry. <b><i>Results:</i></b> Silencing VEGF-A or AP-1 upregulated bcl-2 and ameliorated podocyte apoptosis. Silencing VEGF-A decreased the level of c-fos and c-jun and bevacizumab and SP600125 treatment attenuated podocyte apoptosis. Luciferase reporter activity of VEGF-A-3′-UTR constructs was significantly provoked when stimulated with TGF-β1. In diabetic rat kidneys, VEGF-A co-localized with bcl-2 in podocytes. With bevacizumab and SP600125 treatment, the level of VEGF-A and AP-1 decreased while bcl-2 increased. Podocyte apoptotic rate was reduced with condensed podocyte nuclei less frequently observed. The urine albumin excretion rate (UAER) and albumin/creatinine were improved. <b><i>Conclusion:</i></b> This study demonstrates VEGF-A inhibition ameliorates podocyte apoptosis by regulating AP-1 and bcl-2 signaling. AP-1 is a direct target of VEGF-A and a novel player in podocyte apoptosis.
DOI: 10.6084/m9.figshare.5127382
title: Supplementary Material for: Comprehensive DNA Methylation and Extensive Mutation Analyses of HER2-Positive Breast Cancer

description: <b><i>Objective:</i></b> Resistance to trastuzumab is a problem that remains to be solved in HER2-positive breast cancer. We aimed to characterize profiles of genetic and epigenetic alterations in cancer-related pathways in HER2-positive breast cancers, using biopsy tissue samples obtained from patients enrolled in a prospective neoadjuvant clinical trial. <b><i>Methods:</i></b> HER2-positive breast cancer tissue samples were collected and processed with the PAXgene Tissue System. A total of 24 breast cancers were analyzed. Genetic alterations of 409 cancer-related genes were analyzed by a bench-top next-generation sequencer. DNA methylation statuses were analyzed by a bead array with 485,512 probes. <b><i>Results:</i></b> The WNT pathway was potentially activated by aberrant methylation of its negative regulators, such as <i>DKK3</i> and <i>SFRP1</i>, in 9 breast cancers. The AKT/mTOR pathway was activated by mutations of <i>PIK3CA</i> in 5 breast cancers. The Notch pathway was potentially activated by mutations of <i>NOTCH1</i> and <i>NOTCH2</i> in 4 breast cancers. The p53 pathway was inactivated by mutations of <i>TP53</i> in 13 breast cancers and potentially by aberrant methylation of its downstream genes in 10 breast cancers. Cell adhesion was affected by mutations of <i>CDH1</i> in 1 breast cancer. <b><i>Conclusion:</i></b> Genes involved in cancer-related pathways were frequently affected not only by genetic but also by epigenetic alterations in HER2-positive breast cancer.