cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127388.v1
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.5127373
title: Supplementary Material for: One-Year Survival and Renal Function Recovery of Acute Kidney Injury Patients with Chronic Heart Failure

description: <b><i>Objective:</i></b> To describe and analyze the clinical characteristics of acute kidney injury (AKI) patients with preexisting chronic heart failure (CHF) and to identify the prognostic factors of the 1-year outcome. <b><i>Methods:</i></b> A total of 120 patients with preexisting CHF who developed AKI between January 2005 and December 2010 were enrolled. CHF was diagnosed according to the European Society of Cardiology guidelines, and AKI was diagnosed using the RIFLE criteria. Clinical characteristics were recorded, and nonrecovery from kidney dysfunction as well as mortality were analyzed. <b><i>Results:</i></b> The median age of the patients was 70 years, and 58.33% were male. 60% of the patients had an advanced AKI stage (‘failure') and 90% were classified as NYHA class III/IV. The 1-year mortality rate was 35%. 25.83% of the patients progressed to end-stage renal disease after 1 year. Hypertension, anemia, coronary atherosclerotic heart disease and chronic kidney disease were common comorbidities. Multiple organ dysfunction syndrome (MODS; OR, 35.950; 95% CI, 4.972-259.952), arrhythmia (OR, 13.461; 95% CI, 2.379-76.161), anemia (OR, 6.176; 95% CI, 1.172-32.544) and RIFLE category (OR, 5.353; 95% CI, 1.436-19.952) were identified as risk factors of 1-year mortality. For 1-year nonrecovery from kidney dysfunction, MODS (OR, 8.884; 95% CI, 2.535-31.135) and acute heart failure (OR, 3.281; 95% CI, 1.026-10.491) were independent risk factors. <b><i>Conclusion:</i></b> AKI patients with preexisting CHF were mainly elderly patients who had an advanced AKI stage and NYHA classification. Their 1-year mortality and nonrecovery from kidney dysfunction rates were high. Identifying risk factors may help to improve their outcome.
DOI: 10.6084/m9.figshare.5127376
title: Supplementary Material for: A Bayesian Partitioning Model for the Detection of Multilocus Effects in Case-Control Studies

description: <b><i>Background:</i></b> Genome-wide association studies (GWASs) have identified hundreds of genetic variants associated with complex diseases, but these variants appear to explain very little of the disease heritability. The typical single-locus association analysis in a GWAS fails to detect variants with small effect sizes and to capture higher-order interaction among these variants. Multilocus association analysis provides a powerful alternative by jointly modeling the variants within a gene or a pathway and by reducing the burden of multiple hypothesis testing in a GWAS. <b><i>Methods:</i></b> Here, we propose a powerful and flexible dimension reduction approach to model multilocus association. We use a Bayesian partitioning model which clusters SNPs according to their direction of association, models higher-order interactions using a flexible scoring scheme and uses posterior marginal probabilities to detect association between the SNP set and the disease. <b><i>Results:</i></b> We illustrate our method using extensive simulation studies and applying it to detect multilocus interaction in Atherosclerosis Risk in Communities (ARIC) GWAS with type 2 diabetes. <b><i>Conclusion:</i></b> We demonstrate that our approach has better power to detect multilocus interactions than several existing approaches. When applied to the ARIC study dataset with 9,328 individuals to study gene-based associations for type 2 diabetes, our method identified some novel variants not detected by conventional single-locus association analyses.
DOI: 10.6084/m9.figshare.5127379.v1
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.5127370
title: Supplementary Material for: End-Stage Renal Disease Attributed to Acute Tubular Necrosis in the United States, 2001-2010

description: <b><i>Background/Aims:</i></b> Though end-stage renal disease (ESRD) is increasingly attributed to acute tubular necrosis (ATN), contemporary trends in the rates of incidence and recovery of renal function are poorly defined. Hence, we set out to describe the clinical epidemiology of ESRD due to ATN between 2001 and 2010. <b><i>Methods:</i></b> We examined United States Renal Data System data (n = 1,070,490) for 2001 through 2010 to calculate the incidence rates and rates of renal recovery and death for patients with ESRD due to ATN treated with renal replacement therapy (RRT, n = 27,603). <b><i>Results:</i></b> Standardized incidence ratios increased between 2001-2002 and 2009-2010 in the overall population (ratio 2.14), having risen in all demographic subgroups examined. Recovery of renal function was more likely in patients with ATN than in matched controls (cumulative incidence 23% vs. 2% at 12 weeks, 34% vs. 4% at 1 year), as was death (cumulative incidence 38% vs. 27% at 1 year). Hazards ratios for renal recovery increased stepwise with year of RRT inception to 1.34 (95% confidence interval 1.24-1.45) for 2009-2010 (vs. 2001-2002). In contrast, hazards ratios for death declined stepwise to 0.83 (0.79-0.87) in 2009-2010. <b><i>Conclusion:</i></b> While the incidence of ESRD attributed to ATN has increased, prospects of renal recovery and survival have also increased. Despite substantial mortality risk on RRT, renal recovery is not a rare occurrence.
DOI: 10.6084/m9.figshare.5127382.v1
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.
DOI: 10.6084/m9.figshare.5127385.v1
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.5127361
title: Supplementary Material for: Interactions between Traumatic Brain Injury and Frontotemporal Degeneration

description: <b><i>Background/Aims:</i></b> Prior work in smaller cohorts suggests that traumatic brain injury (TBI) may be a risk factor for frontotemporal degeneration (FTD). We sought to confirm and extend these results using the National Alzheimer's Coordinating Center Uniform Data Set. <b><i>Methods:</i></b> We compared the TBI prevalence between FTD subjects and matched normal controls. Indices of cognitive, behavioral, functional, and global dementia severity were compared between FTD subjects with and without prior TBI. <b><i>Results:</i></b> Remote TBI with extended loss of consciousness (TBI-ext) was more common in individuals with FTD than in controls (OR: 1.67; 95% CI: 1.004-2.778). With TBI-ext, less functional and global impairment was seen in the behavioral variant of FTD, but more behavioral pathology was seen in the semantic variant. <b><i>Conclusion:</i></b> TBI may increase the FTD risk and influence clinical symptomatology and severity in FTD subtypes.
DOI: 10.6084/m9.figshare.5127364
title: Supplementary Material for: Souvenaid Reduces Behavioral Deficits and Improves Social Cognition Skills in Frontotemporal Dementia: A Proof-of-Concept Study

description: <b><i>Background:</i></b> Souvenaid™ is a nutraceutical compound thought to positively enhance synaptic function. In line with this mechanism of action, Souvenaid™ has been shown to improve cognitive function in subjects with mild Alzheimer's disease in randomized clinical trials. To date, however, the potential of Souvenaid™ to improve cognitive functioning in subjects with other neurodegenerative conditions also characterized by synaptic loss has not been explored. <b><i>Objective:</i></b> To evaluate the impact of Souvenaid™ on executive functions, social cognition and behavioral disturbances in subjects with the behavioral variant of frontotemporal dementia (bv-FTD). <b><i>Methods:</i></b> Twenty-six subjects with bv-FTD were enrolled in the study and randomized to Souvenaid™ (125 ml/day) or placebo groups. After 12 weeks, subjects were switched between the two groups. All subjects, blinded to treatment, underwent clinical and cognitive evaluations at enrollment, after 12 weeks and after 24 weeks. <b><i>Results:</i></b> Treatment with Souvenaid™ was associated with a significant reduction of behavioral symptoms and an increase in Theory of Mind skills compared to placebo, which both returned to baseline when Souvenaid™ was discontinued. Souvenaid™ did not have an effect on executive functions. <b><i>Conclusions:</i></b> Our results provide evidence of the potential of Souvenaid™ therapy for the treatment of behavioral disturbances and social cognition skills in FTD.
DOI: 10.6084/m9.figshare.5127367
title: Supplementary Material for: The Effects of Chronic Subcutaneous Administration of an Investigational Kisspeptin Analog, TAK-683, on Gonadotropin-Releasing Hormone Pulse Generator Activity in Goats

description: The continuous activation of the kisspeptin receptor by its agonists causes the abrogation of kisspeptin signaling, leading to decreased pulsatile luteinizing hormone (LH) secretion. Employing this phenomenon as a tool for probing kisspeptin action, this study aimed to clarify the role of kisspeptin in gonadotropin-releasing hormone (GnRH) pulse generation in goats. We examined the effects of chronic administration of TAK-683, an investigational kisspeptin analog, on LH secretion, GnRH immunostaining, pituitary responses to exogenous GnRH, and GnRH pulse generator activity, reflected by a characteristic increase in multiple-unit activity (MUA volley). An osmotic pump containing TAK-683 was subcutaneously implanted on day 0. TAK-683 treatment dose-dependently suppressed pulsatile LH secretion on day 1. Higher doses of chronic TAK-683 profoundly suppressed pulsatile LH secretion but had little effect on GnRH immunostaining patterns and pituitary responses to GnRH on day 5. In ovariectomized goats, MUA volleys occurred at approximately every 30 min on day -1. On day 5 of chronic TAK-683 administration, pulsatile LH secretion was markedly suppressed, whereas MUA volleys were similar to those observed on day -1. Male pheromones and senktide (neurokinin B receptor agonist) induced an MUA volley but had no effect on LH secretion during chronic TAK-683 administration. The results indicate that the chronic administration of a kisspeptin analog profoundly suppresses pulsatile LH secretion without affecting GnRH content, pituitary function or GnRH pulse generator activity, and they suggest an indispensable role for kisspeptin signaling in the cascade driving GnRH/LH pulses by the GnRH pulse generator.
DOI: 10.6084/m9.figshare.5127376.v1
title: Supplementary Material for: A Bayesian Partitioning Model for the Detection of Multilocus Effects in Case-Control Studies

description: <b><i>Background:</i></b> Genome-wide association studies (GWASs) have identified hundreds of genetic variants associated with complex diseases, but these variants appear to explain very little of the disease heritability. The typical single-locus association analysis in a GWAS fails to detect variants with small effect sizes and to capture higher-order interaction among these variants. Multilocus association analysis provides a powerful alternative by jointly modeling the variants within a gene or a pathway and by reducing the burden of multiple hypothesis testing in a GWAS. <b><i>Methods:</i></b> Here, we propose a powerful and flexible dimension reduction approach to model multilocus association. We use a Bayesian partitioning model which clusters SNPs according to their direction of association, models higher-order interactions using a flexible scoring scheme and uses posterior marginal probabilities to detect association between the SNP set and the disease. <b><i>Results:</i></b> We illustrate our method using extensive simulation studies and applying it to detect multilocus interaction in Atherosclerosis Risk in Communities (ARIC) GWAS with type 2 diabetes. <b><i>Conclusion:</i></b> We demonstrate that our approach has better power to detect multilocus interactions than several existing approaches. When applied to the ARIC study dataset with 9,328 individuals to study gene-based associations for type 2 diabetes, our method identified some novel variants not detected by conventional single-locus association analyses.
DOI: 10.6084/m9.figshare.5127364.v1
title: Supplementary Material for: Souvenaid Reduces Behavioral Deficits and Improves Social Cognition Skills in Frontotemporal Dementia: A Proof-of-Concept Study

description: <b><i>Background:</i></b> Souvenaid™ is a nutraceutical compound thought to positively enhance synaptic function. In line with this mechanism of action, Souvenaid™ has been shown to improve cognitive function in subjects with mild Alzheimer's disease in randomized clinical trials. To date, however, the potential of Souvenaid™ to improve cognitive functioning in subjects with other neurodegenerative conditions also characterized by synaptic loss has not been explored. <b><i>Objective:</i></b> To evaluate the impact of Souvenaid™ on executive functions, social cognition and behavioral disturbances in subjects with the behavioral variant of frontotemporal dementia (bv-FTD). <b><i>Methods:</i></b> Twenty-six subjects with bv-FTD were enrolled in the study and randomized to Souvenaid™ (125 ml/day) or placebo groups. After 12 weeks, subjects were switched between the two groups. All subjects, blinded to treatment, underwent clinical and cognitive evaluations at enrollment, after 12 weeks and after 24 weeks. <b><i>Results:</i></b> Treatment with Souvenaid™ was associated with a significant reduction of behavioral symptoms and an increase in Theory of Mind skills compared to placebo, which both returned to baseline when Souvenaid™ was discontinued. Souvenaid™ did not have an effect on executive functions. <b><i>Conclusions:</i></b> Our results provide evidence of the potential of Souvenaid™ therapy for the treatment of behavioral disturbances and social cognition skills in FTD.
DOI: 10.6084/m9.figshare.5127367.v1
title: Supplementary Material for: The Effects of Chronic Subcutaneous Administration of an Investigational Kisspeptin Analog, TAK-683, on Gonadotropin-Releasing Hormone Pulse Generator Activity in Goats

description: The continuous activation of the kisspeptin receptor by its agonists causes the abrogation of kisspeptin signaling, leading to decreased pulsatile luteinizing hormone (LH) secretion. Employing this phenomenon as a tool for probing kisspeptin action, this study aimed to clarify the role of kisspeptin in gonadotropin-releasing hormone (GnRH) pulse generation in goats. We examined the effects of chronic administration of TAK-683, an investigational kisspeptin analog, on LH secretion, GnRH immunostaining, pituitary responses to exogenous GnRH, and GnRH pulse generator activity, reflected by a characteristic increase in multiple-unit activity (MUA volley). An osmotic pump containing TAK-683 was subcutaneously implanted on day 0. TAK-683 treatment dose-dependently suppressed pulsatile LH secretion on day 1. Higher doses of chronic TAK-683 profoundly suppressed pulsatile LH secretion but had little effect on GnRH immunostaining patterns and pituitary responses to GnRH on day 5. In ovariectomized goats, MUA volleys occurred at approximately every 30 min on day -1. On day 5 of chronic TAK-683 administration, pulsatile LH secretion was markedly suppressed, whereas MUA volleys were similar to those observed on day -1. Male pheromones and senktide (neurokinin B receptor agonist) induced an MUA volley but had no effect on LH secretion during chronic TAK-683 administration. The results indicate that the chronic administration of a kisspeptin analog profoundly suppresses pulsatile LH secretion without affecting GnRH content, pituitary function or GnRH pulse generator activity, and they suggest an indispensable role for kisspeptin signaling in the cascade driving GnRH/LH pulses by the GnRH pulse generator.