cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5484658.v1
title: Supplementary Material for: The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design of the Heart-Brain Study

description: <b><i>Background:</i></b> Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. <b><i>Methods:</i></b> The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. <b><i>Results and Conclusions:</i></b> The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.
DOI: 10.6084/m9.figshare.5484658.v2
title: Supplementary Material for: The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design of the Heart-Brain Study

description: <b><i>Background:</i></b> Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. <b><i>Methods:</i></b> The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. <b><i>Results and Conclusions:</i></b> The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.
DOI: 10.6084/m9.figshare.5484544
title: Source code from Modelling pyruvate dehydrogenase under hypoxia and its role in cancer metabolism

description: Matlab script to generate the metabolic predictions
DOI: 10.6084/m9.figshare.5484544.v1
title: Source code from Modelling pyruvate dehydrogenase under hypoxia and its role in cancer metabolism

description: Matlab script to generate the metabolic predictions
DOI: 10.6084/m9.figshare.5484535
title: Flux distribution results from Modelling pyruvate dehydrogenase under hypoxia and its role in cancer metabolism

description: Excel file containing reactions (using KEGG identifiers) in the model and flux values from various conditions.
DOI: 10.6084/m9.figshare.5484532
title: Text-file S1 from Imperial trophy or island relict? A new extinction paradigm for Père David's deer: a Chinese conservation icon

description: Consensus sequence for near-complete mitochondrial genome of NHM 70.2.10.29
DOI: 10.6084/m9.figshare.5484535.v1
title: Flux distribution results from Modelling pyruvate dehydrogenase under hypoxia and its role in cancer metabolism

description: Excel file containing reactions (using KEGG identifiers) in the model and flux values from various conditions.
DOI: 10.6084/m9.figshare.5484523
title: Model

description: Metabolic model in SBML format
DOI: 10.6084/m9.figshare.5484523.v1
title: Model

description: Metabolic model in SBML format
DOI: 10.6084/m9.figshare.5484532.v1
title: Text-file S1 from Imperial trophy or island relict? A new extinction paradigm for Père David's deer: a Chinese conservation icon

description: Consensus sequence for near-complete mitochondrial genome of NHM 70.2.10.29
DOI: 10.6084/m9.figshare.5484511
title: Supplementary Material for: Progression of Coronary Artery Calcification in Living Kidney Donors: A Follow-Up Study

description: <b><i>Background:</i></b> Data on the long-term mortality and morbidity of living kidney donors are scarce. In the general population, coronary artery calcification (CAC) and progression of CAC are predictors of future cardiac risk. We conducted a study to determine the progression of CAC in renal transplant donors. <b><i>Methods:</i></b> We used multidetector computed tomography to examine CAC in 75 former renal transplant donors. A baseline and a follow-up scan were performed and changes in CAC scores were evaluated in each subject individually to calculate the incidence of CAC progression. <b><i>Results:</i></b> Baseline CAC prevalence was 16% and the mean CAC score was 5.3 ± 25.8. At the follow-up scan that was performed after an average of 4.8 ± 0.3 years, CAC prevalence increased to 72% and the mean CAC score to 12.5 ± 23.4. Progression of the individual CAC score was found between 18.7 and 26.7%, depending on the method used to define progression. In patients with baseline CAC, the mean annualized rate of CAC progression was 2.1. Presence of hypertension, high systolic blood pressure and an increase in BMI were the determinants of CAC progression. <b><i>Conclusions:</i></b> The rate of CAC progression does not seem to be high in carefully selected donors.
DOI: 10.6084/m9.figshare.5484376
title: Dataset for: MicroRNA-661 modulates redox and metabolic homeostasis in Colon Cancer

description: Cancer cell survival and metastasis are dependent on a metabolic reprogramming able to increase resistance to oxidative and energetic stress. Targeting these two processes can be crucial for cancer progression. Herein we describe the role of microRNA-661 (miR661) as epigenetic regulator of colon cancer (CC) cell metabolism. miR661 induces a global increase in reactive oxygen species (ROS), specifically in mitochondrial superoxide anions (SO-), that seems to be mediated by decreased carbohydrate metabolism and pentose phosphate pathway, and by a higher dependency on mitochondrial respiration. miR661 overexpression in non-metastatic human CC cells induces an epithelial to mesenchymal transition (EMT) phenotype and a reduced tolerance to metabolic stress. This seems to be a general effect of miR661 in CC, since metastatic CC cells metabolism is also compromised upon miR661 overexpression. We propose hexose 6 phosphate dehydrogenase (H6PD) and pyruvate kinase M2 (PKM2) as two players related to the observed metabolic reprogramming. Finally, the clinical relevance of miR661 expression levels in stage-II and III CC patients is discussed. In conclusion, we propose miR661 as a potential modulator of redox and metabolic homeostasis in CC.
DOI: 10.6084/m9.figshare.5484358
title: Dataset for: DR5-Cbl-b/c-Cbl-TRAF2 complex inhibits TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells

description: Ubiquitination of caspase-8 regulates TRAIL sensitivity in cancer cell, and the preligand assembly complex plays a role in caspase-8 polyubiquitination. However, whether such a complex exists in gastric cancer cells and its role in TRAIL-triggered apoptosis is unclear. In the present study, DR5, Cbl-b/c-Cbl, and TRAF2 formed a complex in TRAIL-resistant gastric cancer cells, and Cbl-b and c-Cbl were the critical adaptors linking DR5 and TRAF2. Treatment with TRAIL induced caspase-8 translocation into the DR5-Cbl-b/c-Cbl-TRAF2 complex to interact with TRAF2, which then mediated the K48-linked polyubiquitination of caspase-8. The proteasome inhibitor bortezomib markedly enriched the p43/41 products of caspase-8 activated by TRAIL, indicating proteasomal degradation of caspase-8. Moreover, TRAF2 knockdown prevented the polyubiquitination of caspase-8, and thus increased TRAIL sensitivity. In addition, the inhibition of Cbl-b or c-Cbl expression and overexpression of miR-141 targeting Cbl-b and c-Cbl partially reversed TRAIL resistance by inhibiting the interaction of TRAF2 and caspase-8 and the subsequent polyubiquitination of caspase-8. These results indicate that the DR5-Cbl-b/c-Cbl-TRAF2 complex inhibited TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells.
DOI: 10.6084/m9.figshare.5484358.v1
title: Dataset for: DR5-Cbl-b/c-Cbl-TRAF2 complex inhibits TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells

description: Ubiquitination of caspase-8 regulates TRAIL sensitivity in cancer cell, and the preligand assembly complex plays a role in caspase-8 polyubiquitination. However, whether such a complex exists in gastric cancer cells and its role in TRAIL-triggered apoptosis is unclear. In the present study, DR5, Cbl-b/c-Cbl, and TRAF2 formed a complex in TRAIL-resistant gastric cancer cells, and Cbl-b and c-Cbl were the critical adaptors linking DR5 and TRAF2. Treatment with TRAIL induced caspase-8 translocation into the DR5-Cbl-b/c-Cbl-TRAF2 complex to interact with TRAF2, which then mediated the K48-linked polyubiquitination of caspase-8. The proteasome inhibitor bortezomib markedly enriched the p43/41 products of caspase-8 activated by TRAIL, indicating proteasomal degradation of caspase-8. Moreover, TRAF2 knockdown prevented the polyubiquitination of caspase-8, and thus increased TRAIL sensitivity. In addition, the inhibition of Cbl-b or c-Cbl expression and overexpression of miR-141 targeting Cbl-b and c-Cbl partially reversed TRAIL resistance by inhibiting the interaction of TRAF2 and caspase-8 and the subsequent polyubiquitination of caspase-8. These results indicate that the DR5-Cbl-b/c-Cbl-TRAF2 complex inhibited TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells.
DOI: 10.6084/m9.figshare.5484376.v1
title: Dataset for: MicroRNA-661 modulates redox and metabolic homeostasis in Colon Cancer

description: Cancer cell survival and metastasis are dependent on a metabolic reprogramming able to increase resistance to oxidative and energetic stress. Targeting these two processes can be crucial for cancer progression. Herein we describe the role of microRNA-661 (miR661) as epigenetic regulator of colon cancer (CC) cell metabolism. miR661 induces a global increase in reactive oxygen species (ROS), specifically in mitochondrial superoxide anions (SO-), that seems to be mediated by decreased carbohydrate metabolism and pentose phosphate pathway, and by a higher dependency on mitochondrial respiration. miR661 overexpression in non-metastatic human CC cells induces an epithelial to mesenchymal transition (EMT) phenotype and a reduced tolerance to metabolic stress. This seems to be a general effect of miR661 in CC, since metastatic CC cells metabolism is also compromised upon miR661 overexpression. We propose hexose 6 phosphate dehydrogenase (H6PD) and pyruvate kinase M2 (PKM2) as two players related to the observed metabolic reprogramming. Finally, the clinical relevance of miR661 expression levels in stage-II and III CC patients is discussed. In conclusion, we propose miR661 as a potential modulator of redox and metabolic homeostasis in CC.
DOI: 10.6084/m9.figshare.5484337
title: Unrecognized species diversity and new insights into colour pattern polymorphism within the widespread Malagasy snake <i>Mimophis</i> (Serpentes: Lamprophiidae)

description: Although many wide-ranging taxa occur in Madagascar, phylogeographic studies for most of these species are still lacking. This is especially the case for snakes, where of more than 100 endemic species, the population structure of only two species has so far been examined. Here, we examine genetic population structure of one of the most common snakes of Madagascar, <i>Mimophis mahfalensis</i> (Grandidier, 1867). This taxon is the only representative of Psammophiinae in Madagascar, where the majority of species in this subfamily is distributed throughout mainland Africa. Applying an integrative approach, where both morphological data and genetic results from coalescent species delimitation analyses are considered, we determine that <i>Mimophis mahfalensis</i> is composed of two distinct taxa: <i>M. mahfa</i><i>lensis</i> in the central montane and southern parts of Madagascar, and a second new species restricted to the north and north-west, which we describe here. We also examine the colour pattern polymorphism exhibited in <i>Mimophis</i>, which has been previously hypothesized as sexually dimorphic and/or geographically correlated. However, we find all three colour morphs in both sexes, and both species of <i>Mimophis</i>. Our work highlights the importance of phylogeographic studies that examine wide-ranging taxa to detect cryptic species diversity, even amongst species that are common, or have been previously considered to be well known. www.zoobank.org/lsid:zoobank.org:pub:9791DC0B-49E5-4571-884C-4AA85EAF2472
DOI: 10.6084/m9.figshare.5484310
title: Dataset for: Characterization of conserved circular RNA in polyploid and its ancestors, Gossypium spp.

description: Circular RNA (circRNA) is a regulatory class of long, non-coding RNA found in both plant and animal kingdoms. The profile and characterization of circRNA in cotton species remains to be explored. Here, using 24 rRNA-depleted RNA-seq libraries of putative diploid progenitors of Gossypium spp., G. arboreum and G. raimondii, their interspecies hybrid (F1) and allotetraploid G. hirsutum, 1,041, 1,478, 1,311 and 499 circRNAs were identified in each cotton species respectively. A prevalence of 23 of exon-circRNAs are non-canonical GT/AG signals, and only ~10% of exon-circRNA are associated with reverse complementary intronic sequences. This result implies that plants employ a method of circRNA splicing distinct from that of animals. In addition, 432 circRNAs are stably expressed in multiple cotton species.
DOI: 10.6084/m9.figshare.5484337.v1
title: Unrecognized species diversity and new insights into colour pattern polymorphism within the widespread Malagasy snake <i>Mimophis</i> (Serpentes: Lamprophiidae)

description: Although many wide-ranging taxa occur in Madagascar, phylogeographic studies for most of these species are still lacking. This is especially the case for snakes, where of more than 100 endemic species, the population structure of only two species has so far been examined. Here, we examine genetic population structure of one of the most common snakes of Madagascar, <i>Mimophis mahfalensis</i> (Grandidier, 1867). This taxon is the only representative of Psammophiinae in Madagascar, where the majority of species in this subfamily is distributed throughout mainland Africa. Applying an integrative approach, where both morphological data and genetic results from coalescent species delimitation analyses are considered, we determine that <i>Mimophis mahfalensis</i> is composed of two distinct taxa: <i>M. mahfa</i><i>lensis</i> in the central montane and southern parts of Madagascar, and a second new species restricted to the north and north-west, which we describe here. We also examine the colour pattern polymorphism exhibited in <i>Mimophis</i>, which has been previously hypothesized as sexually dimorphic and/or geographically correlated. However, we find all three colour morphs in both sexes, and both species of <i>Mimophis</i>. Our work highlights the importance of phylogeographic studies that examine wide-ranging taxa to detect cryptic species diversity, even amongst species that are common, or have been previously considered to be well known. www.zoobank.org/lsid:zoobank.org:pub:9791DC0B-49E5-4571-884C-4AA85EAF2472
DOI: 10.6084/m9.figshare.5484310.v1
title: Dataset for: Characterization of conserved circular RNA in polyploid and its ancestors, Gossypium spp.

description: Circular RNA (circRNA) is a regulatory class of long, non-coding RNA found in both plant and animal kingdoms. The profile and characterization of circRNA in cotton species remains to be explored. Here, using 24 rRNA-depleted RNA-seq libraries of putative diploid progenitors of Gossypium spp., G. arboreum and G. raimondii, their interspecies hybrid (F1) and allotetraploid G. hirsutum, 1,041, 1,478, 1,311 and 499 circRNAs were identified in each cotton species respectively. A prevalence of 23 of exon-circRNAs are non-canonical GT/AG signals, and only ~10% of exon-circRNA are associated with reverse complementary intronic sequences. This result implies that plants employ a method of circRNA splicing distinct from that of animals. In addition, 432 circRNAs are stably expressed in multiple cotton species.
DOI: 10.6084/m9.figshare.5484268
title: Dataset for: NDRG2 acts as a PERK co-factor to facilitate PERK branch and ERS-induced cell death

description: NDRG2, a newly identified tumor suppressor, is also responsive to various stresses, such as hypoxia and DNA damage. Here we reported that in human hepatoma SK-Hep-1 and HepG2 cells, NDRG2 mRNA and protein levels were upregulated by different ER stress inducers including Tg, Tm and DTT. Further, using NDRG2-overexpressing hepatoma cell lines and Ndrg2 KO mice liver tissues, we found that, among the three branches of unfolded protein response (UPR) signaling, NDRG2 facilitates PERK pathway via interaction with PERK, enhancing its downstream ATF4 and CHOP. Functionally, NDRG2 promotes ERS-induced apoptosis partially through ATF4 or CHOP. Thus, NDRG2 is an novel ERS responsive protein and acts as PERK co-factor to facilitate PERK branch, thereby contributing to ERS-induced apoptosis.
DOI: 10.6084/m9.figshare.5484268.v1
title: Dataset for: NDRG2 acts as a PERK co-factor to facilitate PERK branch and ERS-induced cell death

description: NDRG2, a newly identified tumor suppressor, is also responsive to various stresses, such as hypoxia and DNA damage. Here we reported that in human hepatoma SK-Hep-1 and HepG2 cells, NDRG2 mRNA and protein levels were upregulated by different ER stress inducers including Tg, Tm and DTT. Further, using NDRG2-overexpressing hepatoma cell lines and Ndrg2 KO mice liver tissues, we found that, among the three branches of unfolded protein response (UPR) signaling, NDRG2 facilitates PERK pathway via interaction with PERK, enhancing its downstream ATF4 and CHOP. Functionally, NDRG2 promotes ERS-induced apoptosis partially through ATF4 or CHOP. Thus, NDRG2 is an novel ERS responsive protein and acts as PERK co-factor to facilitate PERK branch, thereby contributing to ERS-induced apoptosis.
DOI: 10.6084/m9.figshare.5484250
title: Supplementary Material for: Meta-Analysis of Lipid-Lowering Therapy in Maintenance Dialysis Patients

description: <b><i>Background/Aims:</i></b> The use of lipid-lowering therapy (LLT) in patients on chronic dialysis is contentious. Here we present an aggregate data meta-analysis of randomised controlled trials (RCTs) comparing long-term LLT versus placebo in dialysis patients. <b><i>Method:</i></b> A search of Medline, Google Scholar, COCHRANE database, EMBASE, and cardiovascular and nephrology society proceedings was performed. Criteria for inclusion were RCTs of LLT versus placebo, in which LLT was demonstrated to significantly reduce low-density lipoprotein cholesterol, &gt;12 months of follow-up, and at least one cardiovascular or mortality endpoint in an independently reported dialysis population. Meta-analysis was performed for atherosclerotic cardiovascular events, stroke and mortality using a random-effects method for odds ratio (OR) of risk. <b><i>Results:</i></b> Three studies were included with 7,051 patients (3,541 treatment and 3,510 placebo). Twenty-five percent of the LLT patients suffered an atherosclerotic cardiovascular event versus 27% for placebo. The OR was 0.89 (95% CI: 0.80-0.99, p = 0.04). For stroke (haemorrhagic and non-haemorrhagic combined), the figures were 6.2% (LLT) versus 5.7% (placebo) [OR = 1.11 (95% CI: 0.85-1.46, p = 0.45)]. For all-cause mortality, the figures were 40 versus 42% [OR = 0.97 (95% CI: 0.88-1.06, p = 0.49)]. <b><i>Conclusion:</i></b> There was an overall significant reduction in risk for atherosclerotic cardiovascular events in dialysis patients treated with LLT compared to placebo. There was a numerical but not a statistical reduction in mortality. There was no statistically significant increase in risk of stroke as has been previously reported.