cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.4763692.v1
title: Modulation of transcription factor binding and epigenetic regulation of the <i>MLH1</i> CpG island and shore by polymorphism rs1800734 in colorectal cancer

description: The <i>MLH1</i> promoter polymorphism rs1800734 is associated with <i>MLH1</i> CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with <i>MLH1</i> shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, <i>MLH1</i> CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype. Cell lines containing the variant A allele demonstrated <i>MLH1</i> shore hypomethylation compared to wild type (GG). There was significant enrichment of transcription factor AP4 at the <i>MLH1</i> promoter in GG and GA cell lines, but not the AA cell line, by chromatin immunoprecipitation studies. Preferential binding to the G allele was confirmed by sequencing in the GA cell line. The enhancer-associated histone modification H3K4me1 was enriched at the <i>MLH1</i> shore; however, H3K27ac was not, indicating the shore is an inactive enhancer. These results demonstrate the role of variant rs1800734 in altering transcription factor binding as well as epigenetics at regions beyond the <i>MLH1</i> CpG island in which it is located.
DOI: 10.6084/m9.figshare.4763464
title: WikiPathways SD file (v.2)

description: Second release of a Structure Data File (SDF) containing metabolites found in WikiPathways. The file is created with SMILES strings from Wikidata based on the ID mappings to metabolites in the pathways, and converted into a SD file with CDK 1.5.14.
DOI: 10.6084/m9.figshare.4763446
title: Supplementary Material for: Proteomic Analysis of Mouse Cortex Postsynaptic Density following Neonatal Brain Hypoxia-Ischemia

description: Proteomics of the synapses and postsynaptic densities (PSDs) have provided a deep understanding of protein composition and signal networks in the adult brain, which underlie neuronal plasticity and neurodegenerative or psychiatric disorders. However, there is a paucity of knowledge about the architecture and organization of PSDs in the immature brain, and how it is modified by brain injury in an early developing stage. Mass spectrometry (MS)-based proteomic analysis was performed on PSDs prepared from cortices of postnatal day 9 naïve mice or pups which had suffered hypoxic-ischemic (HI) brain injury. 512 proteins of different functional groups were identified from PSDs collected 1 h after HI injury, among which 60 have not been reported previously. Seven newly identified proteins involved in neural development were highlighted. HI injury increased the yield of PSDs at early time points upon reperfusion, and multiple proteins were recruited into PSDs following the insult. Quantitative analysis was performed using spectral counting, and proteins whose relative expression was more than 50% up- or downregulated compared to the sham animals 1 h after HI insult were reported. Validation with Western blotting demonstrated changes in expression and phosphorylation of the N-methyl-D-aspartate receptor, activation of a series of postsynaptic protein kinases and dysregulation of scaffold and adaptor proteins in response to neonatal HI insult. This work, along with other recent studies of synaptic protein profiling in the immature brain, builds a foundation for future investigation on the molecular mechanisms underlying developing plasticity. Furthermore, it provides insights into the biochemical changes of PSDs following early brain hypoxia-ischemia, which is helpful for understanding not only the injury mechanisms, but also the process of repair or replenishment of neuronal circuits during recovery from brain damage.
DOI: 10.6084/m9.figshare.4763443
title: Supplementary Material for: Cerebrospinal Fluid and Parenchymal Brain Development and Growth in the Healthy Fetus

description: <b><i>Objective:</i></b> The objective of this study was to apply quantitative magnetic resonance imaging to characterize absolute cerebrospinal fluid (CSF) development, as well as its relative development to fetal brain parenchyma in the healthy human fetus. <b><i>Design:</i></b> We created three-dimensional high-resolution reconstructions of the developing brain for healthy fetuses between 18 and 40 weeks' gestation, segmented the parenchymal and CSF spaces, and calculated the volumes for the lateral, third, and fourth ventricles; extra-axial CSF space; and the cerebrum, cerebellum, and brainstem. From these data, we constructed normograms of the resulting volumes according to gestational age and described the relative development of CSF to fetal brain parenchyma. <b><i>Results:</i></b> Each CSF space demonstrated major increases in volumetric growth during the second half of gestation: third ventricle (23-fold), extra-axial CSF (11-fold), fourth ventricle (8-fold), and lateral ventricle (2-fold). Total CSF volume was related to total brain volume (<i>p</i> &lt; 0.01), as was lateral ventricle to cerebral volume (<i>p</i> &lt; 0.01); however, the fourth ventricle was not related to cerebellar or brainstem volume (<i>p</i> = 0.18-0.19). <b><i>Relevance:</i></b> Abnormalities of the CSF spaces are the most common anomalies of neurologic development detected on fetal screening using neurosonography. Normative values of absolute CSF volume, as well as relative growth in comparison to intracranial parenchyma, provide valuable insight into normal fetal neurodevelopment. These data may provide important biomarkers of early deviations from normal growth, better distinguish between benign variants and early disease, and serve as reference standards for postnatal growth and development in the premature infant.
DOI: 10.6084/m9.figshare.4763443.v1
title: Supplementary Material for: Cerebrospinal Fluid and Parenchymal Brain Development and Growth in the Healthy Fetus

description: <b><i>Objective:</i></b> The objective of this study was to apply quantitative magnetic resonance imaging to characterize absolute cerebrospinal fluid (CSF) development, as well as its relative development to fetal brain parenchyma in the healthy human fetus. <b><i>Design:</i></b> We created three-dimensional high-resolution reconstructions of the developing brain for healthy fetuses between 18 and 40 weeks' gestation, segmented the parenchymal and CSF spaces, and calculated the volumes for the lateral, third, and fourth ventricles; extra-axial CSF space; and the cerebrum, cerebellum, and brainstem. From these data, we constructed normograms of the resulting volumes according to gestational age and described the relative development of CSF to fetal brain parenchyma. <b><i>Results:</i></b> Each CSF space demonstrated major increases in volumetric growth during the second half of gestation: third ventricle (23-fold), extra-axial CSF (11-fold), fourth ventricle (8-fold), and lateral ventricle (2-fold). Total CSF volume was related to total brain volume (<i>p</i> &lt; 0.01), as was lateral ventricle to cerebral volume (<i>p</i> &lt; 0.01); however, the fourth ventricle was not related to cerebellar or brainstem volume (<i>p</i> = 0.18-0.19). <b><i>Relevance:</i></b> Abnormalities of the CSF spaces are the most common anomalies of neurologic development detected on fetal screening using neurosonography. Normative values of absolute CSF volume, as well as relative growth in comparison to intracranial parenchyma, provide valuable insight into normal fetal neurodevelopment. These data may provide important biomarkers of early deviations from normal growth, better distinguish between benign variants and early disease, and serve as reference standards for postnatal growth and development in the premature infant.
DOI: 10.6084/m9.figshare.4763416
title: Research data management practices of emerging researchers at a South African research institute

description: Research data management (RDM) practices of emerging researchers at a South African research institute.<br>
DOI: 10.6084/m9.figshare.4763419
title: Vasoactive peptides associate with treatment outcome ofbevacizumab-containing therapy in metastatic colorectal cancer

description: <b>Background:</b> Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking. In disease associated with hypertension, vasoactive peptides have been linked to cardiovascular pressure load. Here, we have explored potential associations between circulating levels of vasoactive peptides and tumor response during bevacizumab-containing treatment of colorectal cancer. <b>Material and methods:</b> Metastatic colorectal cancer (mCRC) patients with available best objective response (ORR) and time to tumor progression (TTP) data were included from a randomized clinical trial investigating maintenance therapy after first line chemotherapy plus bevacizumab. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial-natriuretic-peptide (MR-proANP), and C-terminal-prepro-vasopressin (Copeptin) vasoactive peptide concentrations were measured in plasma at baseline and after 6 weeks of chemotherapy and bevacizumab treatment (<i>n</i> = 97). We determined associations among clinical outcome (ORR and TTP), peptide levels, and hypertension (NCI-CTCAE 4.0 criteria), using Spearman’s test, multiple linear regression, and Mann–Whitney’s test. <b>Results:</b> Increasing levels of vasoactive peptides from baseline and after six weeks of treatment were associated with improved treatment outcome (MR-proADM: ORR, <i>p</i> = .0003; TTP, <i>p</i> = .05; MR-proANP: ORR, <i>p</i> = .05; TTP, <i>p</i> = .03; Copeptin: ORR, <i>p</i> = .10; TTP, <i>p</i> = .02). Patients with increasing levels of all three peptides (n = 28) versus increasing levels of one or two peptides (<i>n</i> = 59) showed a median TTP of 284 and 225 d, respectively (<i>p</i> = .02). <b>Conclusions:</b> Our results suggest that increasing systemic levels of vasoactive peptides associate with improved tumor response and TTP in mCRC patients treated with a bevacizumab-containing regimen. These findings support the proposed link between the tumor vasculature and the cardiovascular system of the host. This should motivate further studies that investigate the potential role of vasoactive peptides as a novel class of dynamic biomarkers in the treatment of cancer.
DOI: 10.6084/m9.figshare.4763410
title: Supplementary Material for: Vitamin D Status, Gender Differences, and Cardiometabolic Health Disparities

description: <b><i>Background:</i></b> Vitamin D deficiency is an unrecognized epidemic found in India and also worldwide. Despite the high prevalence of diabetes among Indians, there is a paucity of data showing the relationship between vitamin D status and cardiometabolic disparities. In this study, we have examined the relationship between vitamin D and cardiometabolic traits in a population from India. <b><i>Methods:</i></b> Circulating 25(OH)D levels were measured in 3,879 participants from the Asian Indian Diabetic Heart Study using ELISA kits. <b><i>Results:</i></b> Vitamin D levels were significantly reduced (<i>p</i> &lt; 0.0001) in both men and women with obesity. However, compared to women, serum vitamin D was consistently lower in men (<i>p</i> &lt; 0.02), irrespective of the presence of obesity and type 2 diabetes. Multivariate regression revealed strong interaction of vitamin D with body mass index that resulted in increased fasting glucose (<i>p</i> = 0.001) and reduced homeostasis model assessment of β-cell function (HOMA-B; <i>p</i> = 0.01) in normoglycemic individuals. However, in gender-stratified analysis, this association was restricted to men for both fasting glucose (<i>p</i> = 2.4 × 10<sup>-4</sup>) and HOMA-B (<i>p</i> = 0.001). <b><i>Conclusions:</i></b> Our findings suggest that vitamin D deficiency may significantly enhance the risk of cardiometabolic disease among Asian Indians. Future randomized trials and genetic studies are expected to clarify the underlying mechanisms for gender differences in vitamin D deficiency, and whether vitamin D-driven improvement in testosterone may contribute to beneficial cardiometabolic outcomes in men.
DOI: 10.6084/m9.figshare.4763416.v2
title: Research data management practices of emerging researchers at a South African research institute

description: Research data management (RDM) practices of emerging researchers at a South African research institute.<br>
DOI: 10.6084/m9.figshare.4763419.v1
title: Vasoactive peptides associate with treatment outcome ofbevacizumab-containing therapy in metastatic colorectal cancer

description: <b>Background:</b> Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking. In disease associated with hypertension, vasoactive peptides have been linked to cardiovascular pressure load. Here, we have explored potential associations between circulating levels of vasoactive peptides and tumor response during bevacizumab-containing treatment of colorectal cancer. <b>Material and methods:</b> Metastatic colorectal cancer (mCRC) patients with available best objective response (ORR) and time to tumor progression (TTP) data were included from a randomized clinical trial investigating maintenance therapy after first line chemotherapy plus bevacizumab. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial-natriuretic-peptide (MR-proANP), and C-terminal-prepro-vasopressin (Copeptin) vasoactive peptide concentrations were measured in plasma at baseline and after 6 weeks of chemotherapy and bevacizumab treatment (<i>n</i> = 97). We determined associations among clinical outcome (ORR and TTP), peptide levels, and hypertension (NCI-CTCAE 4.0 criteria), using Spearman’s test, multiple linear regression, and Mann–Whitney’s test. <b>Results:</b> Increasing levels of vasoactive peptides from baseline and after six weeks of treatment were associated with improved treatment outcome (MR-proADM: ORR, <i>p</i> = .0003; TTP, <i>p</i> = .05; MR-proANP: ORR, <i>p</i> = .05; TTP, <i>p</i> = .03; Copeptin: ORR, <i>p</i> = .10; TTP, <i>p</i> = .02). Patients with increasing levels of all three peptides (n = 28) versus increasing levels of one or two peptides (<i>n</i> = 59) showed a median TTP of 284 and 225 d, respectively (<i>p</i> = .02). <b>Conclusions:</b> Our results suggest that increasing systemic levels of vasoactive peptides associate with improved tumor response and TTP in mCRC patients treated with a bevacizumab-containing regimen. These findings support the proposed link between the tumor vasculature and the cardiovascular system of the host. This should motivate further studies that investigate the potential role of vasoactive peptides as a novel class of dynamic biomarkers in the treatment of cancer.
DOI: 10.6084/m9.figshare.4763416.v1
title: dataset.xlsx

description: Research data management (RDM) practices of emerging researchers at a South African research institute.<br>
DOI: 10.6084/m9.figshare.4763395
title: Recent mass spectrometry-based proteomics for biomarker discovery in lung cancer, COPD, and asthma

description: <b>Introduction</b>: Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges. <b>Areas covered</b>: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches. Since lung cancer is a multifactorial disease that is biologically associated with asthma and COPD among various lung diseases, this study focused on proteomic studies on biomarker discovery using various clinical specimens for lung cancer, COPD, and asthma. <b>Expert commentary</b>: MS-based exploratory proteomics utilizing clinical specimens, which can incorporate both experimental and bioinformatic analysis of protein-protein interaction and also can adopt proteogenomic approaches, makes it possible to reveal molecular networks that are relevant to a disease subgroup and that could differentiate between drug responders and non-responders, good and poor prognoses, drug resistance, and so on.
DOI: 10.6084/m9.figshare.4763395.v1
title: Recent mass spectrometry-based proteomics for biomarker discovery in lung cancer, COPD, and asthma

description: <b>Introduction</b>: Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges. <b>Areas covered</b>: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches. Since lung cancer is a multifactorial disease that is biologically associated with asthma and COPD among various lung diseases, this study focused on proteomic studies on biomarker discovery using various clinical specimens for lung cancer, COPD, and asthma. <b>Expert commentary</b>: MS-based exploratory proteomics utilizing clinical specimens, which can incorporate both experimental and bioinformatic analysis of protein-protein interaction and also can adopt proteogenomic approaches, makes it possible to reveal molecular networks that are relevant to a disease subgroup and that could differentiate between drug responders and non-responders, good and poor prognoses, drug resistance, and so on.
DOI: 10.6084/m9.figshare.4763371
title: Mitochondrial DNA sequence variation in Iranian native dogs

description: The dog mtDNA diversity picture from wide geographical sampling but from a small number of individuals per region or breed, displayed little geographical correlation and high degree of haplotype sharing between very distant breeds. For a clear picture, we extensively surveyed Iranian native dogs (<i>n</i> = 305) in comparison with published European (<i>n</i> = 443) and Southwest Asian (<i>n</i> = 195) dogs. Twelve haplotypes related to haplogroups A, B and C were shared by Iranian, European, Southwest Asian and East Asian dogs. In Iran, haplotype and nucleotide diversities were highest in east, southeast and northwest populations while western population had the least. Sarabi and Saluki dog populations can be assigned into haplogroups A, B, C and D; Qahderijani and Kurdi to haplogroups A, B and C, Torkaman to haplogroups A, B and D while Sangsari and Fendo into haplogroups A and B, respectively. Evaluation of population differentiation using pairwise <i>F</i><sub>ST</sub> generally revealed no clear population structure in most Iranian dog populations. The genetic signal of a recent demographic expansion was detected in East and Southeast populations. Further, in accordance with previous studies on dog-wolf hybridization for haplogroup d2 origin, the highest number of d2 haplotypes in Iranian dog as compared to other areas of Mediterranean basin suggests Iran as the probable center of its origin. Historical evidence showed that Silk Road linked Iran to countries in South East Asia and other parts of the world, which might have probably influenced effective gene flow within Iran and these regions. The medium nucleotide diversity observed in Iranian dog calls for utilization of appropriate management techniques in increasing effective population size.
DOI: 10.6084/m9.figshare.4763371.v1
title: Mitochondrial DNA sequence variation in Iranian native dogs

description: The dog mtDNA diversity picture from wide geographical sampling but from a small number of individuals per region or breed, displayed little geographical correlation and high degree of haplotype sharing between very distant breeds. For a clear picture, we extensively surveyed Iranian native dogs (<i>n</i> = 305) in comparison with published European (<i>n</i> = 443) and Southwest Asian (<i>n</i> = 195) dogs. Twelve haplotypes related to haplogroups A, B and C were shared by Iranian, European, Southwest Asian and East Asian dogs. In Iran, haplotype and nucleotide diversities were highest in east, southeast and northwest populations while western population had the least. Sarabi and Saluki dog populations can be assigned into haplogroups A, B, C and D; Qahderijani and Kurdi to haplogroups A, B and C, Torkaman to haplogroups A, B and D while Sangsari and Fendo into haplogroups A and B, respectively. Evaluation of population differentiation using pairwise <i>F</i><sub>ST</sub> generally revealed no clear population structure in most Iranian dog populations. The genetic signal of a recent demographic expansion was detected in East and Southeast populations. Further, in accordance with previous studies on dog-wolf hybridization for haplogroup d2 origin, the highest number of d2 haplotypes in Iranian dog as compared to other areas of Mediterranean basin suggests Iran as the probable center of its origin. Historical evidence showed that Silk Road linked Iran to countries in South East Asia and other parts of the world, which might have probably influenced effective gene flow within Iran and these regions. The medium nucleotide diversity observed in Iranian dog calls for utilization of appropriate management techniques in increasing effective population size.
DOI: 10.6084/m9.figshare.4763383.v1
title: Kalara - Reveal - Make Seen

description: Kalara - Reveal - Make Seen - a diagrammatic graphic representation of the filmmakers process of working with Aboriginal communities in Australia, the cycles, the journey as communities decide their own development focus on booroo - Nyikina Aboriginal term from the Kimberley region of Australia meaning 'country' - content by Magali McDuffie - graphic design by Alexander Hayes.
DOI: 10.6084/m9.figshare.4763383.v3
title: Kalara - Reveal - Make Seen

description: A data set containing the diagrammatic graphic representation of the filmmakers process of working with Aboriginal communities in Australia, the cycles, the journey as communities decide their own development focus on BOOROO - Nyikina Aboriginal term from the Kimberley region of Australia meaning 'country'. Content by Magali McDuffie, graphic design by Alexander Hayes. *NOTE* - final graphic is the 2017-Kalara-Make-Seen-Liyan