cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5001305.v2
title: Optimal Interim Decision Rules Based on a Binary Surrogate Outcome for Adaptive Biomarker-Based Trials in Oncology

description: Adaptive enrichment designs represent a promising approach to evaluate targeted therapies, for example, in oncology. They allow selection of the most promising target population in an interim analysis and then combination of the data from the two trial stages for the final proof of efficacy. Application of these designs is motivated by the assumption that there might be a biomarker-defined subgroup of patients with an increased treatment benefit as compared to the total patient population. If the primary outcome is a time-to-event variable and the respective event takes a relatively long time to be observed, it could be beneficial to select the most promising patient population based on an earlier available binary surrogate, for example, response, to save time and costs. We propose an adaptive enrichment design which allows us to implement such a trial setting. For this design, optimal decision rules are derived minimizing the expected loss incurred due to a false interim decision. These rules are compared to ad hoc rules in terms of selection probability and power within a simulation study which is motivated by a clinical trial example. Furthermore, the impact of the correlation between surrogate and primary outcome on power is investigated. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.5001296
title: Small interference ITGA6 gene targeting in the human thymic epithelium differentially regulates the expression of immunological synapse-related genes

description: The thymus supports differentiation of T cell precursors. This process requires relocation of developing thymocytes throughout multiple microenvironments of the organ, mainly with thymic epithelial cells (TEC), which control intrathymic T cell differentiation influencing the formation and maintenance of the immunological synapse. In addition to the proteins of the major histocompatibility complex (MHC), this structure is supported by several adhesion molecules. During the process of thymopoiesis, we previously showed that laminin-mediated interactions are involved in the entrance of T-cell precursors into the thymus, as well as migration of differentiating thymocytes within the organ. Using small interference RNA strategy, we knocked-down the ITGA6 gene (which encodes the CD49f integrin α-chain) in cultured human TEC, generating a decrease in the expression of the corresponding CD49f subunit, in addition to modulation in several other genes related to cell adhesion and migration. Thymocyte adhesion to TEC was significantly impaired, comprising both immature and mature thymocyte subsets. Moreover, we found a modulation of the MHC, with a decrease in membrane expression of HLA-ABC, in contrast with increase in the expression of HLA-DR. Interestingly, the knockdown of the B2M gene (encoding the β-2 microglobulin of the HLA-ABC complex) increased CD49f expression levels, thus unraveling the existence of a cross-talk event in the reciprocal control of CD49f and HLA-ABC. Our data suggest that the expression levels of CD49f may be relevant in the general control of MHC expression by TEC and consequently the corresponding synapse with developing thymocytes mediated by the T-cell receptor.
DOI: 10.6084/m9.figshare.5001302.v1
title: Increased placental sFlt-1 but unchanged PlGF expression in late-onset preeclampsia

description: <i>Objective</i>: To investigate whether differences between late-onset preeclampsia (PE) and intrauterine growth restriction (IUGR) can be explained by differential placental expression patters of sFlt-1, Flt-1, and placental growth factor (PlGF). <i>Methods</i>: Placental tissues and maternal blood samples from seven patients with PE, five IUGR, and seven age-matched controls were studied for mRNA and protein levels as well as protein localization and expression intensity. <i>Results</i>: Placental PlGF mRNA and protein expression were not altered by placental dysfunction while placental villous trophoblast expression intensity of PlGF was increased. <i>Conclusion</i>: High sFlt-1 concentrations may account for diminished maternal serum PlGF levels.
DOI: 10.6084/m9.figshare.5001305.v1
title: Optimal interim decision rules based on a binary surrogate outcome for adaptive biomarker-based trials in oncology

description: Adaptive enrichment designs represent a promising approach to evaluate targeted therapies, e.g. in oncology. They allow selection of the most promising target population in an interim analysis and then combination of the data from the two trial stages for the final proof of efficacy. Application of these designs is motivated by the assumption that there might be a biomarker-defined subgroup of patients with an increased treatment benefit as compared to the total patient population. If the primary outcome is a time-to-event variable and the respective event takes a relatively long time to be observed, it could be beneficial to select the most promising patient population based on an earlier available binary surrogate, e.g. response, to save time and costs. We propose an adaptive enrichment design which allows to implement such a trial setting. For this design, optimal decision rules are derived minimizing the expected loss incurred due to a false interim decision. These rules are compared to <i>ad hoc</i> rules in terms of selection probability and power within a simulation study which is motivated by a clinical trial example. Furthermore, the impact of the correlation between surrogate and primary outcome on power is investigated.
DOI: 10.6084/m9.figshare.5001296.v1
title: Small interference ITGA6 gene targeting in the human thymic epithelium differentially regulates the expression of immunological synapse-related genes

description: The thymus supports differentiation of T cell precursors. This process requires relocation of developing thymocytes throughout multiple microenvironments of the organ, mainly with thymic epithelial cells (TEC), which control intrathymic T cell differentiation influencing the formation and maintenance of the immunological synapse. In addition to the proteins of the major histocompatibility complex (MHC), this structure is supported by several adhesion molecules. During the process of thymopoiesis, we previously showed that laminin-mediated interactions are involved in the entrance of T-cell precursors into the thymus, as well as migration of differentiating thymocytes within the organ. Using small interference RNA strategy, we knocked-down the ITGA6 gene (which encodes the CD49f integrin α-chain) in cultured human TEC, generating a decrease in the expression of the corresponding CD49f subunit, in addition to modulation in several other genes related to cell adhesion and migration. Thymocyte adhesion to TEC was significantly impaired, comprising both immature and mature thymocyte subsets. Moreover, we found a modulation of the MHC, with a decrease in membrane expression of HLA-ABC, in contrast with increase in the expression of HLA-DR. Interestingly, the knockdown of the B2M gene (encoding the β-2 microglobulin of the HLA-ABC complex) increased CD49f expression levels, thus unraveling the existence of a cross-talk event in the reciprocal control of CD49f and HLA-ABC. Our data suggest that the expression levels of CD49f may be relevant in the general control of MHC expression by TEC and consequently the corresponding synapse with developing thymocytes mediated by the T-cell receptor.
DOI: 10.6084/m9.figshare.5001281
title: Uveal Melanoma Risk Factors: A Systematic Review of Meta-Analyses

description: <i>Purpose</i>: There is currently no clinical risk-assessment tool allowing identification of patients at risk for developing uveal melanoma (UM) who might benefit from regular screening. As a first step toward the elaboration of such a tool, we systematically reviewed UM risk factors already established by meta-analysis. <i>Methods</i>: Two reviewers independently screened Pubmed, Medline, Embase, and Web of Science from their respective inception dates until July 2016 using a combination of keywords and MeSH terms. Eligible studies were meta-analyses or systematic reviews providing pooled odds ratios (ORs) of risk factors for UM development or sufficient information to calculate them. Methodological quality was evaluated using the Assessment of Multiple Systematic Reviews tool. <i>Results</i>: Four meta-analyses with a mean methodological quality score of 65.9% (min: 54.5%; max: 72.7%) were included. The following significant risk factors were identified: atypical cutaneous nevi (OR 2.82, 95% CI 1.10–7.26), welding (OR 2.05, 95% CI 1.20–3.51), occupational cooking (OR 1.81, 95% CI 1.33–2.46), fair skin color (OR 1.80, 95% CI 1.31–2.47), light eye color (OR 1.75, 95% CI 1.31–2.34), common cutaneous nevi (OR 1.74, 95% CI 1.27–2.39), propensity to sunburn (OR 1.64, 95% CI 1.29–2.09), iris nevi (OR 1.53, 95% CI 1.03–2.27), and cutaneous freckles (OR 1.27, 95% CI 1.09–1.49). Non-significant factors included outdoor leisure activity, occupational sunlight exposure, latitude of birth, and hair color. <i>Conclusion</i>: Moderate quality of evidence determined nine significant risk factors for developing UM. Knowledge of these variables will assist researchers in the elaboration of a formal risk-assessment tool allowing clinicians to estimate susceptibility to the disease and necessity of regular screening.
DOI: 10.6084/m9.figshare.5001281.v1
title: Uveal Melanoma Risk Factors: A Systematic Review of Meta-Analyses

description: <i>Purpose</i>: There is currently no clinical risk-assessment tool allowing identification of patients at risk for developing uveal melanoma (UM) who might benefit from regular screening. As a first step toward the elaboration of such a tool, we systematically reviewed UM risk factors already established by meta-analysis. <i>Methods</i>: Two reviewers independently screened Pubmed, Medline, Embase, and Web of Science from their respective inception dates until July 2016 using a combination of keywords and MeSH terms. Eligible studies were meta-analyses or systematic reviews providing pooled odds ratios (ORs) of risk factors for UM development or sufficient information to calculate them. Methodological quality was evaluated using the Assessment of Multiple Systematic Reviews tool. <i>Results</i>: Four meta-analyses with a mean methodological quality score of 65.9% (min: 54.5%; max: 72.7%) were included. The following significant risk factors were identified: atypical cutaneous nevi (OR 2.82, 95% CI 1.10–7.26), welding (OR 2.05, 95% CI 1.20–3.51), occupational cooking (OR 1.81, 95% CI 1.33–2.46), fair skin color (OR 1.80, 95% CI 1.31–2.47), light eye color (OR 1.75, 95% CI 1.31–2.34), common cutaneous nevi (OR 1.74, 95% CI 1.27–2.39), propensity to sunburn (OR 1.64, 95% CI 1.29–2.09), iris nevi (OR 1.53, 95% CI 1.03–2.27), and cutaneous freckles (OR 1.27, 95% CI 1.09–1.49). Non-significant factors included outdoor leisure activity, occupational sunlight exposure, latitude of birth, and hair color. <i>Conclusion</i>: Moderate quality of evidence determined nine significant risk factors for developing UM. Knowledge of these variables will assist researchers in the elaboration of a formal risk-assessment tool allowing clinicians to estimate susceptibility to the disease and necessity of regular screening.
DOI: 10.6084/m9.figshare.5001179
title: Who is Bilingual? Snapshots Across the Lifespan

description: Children and older adult version of the Language and Social Background Questionnaire to accompany the paper "Who is Bilingual? Snapshots Across the Lifespan"
DOI: 10.6084/m9.figshare.5000960
title: 2016 Collaboration in Science PubMed data - AJE.xlsx

description: These data support the infographics found in our article, "Collaboration in Science Annual Report: New Data," found on the AJE Author Resource Center at http://www.aje.com/en/arc/research-collaboration-2016/. In particular, we focused on the top ten pairs of collaboration countries globally in 2016 (based on PubMed author affiliations), as well as specific lists for China, Japan, South Korea, Brazil, and Europe
DOI: 10.6084/m9.figshare.4996754
title: Tracy et al. 2017 Octocoral co-infection

description: CSV files of data on octocoral co-infection; surveys from Puerto Rico 2013<br>
DOI: 10.6084/m9.figshare.4996754.v1
title: Tracy et al. 2017 Octocoral co-infection

description: CSV files of data on octocoral co-infection; surveys from Puerto Rico 2013<br>
DOI: 10.6084/m9.figshare.4996370
title: Metabolite BridgeDb ID Mapping Database (20170504)

description: BridgeDb ID mapping database for metabolites, using HMDB 3.6, ChEBI 151, and Wikidata (4 May 2017) as data sources. No significant changes, and just updated mappings. See the attached QC for more details on the changes.
DOI: 10.6084/m9.figshare.4996415
title: Genome-guided identification of novel head-to-tail cyclized antimicrobial peptides, exemplified by the discovery of pumilarin

description: Supplementary Tables S2, S3 and S4. Genome-guided identification of novel head-to-tail cyclized antimicrobial peptides, exemplified by the discovery of pumilarin as published in <em>Microbial Genomics.</em>
DOI: 10.6084/m9.figshare.4996370.v1
title: Metabolite BridgeDb ID Mapping Database (20170504)

description: BridgeDb ID mapping database for metabolites, using HMDB 3.6, ChEBI 151, and Wikidata (4 May 2017) as data sources. No significant changes, and just updated mappings. See the attached QC for more details on the changes.
DOI: 10.6084/m9.figshare.4996415.v1
title: Genome-guided identification of novel head-to-tail cyclized antimicrobial peptides, exemplified by the discovery of pumilarin

description: Supplementary Tables S2, S3 and S4. Genome-guided identification of novel head-to-tail cyclized antimicrobial peptides, exemplified by the discovery of pumilarin as published in <em>Microbial Genomics.</em>
DOI: 10.6084/m9.figshare.4996217
title: Mumps virion

description: Mumps virion schematic representation. The I and V protein are not depicted. Created by Jonas Van Cleemput (2016)
DOI: 10.6084/m9.figshare.4996220
title: Supplementary Material for: Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury

description: Excitotoxicity plays a key role during insults to the developing brain such as neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults affect many thousands of infants each year. Excitotoxicity causes frank lesions due to cell death and gliosis and disturbs normal developmental process, leading to deficits in learning, memory, and social integration that persist into adulthood. Understanding the underlying processes of the acute effects of excitotoxicity and its persistence during brain maturation provides an opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and designing possible therapies. We applied mass spectrometry to provide metabolic profiles of brain tissue and plasma over time following an excitotoxic lesion (intracerebral ibotenate) to the neonatal (postnatal day 5) mouse brain. We found no differences between the plasma from the control (PBS-injected) and excitotoxic (ibotenate-injected) groups over time (on postnatal days 8, 9, 10, and 30). In the brain, we found that variations in amino acids (arginine, glutamine, phenylananine, and proline) and glycerophospholipids were sustaining acute and delayed (tertiary) responses to injury. In particular, the effect of the excitotoxic lesion on the normal profile of development was linked to alterations in a fingerprint of glycerophospolipids and amino acids. Specifically, we identified increases in the amino acids glutamine, proline, serine, threonine, tryptophan, valine, and the sphingolipid SM C26:1, and decreases in the glycerophospholipids, i.e., the arachidonic acid-containing phosphatidylcholine (PC aa) C30:2 and the PC aa C32:3. This study demonstrates that metabolic profiling is a useful approach to identify acute and tertiary effects in an excitotoxic lesion model, and generating a short list of targets with future potential in the hunt for identification, stratification, and possibly therapy.
DOI: 10.6084/m9.figshare.4996217.v1
title: Mumps virion

description: Mumps virion schematic representation. The I and V protein are not depicted. Created by Jonas Van Cleemput (2016)
DOI: 10.6084/m9.figshare.4996193
title: Supplementary Material for: The Peptidoglycan Recognition Proteins PGRPLA and PGRPLB Regulate Anopheles Immunity to Bacteria and Affect Infection by Plasmodium

description: Peptidoglycan recognition proteins (PGRPs) form a family of immune regulators that is conserved from insects to mammals. In the malaria vector mosquito <i>Anopheles</i><i>coluzzii</i>, the peptidoglycan receptor PGRPLC activates the immune-deficiency (Imd) pathway limiting both the microbiota load and <i>Plasmodium</i> infection. Here, we carried out an RNA interference screen to examine the role of all 7 <i>Anopheles</i> PGRPs in infections with <i>Plasmodium berghei</i> and <i>P. falciparum</i>. We show that, in addition to PGRPLC, PGRPLA and PGRPS2/PGRPS3 also participate in antiparasitic defenses, and that PGRPLB promotes mosquito permissiveness to <i>P. falciparum</i>. We also demonstrate that following a mosquito blood feeding, which promotes growth of the gut microbiota, PGRPLA and PGRPLB positively and negatively regulate the activation of the Imd pathway, respectively. Our data demonstrate that PGRPs are important regulators of the mosquito epithelial immunity and vector competence.
DOI: 10.6084/m9.figshare.4996169
title: Supplementary Material for: Genes Involved in Neurodevelopment, Neuroplasticity, and Bipolar Disorder: CACNA1C, CHRNA1, and MAPK1

description: <b><i>Background:</i></b> Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study, we tested the association of several single-nucleotide polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These genes are involved in monoamine-related pathways, as well as in dendrite development, neuronal survival, synaptic plasticity, and memory/learning. <b><i>Methods:</i></b> One hundred and thirty-two subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1. Distribution of alleles and block of haplotypes within each gene were compared in cases and controls. Interactions between variants in different loci were also tested. <b><i>Results:</i></b> Significant differences in the distribution of alleles between the cases and controls were detected for rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7, and rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement of variations within these genes in BPD. Finally, exploratory epistatic analyses demonstrated potential interactive effects, especially regarding variations in CACNA1C and CHRNA7. <b><i>Limitations:</i></b> Limited sample size and risk of false-positive findings. <b><i>Discussion:</i></b> Our data suggest a possible role of these 3 genes in BPD. Alterations of 1 or more common brain pathways (e.g., neurodevelopment and neuroplasticity, calcium signaling) may explain the obtained results.
DOI: 10.6084/m9.figshare.4996169.v1
title: Supplementary Material for: Genes Involved in Neurodevelopment, Neuroplasticity, and Bipolar Disorder: CACNA1C, CHRNA1, and MAPK1

description: <b><i>Background:</i></b> Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study, we tested the association of several single-nucleotide polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These genes are involved in monoamine-related pathways, as well as in dendrite development, neuronal survival, synaptic plasticity, and memory/learning. <b><i>Methods:</i></b> One hundred and thirty-two subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1. Distribution of alleles and block of haplotypes within each gene were compared in cases and controls. Interactions between variants in different loci were also tested. <b><i>Results:</i></b> Significant differences in the distribution of alleles between the cases and controls were detected for rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7, and rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement of variations within these genes in BPD. Finally, exploratory epistatic analyses demonstrated potential interactive effects, especially regarding variations in CACNA1C and CHRNA7. <b><i>Limitations:</i></b> Limited sample size and risk of false-positive findings. <b><i>Discussion:</i></b> Our data suggest a possible role of these 3 genes in BPD. Alterations of 1 or more common brain pathways (e.g., neurodevelopment and neuroplasticity, calcium signaling) may explain the obtained results.
DOI: 10.6084/m9.figshare.4994537
title: Framester

description: Framester is a frame-oriented knowledge graph serving as a hub for many linguistic and factual resources including FrameNet, WordNet, VerbNet, BabelNet, DBpedia, Yago, DOLCE-Zero. Framester creates a highly connected knowledge graph based on a formalisation of Fillmore's frame semantics, hence enabling full-fledged OWL querying and reasoning.
DOI: 10.6084/m9.figshare.4994537.v1
title: Framester

description: Framester is a hub between FrameNet, WordNet, VerbNet, BabelNet, DBpedia, Yago, DOLCE-Zero, as well as other resources. Framester does not simply creates a strongly connected knowledge graph, but also applies a rigorous formal treatment for Fillmore's frame semantics, enabling full-fledged OWL querying and reasoning on the created joint frame-based knowledge graph.
DOI: 10.6084/m9.figshare.4994537.v2
title: Framester

description: Framester is a hub between FrameNet, WordNet, VerbNet, BabelNet, DBpedia, Yago, DOLCE-Zero, as well as other resources. Framester does not simply creates a strongly connected knowledge graph, but also applies a rigorous formal treatment for Fillmore's frame semantics, enabling full-fledged OWL querying and reasoning on the created joint frame-based knowledge graph.
DOI: 10.6084/m9.figshare.4994456
title: Greenhouse gas emissions and dung weights vary with dung beetle species

description: Data used in the paper: "<b>Greenhouse gas emissions from dung pats vary with dung beetle species and with assemblage composition</b>"Data of GHG fluxes from dung pats and data for dry dung weights
DOI: 10.6084/m9.figshare.4994468
title: Physiological and self-reported disgust reactions to obesity

description: There is accumulating evidence that disgust plays an important role in prejudice toward individuals with obesity, but that research is primarily based on self-reported emotions. In four studies, we examined whether participants displayed a physiological marker of disgust (i.e. levator labii activity recorded using facial electromyography) in response to images of obese individuals, and whether these responses corresponded with their self-reported disgust to those images. All four studies showed the predicted self-reported disgust response toward images of obese individuals. Study 1 further showed that participants exhibited more levator activity to images of obese individuals than to neutral images. However, Studies 2–4 failed to provide any evidence that the targets’ body size affected levator responses. These findings suggest that disgust may operate at multiple levels, and that the disgust response to images of obese individuals may be more of a cognitive-conceptual one than a physiological one.