cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123362.v1
title: Supplementary Material for: Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

description: Microglial-neuronal interactions are essential for brain physiopathology. In this framework, recent data have changed the concept of microglia from essentially macrophagic cells to crucial elements in maintaining neuronal homeostasis and function through the release of neuroprotective molecules. Using proteomic analysis, here we identify copper-zinc superoxide dismutase (SOD1) as a protein produced and released by cultured rat primary microglia. Evidence for a neuroprotective role of microglia-derived SOD1 resulted from experiments in which primary cerebellar granule neurons (CGNs) were exposed to the dopaminergic toxin 6-hydroxydopamine (6-OHDA). Microglial conditioned medium, in which SOD1 had accumulated, protected CGNs from degeneration, and neuroprotection was abrogated by SOD1 inhibitors. These effects were replicated when exogenous SOD1 was added to a nonconditioned medium. SOD1 neuroprotective action was mediated by increased cell calcium from an external source. Further experiments demonstrated the specificity of SOD1 neuroprotection against 6-OHDA compared to other types of neurotoxic challenges. SOD1, constitutively produced and released by microglia through a lysosomal secretory pathway, is identified here for the first time as an essential component of neuroprotection mediated by microglia. This novel information is relevant to stimulating further studies of microglia-mediated neuroprotection in in vivo models of neurodegenerative diseases.
DOI: 10.6084/m9.figshare.5123365.v1
title: Supplementary Material for: Measuring Impact in Stereotactic and Functional Neurosurgery: An Analysis of the Top 100 Most Highly Cited Works and the Citation Classics in the Field

description: <b><i>Background:</i></b> Functional neurosurgery is a rapidly expanding field, with an exponentially growing literature. However, as with other fields, it can sometimes be difficult to distinguish between what is incremental and what is transformational. One way of measuring durable impact is examining the number of times a specific piece of scholarship is cited by others in the field. For example, papers that have been cited at least 400 times are designated ‘citation classics’ or works that, by virtue of very high citations, have been deemed of particular importance by researchers working in related disciplines. <b><i>Methods:</i></b> We queried a large, web-based scholarly database using 49 pre-selected search terms. The results for each individual query was manually examined for relevance to the functional neurosurgery field in order to arrive at the top 100 most highly cited papers as well as the citation classics. <b><i>Results:</i></b> The top 100 most cited papers, including 61 citation classics, in the stereotactic and functional neurosurgery field can be divided into 7 categories: functional/anatomic studies, technological innovations, and papers relevant to movement disorders, pain, psychiatry, radiosurgery and epilepsy. <b><i>Conclusions:</i></b> We have attempted to ascertain which papers have had, and continue to have, significant impact in our rapidly advancing field. At a minimum, the citation classics in functional neurosurgery provide both trainees and seasoned surgeons with a reading list of the ‘must-know’ works in the field – works whose influence have helped shape the direction of functional neurosurgery well into the future.
DOI: 10.6084/m9.figshare.5123371.v1
title: Supplementary Material for: Amyloid Oligomers Exacerbate Tau Pathology in a Mouse Model of Tauopathy

description: <b><i>Background:</i></b> We aimed to investigate the influence of oligomeric forms of β-amyloid (Aβ) and the influence of the duration of exposure on the development of tau phosphorylation. <b><i>Methods:</i></b> Aβ oligomers were injected intracranially either acutely into 5-month-old rTg4510 mice and tissue was collected 3 days later, or chronically into 3-month-old mice and tissue was collected 2 months later. Several forms of phosphorylated tau (p-tau), GSK3 (glycogen synthase kinase-3) and microglial and astrocyte activation were measured. <b><i>Results:</i></b> Acute injections of Aβ oligomers had no effect on p-tau epitopes but did result in elevation of phosphorylated/activated GSK3 (pGSK3). Chronic infusion of Aβ oligomers into the right hippocampus resulted in 3- to 4-fold elevations in several p-tau isoforms with no changes in total tau levels. A significant elevation in pGSK3 accompanied these changes. Microglial staining with CD68 paralleled the increase in tau phosphorylation, however, CD45 staining was unaffected by Aβ. Control experiments revealed that the infusion of Aβ from the minipumps was largely complete by 10 days after implantation. Thus, the elevation in p-tau 2 months after implantation implies that the changes are quite persistent. <b><i>Conclusion:</i></b> Soluble Aβ<sub>1-42</sub> oligomers have long-lasting effects on tau phosphorylation in the rTg4510 model, possibly due to elevations in GSK3. These data suggest that even brief elevations in Aβ production, may have enduring impact on the risk for tauopathy.
DOI: 10.6084/m9.figshare.5123344
title: Supplementary Material for: Medial Prefrontal Cortex Activity during the Extinction of Conditioned Fear: An Investigation Using Functional Near-Infrared Spectroscopy

description: The majority of fear conditioning studies in humans have focused on fear acquisition rather than fear extinction. For this reason only a few functional imaging studies on fear extinction are available. A large number of animal studies indicate the medial prefrontal cortex (mPFC) as neuronal substrate of extinction. We therefore determined mPFC contribution during extinction learning after a discriminative fear conditioning in 34 healthy human subjects by using functional near-infrared spectroscopy. During the extinction training, a previously conditioned neutral face (conditioned stimulus, CS+) no longer predicted an aversive scream (unconditioned stimulus, UCS). Considering differential valence and arousal ratings as well as skin conductance responses during the acquisition phase, we found a CS+ related increase in oxygenated haemoglobin concentration changes within the mPFC over the time course of extinction. Late CS+ trials further revealed higher activation than CS– trials in a cluster of probe set channels covering the mPFC. These results are in line with previous findings on extinction and further emphasize the mPFC as significant for associative learning processes. During extinction, the diminished fear association between a former CS+ and a UCS is inversely correlated with mPFC activity – a process presumably dysfunctional in anxiety disorders.
DOI: 10.6084/m9.figshare.5123353
title: Supplementary Material for: Influence of Age, Gender and Lifestyle in Lymphocyte Subsets: Report from the Spanish Gait-2 Study

description: <b><i>Introduction:</i></b> Flow cytometry analysis of lymphocyte subsets in peripheral blood is a common technique in diagnostic laboratories. Abnormal values have been identified in prevalent infections, autoimmune disorders and neoplastic diseases. Reference ranges for lymphocyte subsets of a healthy population from Spain are scarce. <b><i>Methods:</i></b> The study was performed on 319 healthy subjects, aged 4–88 years, from 709 individuals enrolled in the GAIT-2 Project (Genetic Analysis of Idiopathic Thrombophilia). Health status, age, sex, fertility, BMI and lifestyle (physical activity, cigarette smoking and ethanol intake) were assessed using standardized criteria. The percentage of lymphocyte subsets was determined using flow cytometry (Lymphogram™). Percentages of CD3+, CD4+, CD8+, CD19+, CD3–CD56+, CD3+CD4–CD8– double-negative (DN) T cells, CD3+CD4+CD8+ double-positive T cells and the CD4+/CD8+ ratio were recorded for each case. <b><i>Results:</i></b> Children had a significantly higher percentage of CD19+ and DN cells than adults. Women had a significantly higher percentage of CD3+ and CD4+ and a lower percentage of natural killer cells than men. Increases in BMI were inversely associated with the percentage of DN cells. Physical activity increased the percentage of lymphocytes and DN cells. Alcohol consumers had a lower percentage of CD19+ and DN cells, and a higher percentage of CD4+. <b><i>Conclusion:</i></b> This study provides reference ranges for lymphocyte subsets of healthy children and adults in a Mediterranean population (Spain) and determines the influence of lifestyle factors on these values.
DOI: 10.6084/m9.figshare.5123347
title: Supplementary Material for: Structural Analysis of the Leptospiral Sphingomyelinases: in silico and Experimental Evaluation of Sph2 as an Mg<sup>++</sup>-Dependent Sphingomyelinase

description: <i>Background:</i> Leptospiral sphingomyelinases are candidate virulence factors present only in pathogenic <i>Leptospira</i> spp. <i>Leptospira interrogans</i> serovar Lai encodes Sph1, Sph2, Sph3, Sph4 and SphH. Except for Sph4, they all possess the exo-endo-phosphatase domain that groups them under the DNase I superfamily. <i>Methods, Results and Conclusions:</i> Modeling of exo-endo-phosphatase domains reveals high-level structural similarity of Sph2 with the crystal structure of SmcL and BC SMase sphingomyelinases from <i>Listeria ivanovii</i> and <i>Bacillus cereus, </i>respectively. A β-hairpin loop, essential for host cell membrane interaction, is absent in leptospiral sphingomyelinases. Instead, several aromatic amino acids were oriented outward from the surface of these molecules and formed clusters of hydrophobic regions that possibly enables the anchoring of these molecules into the host cell membrane, as demonstrated in Sph2 and Sph3. Sph2 is unique and possesses the Mg<sup>++</sup>-binding Glu53 residue in the metal-binding site and two His residues (His151 and His286) in the catalytic site. We demonstrate experimentally the Mg<sup>++</sup>-dependent hemolysis of erythrocytes by rSph2 and its ability to cleave sphingomyelin to ceramide. Anti-Sph2 antibodies neutralized the hemolytic activity of Sph2. In conclusion, we provide evidence showing that Sph2 is a Mg<sup>++</sup>-dependent hemolysin with both sphingomyelinase and hemolytic activities.
DOI: 10.6084/m9.figshare.5123350
title: Supplementary Material for: BMI Trends, Socioeconomic Status, and the Choice of Dataset

description: <i>Objective:</i>This study is a descriptive investigation of trends in BMI in the USA over time, across race/ethnicity, gender, and socioeconomic status (SES) groups, and across different datasets. <i>Methods: </i>The study analyzes micro-level data from three widely used cross-sectional US health datasets: the National Health and Nutrition Examination Survey (NHANES), the National Health Interview Survey (NHIS), and the Behavioral Risk Factor Surveillance System (BRFSS), from the 1970s to 2008. Consistent race/ethnicity and SES groups are constructed for all datasets. SES is measured by education and income. Focusing on adults aged 20–74 years, the study estimates BMI time trends, distributional shifts, and incremental associations (gradients) with SES. <i>Results:</i> SES-BMI gradients are consistently larger for women than for men, differ across race/ethnicity groups, and are similar across datasets. Trends in mean BMI are comparable across White, Black and Hispanic males, while Hispanic females range between White and Black females. Self-reported BMI in the NHANES differs markedly from self-reports in the NHIS and BRFSS. <i>Conclusion:</i> The NHANES, NHIS, and BRFSS provide similar evidence regarding BMI trends over time and across race/ethnicity, gender, and SES groups. Racial disparities in BMI remain after adjusting for SES and should be studied further.
DOI: 10.6084/m9.figshare.5123356
title: Supplementary Material for: Enhancement of the Antitumor Effect on Combination Therapy of an Anticancer Drug and Its Antibody against Carcinoembryonic Antigen

description: <i>Background:</i> Carcinoembryonic antigen (CEA) is frequently overexpressed in various types of human cancers and is associated with cell adhesion. There are three possible mechanisms of cancer therapy that employ anti-CEA antibody (Ab): Ab-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) or the prevention of CEA interaction with the extracellular matrix and/or intercellular adhesion molecules resulting in anoikis. In this study, the effect of C2-74, a human anti-CEA monoclonal Ab was evaluated. <i>Methods:</i> ADCC, CDC and anoikis assays in combination with C2-74 and an anticancer drug (5-fluorouracil or cisplatin) were investigated using tumor cell lines (MKN-45, MKN-74 and KATO III). In the anoikis assay, other human anti-CEA Abs and mouse anti-CEA-related cell adhesion molecule 6 Abs were also investigated using HLC-1 cells. <i>Results:</i> Additive cytotoxicity was observed when the anticancer drug and C2-74 on tumor cells were combined in the CDC assays, whereas in the anoikis assay, no such additive effect was observed. Anti-CEA-related cell adhesion molecule 6 Abs, but not anti-CEA Abs, accelerated anoikis in HLC-1 cells. <i>Conclusion:</i> A mechanism for the additive antitumor effect when an anticancer drug and C2-74 are combined is indicated mainly by CDC activity but is irrelevant to anoikis in tumor cells.
DOI: 10.6084/m9.figshare.5123338
title: Supplementary Material for: Experimental and Modeling Analysis of <i> Synechocystis </i>sp. PCC 6803 Growth

description: <i>Background/Aims:</i> The influence of different parameters such as temperature, irradiance, nitrate concentration, pH, and an external carbon source on <i>Synechocystis </i>PCC 6803 growth was evaluated. <i>Methods:</i> 4.5-ml cuvettes containing 2 ml of culture, a high-throughput system equivalent to batch cultures, were used with gas exchange ensured by the use of a Parafilm™ cover. The effect of the different variables on maximum growth was assessed by a multi-way statistical analysis. <i>Results:</i> Temperature and pH were identified as the key factors. It was observed that <i>Synechocystis</i> cells have a strong influence on the external pH. The optimal growth temperature was 33°C while light-saturating conditions were reached at 40 µE·m<sup>–2</sup>·s<sup>–1</sup>. <i>Conclusion:</i> It was demonstrated that <i>Synechocystis</i> exhibits a marked difference in behavior between autotrophic and glucose-based mixotrophic conditions, and that nitrate concentrations did not have a significant influence, probably due to endogenous nitrogen reserves. Furthermore, a dynamic metabolic model of <i>Synechocystis</i> photosynthesis was developed to gain insights on the underlying mechanism enabling this cyanobacterium to control the levels of external pH. The model showed a coupled effect between the increase of the pH and ATP production which in turn allows a higher carbon fixation rate.
DOI: 10.6084/m9.figshare.5123341
title: Supplementary Material for: ARIEL and AMELIA: Testing for an Accumulation of Rare Variants Using Next-Generation Sequencing Data

description: <i>Objectives:</i> There is increasing evidence that rare variants play a role in some complex traits, but their analysis is not straightforward. Locus-based tests become necessary due to low power in rare variant single-point association analyses. In addition, variant quality scores are available for sequencing data, but are rarely taken into account. Here, we propose two locus-based methods that incorporate variant quality scores: a regression-based collapsing approach and an allele-matching method. <i>Methods:</i> Using simulated sequencing data we compare 4 locus-based tests of trait association under different scenarios of data quality. We test two collapsing-based approaches and two allele-matching-based approaches, taking into account variant quality scores and ignoring variant quality scores. We implement the collapsing and allele-matching approaches accounting for variant quality in the freely available ARIEL and AMELIA software. <i>Results:</i> The incorporation of variant quality scores in locus-based association tests has power advantages over weighting each variant equally. The allele-matching methods are robust to the presence of both protective and risk variants in a locus, while collapsing methods exhibit a dramatic loss of power in this scenario. <i>Conclusions:</i> The incorporation of variant quality scores should be a standard protocol when performing locus-based association analysis on sequencing data. The ARIEL and AMELIA software implement collapsing and allele-matching locus association analysis methods, respectively, that allow the incorporation of variant quality scores.
DOI: 10.6084/m9.figshare.5123350.v1
title: Supplementary Material for: BMI Trends, Socioeconomic Status, and the Choice of Dataset

description: <i>Objective:</i>This study is a descriptive investigation of trends in BMI in the USA over time, across race/ethnicity, gender, and socioeconomic status (SES) groups, and across different datasets. <i>Methods: </i>The study analyzes micro-level data from three widely used cross-sectional US health datasets: the National Health and Nutrition Examination Survey (NHANES), the National Health Interview Survey (NHIS), and the Behavioral Risk Factor Surveillance System (BRFSS), from the 1970s to 2008. Consistent race/ethnicity and SES groups are constructed for all datasets. SES is measured by education and income. Focusing on adults aged 20–74 years, the study estimates BMI time trends, distributional shifts, and incremental associations (gradients) with SES. <i>Results:</i> SES-BMI gradients are consistently larger for women than for men, differ across race/ethnicity groups, and are similar across datasets. Trends in mean BMI are comparable across White, Black and Hispanic males, while Hispanic females range between White and Black females. Self-reported BMI in the NHANES differs markedly from self-reports in the NHIS and BRFSS. <i>Conclusion:</i> The NHANES, NHIS, and BRFSS provide similar evidence regarding BMI trends over time and across race/ethnicity, gender, and SES groups. Racial disparities in BMI remain after adjusting for SES and should be studied further.
DOI: 10.6084/m9.figshare.5123335
title: Supplementary Material for: MicroRNA-372 Is Associated with Poor Prognosis in Colorectal Cancer

description: <i>Objective:</i> MicroRNA-372 <i>(miR-372)</i> is reportedly shown to be an oncogene in human testicular germ cell tumors and gastric cancers, but its expression in colorectal cancer (CRC) is not yet determined. This study investigated the clinical significance of <i>miR-372</i> expression in CRC. <i>Methods: </i>qRT-PCR was used to evaluate <i>miR-372</i> in 144 CRC patients, and large tumor suppressor 2 <i>(LATS2)</i> expression was also examined as the likely target gene of <i>miR-372</i>. In vitroassays were performed to evaluate the biological function of<i> miR-372. </i><i>Results: </i>Multivariate analysis indicated that high<i> miR-372</i> expression was an independent prognostic factor (p = 0.006). High <i>miR-372</i> expression was associated with synchronous liver metastasis (p = 0.035). We found an inverse relationship between<i> miR-372 </i>and <i>LATS2 by</i> qRT-PCR (p = 0.007) and immunohistochemistry (p = 0.042) using CRC tissue samples. Furthermore, pre-miR-372 led to a decrease in the LATS2 protein and an increase in proliferative activity of LoVo cells. We also found a significant association between low <i>LATS2</i> expression and liver metastasis (p = 0.042). <i>Conclusions:</i> This study suggested that <i>miR-372</i> was a novel independent prognostic factor in CRC. Our data suggest that <i>LATS2 </i>may serve as one of the target genes of <i>miR-372 </i>in clinical CRC tissues.
DOI: 10.6084/m9.figshare.5123332
title: Supplementary Material for: Clinical Benefit of High-Sensitivity KRAS Mutation Testing in Metastatic Colorectal Cancer Treated with Anti-EGFR Antibody Therapy

description: <b><i>Objective:</i></b> We compared high-sensitivity KRAS mutation testing with direct sequencing for predicting the efficacy of antiepidermal growth factor receptor antibodies in patients with metastatic colorectal cancer (mCRC). <b><i>Methods:</i></b> We analyzed the KRAS status in 61 tumors from cetuximab-treated mCRC patients by both direct sequencing and a high-sensitivity method: 2-step PCR restriction fragmentation length polymorphism (RFLP). Therapeutic effects in each mutational status were evaluated. <b><i>Results:</i></b> The incidences of KRAS mutations determined by direct sequencing and 2-step PCR RFLP were 34.4 and 52.5%, respectively (p = 0.02). Patients were categorized into 3 groups [W/W, wild-type by both methods (n = 29); W/M, wild-type by direct sequencing, detected mutation by 2-step PCR RFLP (n = 11); M/M, mutant-type by both methods (n = 21)]. The response rate for cetuximab in the W/M group (0%) was the same as that in the M/M group, and was significantly lower than in the W/W group (41.4%) (p &lt; 0.001). Progression-free survival in the W/M group (11.0 weeks) was similar to that in the M/M group (8.0 weeks), and was significantly shorter than in the W/W group (18.0 weeks) (p &lt; 0.002). <b><i>Conclusion:</i></b> High-sensitivity KRAS mutation testing is useful for selecting true responders to cetuximab.
DOI: 10.6084/m9.figshare.5123329
title: Supplementary Material for: Spatiotemporal Distribution of Neurovascular Alignment in Remodeling Adult Rat Mesentery Microvascular Networks

description: An emerging area of microvascular research focuses on the links between neural and vascular patterning. However, the functional dependence between vascular and neural growth in adult tissues remains underinvestigated. The objective of this study was to determine the spatial and temporal coordination between vascular and neural networks over a time course of adult microvascular growth. Mesentery tissues from adult male Wistar rats were harvested prior to stimulation, and 2, 10 and 30 days after angiogenesis stimulated by mast cell degranulation. Tissues were immunolabeled for PECAM (endothelial cell marker) and class III β-tubulin (peripheral nerve marker). Neurovascular alignment was quantified per vessel category: arterioles (&gt;20 µm), pre-capillary arterioles (10–20 µm), post-capillary venules (10–20 µm), venules (&gt;20 µm), capillaries (&lt;10 µm) and capillary sprouts. Neurovascular alignment along pre-capillary arterioles, capillaries, post-capillary venules and venules was decreased compared to unstimulated levels on days 2 and 10. These decreases inversely correlated with increases in vessel density per vessel category. By day 30, alignment either returned to unstimulated levels or was increased compared to day 10. These results suggest that neurovascular alignment arises after microvascular network growth and is present along arterioles, venules and even capillaries.