cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123392
title: Supplementary Material for: A Critical Evaluation of the Preventive Effect of Antiviral Therapy on the Development of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C or B: A Novel Approach by Using Meta-Regression

description: <b><i>Background:</i></b> The extent of the effect of antiviral therapy and its predictors in preventing hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C (CHC) or B (CHB) remain unclear. <b><i>Methods:</i></b> We conducted a systemic review and meta-analysis of published randomized controlled trials (RCTs) and cohort studies (CSs) up to December 2010. Preventive efficacy was measured as absolute reduction in 3- and 5-year cumulative incidence of HCC with antiviral therapy. Predictors for efficacy were identified by using meta-regression. <b><i>Results:</i></b> Twenty-two studies (5 RCTs; 17 CSs) were included for analysis. Antiviral therapy reduced 5-year cumulative incidence of HCC by 7.8% (95% CI 4.6–11.1; p &lt; 0.0001) in patients with CHC and by 7.1% (95% CI 4.1–10.2; p &lt; 0.0001) in patients with CHB. The efficacy was significant as early as 3 years after antiviral therapy. While adjusting for available study-level, patient and virological factors, RCT and higher sustained virological response were identified as pertinent predictors of superior preventive efficacy in patients with CHC, whereas lower hepatitis B virus e antigen seropositivity was identified in patients with CHB. Antiviral therapy did not result in differential preventive efficacy between cirrhotic and noncirrhotic patients with CHC or CHB. <b><i>Conclusion:</i></b> Antiviral therapy can reduce 3- and 5-year cumulative incidence of HCC in patients with CHC or CHB.
DOI: 10.6084/m9.figshare.5123386
title: Supplementary Material for: The Release of a Troop of Rehabilitated Vervet Monkeys <i>(Chlorocebus aethiops)</i> in KwaZulu-Natal, South Africa: Outcomes and Assessment

description: Rehabilitation and release have become central to the management and welfare of primate species in South Africa such as the vervet monkey <i>(Chlorocebus aethiops)</i>. However, limited research means that it is unknown whether rehabilitation is a successful management strategy for this species. This study describes the release of a troop of rehabilitated vervet monkeys and evaluates the results of 1 year of post-release monitoring. The released animals exhibited wild behaviours and established a home range. Survival could not be adequately evaluated due to the high number of untraceable animals, and troop composition was significantly different from that of wild troops. Improvement may be gained by radio-collaring more animals using improved technology, ensuring that troop composition is comparable to wild troops, excluding ex-pets from re-introduction and a more detailed assessment of the release site.
DOI: 10.6084/m9.figshare.5123389
title: Supplementary Material for: A Methyl-Deficient Diet Modifies Early B Cell Development

description: A functional methyl group donor is essential for the epigenetic regulation of all biological events due to the importance of DNA methylation and histone methylation as an epigenetic marker. However, the epigenetic alterations in the immune system due to methyl donor deficiency are not well known. In this study, we tried to address this question by studying the lymphocyte development and DNA methylation changes caused by a methyl-deficient diet (MDD). We fed one group of C57BL/6J mice with a methyl-sufficient diet (MSD) and the other group with an MDD for 5 months. Flow cytometry analyses of their immune systems showed a decrease in B220+ IgM+ (immature B) cells and an increase in B220+ IgM– (pro/pre-B) cells in the bone marrow of mice fed an MDD. By means of an in vitro OP9 coculture system, we recognized that this B220+ IgM– cell fraction from the MDD has an intrinsic developmental defect. When we quantitatively measured the mRNA expression levels of transcription factors and recombination machinery related to B cell development in the B220+ IgM– cell fraction of their bone marrow, we found that <i>ADA, EBF1, DNTT </i>and <i>Pax5 </i>mRNA expression levels were significantly downregulated in mice fed with an MDD. In addition, there was a drastic decrease in histone methylation profile H3K4me3 in the <i>Pax5 </i>and <i>EBF1 </i>promoters in these B220+ IgM– B cells. However, CpG-DNA methylation profiles had not changed and this revealed that these two promoters are demethylated even under an MSD condition. We also found changed expression levels of the <i>Polycomb </i>group genes <i>(mel18</i>, <i>bmi1</i>, <i>Pc1</i>, <i>Pc2</i>, <i>Ring1A</i>, <i>Ring1B</i>, <i>Ph1)</i> on semi-quantitative RT-PCR. These results indicate that under an MDD condition, early B cell development in bone marrow is easily affected by epigenetic alterations.
DOI: 10.6084/m9.figshare.5123398.v1
title: Supplementary Material for: Integrated Analysis of Gene Copy Number, Copy Neutral LOH, and microRNA Profiles in Adult Acute Lymphoblastic Leukemia

description: We adopted an integrated analysis of gene copy number alterations (CNAs), copy number neutral loss of heterozygosity (CNN LOH), and microRNA (miRNA) profiling in 21 adult acute lymphoblastic leukemia (ALL) patients. This study revealed the most frequent CNAs to be at chromosomes 9p, 7, and 17 and recurrent CNN LOH at 5p, 9p, and Xq. As for the most differentially expressed miRNAs, they included 8 upregulated and 14 downregulated miRNAs, of which miR-148a at 7p15.2, miR-22 at 17p13.3, miR-223 at Xq12, as well as miR-101-2 at 9p24.1 exhibited recurrent CNAs or CNN LOH. miR-101-2 was recurrently downregulated, and although the related CNN LOH was detected only in <i>BCR-ABL1</i> negative cases (2/14), deletions of miR-101-2 were observed solely in <i>BCR-ABL1</i> positive cases (4/7). Finally, <i>BCR-ABL1</i> positive cases, in contrast to negative ones, were characterized by slightly, but still significantly, higher expression levels of miR-29b.
DOI: 10.6084/m9.figshare.5123380
title: Supplementary Material for: Synergistic Effects of Erlotinib and Everolimus on Bronchial Carcinoids and Large-Cell Neuroendocrine Carcinomas with Activated EGFR/AKT/mTOR Pathway

description: <b><i>Background:</i></b> Epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) are crucial targets in cancer therapy. Combined inhibition of both targets yielded synergistic effects in vitro and in vivo in several cancer entities. However, the impact of EGFR and mTOR expression and combined inhibition in neuroendocrine lung tumors other than small-cell lung cancer remains unclear. <b><i>Material and Methods:</i></b> Expression and activation of EGFR/AKT/mTOR pathway constituents were investigated in typical and atypical bronchial carcinoid (AC) tumors and large-cell neuroendocrine lung carcinomas (LCNEC) by immunohistochemistry in 110 tumor samples, and correlated with clinicopathological parameters and patient survival. Cytotoxicity of mTOR inhibitor everolimus and EGFR inhibitor erlotinib alone and in combination was assessed using growth inhibition assay in NCI-H720 AC and SHP-77 LCNEC cells. Cell cycle phase distribution was determined by FACS. Apoptosis-associated activation of caspase-3/7 was measured by Caspase-Glo® assay. Activity status of EGFR and mTOR pathway components was analyzed by immunoblotting. <b><i>Results:</i></b> Activation of the EGFR/AKT/mTOR axis could be demonstrated in all entities and was significantly increased in higher grade tumors. Neoadjuvant chemotherapy correlated significantly with p-AKT expression and p-ERK loss. Erlotinib combined with everolimus exerted synergistic combination effects in AC and LCNEC cells by induction of apoptosis, while cell cycle phase distribution remained unaffected. These effects could be explained by synergistic downregulation of phospho-mTOR, phospho-p70S6 kinase and phospho-AKT expression by everolimus and erlotinib. <b><i>Conclusions:</i></b> Our study indicates that EGFR and mTOR are clinically important targets in bronchial neuroendocrine tumors, and further in vivo and clinical exploration of combined inhibition is warranted.
DOI: 10.6084/m9.figshare.5123383
title: Supplementary Material for: Evaluation of Falls Risk in Community-Dwelling Older Adults Using Body-Worn Sensors

description: <b><i>Background:</i></b> Falls are the most common cause of injury and hospitalization and one of the principal causes of death and disability in older adults worldwide. This study aimed to determine if a method based on body-worn sensor data can prospectively predict falls in community-dwelling older adults, and to compare its falls prediction performance to two standard methods on the same data set. <b><i>Methods:</i></b> Data were acquired using body-worn sensors, mounted on the left and right shanks, from 226 community-dwelling older adults (mean age 71.5 ± 6.7 years, 164 female) to quantify gait and lower limb movement while performing the ‘Timed Up and Go’ (TUG) test in a geriatric research clinic. Participants were contacted by telephone 2 years following their initial assessment to determine if they had fallen. These outcome data were used to create statistical models to predict falls. <b><i>Results:</i></b> Results obtained through cross-validation yielded a mean classification accuracy of 79.69% (mean 95% CI: 77.09–82.34) in prospectively identifying participants that fell during the follow-up period. Results were significantly (p &lt; 0.0001) more accurate than those obtained for falls risk estimation using two standard measures of falls risk (manually timed TUG and the Berg balance score, which yielded mean classification accuracies of 59.43% (95% CI: 58.07–60.84) and 64.30% (95% CI: 62.56–66.09), respectively). <b><i>Conclusion:</i></b> Results suggest that the quantification of movement during the TUG test using body-worn sensors could lead to a robust method for assessing future falls risk.
DOI: 10.6084/m9.figshare.5123377
title: Supplementary Material for: Remineralisation by Chewing Sugar-Free Gums in a Randomised, Controlled in situ Trial Including Dietary Intake and Gauze to Promote Plaque Formation

description: Remineralisation has been shown to be an effective mechanism of preventing the progression of enamel caries. The aim of this double-blind, randomised, cross-over in situ study was to compare enamel remineralisation by chewing sugar-free gum with or without casein phosphopeptide amorphous calcium phosphate (CPP-ACP) where the enamel lesions were exposed to dietary intake and some were covered with gauze to promote plaque formation. Participants wore removable palatal appliances containing 3 recessed enamel half-slabs with subsurface lesions covered with gauze and 3 without gauze. Mineral content was measured by transverse microradiography, and plaque composition was analysed by real-time polymerase chain reaction. For both the gauze-free and gauze-covered lesions, the greatest amount of remineralisation was produced by the CPP-ACP sugar-free gum, followed by the gum without CPP-ACP and then the no-gum control. Recessing the enamel in the appliance allowed plaque accumulation without the need for gauze. There was a trend of less remineralisation and greater variation in mineral content for the gauze-covered lesions. The cell numbers of total bacteria and streptococci were slightly higher in the plaque from the gauze-covered enamel for 2 of the 3 treatment legs; however, there was no significant difference in<i> Streptococcus mutans</i> cell numbers. In conclusion, chewing sugar-free gum containing CPP-ACP promoted greater levels of remineralisation than a sugar-free gum without CPP-ACP or a no-gum control using an in situ remineralisation model including dietary intake irrespective of whether gauze was used to promote plaque formation or not.
DOI: 10.6084/m9.figshare.5123380.v1
title: Supplementary Material for: Synergistic Effects of Erlotinib and Everolimus on Bronchial Carcinoids and Large-Cell Neuroendocrine Carcinomas with Activated EGFR/AKT/mTOR Pathway

description: <b><i>Background:</i></b> Epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) are crucial targets in cancer therapy. Combined inhibition of both targets yielded synergistic effects in vitro and in vivo in several cancer entities. However, the impact of EGFR and mTOR expression and combined inhibition in neuroendocrine lung tumors other than small-cell lung cancer remains unclear. <b><i>Material and Methods:</i></b> Expression and activation of EGFR/AKT/mTOR pathway constituents were investigated in typical and atypical bronchial carcinoid (AC) tumors and large-cell neuroendocrine lung carcinomas (LCNEC) by immunohistochemistry in 110 tumor samples, and correlated with clinicopathological parameters and patient survival. Cytotoxicity of mTOR inhibitor everolimus and EGFR inhibitor erlotinib alone and in combination was assessed using growth inhibition assay in NCI-H720 AC and SHP-77 LCNEC cells. Cell cycle phase distribution was determined by FACS. Apoptosis-associated activation of caspase-3/7 was measured by Caspase-Glo® assay. Activity status of EGFR and mTOR pathway components was analyzed by immunoblotting. <b><i>Results:</i></b> Activation of the EGFR/AKT/mTOR axis could be demonstrated in all entities and was significantly increased in higher grade tumors. Neoadjuvant chemotherapy correlated significantly with p-AKT expression and p-ERK loss. Erlotinib combined with everolimus exerted synergistic combination effects in AC and LCNEC cells by induction of apoptosis, while cell cycle phase distribution remained unaffected. These effects could be explained by synergistic downregulation of phospho-mTOR, phospho-p70S6 kinase and phospho-AKT expression by everolimus and erlotinib. <b><i>Conclusions:</i></b> Our study indicates that EGFR and mTOR are clinically important targets in bronchial neuroendocrine tumors, and further in vivo and clinical exploration of combined inhibition is warranted.
DOI: 10.6084/m9.figshare.5123368
title: Supplementary Material for: Visualization of Sex-Dimorphic Changes in the Intestinal Transcriptome of <b><i>Fabp2</i></b> Gene-Ablated Mice

description: <b><i>Background/Aims:</i></b> Sex differences in gene expression program have not been effectively explored at the transcriptome level. We aimed to develop a method for the analysis of transcriptome data to identify sex differences and sex-dimorphic responses to experimental conditions in mice. <b><i>Methods:</i></b> Profiling of the small intestine transcriptome of chow-fed C57BL/6J (wild-type, WT) and <i>Fabp2</i><sup>–/–</sup> mice was carried out by microarray analysis. Sex-specific and androgynous effects of <i>Fabp2</i> gene ablation were examined using FlexArray V1.6 by comparing WT to <i>Fabp2</i><sup>–/–</sup> mice. The data generated were exported into a single spreadsheet, collated and transformed to identify the differentially expressed genes for pathway analysis. <b><i>Results:</i></b> The method revealed enrichment of 17 sex-dimorphic pathways in the small intestine of WT mice compared to only 4 in <i>Fabp2</i><sup>–/–</sup> mice. Comparison of the effects of Fabp2 loss in individual sexes revealed a male-specific upregulation of 5 pathways involved in the production of unsaturated fatty acids, and a female-specific downregulation of pathways involved in xenobiotic metabolism. <b><i>Conclusions:</i></b> Our approach detected the common as well as sex-differential pathways that are modified due to the loss of Fabp2. These findings suggest that the pathways involved in nutrient and xenobiotic metabolism in the intestine are regulated by sex-specific mechanisms.
DOI: 10.6084/m9.figshare.5123371
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.5123362
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
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.5123359
title: Supplementary Material for: An in vitro Comparison of Detection Methods for Approximal Carious Lesions in Primary Molars

description: <i>Background/Aims:</i> This study aimed to compare and contrast in vitro six methods to determine the most accurate method for detecting approximal carious lesions in primary molars. <i>Methods:</i> Extracted primary molars (n = 140) were stored in 0.02% chlorhexidine solution and mounted in light-cured resin in pairs. The six carious lesion detection methods used by the three examiners to assess approximal carious lesions were visual inspection, digital radiography, two transillumination lights (SDI and NSK), and two laser fluorescence instruments (CDD and DDP). Five damaged teeth were discarded. The teeth (n = 135) were sectioned, serially ground, and examined under light microscopy using Downer’s histological (HST) criteria as the gold standard. Intra- and inter-examiner reliability, agreement with HST, specificity, sensitivity, receiver operating characteristic (ROC) curves, and areas under the curve were calculated. <i>Results:</i> This study found visual inspection to be the most accurate method when validated by histology. Transillumination with NSK light had the highest specificity, and digital radiography had the highest sensitivity for detecting enamel and/or dentinal carious lesions. Combining specificity and sensitivity into the area under ROC curves, enamel plus dentinal lesions were detected most accurately by visual inspection followed by digital radiography; dentinal lesions were detected most accurately by digital radiography followed by visual inspection. <i>Conclusions:</i> None of the four newly developed methods can be recommended as suitable replacements for visual inspection and digital radiography in detecting carious lesions on approximal surfaces of primary molars, and further developmental work is needed.