Presence of the Metabolic Syndrome Is Not a Better Predictor of Cardiovascular Disease Than the Sum of Its Components in HIV-Infected Individuals: Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study*

OBJECTIVE—It is much debated whether the metabolic syndrome contributes additional information over and above that provided by the individual components of the syndrome alone. Among HIV-infected individuals, we investigated whether any particular combinations of the components included in the definition of the metabolic syndrome are associated with a higher risk of cardiovascular disease (CVD)

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Extensive HIV-1 Intra-Host Recombination Is Common in Tissues with Abnormal Histopathology

There is evidence that immune-activated macrophages infected with the Human Immunodeficiency Virus (HIV) are associated with tissue damage and serve as a long-lived viral reservoir during therapy. In this study, we analyzed 780 HIV genetic sequences generated from 53 tissues displaying normal and abnormal histopathology. We found up to 50% of the sequences from abnormal lymphoid and macrophage rich non-lymphoid tissues were intra-host viral recombinants. The presence of extensive recombination, especially in non-lymphoid tissues, implies that HIV-1 infected macrophages may significantly contribute to the generation of elusive viral genotypes in vivo. Because recombination has been implicated in immune evasion, the acquisition of drug-resistance mutations, and alterations of viral co-receptor usage, any attempt towards the successful eradication of HIV-1 requires therapeutic approaches targeting tissue macrophages

A proteomics sample metadata representation for multiomics integration and big data analysis

The amount of public proteomics data is rapidly increasing but there is no standardized format to describe the sample metadata and their relationship with the dataset files in a way that fully supports their understanding or reanalysis. Here we propose to develop the transcriptomics data format MAGE-TAB into a standard representation for proteomics sample metadata. We implement MAGE-TAB-Proteomics in a crowdsourcing project to manually curate over 200 public datasets. We also describe tools and libraries to validate and submit sample metadata-related information to the PRIDE repository. We expect that these developments will improve the reproducibility and facilitate the reanalysis and integration of public proteomics datasets.publishedVersio

Validity of the Falls Risk for Older People in the Community (FROP‑Com) tool to predict falls and fall injuries for older people presenting to the emergency department after falling

The aims of this study were to (1) externally validate the accuracy of the Falls Risk for Older People in the Community (FROP-Com) falls risk assessment tool in predicting falls and (2) undertake initial validation of the accuracy of the FROPCom to predict injurious falls (requiring medical attention) in people aged ≥ 60 years presenting to emergency departments (EDs) after falling. Two hundred and thirteen participants (mean age = 72.4 years; 59.2% women) were recruited (control group of a randomised controlled trial). A FROP-Com assessment was completed at a home visit within 2 weeks of ED discharge. Data on falls and injurious falls requiring medical attention were collected via monthly falls calendars for the next 12 months. Predictive accuracy was evaluated using sensitivity and specificity of a high-risk FROP-Com classification (score ≥ 19) in predicting a fall and injurious falls requiring medical attention. Fifty per cent of participants fell, with 60.4% of falls requiring medical attention. Thirty-two per cent were classified as high, 49% as moderate and 19% low falls risk. Low sensitivity was achieved for the FROP-Com high-risk classification for predicting falls (43.4%) and injurious falls (34.4%), although specificity was high (79.4% and 78.6%, respectively). Despite the FROP-Com’s low predictive accuracy, the high fall rate and high falls risk of the sample suggest that older people who fall, present to ED and are discharged home are at high risk of future falls. In high-falls-risk populations such as in this study, the FROP-Com is not a valid tool for classifying risk of falls or injurious falls. Its potential value may instead be in identifying risk factors for falling to direct tailoring of falls prevention interventions to reduce future falls

Prevalence of metabolic syndrome among HIV-positive and HIV-negative populations in sub-Saharan Africa-a systematic review and meta-analysis

BACKGROUND: Metabolic syndrome (MetS) is a constellation of conditions that increase the risk of cardiovascular diseases. It is an emerging concern in sub-Saharan African (SSA) countries, particularly because of an increasingly aging population and lifestyle changes. There is an increased risk of MetS and its components among people living with Human immune deficiency syndrome (HIV) individuals; however, the prevalence of metabolic syndrome in the SSA population and its differential contribution by HIV status is not yet established. This systematic review and meta-analysis were conducted to estimate the pooled prevalence of metabolic syndrome in people living with HIV and uninfected populations, its variation by sub-components. METHODS: We performed a comprehensive search on major databases-MEDLINE (PubMed), EBSCOhost, and Cochrane Database of Systematic Reviews and Web of sciences for original epidemiological research articles that compared proportions of the MetS and its subcomponents between people living with HIV and uninfected patients and published between January 1990-December 2017. The inclusion criteria were adults aged ≥ 18 years, with confirmed HIV status. We assessed the risk of bias using a prevalence studies tool, and random effect meta-analyses were used to compute the pooled overall prevalence. RESULTS: A total of four cross-sectional studies comprising 496 HIV uninfected and 731 infected participants were included in the meta-analysis. The overall prevalence of MetS among people living with HIV was 21.5% (95% CI 15.09-26.86) versus uninfected 12.0% (95% CI 5.00-21.00%), with substantial heterogeneity. The reported relative risk estimate for MetS among the two groups was twofold (RR 1.83, 95% CI 0.98-3.41), with an estimated predictive interval of 0.15 to 22.43 and P = 0.055 higher for the infected population. Hypertension was the most prevalent MetS sub-components, with diverse proportions of people living with HIV (5.2-50.0%) and uninfected (10.0-59.0%) populations. CONCLUSIONS: The high range of MetS prevalence in the HIV-infected population compared to the uninfected population highlights the possible presence of HIV related drivers of MetS. Also, the reported high rate of MetS, irrespective of HIV status, indicates a major metabolic disorder epidemic that requires urgent prevention and management programs in SSA. Similarly, in the era of universal test and treat strategy among people living with HIV cohorts, routine check-up of MetS sub-components is required in HIV management as biomarkers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016045727

Disruption of a GATA4/Ankrd1 Signaling Axis in Cardiomyocytes Leads to Sarcomere Disarray: Implications for Anthracycline Cardiomyopathy

Doxorubicin (Adriamycin) is an effective anti-cancer drug, but its clinical usage is limited by a dose-dependent cardiotoxicity characterized by widespread sarcomere disarray and loss of myofilaments. Cardiac ankyrin repeat protein (CARP, ANKRD1) is a transcriptional regulatory protein that is extremely susceptible to doxorubicin; however, the mechanism(s) of doxorubicin-induced CARP depletion and its specific role in cardiomyocytes have not been completely defined. We report that doxorubicin treatment in cardiomyocytes resulted in inhibition of CARP transcription, depletion of CARP protein levels, inhibition of myofilament gene transcription, and marked sarcomere disarray. Knockdown of CARP with small interfering RNA (siRNA) similarly inhibited myofilament gene transcription and disrupted cardiomyocyte sarcomere structure. Adenoviral overexpression of CARP, however, was unable to rescue the doxorubicin-induced sarcomere disarray phenotype. Doxorubicin also induced depletion of the cardiac transcription factor GATA4 in cardiomyocytes. CARP expression is regulated in part by GATA4, prompting us to examine the relationship between GATA4 and CARP in cardiomyocytes. We show in co-transfection experiments that GATA4 operates upstream of CARP by activating the proximal CARP promoter. GATA4-siRNA knockdown in cardiomyocytes inhibited CARP expression and myofilament gene transcription, and induced extensive sarcomere disarray. Adenoviral overexpression of GATA4 (AdV-GATA4) in cardiomyocytes prior to doxorubicin exposure maintained GATA4 levels, modestly restored CARP levels, and attenuated sarcomere disarray. Interestingly, siRNA-mediated depletion of CARP completely abolished the Adv-GATA4 rescue of the doxorubicin-induced sarcomere phenotype. These data demonstrate co-dependent roles for GATA4 and CARP in regulating sarcomere gene expression and maintaining sarcomeric organization in cardiomyocytes in culture. The data further suggests that concurrent depletion of GATA4 and CARP in cardiomyocytes by doxorubicin contributes in large part to myofibrillar disarray and the overall pathophysiology of anthracycline cardiomyopathy

P2P, ad hoc and sensor networks – All the different or all the same?

Currently, data management technologies are in the process of finding their way into evolving networks, i.e. P2P, ad hoc and wireless sensor networks. We examine the properties, differences and commonalities of the different types of evolving networks, in order to enable the development of adequate technologies suiting their characteristics. We start with presenting definitions for the different network types, before arranging them in a network hierarchy, to gain a clear view of the area. Then, we analyze and compare the example applications for each of the types using different design dimensions. Based on this work, we finally present a comparison of P2P, ad hoc and wireless sensor networks