bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipidome association with vascular disease and inflammation in HIV+ Ugandan children
Authors: Dirajlal-Fargo Sahera , Sattar Abdus , Yu Jiao , Albar Zainab , Chaves Fabio C. , Riedl Ken , Kityo Cissy , Bowman Emily , McComsey Grace A. , Funderburg Nicholas 
Published: April 2021

Objective:
HIV infection and antiretroviral therapy (ART) have both been linked to dyslipidemia and increased cardiovascular disease (CVD). The relationships among the lipidome, immune activation, and subclinical vascular disease in children with perinatally acquired HIV (PHIV) have not been investigated.

Methods:
Serum lipid composition, including 13 lipid classes constituting 850 different lipid species were measured by direct infusion-tandem mass spectrometry in samples from 20 ART-treated PHIV and 20 age-matched and sex-matched HIV− Ugandan children. All participants were between 10 and 18 years of age with no other known active infections. PHIVs had HIV-1 RNA level 50 copies/ml or less. In addition, common carotid artery intima--media thickness (IMT), as well as plasma marker of systemic inflammation (hsCRP, IL6, sTNFRa I), monocyte activation (soluble CD14 and CD163), and T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+) were evaluated.

Results:
Median age (Q1, Q3) of study participants was 13 years (11, 15), 37% were boys, 75% were on an NNRTI-based ART regimen. The concentrations of cholesterol ester, LCER, phosphatidylcholines, and sphingomyelin lipid classes were significantly increased in serum of PHIV compared with HIV (P≤0.04). Biomarkers associated with CVD risk including hsCRP, sCD163, and T-cell activation were directly correlated with lipid species in PHIV (P ≤ 0.04). Contents of free fatty acids including palmitic (16 : 0), stearic (18 : 0), and arachidic acid (20 : 0) were positively correlated with IMT in PHIV.

Conclusion:
Serum lipidome is altered in young virally suppressed PHIV on ART. A direct association between inflammation and lipid species known to be associated with CVD was observed.
Permianibacter fluminis sp. nov., isolated from a freshwater stream
Authors: Park Miri S. , Song Jaeho , Chang Jaeho , Joung Yochan , Kang Ilnam , Cho Jang-Cheon 
Published: April 2021

A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, designated as IMCC34836T, was isolated from a freshwater stream. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain IMCC34836T was most closely related to

Permianibacter aggregans

HW001T (of the family

Pseudomonadaceae

) with 95.6 % sequence similarity and formed a robust clade with

P. aggregans

HW001T. The draft genome sequence of strain IMCC34836T was 4.4 Mbp in size with 59.1 mol% DNA G+C content. Average nucleotide identity and digital DNA–DNA hybridization values between strain IMCC34836T and

P. aggregans

HW001T were 71.2 and 22.0 %, respectively, indicating that the new strain represents a novel species. The strain contained iso-C15 : 0, summed feature 3 (C16 : 1
ω6c and/or C16 : 1
ω7c) and summed feature 9 (iso-C17 : 1
ω9c and/or C16 : 1 10-methyl) as the major fatty acids and harboured phosphatidylethanolamine, two unidentified aminophospholipids and three unidentified lipids as major polar lipids. The isoprenoid quinone detected in the strain was ubiquinone-8. Based on the phylogenetic and phenotypic characteristics, strain IMCC34836T is considered to represent a novel species of the genus

Permianibacter

, for which the name Permianibacter fluminis sp. nov. is proposed. The type strain is IMCC34836T (=KACC 21755T=NBRC 114416T).
Effect of viral replication and liver fibrosis on all-cause mortality in HIV/HBV coinfected patients: a retrospective analysis of a 15-year longitudinal cohort
Authors: Dezanet Lorenza N. C. , Kassime Raisha , Miailhes Patrick , Lascoux-Combe Caroline , Chas Julie , Maylin Sarah , Gabassi Audrey , Rougier Hayette , Delaugerre Constance , Lacombe Karine , Boyd Anders 
Published: April 2021

AbstractBackgroundIn patients co-infected with HIV and hepatitis B virus (HBV), widespread tenofovir (TDF)-containing antiretroviral therapy (ART) has led to substantial decreases in HBV-DNA and HIV-RNA detection. However, the link between viral replication, liver fibrosis, and mortality remains unclear.Methods300 HIV-HBV co-infected patients undergoing ART were prospectively followed. Virological and clinical data were obtained at baseline and every 6-12 months. We quantified the association between HBV-DNA, HIV-RNA, and liver fibrosis with risk of all-cause mortality using a joint longitudinal-survival model. Viral detection, viral loads, and time-averaged cumulative viral loads of HIV and HBV were modeled as three separate exposures.ResultsDuring a median 10.5 years (IQR=4.0-14.6), the proportion undergoing TDF-containing ART (baseline=18.7%, end of follow-up=79.1%) and with undetectable HBV-DNA (baseline=36.7%, end of follow-up=94.8%) substantially increased. HIV-RNA was mostly undetectable during follow-up (76.6%). 42 participants died (incidence rate=1.30/100person-years, 95%CI=0.96-1.76). The leading causes of death were non-AIDS/non-liver-related malignancies (28.6%), closely followed by liver-related (16.7%), AIDS-related (16.7%), and other (16.7%). All-cause mortality was associated with HBV-DNA viral load (adjusted-HR per log10IU/mL=1.41, 95%CI=1.04-1.93,p=0.03) or time-averaged cumulative HBV-DNA (adjusted-HR per log10IU-years=1.37, 95%CI=1.03-1.83,p=0.03), but not undetectable HBV-DNA (adjusted-HR=0.30, 95%CI=0.08-1.09,p=0.08). Liver fibrosis at baseline also significantly increased mortality rates (adjusted-HR=2.35, 95%CI=1.16-4.76, p=0.02). No significant association between HIV-RNA replication and mortality was observed.ConclusionsConcurrent and historical HBV replication and liver fibrosis are important drivers of all-cause mortality in largely TDF-treated HIV-HBV co-infected patients, despite one-fifth of deaths being liver-related. HBV-DNA and liver fibrosis remain important prognostic indicators for this patient population.Key-pointsHBV-DNA levels and cumulative exposure over time increases risk of all-cause mortality in HIV-HBV co-infected patients. Fibrosis was a major determinant of mortality; however, the leading causes of death were malignancies not related to AIDS or HBV-infection.
Proteomic Profiling of MIS-C Patients Reveals Heterogeneity Relating to Interferon Gamma Dysregulation and Vascular Endothelial Dysfunction
Authors: Diorio Caroline , Shraim Rawan , Vella Laura A. , Giles Josephine R. , Baxter Amy E. , Oldridge Derek A. , Canna Scott W. , Henrickson Sarah E. , McNerney Kevin O. , Balamuth Frances , Burudpakdee Chakkapong , Lee Jessica , Leng Tomas , Farrell Alvin , Lambert Michele P. , Sullivan Kathleen E. , John Wherry E. , Teachey David T. , Bassiri Hamid , Behrens Edward M. 
Published: April 2021

AbstractMulti-system Inflammatory Syndrome in Children (MIS-C) is a major complication of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. We performed a comprehensive analysis of the plasma proteome of more than 1400 proteins in children with SARS-CoV-2. We hypothesized that the proteome would reflect heterogeneity in hyperinflammation and vascular injury, and further identify pathogenic mediators of disease. Protein signatures demonstrated overlap between MIS-C, and the inflammatory syndromes macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). We demonstrate that PLA2G2A is a key marker of MIS-C that associates with TMA. We found that IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.
Learning longitudinal patterns and identifying subtypes of pediatric Crohn disease treated with infliximab via trajectory cluster analysis of electronic health records
Authors: Chen Andrew , Stein Ronen , Baldassano Robert N. , Huang Jing 
Published: April 2021

ABSTRACTBackgroundThe current classification of pediatric CD is mainly based on cross-sectional data. The objective of this study is to identify subgroups of pediatric CD through trajectory cluster analysis of disease activity using data from electronic health records.MethodsWe conducted a retrospective study of pediatric CD patients who had been treated with infliximab. The evolution of disease over time was described using trajectory analysis of longitudinal data of C-Reactive Protein (CRP). Patterns of disease evolution were extracted through functional principal components analysis and subgroups were identified based on those patterns using the Gaussian mixture model. We compared patient characteristics, a biomarker for disease activity, received treatments, and long-term surgical outcomes across subgroups.ResultsWe identified four subgroups of pediatric CD patients with differential relapse-and-remission risk profiles. They had significantly different disease phenotype (p < 0.001), CRP (p < 0.001) and calprotectin (p = 0.037) at diagnosis, with increasing percentage of inflammatory phenotype and declining CRP and fecal calprotectin levels from Subgroup 1 through 4. The risk of colorectal surgery within 10 years after diagnosis was significantly different between groups (p < 0.001). We did not find statistical significance in gender or age at diagnosis across subgroups, but the BMI z-score was slightly smaller in subgroup 1 (p =0.055).ConclusionsReadily available longitudinal data from electronic health records can be leveraged to provide a deeper characterization of pediatric Crohn disease. The identified subgroups captured novel forms of variation in pediatric Crohn disease that were not explained by baseline measurements and treatment information.SummaryThe current classification of pediatric Crohn disease mainly relies on cross-sectional data, e.g., the Paris classification. However, the phenotypic classification may evolve over time after diagnosis. Our study utilized longitudinal measures from the electronic health records and stratified pediatric Crohn disease patients with differential relapse-and-remission risk profiles based on patterns of disease evolution. We found trajectories of well-maintained low disease activity were associated with less severe disease at baseline, early initiation of infliximab treatment, and lower risk of surgery within 10 years of diagnosis, but the difference was not fully explained by phenotype at diagnosis.
Design and user experience testing of a polygenic score report: a qualitative study of prospective users
Authors: Brockman Deanna G. , Petronio Lia , Dron Jacqueline S. , Kwon Bum Chul , Vosburg Trish , Nip Lisa , Tang Andrew , O’Reilly Mary , Lennon Niall , Wong Bang , Ng Kenney , Huang Katherine H. , Fahed Akl C. , Khera Amit V. 
Published: April 2021

AbstractBackgroundPolygenic scores – which quantify inherited risk by integrating information from many common sites of DNA variation – may enable a tailored approach to clinical medicine. However, alongside considerable enthusiasm, we and others have highlighted a lack of systematic approaches for score disclosure. Here, we review the landscape of polygenic score reporting and describe a generalizable approach for development of polygenic score disclosure tools for coronary artery disease.MethodsFirst, we assembled a working group of clinicians, geneticists, data visualization specialists, and software developers. The group reviewed existing polygenic score reports and then designed a two-page mock polygenic score report for coronary artery disease. We then conducted a qualitative user-experience study with this report and an interview guide focused on comprehension, experience, and attitudes. Interviews were transcribed and thematically analyzed for themes identification.ResultsWe conducted interviews with ten adult individuals (50% females, 70% without prior genetic testing experience, age range 20 to 70 years) recruited via an online platform. We identified three themes from interviews: (1) visual elements, such as color and simple graphics, enable participants to interpret, relate to, and contextualize their polygenic score, (2) word-based descriptions of risk and polygenic scores presented as percentiles were most often recognized and understood, (3) participants had varying levels of interest in understanding complex genomic information and therefore would benefit from additional resources that can adapt to their individual needs in real time. In response to user feedback, colors used for communicating risk were modified to minimize unintended color associations and odds ratios were removed. Of note, all 10 participants expressed interest in receiving this report based on their personal genomic information.ConclusionsOur findings describe a generalizable approach to develop and test a polygenic score disclosure tool that is desired by the general public. These results are likely to inform ongoing efforts related to polygenic score disclosure within clinical practice.
A data-driven pipeline to extract potential side effects through co-prescription analysis: application to a cohort study of 2,010 patients taking hydroxychloroquine with an 11-year follow-up
Authors: Sabatier P. , Wack M. , Pouchot J. , Danchin N. , Jannot AS. 
Published: April 2021

ABSTRACTContextReal-life data consist of exhaustive and unbiased data to study drug-safety profiles but are underused because of their complex temporality (i.e., safety depends on the dose, timing, and duration of treatment) and the considerable number of potential side effects to study. We aimed to create a pipeline that manages the complex temporality of real-life data using a data-driven strategy (i.e., without any hypothesis on the potential side effects to search for) to highlight the safety profile of a given drug. We used hydroxychloroquine (HCQ) and its co-prescription in a real-life database to illustrate this pipeline.MethodsWe incorporated a weighted cumulative exposure statistical model into a data-driven strategy. This pipeline makes it possible to highlight both long-term and short-term side effects, while avoiding false positives due to the natural course of the underlying disease. We applied the proposed pipeline to a cohort of 2,010 patients with a prescription of HCQ and used their drug prescription as the source of data to highlight the HCQ safety profile.ResultsThe proposed pipeline introduces a bootstrap strategy into weighted cumulative-exposure statistics estimates to highlight significant drug signals. As applied to HCQ, the proposed pipeline showed nine drugs to be significantly associated with HCQ exposure. Of note, one of them has therapeutic indications for known HCQ side effects. Other associations could be explained by therapeutic indications linked to conditions associated with HCQ indications in France.ConclusionWe propose a data-driven pipeline that makes it possible to provide a broad picture of the side effects of a given drug. It would be informative to pursue the development of this pipeline using other sources of data.
The evaluation of a novel tool to remotely assess visual acuity in chronic uveitis patients during the COVID-19 pandemic
Authors: Claessens J.L.J. , van Egmond J. , de Boer J.H. , Wisse R.P.L. 
Published: April 2021

AbstractBackgroundRestrictions due to the recent COVID-19 pandemic catalysed the deployment of telehealth solutions. A novel web‐based visual acuity test, validated in a healthy population, may be of great value in the follow‐up of uveitis patients.ObjectiveTo determine the measurement accuracy of the unsupervised remote Easee web‐based visual acuity test in uveitis patients, when compared to a conventional in‐hospital assessment.MethodsCross‐sectional diagnostic accuracy study. Between April 2020 and September 2020, consecutive adult uveitis patients were invited for the web‐based visual acuity test (index test) within two weeks prior to their conventional in‐hospital assessment (reference test).ResultsA total of 269 patients were invited by mail, of whom 84 visited the website (31%). Ultimately 98 eyes met the criteria for statistical analysis. The mean difference between the two tests was low and non‐significant: 0.02 logMAR (SD 0.12, P = 0.085). The 95% limits of agreement ranged from ‐0.21 to 0.26 logMAR. No relevant differences were identified in clinical characteristics between subgroups with a good performance (i.e. difference between the tests 0.15 logMAR) or underperformance (i.e. difference >0.15 logMAR) on the web‐based test.ConclusionThe web‐based visual acuity test is a promising tool to remotely assess visual acuity in the majority of uveitis patients, especially relevant when access to ophthalmic care is limited. No association between patient‐ or uveitis‐related variables and (under)performance of the test were identified. These outcomes underline the potential of remote vision testing in other common ophthalmic conditions. A proper implementation of this web‐based tool in health care could be of great value for revolutionizing teleconsultations.
Progressive dysmorphia of retinal pigment epithelium in age related macular degeneration revealed by fluorescence lifetime imaging
Authors: Hammer Martin , Jakob-Girbig Juliane , Schwanengel Linda , Curcio Christine A. , Hasan Somar , Meller Daniel , Schultz Rowena 
Published: April 2021

AbstractPurposeTo observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO).MethodsMultimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization) (mean age: 74.2±7.0 years). Twenty-three eyes were followed for 28.3±18.3 months. Seven eyes had a second follow up after 46.6±9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, and migrated RPE, seen as hyperreflective foci (HRF) on OCT, were identified. Fluorescence lifetimes in two spectral channels (SSC: 500-560 nm, LSC: 560-720 nm) as well as emission spectrum intensity ratio (ESIR) of the lesions were measured by FLIO.ResultsAs hyperpigmented areas form and RPE migrates into the retina, FAF lifetimes lengthen and ESRI of RPE cells increase. Thickened RPE showed lifetimes of 256±49 ps (SSC) and 336±35 ps (LSC) and an ESIR of 0.552±0.079. For hyperpigmentation, these values were 317±68 ps (p<0.001), 377±56 ps (p<0.001), and 0.609±0.081 (p=0.001), respectively, and for HRF 337±79 ps (p<0.001), 414±50 ps (p<0.001), and 0.654±0.075 (p<0.001).ConclusionsIn the process of RPE degeneration, comprising different steps of dysmorphia, hyperpigmentation, and migration, lengthening of FAF lifetimes and a hypsochromic shift of emission spectra can be observed by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.
The risk of symptomatic reinfection during the second COVID-19 wave in individuals previously exposed to SARS-CoV-2
Authors: Manica Mattia , Pancheri Serena , Poletti Piero , Giovanazzi Giulia , Guzzetta Giorgio , Trentini Filippo , Marziano Valentina , Ajelli Marco , Zuccali Maria Grazia , Benetollo Pier Paolo , Merler Stefano , Ferro Antonio 
Published: April 2021

AbstractTo what extent infection with SARS-CoV-2 protects against subsequent reinfection or symptomatic reinfection is still unclear. In this cohort study, we analyzed surveillance records of COVID-19 cases identified between June 2020 and January 2021 in five Italian municipalities, where 77.7% of the entire population was screened for IgG antibodies in May 2020. We compared the risk of observing symptomatic infections in two mutually exclusive groups defined by the initial serological response. We estimated that the cumulative incidence of identified symptomatic infections in the IgG negative and positive cohorts was 2.67% (95%CI: 2.12% – 3.37%) and 0.14% (95%CI: 0.04% – 0.58%), respectively. The adjusted odd ratio of developing symptomatic infection in individuals previously exposed to SARS-CoV-2 was estimated at 0.054 (95%CI: 0.009 - 0.169). Quantifying protective immunity against COVID-19 disease elicited by natural infection with SARS-CoV-2 is essential to inform strategies for controlling the pandemic in the forthcoming months.
A seq2seq model to forecast the COVID-19 cases, deaths and reproductive R numbers in US counties
Authors: Zhang-James Yanli , Hess Jonathan , Salekin Asif , Wang Dongliang , Chen Samuel , Winkelstein Peter , Morley Christopher P , Faraone Stephen V 
Published: April 2021

AbstractThe global pandemic of coronavirus disease 2019 (COVID-19) has killed almost two million people worldwide and over 400 thousand in the United States (US). As the pandemic evolves, informed policy-making and strategic resource allocation relies on accurate forecasts. To predict the spread of the virus within US counties, we curated an array of county-level demographic and COVID-19-relevant health risk factors. In combination with the county-level case and death numbers curated by John Hopkins university, we developed a forecasting model using deep learning (DL). We implemented an autoencoder-based Seq2Seq model with gated recurrent units (GRUs) in the deep recurrent layers. We trained the model to predict future incident cases, deaths and the reproductive number, R. For most counties, it makes accurate predictions of new incident cases, deaths and R values, up to 30 days in the future. Our framework can also be used to predict other targets that are useful indices for policymaking, for example hospitalization or the occupancy of intensive care units. Our DL framework is publicly available on GitHub and can be adapted for other indices of the COVID-19 spread. We hope that our forecasts and model can help local governments in the continued fight against COVID-19.