Faculty Bibliography

Background and Aims: Background: There is growing evidence that Hybrid Closed Loop Systems (HCLS) are associated with a lower risk of severe hypoglycemia (SH) in people with type 1 diabetes. In this study, we use real-world data from the T1D Exchange (T1DX-QI) EMR database to investigate the association between HCLS use and patient-reported SH events using propensity score matching.
Method(s): In this analysis, we examined SH events across propensity score-matched HCLS user and HCLS non-user groups. All available data for the pediatric (6 years and older) and adult population with T1D from March 2018-March 2022 were included in this analysis. Patient-reported SH events are defined as SH events reported by the patient at their most recent clinic visit and were classified as a binary variable (Yes/No), with those reporting one or more SH events being classified under 'Yes' Similarly, HCLS device use was defined as the use of HCLS reported by the patient at their most recent clinic encounter.
Result(s): Propensity scores were estimated using a logit model, including age, gender, race/ethnicity, and insurance status as covariates. Matching was done using 1:1 matching with the nearest neighbor approach and a caliper of 0.1. There were 1537 matched people with T1D in the HCLS user and non-users group. Analysis showed that HCLS users were less likely than HCLS non-users to report >1 SH event (OR [95% CI]: 0.2 [0.1, 0.4] when controlling for covariates.
Conclusion(s): In this population-level real-world data analysis, we found HCLS use among people with T1D associated with lower patient-reported SH events

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.

GWAS, immune analyses and biomarker screenings have identified host factors associated with in vivo HIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. To this end, whole DNA methylome in 70 untreated HIV-1 infected individuals with either high (>50,000 HIV-1-RNA copies/ml, n = 29) or low (<10,000 HIV-1-RNA copies/ml, n = 41) plasma viral load (pVL) levels were compared and identified 2,649 differentially methylated positions (DMPs). Of these, a classification random forest model selected 55 DMPs that correlated with virologic (pVL and proviral levels) and HIV-1 specific adaptive immunity parameters (IFNg-T cell responses and neutralizing antibodies capacity). Then, cluster and functional analyses identified two DMP clusters: cluster 1 contained hypo-methylated genes involved in antiviral and interferon response (e.g. PARP9, MX1, and USP18) in individuals with high viral loads while in cluster 2, genes related to T follicular helper cell (Tfh) commitment (e.g. CXCR5 and TCF7) were hyper-methylated in the same group of individuals with uncontrolled infection. For selected genes, mRNA levels negatively correlated with DNA methylation, confirming an epigenetic regulation of gene expression. Further, these gene expression signatures were also confirmed in early and chronic stages of infection, including untreated, cART treated and elite controllers HIV-1 infected individuals (n = 37). These data provide the first evidence that host genes critically involved in immune control of the virus are under methylation regulation in HIV-1 infection. These insights may offer new opportunities to identify novel mechanisms of in vivo virus control and may prove crucial for the development of future therapeutic interventions aimed at HIV-1 cure.

BACKGROUND:Public health strategies are urgently needed to improve HIV disparities among transgender women, including holistic intervention approaches that address those health needs prioritized by the community. Hormone therapy is the primary method by which many transgender women medically achieve gender affirmation. Peer navigation has been shown to be effective to engage and retain underserved populations living with HIV in stable primary medical care. OBJECTIVE:This study aims to assess the feasibility and acceptability of an integrated innovative HIV service delivery model designed to improve HIV prevention and care by combining gender-affirming primary care and peer navigation with HIV prevention and treatment services. METHODS:A 12-month, nonrandomized, single-arm cohort study was implemented in Lima, Peru, among adult individuals, assigned a male sex at birth, who identified themselves as transgender women, regardless of initiation or completion of medical gender affirmation, and who were unaware of their HIV serostatus or were living with HIV but not engaged in HIV treatment. HIV-negative participants received quarterly HIV testing and were offered to initiate pre-exposure prophylaxis. HIV-positive participants were offered to initiate antiretroviral treatment and underwent quarterly plasma HIV-1 RNA and peripheral CD4+ lymphocyte cell count monitoring. All participants received feminizing hormone therapy and adherence counseling and education on their use. Peer health navigation facilitated retention in care by visiting participants at home, work, or socialization venues, or by contacting them by social media and phone. RESULTS:Patient recruitment started in October 2016 and finished in March 2017. The cohort ended follow-up on March 2018. Data analysis is currently underway. CONCLUSIONS:Innovative and culturally sensitive strategies to improve access to HIV prevention and treatment services for transgender women are vital to curb the burden of HIV epidemic for this key population. Findings of this intervention will inform future policies and research, including evaluation of its efficacy in a randomized controlled trial. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03757117; https://clinicaltrials.gov/ct2/show/NCT03757117. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)/UNASSIGNED:DERR1-10.2196/14091.