Publications by authors named "J E Andrews"

3,616 Publications

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All-cause and cause-specific mortality during and following incarceration in Brazil: A retrospective cohort study.

PLoS Med 2021 Sep 17;18(9):e1003789. Epub 2021 Sep 17.

Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford, California, United States of America.

Background: Mortality during and after incarceration is poorly understood in low- and middle-income countries (LMICs). The need to address this knowledge gap is especially urgent in South America, which has the fastest growing prison population in the world. In Brazil, insufficient data have precluded our understanding of all-cause and cause-specific mortality during and after incarceration.

Methods And Findings: We linked incarceration and mortality databases for the Brazilian state of Mato Grosso do Sul to obtain a retrospective cohort of 114,751 individuals with recent incarceration. Between January 1, 2009 and December 31, 2018, we identified 3,127 deaths of individuals with recent incarceration (705 in detention and 2,422 following release). We analyzed age-standardized, all-cause, and cause-specific mortality rates among individuals detained in different facility types and following release, compared to non-incarcerated residents. We additionally modeled mortality rates over time during and after incarceration for all causes of death, violence, or suicide. Deaths in custody were 2.2 times the number reported by the national prison administration (n = 317). Incarcerated men and boys experienced elevated mortality, compared with the non-incarcerated population, due to increased risk of death from violence, suicide, and communicable diseases, with the highest standardized incidence rate ratio (IRR) in semi-open prisons (2.4; 95% confidence interval [CI]: 2.0 to 2.8), police stations (3.1; 95% CI: 2.5 to 3.9), and youth detention (8.1; 95% CI: 5.9 to 10.8). Incarcerated women experienced increased mortality from suicide (IRR = 6.0, 95% CI: 1.2 to 17.7) and communicable diseases (IRR = 2.5, 95% CI: 1.1 to 5.0). Following release from prison, mortality was markedly elevated for men (IRR = 3.0; 95% CI: 2.8 to 3.1) and women (IRR = 2.4; 95% CI: 2.1 to 2.9). The risk of violent death and suicide was highest immediately post-release and declined over time; however, all-cause mortality remained elevated 8 years post-release. The limitations of this study include inability to establish causality, uncertain reliability of data during incarceration, and underestimation of mortality rates due to imperfect database linkage.

Conclusions: Incarcerated individuals in Brazil experienced increased mortality from violence, suicide, and communicable diseases. Mortality was heightened following release for all leading causes of death, with particularly high risk of early violent death and elevated all-cause mortality up to 8 years post-release. These disparities may have been underrecognized in Brazil due to underreporting and insufficient data.
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http://dx.doi.org/10.1371/journal.pmed.1003789DOI Listing
September 2021

-Specific T Cell Functional, Memory, and Activation Profiles in QuantiFERON-Reverters Are Consistent With Controlled Infection.

Front Immunol 2021 30;12:712480. Epub 2021 Aug 30.

South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

Reversion of immune sensitization tests for (M.tb) infection, such as interferon-gamma release assays or tuberculin skin test, has been reported in multiple studies. We hypothesized that QuantiFERON-TB Gold (QFT) reversion is associated with a decline of M.tb-specific functional T cell responses, and a distinct pattern of T cell and innate responses compared to persistent QFT+ and QFT- individuals. We compared groups of healthy adolescents (n=~30 each), defined by four, 6-monthly QFT tests: reverters (QFT+/+/-/-), non-converters (QFT-/-/-/-) and persistent positives (QFT+/+/+/+). We stimulated peripheral blood mononuclear cells with M.tb antigens (M.tb lysate; CFP-10/ESAT-6 and EspC/EspF/Rv2348 peptide pools) and measured M.tb-specific adaptive T cell memory, activation, and functional profiles; as well as functional innate (monocytes, natural killer cells), donor-unrestricted T cells (DURT: γδ T cells, mucosal-associated invariant T and natural killer T-like cells) and B cells by flow cytometry. Projection to latent space discriminant analysis was applied to determine features that best distinguished between QFT reverters, non-converters and persistent positives. No longitudinal changes in immune responses to M.tb were observed upon QFT reversion. M.tb-specific Th1 responses detected in reverters were of intermediate magnitude, higher than responses in QFT non-converters and lower than responses in persistent positives. About one third of reverters had a robust response to CFP-10/ESAT-6. Among those with measurable responses, lower proportions of T (CD45RA+CCR7+CD27+) and early differentiated (CD45RA-) IFN-γ-TNF+IL-2- M.tb lysate-specific CD4+ cells were observed in reverters compared with non-converters. Conversely, higher proportions of early differentiated and lower proportions of effector (CD45RA-CCR7-) CFP10/ESAT6-specific Th1 cells were observed in reverters compared to persistent-positives. No differences in M.tb-specific innate, DURT or B cell functional responses were observed between the groups. Statistical modelling misclassified the majority of reverters as non-converters more frequently than they were correctly classified as reverters or misclassified as persistent positives. These findings suggest that QFT reversion occurs in a heterogeneous group of individuals with low M.tb-specific T cell responses. In some individuals QFT reversion may result from assay variability, while in others the magnitude and differentiation status of M.tb-specific Th1 cells are consistent with well-controlled M.tb infection.
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http://dx.doi.org/10.3389/fimmu.2021.712480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435731PMC
August 2021

AUF1 gene transfer increases exercise performance and improves skeletal muscle deficit in adult mice.

Mol Ther Methods Clin Dev 2021 Sep 29;22:222-236. Epub 2021 Jul 29.

Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.

Muscle function and mass begin declining in adults long before evidence of sarcopenia and include reduced mitochondrial function, although much remains to be characterized. We found that mRNA decay factor AU-rich mRNA binding factor 1 (AUF1), which stimulates myogenesis, is strongly reduced in skeletal muscle of adult and older mice in the absence of evidence of sarcopenia. Muscle-specific adeno-associated virus (AAV)8-AUF1 gene therapy increased expression of AUF1, muscle function, and mass. AAV8 AUF1 muscle gene transfer in 12-month-old mice increased the levels of activated muscle stem (satellite) cells, increased muscle mass, reduced markers of muscle atrophy, increased markers of mitochondrial content and muscle fiber oxidative capacity, and enhanced exercise performance to levels of 3-month-old mice. With wild-type and AUF1 knockout mice and cultured myoblasts, AUF1 supplementation of muscle fibers was found to increase expression of Peroxisome Proliferator-activated Receptor Gamma Co-activator 1-alpha (PGC1α), a major effector of skeletal muscle mitochondrial oxidative metabolism. AUF1 stabilized and increased translation of the mRNA, which is strongly reduced in adult muscle in the absence of AUF1 supplementation. Skeletal muscle-specific gene transfer of AUF1 therefore restores muscle mass, increases exercise endurance, and may provide a therapeutic strategy for age-related muscle loss.
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http://dx.doi.org/10.1016/j.omtm.2021.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399044PMC
September 2021

Loss of synergistic transcriptional feedback loops drives diverse B-cell cancers.

EBioMedicine 2021 Aug 27;71:103559. Epub 2021 Aug 27.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

Background: The most common B-cell cancers, chronic lymphocytic leukemia/lymphoma (CLL), follicular and diffuse large B-cell (FL, DLBCL) lymphomas, have distinct clinical courses, yet overlapping "cell-of-origin". Dynamic changes to the epigenome are essential regulators of B-cell differentiation. Therefore, we reasoned that these distinct cancers may be driven by shared mechanisms of disruption in transcriptional circuitry.

Methods: We compared purified malignant B-cells from 52 patients with normal B-cell subsets (germinal center centrocytes and centroblasts, naïve and memory B-cells) from 36 donor tonsils using >325 high-resolution molecular profiling assays for histone modifications, open chromatin (ChIP-, FAIRE-seq), transcriptome (RNA-seq), transcription factor (TF) binding, and genome copy number (microarrays).

Findings: From the resulting data, we identified gains in active chromatin in enhancers/super-enhancers that likely promote unchecked B-cell receptor signaling, including one we validated near the immunoglobulin superfamily receptors FCMR and PIGR. More striking and pervasive was the profound loss of key B-cell identity TFs, tumor suppressors and their super-enhancers, including EBF1, OCT2(POU2F2), and RUNX3. Using a novel approach to identify transcriptional feedback, we showed that these core transcriptional circuitries are self-regulating. Their selective gain and loss form a complex, iterative, and interactive process that likely curbs B-cell maturation and spurs proliferation.

Interpretation: Our study is the first to map the transcriptional circuitry of the most common blood cancers. We demonstrate that a critical subset of B-cell TFs and their cognate enhancers form self-regulatory transcriptional feedback loops whose disruption is a shared mechanism underlying these diverse subtypes of B-cell lymphoma.

Funding: National Institute of Health, Siteman Cancer Center, Barnes-Jewish Hospital Foundation, Doris Duke Foundation.
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http://dx.doi.org/10.1016/j.ebiom.2021.103559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403728PMC
August 2021

Socioecological Factors Associated with an Urban Exercise Prescription Program for Under-Resourced Women: A Mixed Methods Community-Engaged Research Project.

Int J Environ Res Public Health 2021 08 18;18(16). Epub 2021 Aug 18.

Department of Nursing, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA.

One strategy to promote physical activity (PA) is for health care providers to give exercise prescriptions (ExRx) that refer to community-based facilities. However, facilitators and barriers specific to urban programs in the US for under-resourced women are unknown. Thus the purpose of this formative research was to explore ExRx barriers and facilitators specific to US under-resourced women to inform future intervention targets and strategies. This mixed-methods community-engaged research was conducted in partnership with an urban women's only wellness center that exchanged ExRx for free access (1-3 months). Qualitative semi-structured interviews and validated quantitative questionnaires (SF-12, International Physical Activity Questionnaire, Physical Activity Self-Efficacy, Physical Activity Stage of Change, and Barriers to Physical Activity, Social Support for Exercise, and Confusion, Hubbub, and Order Scale) were administered by phone and guided by the socio-ecological model. ExRx utilization was defined as number visits/week divided by membership duration. Means and percentages were compared between ≥1 visit/week vs. <1 visit/week with -tests and chi-square, respectively. Women ( = 30) were 74% Black, 21-78 years of age, 50% had ≤ high school diploma, and 69% had household incomes ≤45,000/year. Women with ≥1 visit/week ( = 10; 33%) reported more education and higher daily activity, motivation, number of family CVD risk factors and family history of dyslipidemia compared with <1 visit/week. Facilitators among women with ≥1 visit/week were "readiness" and "right timing" for ExRx utilization. Barriers among women with <1 visit/week ( = 20; 67%) were "mismatched expectations" and "competing priorities". Common themes among all women were "sense of community" and "ease of location". ExRx utilization at an US urban wellness center may be dependent on a combination of multi-level factors including motivation, confidence, peer support, location and ease of access in under-sourced women. Additional resources may be needed to address mental and/or physical health status in additional to physical activity specific programming.
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http://dx.doi.org/10.3390/ijerph18168726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394072PMC
August 2021
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