Publications by Year: 2026

Heavy metal pollution is a global environmental problem. Enterococci have been recognized as sentinels of environmental pollution.This study investigates metal tolerance genes (arsA, merA, and tcrB) among enterococci isolated from fecal samples of domestic and wild animals from Atlantic Forest, Pampa biomes, and coastal regions of southern Brazil. Among the 238 enterococci analyzed, 38% harbored arsA_I/arsA_II and 10% contained tcrB, while none tested positive for merA genes. These results suggest that the selective pressure exerted by anthropogenic activities in the animals' habitats may contribute to the occurrence of heavy metal tolerance genes in host-associated enterococci.

Hypertrophic cardiomyopathy (HCM), a genetic heart disease defined by unexplained cardiac wall thickening, is a leading cause of sudden death worldwide. However, the three-dimensional organization of cardiac tissue underlying left ventricular hypertrophy remains poorly understood. We developed CaMVIA-3D, a deep-learning volumetric imaging and analysis pipeline to characterize cardiac microarchitecture. Analysis of tissues from HCM hearts revealed genotype-specific differences in cardiomyocyte volume, morphology, and extracellular volume, with pathogenic variants exhibiting greater concentric cellular hypertrophy and disarray and variant-negative cases showing predominant fibrosis. Longitudinal profiling of a pig HCM model revealed early-onset fibrosis preceding cardiomyocyte hypertrophy. Integrating transcriptomic and morphologic changes, we identified genes associated with cellular and extracellular remodeling. These findings define genotype-specific microstructural differences in HCM, offering insights to improve diagnostics and targeted therapies.

Despite major advances in medical therapies and prevention strategies, the risk of cardiovascular complications in patients with both type I and type II diabetes remains substantially elevated. In 2019, the American Heart Association sought applications for a Strategically Focused Research Network on Cardiometabolic Health and Type 2 Diabetes. In 2020, 4 centers were named, including Brigham and Women's Hospital, Johns Hopkins University, New York University, and the University of Iowa. These centers performed basic, translational, and clinical studies to provide insights to explain the over 2-fold risk of cardiovascular complications in diabetes. Clinical studies and studies in cells and animals aimed to uncover new mechanisms responsible for disease development. Studies using human populations sought to uncover new biomarkers to prognosticate risk. In this review, we discuss several key issues and current and developing methods to understand why diabetes drives atherosclerotic cardiovascular disease and heart failure. Both human data and experimental models are considered. We integrate a review of these topics with work from the Strategically Focused Research Network and conclude with suggestions for identifying novel risk factors and future experimental research.

Optimization of prophylactic vaccine regimens to elicit strong, long-lasting immunity is an urgent need highlighted by the COVID-19 pandemic. Stronger vaccine immunogenicity is frequently reported in individuals living in high-income countries compared to individuals living in low- and middle-income countries. While numerous host genetic and immune factors may influence vaccine responses, geographic restrictions to vaccine effectiveness may also be influenced by the intestinal microbiota, which modulates host immune systems. However, the potential role of the gut microbiota on responses to HIV-1 vaccines has not yet been explored. We analyzed the bacteriome by targeted 16S sequencing and the virome by virus-like particle sequencing of 154 fecal samples collected from healthy individuals in Uganda, Rwanda, and the United States early (week 2) and late (week 26) after vaccination with multivalent adenovirus serotype 26 (Ad26)-vectored mosaic HIV-1 vaccines. Vaccination did not affect the enteric bacteriome or virome regardless of geographic location. However, geography was the major driver of microbiota differences within this cohort. Differences in overall bacterial and viral diversity and in specific microbial taxa, including Bacteroidota and Bacillota, between participants from the United States and East African countries correlated with differential immune responses, including specific antibody titers, antibody functionality, and cellular immune responses to vaccination regimens. These findings support the microbiota as a putative modifier of vaccine immunogenicity.IMPORTANCEOur research examined how gut bacteria might influence vaccine effectiveness in different parts of the world. We studied adults from the United States, Rwanda, and Uganda who received an experimental HIV vaccine. We found that participants from East Africa had more diverse gut bacteria than those from the United States, but their immune responses to the vaccine were weaker. This is the first study to directly show this relationship between higher gut bacterial diversity and reduced vaccine effectiveness in the same group of people. We also identified specific types of bacteria that were linked to either stronger or weaker immune responses. These findings are particularly relevant now as we use vaccines globally to fight diseases like COVID-19, as they suggest that regional differences in gut bacteria Bacteroidota and Bacillota might help explain why vaccines work better in some places than others. This could inform how we design and test future vaccines.

INTRODUCTION: In a national US-based group, we sought to describe barriers identified by sexual and gender minority (SGM) patients and primary care providers (PCPs) that challenge the provision of SGM-affirming digestive health care by qualitative methodology.

METHODS: Forty patient participants and 24 PCPs were recruited from a random sample of 18 states within the 9 principal US Census Divisions and 2 states near the home institution. Patient participants selected completed a virtual semi-structured qualitative interview regarding their experiences with digestive health care and their views on barriers to engaging in digestive health care. PCPs were interviewed on treating SGM patients with gastrointestinal (GI) disorders and interactions with GI consultants. Interviews were conducted until thematic saturation was achieved. The study was conducted from November 2023 to August 2024.

RESULTS: Thematic saturation was achieved at 36 patient participants and 21 PCPs. Major themes included SGM discrimination in digestive health care, SGM issues in engaging in digestive health care, GI symptoms and other aspects of health-specific conditions, and ways to improve digestive health care for the SGM community. Participants noted a link between psychological distress in the SGM population and GI symptoms and offered actionable suggestions to improve SGM-focused digestive health care.

DISCUSSION: Systematic deficiencies were identified in the provision of SGM-affirming digestive care, related to bias within health care systems and a lack of understanding of unique SGM-related needs throughout the United States. Further research studying improved shared clinician and SGM GI patient engagement is needed to address these sources of health inequity.

AIMS: Cutaneous plasmablastic lymphoma (cPBL) is a rare and aggressive neoplasm that presents as skin nodules. Despite occurring in  5% of PBL cases, the World Health Organization (WHO) does not distinguish primary cutaneous PBL (pcPBL) from secondary cutaneous PBL (scPBL), and their clinical differences remain poorly defined. To determine whether pcPBL represents a distinct clinical entity, we compare the clinicopathologic features, immunohistochemical profiles, and survival outcomes of pcPBL and scPBL.

METHODS AND RESULTS: Retrospective comparative study analysing 40 cases of cPBL (6 newly identified institutional cases and 34 cases from the literature), categorized as pcPBL (n = 25; no extracutaneous disease at diagnosis) or scPBL (n = 15; concurrent extracutaneous disease). Patients with pcPBL were older than those with scPBL (median 62 vs. 43 years; Mann-Whitney P = 0.018). Leg involvement was significantly associated with pcPBL (OR = 6.22; 95% CI: 1.21-31.9; P = 0.031). Disease-specific survival (DSS) analysis included 17 evaluable cases (pcPBL n = 11; scPBL n = 6). Median DSS was 42.0 months in pcPBL and 8.0 months in scPBL (log-rank χ2 = 3.98; p = 0.046). Median follow-up (reverse Kaplan-Meier) was 20.0 months in pcPBL and not reached in scPBL. Cox models were directionally consistent but underpowered.

CONCLUSION: In this pooled analysis, cases presenting with primary cutaneous involvement tended to occur in older patients and more often involved the legs. However, these observations should be interpreted cautiously given small numbers and heterogeneity of the available data. Within pcPBL, EBV positivity correlated with better survival. These hypothesis-generating findings provide a basis for prospective, multi-centre studies to clarify classification, staging implications, and management of this rare lymphoma.

The E3 ubiquitin ligase Casitas B-lineage lymphoma (CBL) promotes positive selection and antigen responses in mouse T lymphocytes by ubiquitinating ZAP70. Conversely, mouse CBL and CBL-B mutually redundantly regulate SYK ubiquitination and B cell receptor signaling. Here we studied individuals with somatically homozygous CBL loss-of-function variants in leukocytes. Human CBL is largely redundant for the development and function of human T cells. Conversely, B cell development is altered at the immature stage, with a tenfold increase in transitional cells, enhanced survival of autoreactive clones and impaired tolerance manifested by autoantibody production. B cell maturation is intrinsically impaired by reduced apoptosis and dysregulated B cell receptor signaling. CBL deficiency impairs humoral immunity by limiting memory B cell formation and reducing class switching and somatic hypermutation. Consequently, antigen-specific B cell generation and adaptive immune memory are disrupted, predisposing individuals to infection. Human CBL is critical for B cell development and function but redundant for T cell biology.