Jacobs Institute of Women's Health
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Association of HDV infection and HCC, hepatic decompensation, and all-cause and liver-related death in a national cohort
No full textBACKGROUND AND AIMS: HDV infection is the most severe form of chronic hepatitis. However, studies on outcomes and causes of death in a US-born population, with primarily horizontal transmission of HDV, are lacking. The aim of this study was to conduct a national study of patients with hepatitis D to understand the natural history and outcomes compared to patients with HBV infection. APPROACH AND RESULTS: In a national cohort of 4817 veterans infected with HBV tested for HDV (99.6% US-born, 3.3% HDV-positive) over a 23-year period, we used multivariable models to identify the factors associated with a composite outcome of HCC, decompensation, and liver-related mortality, and all-cause mortality of patients with HDV compared to HBV mono-infection. HDV coinfection (vs. HBV mono-infection) was associated with a significantly higher incidence of composite liver-related outcomes at both 5 (23.84 vs. 7.98, p \u3c 0.001) and 10 years (19.14 vs. 10.18, p \u3c 0.001), respectively. The most common cause of death was liver-related (33.8% for HDV vs. 24.7% for HBV), followed by nonhepatic malignancies (15.6% vs. 14.8%), cardiac (11.7% vs. 15.2%), and lung disease (5.2% vs. 3.7%). In multivariable models, HDV was associated with an increased risk of composite liver outcomes (adjusted hazard ratio: 2.57, 95% CI: 1.87-3.52, p \u3c 0.001) and all-cause mortality (adjusted hazard ratio: 1.52, 95% CI: 1.20-1.93, p \u3c 0.001). CONCLUSIONS: In a predominantly US-born cohort of veterans, HDV coinfection was associated with an increased risk of liver-related outcomes and all-cause mortality. Our findings support widespread testing for early identification of HDV
Predatory Publishing
No full texthttps://hsrc.himmelfarb.gwu.edu/survivingthestackscomic/1005/thumbnail.jp
Metabolism-Driven Colorimetric Read-to-Answer Sensor Array for Bacterial Discrimination and Antimicrobial Susceptibility Testing
No full textDue to the complexity of clinical samples, rapid and reliable bacterial identification and antimicrobial susceptibility testing (AST) remain challenging. To address these challenges, we developed a colorimetric sensing platform for bacterial identification and AST in clinical samples based on bacterial metabolism-driven synthesis of gold nanoparticles (AuNPs) via hydrogen peroxide (HO) mediation. In this strategy, bacteria metabolic differences among bacterial species were converted into distinct colorimetric signals. Integrated with linear discriminant analysis (LDA), our developed sensing system enables automated and high-resolution profiling of bacterial species and strains. We achieved 100% classification accuracy for seven bacterial species in serum and urine and successfully differentiated nine Escherichia coli strains. For AST, the system correctly assessed antibiotic resistance profiles in six clinical isolates, reaching an overall accuracy of 97.62%. Unlike the conventional AuNP-based aggregation sensors, our approach is more user-friendly, robust against environmental variability, and directly reflects bacterial metabolic activities. By directly converting metabolic signatures to diagnostic outcomes, this read-to-answer sensor array offers a powerful and accessible solution for bacterial identification and AST, with broad applicability in clinical and field settings
A network analysis of carbapenem-resistant Klebsiella pneumoniae among healthcare facilities
No full textWith limited treatments for carbapenem-resistant Klebsiella pneumoniae (CRKp), curtailing transmission is critical. We applied a network analysis using epidemiological admission data and bacterial genetics to characterize CRKp spread among patients in 16 acute care hospitals linked to 217 other healthcare facilities in the United States. Patients with diagnosed CRKp infection were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a prospective, observational study conducted from 12/2011 to 6/2016. A network analysis was performed using epidemiological admission data and bacterial genetics to characterize putative CRKp transmission among patients across various healthcare facilities and the community. Overall, 347/526 patients (66%) had a putative transmission link to at least one other patient within the network. Most transmission chains were small (i.e., between 2 patients); however, the largest included 172 patients diagnosed over 1575 days. One-third of patients shared a genetically similar CRKp isolate with another patient but had no observed epidemiological linkages at any healthcare location. Patients with CRKp are part of extensive regional networks involving a large number of non-hospital healthcare settings such as skilled nursing facilities. Thus, controlling spread necessitates integrated surveillance and control initiatives at regional and national levels in addition to institution-specific approaches
A systematic benchmark of integrative strategies for microbiome-metabolome data
No full textThe rapid advancement of high-throughput sequencing technologies has enabled the integration of various omic layers into computational frameworks. Among these, metagenomics and metabolomics are increasingly studied for their roles in complex diseases. However, no standard currently exists for jointly integrating microbiome and metabolome datasets within statistical models. We benchmarked nineteen integrative methods to disentangle the relationships between microorganisms and metabolites. These methods address key research goals, including global associations, data summarization, individual associations, and feature selection. Through realistic simulations, we identified the best-performing methods and validated them on real gut microbiome datasets, revealing complementary biological processes across the two omic layers. Practical guidelines are provided for specific scientific questions and data types. This work establishes a foundation for research standards in metagenomics-metabolomics integration and supports future methodological developments, while also providing guidance for designing optimal analytical strategies tailored to specific integration questions
A ROS-mediated oxidation-O-GlcNAcylation cascade governs ferroptosis
No full textReactive oxygen species (ROS) play a crucial role in lipid peroxidation and the initiation of ferroptosis, markedly affecting chemotherapeutic drug resistance. However, the mechanisms by which ROS function and are sensed remain poorly understood. In this study, we identified O-GlcNAc transferase (OGT), a key enzyme in protein O-GlcNAcylation, as a sensor for ROS during ferroptosis. The ROS-induced oxidation of OGT at C845 in its catalytic domain activates the enzyme. Once activated, OGT O-GlcNAcylates FOXK2, enhancing its interaction with importin α, which facilitates FOXK2\u27s nuclear translocation and binding to the SLC7A11 promoter region. This, in turn, boosts SLC7A11 transcription, thereby inhibiting ferroptosis. The elevated OGT-FOXK2-SLC7A11 axis contributes to tumorigenesis and resistance to chemoradiotherapy in hepatocellular carcinoma (HCC). Our findings elucidate a ROS-induced oxidation-O-GlcNAcylation cascade that integrates ROS signalling, O-GlcNAcylation, FOXK2-mediated SLC7A11 transcription and resistance to both ferroptosis and chemoradiotherapy
Health-related quality-of-life for people with a Fontan circulation, their parents, and siblings
No full textAIMS: The Fontan procedure has revolutionized care for individuals born with single ventricle heart disease, with over 80% of patients surviving into adulthood. This study aimed to estimate the long-term health-related quality-of-life (HRQoL) experienced by patients and families. METHODS AND RESULTS: Patients, parents, and siblings were recruited through the Australian and New Zealand Fontan Registry and self-reported their HRQoL the Child Health Utility 9D index for children and EuroQol 5-Dimensions for adults. Responses included 125 patients, 69 siblings, and 144 parents. Child patients reported more sadness, challenges with school and homework, and problems joining in activities, resulting in a lower HRQoL summary score compared with the general child population(0.74 vs 0.80,p=0.03). Adult patients reported more problems with anxiety and depression, usual activities, and self-care. While 60% of adult patients reported a summary score comparable with the general population, the 40% of adult patients who perceived their heart condition as serious reported lower HRQoL(0.77 vs 0.90,p=0.01). Child siblings experienced more tiredness and annoyance, while adult siblings reported more anxiety and/or depression; however, total HRQoL summary scores did not differ from the general population. Parents\u27 HRQoL was comparable with the general population. CONCLUSION: Overall, child patients, and adult patients who perceived their heart condition as serious, reported lower HRQoL than the general population. Siblings reported concerns in specific HRQoL domains. The reported utility scores can serve as references for the Fontan population and their family members, as well as formal inputs for economic evaluations of interventions to assist with resource allocation decisions
Perspective: Framework for Developing Prediction Equations for Estimating the Absorption and Bioavailability of Nutrients from Foods
No full textCurrent nutrient intake recommendations, nutritional assessments, and food labeling rely on estimated total nutrient content in foods and dietary supplements. However, the adequacy of nutrient intake depends not only on the total amount consumed but also on the fraction absorbed and utilized by the body. Accurate assessments of nutrient bioavailability require predictive equations or algorithms. This paper outlines a four-step framework designed to guide researchers in developing such equations. The framework includes: (1) identifying key factors that influence nutrient or bioactive compound bioavailability; (2) conducting a comprehensive literature review of high-quality human studies to inform development of predictive equations; (3) constructing predictive equations based on these insights; and (4) validate the equation, when feasible, to potentiate translation. This structured approach aims to enhance the accuracy and precision of nutrient bioavailability estimates, address data limitations, and highlight evidence gaps to inform future research and policy on nutrients and bioactive compounds
Reimagining Integrative Medicine Fellowship Core Competencies with a Health Equity Lens
No full textIntegrative medicine (IM) fellowships have grown significantly over the past decade. This review examines gaps in the original IM competencies and key revisions aligned with the Accreditation Council for Graduate Medical Education (ACGME) domains, informed by a multi-phase stakeholder engagement process. A task force from the Academic Consortium for Integrative Medicine and Health conducted a systematic review of existing IM competencies, ACGME core competencies, and relevant Diversity, Equity, and Inclusion (DEI) frameworks. A survey was sent to 23 IM fellowship programs, yielding a 96% response rate. Competencies were revised and refined through stakeholder input via conferences, focus groups, and surveys. Thematic analysis in December 2024 identified priorities for final revisions. Key updates include inclusive language and integration of underrepresented areas such as health equity, trauma-informed care, clinician well-being, interprofessional collaboration, and planetary health. Cultural humility and epistemic inclusivity are emphasized throughout, with health equity principles embedded across all domains. These updates mark a shift toward an inclusive, equity-centered model of whole-person care. Future efforts will focus on implementation, faculty development, and standardized assessment to support adoption in IM fellowship programs