Large language models to identify social determinants of health in electronic health records.

Social determinants of health (SDoH) play a critical role in patient outcomes, yet their documentation is often missing or incomplete in the structured data of electronic health records (EHRs). Large language models (LLMs) could enable high-throughput extraction of SDoH from the EHR to support research and clinical care. However, class imbalance and data limitations present challenges for this sparsely documented yet critical information. Here, we investigated the optimal methods for using LLMs to extract six SDoH categories from narrative text in the EHR: employment, housing, transportation, parental status, relationship, and social support. The best-performing models were fine-tuned Flan-T5 XL for any SDoH mentions (macro-F1 0.71), and Flan-T5 XXL for adverse SDoH mentions (macro-F1 0.70). Adding LLM-generated synthetic data to training varied across models and architecture, but improved the performance of smaller Flan-T5 models (delta F1 + 0.12 to +0.23). Our best-fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models in the zero- and few-shot setting, except GPT4 with 10-shot prompting for adverse SDoH. Fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias (p < 0.05). Our models identified 93.8% of patients with adverse SDoH, while ICD-10 codes captured 2.0%. These results demonstrate the potential of LLMs in improving real-world evidence on SDoH and assisting in identifying patients who could benefit from resource support.

Deletions within intronic T-DNA lead to reversion of T-DNA mutant phenotypes.

Agrobacterium-mediated transformation enables random transfer-DNA (T-DNA) insertion into plant genomes. T-DNA insertion into a gene's exons, introns or untranscribed regions close to the start or stop codon can disrupt gene function. Such T-DNA mutants have been useful for reverse genetics analysis, especially in Arabidopsis thaliana. As T-DNAs are inserted into genomic DNA, they are generally believed to be stably inherited. Here, we report a phenomenon of reversion of intronic T-DNA mutant phenotypes. From a suppressor screen using intronic T-DNA pi4kß1,2 double mutant, we recovered intragenic mutants of pi4kß1, which suppressed the autoimmunity of the double mutant. These mutants carried deletions in the intronic T-DNAs, resulting in elevated transcription of normal PI4Kß1. Such reversion of T-DNA insertional mutant phenotype stresses the need for caution when using intronic T-DNA mutants and reiterates the importance of using irreversible null mutant alleles in genetic analyses.

A qualitative analysis examining intersectional stigma among young adults living with HIV in Atlanta, Georgia.

HIV-related stigma is a barrier to engagement in care for young adults living with HIV. Other intersecting forms of stigma (e.g., racism, sexism, homophobia), may worsen HIV-related stigma and impact engagement in care. From November 2020 to February 2021, we conducted 20 in-depth qualitative interviews among young adults living with HIV attending a large, comprehensive HIV care center in Atlanta, Georgia. Semi-structured interview guides based on Earnshaw and Chaudoir's HIV Stigma Framework and the theory of intersectionality facilitated discussion around experiences with various forms of stigma and its possible influence on healthcare engagement. Using the social-ecological model, we used thematic analysis to contextualize how young adults living with HIV experienced intersectional stigma and enacted, anticipated, and internalized HIV stigma in both healthcare and non-healthcare settings. Most participants identified as male, Black/African American, and gay. Participants described stigma at intrapersonal, interpersonal, clinic, and community levels. Intrapersonal stigma was associated with delayed care seeking, isolation, and fear of disclosure. Interpersonal stigma included discrimination from family and friends and avoidance of close relationships to elude disclosure. At the clinic level, stigma included negative experiences with staff in HIV and non-HIV healthcare settings, which contributed to decreased engagement in care. Stigma in the community included differential treatment from employers, community leaders, and religious community and was associated with feelings of helplessness related to current societal inequalities. Coping/motivating mechanisms for stigma included prioritizing health, eliciting support from the medical care team and peers. Our findings show different intersecting stigmas are barriers to healthcare at multiple levels for young adults living with HIV, potentially exacerbating existing health and social disparities. To improve engagement in care among young adults living with HIV, future interventions should address the different mechanisms of stigma at community, clinic, interpersonal and intrapersonal levels by enhancing social support and improving healthcare structural competency.

Human Immunodeficiency Virus (HIV) Care Continuum Outcomes After Transition to Adult Care Among a Prospective Cohort of Youth With HIV in Atlanta, Georgia.

BACKGROUND: Healthcare transition from pediatric to adult-oriented clinical settings is often viewed as a high-risk time for care disengagement. However, there is a paucity of prospective, longitudinal research documenting human immunodeficiency virus (HIV) care outcomes after healthcare transition. METHODS: We conducted a prospective, observational cohort study of healthcare transition among youth enrolled at an HIV care center in Atlanta, Georgia. Pediatric clinic patients (average age, 24 years) were enrolled up to 3 months before the expected transition and were followed up to determine linkage, retention, and viral suppression in adult care through electronic medical record abstractions at the baseline and at 6, 12, 18, and 24 months. RESULTS: The majority of our cohort (n = 70) was male (88.6%) and black (92.9%) and acquired HIV horizontally (80%). Most of our cohort was linked to adult care by 12 months (84%) after enrollment. Of those who linked to adult care by 12 months, retention rates were 86% (95% confidence interval, 78%-94%) at 6 months, 76% (66%-86%) at 12 months, and 66% (55%-78%) at 18 and 24 months. Once in adult care, the proportion with viral suppression was stable (73% at baseline and 74%, 77%, 67%, and 78% at 6, 12, 18, and 24 months, respectively). CONCLUSIONS: Although most youth successfully linked to adult care, retention rates decreased over the 24-month follow-up period. Rates of viral suppression were stable for those who remained in care. Strategies to support retention in adult care will be critical to optimizing this transition for youth with HIV.

Systematic Review of mHealth Interventions for Adolescent and Young Adult HIV Prevention and the Adolescent HIV Continuum of Care in Low to Middle Income Countries.

Adolescents and young adults (AYA) in low to middle income countries (LMIC) have poorer outcomes along each step in the HIV continuum of prevention and care compared to younger children or older adults. The use of mHealth technology provides a potentially promising implementation strategy for interventions to remedy these disparities. We therefore conducted a systematic review of the English literature and conference proceedings from January 1, 2000 to April 1, 2021 evaluating mHealth interventions targeting AYA along each step of the HIV continuum of care in LMIC. We identified 27 mHealth interventions across the HIV continuum, with no interventions addressing transition from pediatric to adult care. The majority of studies were single arm, uncontrolled or underpowered, with few randomized trials resulting in mixed and inconclusive outcomes. mHealth interventions have potential to remedy disparities along the HIV continuum of care for AYA in LMIC but larger, powered randomized trials are needed.

RESUMEN: Los adolescentes y adultos jóvenes (AYA) en países de ingresos bajos a medianos (LMIC) tienen peores resultados en cada paso del continuo de prevención y atención del VIH en comparación con los niños más pequeños o los adultos mayores. El uso de la tecnología mHealth proporciona una estrategia de implementación potencialmente prometedora para las intervenciones para remediar estas disparidades. Por lo tanto, realizamos una revisión sistemática de los resúmenes y artículos publicados en inglés desde el 1 de enero de 2000 hasta el 1 de abril de 2021 para evaluar las intervenciones de mHealth dirigidas a AYA a lo largo de cada paso del continuo de atención del VIH en LMIC. Identificamos 27 intervenciones de mHealth en todo el continuo del VIH, sin intervenciones que abordaran la transición de la atención pediátrica a la de adultos. La mayoría de los estudios fueron de un solo brazo, no controlados o con bajo poder estadístico, con pocos ensayos aleatorios que dieron resultados mixtos y no concluyentes. Las intervenciones de mHealth tienen el potencial de remediar las disparidades a lo largo de la continuidad de la atención del VIH para AYA en LMIC, pero se necesitan ensayos aleatorios más grandes y potentes.

"I am not shy anymore": A qualitative study of the role of an interactive mHealth intervention on sexual health knowledge, attitudes, and behaviors of South African adolescents with perinatal HIV.

BACKGROUND: South Africa has one of the highest burdens of adolescents with perinatally-acquired HIV (APHIV) in the world. APHIV in South Africa have limited access to sexual and reproductive health (SRH) education and services specific to their HIV status. When lacking comprehensive SRH education, APHIV are prone to sexual risk behaviors that can lead to unintended pregnancy, sexually transmitted infections, and HIV transmission. The use of mHealth interventions has been shown to deliver information, foster social support, and improve decision-making skills. In this study, we evaluate how an mHealth intervention influences sexual health knowledge and behaviors in APHIV. METHODS: We purposively enrolled adolescents from the intervention arm of a randomized clinical trial assessing a multi-module, moderated WhatsApp-based intervention-Interactive Transition Support for Adolescents Living with HIV (InTSHA)-within a government supported clinic in KwaMashu, an urban township of KwaZulu-Natal, South Africa. We conducted in-depth interviews based on World Health Organization guidelines for asking adolescents about SRH. We thematically analyzed data through an iterative, team-based coding approach combining deductive and inductive elements to contextualize SRH attitudes, knowledge, and behaviors before and after receiving the InTSHA intervention. RESULTS: Of the 21 participants, 13 (61.9%) were female and the mean age was 16.6 years. Most participants reported first learning about SRH as young teenagers in school through non-targeted and negative ways, seeking clarification through peers and the internet rather than clinicians or caregivers. Participants reported that InTSHA provided a holistic perspective on relationships, gender, and sexuality specific to growing up with HIV in South Africa. They praised the ability to give and receive information from peers in a moderated setting through the mHealth intervention, building their confidence, decision-making skills, and communication with partners and caregivers throughout their everyday lives. Despite reporting some technological challenges, adolescents agreed that InTSHA was convenient, confidential, and user-friendly. CONCLUSIONS: South African APHIV receive incomplete and conflicting sexual education from peers, caregivers, teachers, and technology that can be supplemented by mHealth curricula targeted for the unique needs of APHIV. Future, scaled-up mHealth interventions can lower SRH stigma by expanding access to sexual education and peer support, supplementing adolescents' existing SRH education.

South African adolescents with perinatally-acquired HIV (APHIV)­teenagers who were born with HIV­lack access to sexual and reproductive health (SRH) education specific to their HIV status. Ineffective SRH education often leads to risky behaviors (such as unprotected sex), teenage pregnancy, and the spread of HIV. Mobile health (mHealth) interventions, such as phone apps, can help improve adolescent SRH knowledge and decision-making. In this study, we evaluate how a WhatsApp-based intervention­Interactive Transition Support for Adolescents Living with HIV (InTSHA)­influences SRH attitudes and behaviors of APHIV. InTSHA involved long-term, weekly group chats of APHIV, run by trained facilitators, that included two modules discussing SRH. This study analyzes in-depth interviews we conducted with adolescents who completed InTSHA, asking them about their SRH knowledge and behaviors before and after the intervention. The interviews took place in a government-supported clinic in an urban township of KwaZulu-Natal. Interviews were recorded, transcribed, translated, coded, and analyzed. Of 21 participants, 13 were female and the average age was 16.6 years. Most participants reported first learning about SRH as young teenagers in school, through peers, or on the internet, rather than through healthcare workers or family members. Participants reported that InTSHA provided a comfortable platform to discuss relationships, gender, and sexuality as APHIV. Adolescents enjoyed giving and receiving information from peers in a moderated setting. They reported that InTSHA built their confidence, decision-making skills, and communication with partners and caregivers. South African SRH education for APHIV can be supplemented by targeted mHealth interventions.

The Putative Endonuclease Activity of MutL Is Required for the Segmental Gene Conversion Events That Drive Antigenic Variation of the Lyme Disease Spirochete.

The Lyme disease spirochete Borrelia burgdorferi, encodes an elaborate antigenic variation system that promotes the ongoing variation of a major surface lipoprotein, VlsE. Changes in VlsE are continual and always one step ahead of the host acquired immune system, which requires 1-2 weeks to generate specific antibodies. By the time this happens, new VlsE variants have arisen that escape immunosurveillance, providing an avenue for persistent infection. This antigenic variation system is driven by segmental gene conversion events that transfer information from a series of silent cassettes (vls2-16) to the expression locus, vlsE. The molecular details of this process remain elusive. Recombinational switching at vlsE is RecA-independent and the only required factor identified to date is the RuvAB branch migrase. In this work we have used next generation long-read sequencing to analyze the effect of several DNA replication/recombination/repair gene disruptions on the frequency of gene conversions at vlsE and report a requirement for the mismatch repair protein MutL. Site directed mutagenesis of mutL suggests that the putative MutL endonuclease activity is required for recombinational switching at vlsE. This is the first report of an unexpected essential role for MutL in a bacterial recombination system and expands the known function of this protein as well as our knowledge of the details of the novel recombinational switching mechanism for vlsE variation.

Mobile Phone-Based Intervention Among Adolescents Living With Perinatally Acquired HIV Transitioning from Pediatric to Adult Care: Protocol for the Interactive Transition Support for Adolescents Living With HIV using Social Media (InTSHA) Study.

BACKGROUND: Adolescents living with perinatally acquired HIV often have poor retention in care and viral suppression during the transition from pediatric to adult-based care. OBJECTIVE: The aim of this study is to evaluate a mobile phone-based intervention, Interactive Transition Support for Adolescents Living With HIV using Social Media (InTSHA), among adolescents living with perinatally acquired HIV as they transition from pediatric to adult care in South Africa. METHODS: InTSHA uses encrypted, closed group chats delivered via WhatsApp (Meta Platforms Inc) to develop peer support and improve communication between adolescents, their caregivers, and health care providers. The intervention is based on formative work with adolescents, caregivers, and health care providers and builds on several existing adolescent support programs as well as the Social-ecological Model of Adolescent and Young Adult Readiness for Transition (SMART). The final InTSHA intervention involves 10 modules conducted weekly through moderated WhatsApp group chats with adolescents and separately with their caregivers. We will randomly assign 80 South African adolescents living with perinatally acquired HIV who are aware of their HIV status and aged between 15 and 19 years to receive either the intervention (n=40) or standard of care (n=40). RESULTS: We will measure acceptability of the intervention as the primary outcome and evaluate feasibility and preliminary effectiveness for retention in care and viral suppression after completion of the intervention and at least 6 months after randomization. In addition, we will measure secondary outcomes evaluating the impact of the InTSHA intervention on peer support, self-esteem, depression, stigma, sexual education, connection to health care providers, and transition readiness. Enrollment began on April 15, 2021. As of December 31, 2021 a total of 78 out of expected 80 participants have been enrolled. CONCLUSIONS: If successful, the intervention will be evaluated in a fully powered randomized controlled trial with a larger number of adolescents from urban and rural populations to further evaluate the generalizability of InTSHA. TRIAL REGISTRATION: ClinicalTrials.gov NCT03624413; https://clinicaltrials.gov/ct2/show/NCT03624413. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35455.

Detection of the Amphibian Pathogens Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in West Texas, USA, Using Environmental DNA.

Environmental DNA (eDNA) methods provide novel options for the detection of pathogens. The amphibian pathogens Batrachochytrium dendrobatidis (Bd) and Ranavirus have been relatively understudied in Texas, US, so we applied eDNA assays for the surveillance of these pathogens in the upper Brazos River basin near the Texas panhandle. We collected water samples from five urban playa lakes and one reservoir in and around Lubbock, Texas. Quantitative PCR detected both Bd and Ranavirus at one playa lake, representing novel detection of both pathogens in the region. Based on these results, we recommend increased monitoring for the pathogens and symptoms of amphibian disease throughout the region.