Exploring the prognostic significance of arm-level copy number alterations in triple-negative breast cancer.

Somatic copy number alterations (SCNAs) are prevalent in cancer and play a significant role in both tumorigenesis and therapeutic resistance. While focal SCNAs have been extensively studied, the impact of larger arm-level SCNAs remains poorly understood. Here, we investigated the association between arm-level SCNAs and overall survival in triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer lacking targeted therapies. We identified frequent arm-level SCNAs, including 21q gain and 7p gain, which correlated with poor overall survival in TNBC patients. Further, we identified the expression of specific genes within these SCNAs associated with survival. Notably, we found that the expression of RIPK4, a gene located on 21q, exhibited a strong correlation with poor overall survival. In functional assays, we demonstrated that targeting Ripk4 in a murine lung metastatic TNBC model significantly reduced tumor burden, improved survival, and increased CD4+ and CD8+ T cell infiltration. RIPK4 enhanced the survival of triple-negative breast cancer cells at secondary sites, thereby facilitating the formation of metastatic lesions. Our findings highlight the significance of arm-level SCNAs in breast cancer progression and identify RIPK4 as a putative driver of TNBC metastasis and immunosuppression.

Epigenetic associations in HPA axis genes related to bronchopulmonary dysplasia and antenatal steroids.

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common morbidity among very preterm infants, is associated with chronic disease and neurodevelopmental impairments. A hypothesized mechanism for these outcomes lies in altered glucocorticoid (GC) activity. We hypothesized that BPD and its treatments may result in epigenetic differences in the hypothalamic-pituitary-adrenal (HPA) axis, which is modulated by GC, and could be ascertained using an established GC risk score and DNA methylation (DNAm) of HPA axis genes. METHODS: DNAm was quantified from buccal tissue (ECHO-NOVI) and from neonatal blood spots (ELGAN ECHO) via the EPIC microarray. Prenatal maternal characteristics, pregnancy complication, and neonatal medical complication data were collected from medical record review and maternal interviews. RESULTS: The GC score was not associated with steroid exposure or BPD. However, six HPA genes involved in stress response regulation demonstrated differential methylation with antenatal steroid exposure; two CpGs within FKBP5 and POMC were differentially methylated with BPD severity. These findings were sex-specific in both cohorts; males had greater magnitude of differential methylation within these genes. CONCLUSIONS: These findings suggest that BPD severity and antenatal steroids are associated with DNAm at some HPA genes in very preterm infants and the effects appear to be sex-, tissue-, and age-specific. IMPACT: This study addresses bronchopulmonary dysplasia (BPD), an important health outcome among preterm neonates, and interrogates a commonly studied pathway, the hypothalamic-pituitary-adrenal (HPA) axis. The combination of BPD, the HPA axis, and epigenetic markers has not been previously reported. In this study, we found that BPD itself was not associated with epigenetic responses in the HPA axis in infants born very preterm; however, antenatal treatment with steroids was associated with epigenetic responses.

Correlation between gender-based violence and poor treatment outcomes among transgender women living with HIV in Brazil.

BACKGROUND: Transgender women are disproportionately affected by both HIV and gender-based violence (GBV), defined as physical, sexual, or emotional violence perpetrated against an individual based on their gender identity/expression. While a growing body of evidence demonstrates that GBV leads to poor HIV care and treatment outcomes among cisgender women, less research has examined this association among transgender women. We assessed the impact of lifetime experiences of GBV on subsequent retention in HIV care and laboratory confirmed viral suppression among a sample of transgender women living with HIV (TWH) in Brazil. METHODS: A pilot trial of a peer navigation intervention to improve HIV care and treatment among TWH was conducted in São Paulo, Brazil between 2018 and 2019. TWH were recruited and randomized into the intervention or control arm and participated in a baseline and 9-month follow-up survey and ongoing extraction of clinical visit, prescribing, and laboratory data. Generalized linear model regressions with a Poisson distribution estimated the relative risk (RR) for the association of lifetime physical and sexual violence reported at baseline with treatment outcomes (retention in HIV care and viral suppression) at follow-up, adjusting for baseline sociodemographic characteristics. RESULTS: A total of 113 TWH participated in the study. At baseline, median age was 30 years, and the prevalence of lifetime physical and sexual violence was 62% and 45%, respectively. At follow-up, 58% (n = 66/113) were retained in care and 35% (n = 40/113) had evidence of viral suppression. In adjusted models, lifetime physical violence was non-significantly associated with a 10% reduction in retention in care (aRR: 0.90, 95% CI: 0.67, 1.22) and a 31% reduction in viral suppression (aRR: 0.69; 95% CI: 0.43, 1.11). Lifetime sexual violence was non-significantly associated with a 28% reduction in retention in HIV care (aRR: 0.72, 95% CI: 0.52, 1.00) and significantly associated with a 56% reduction in viral suppression (aRR: 0.44; 95% CI: 0.24, 0.79). CONCLUSION: Our findings are among the first to demonstrate that lifetime experiences with physical and sexual violence are associated with poor HIV outcomes over time among transgender women. Interventions seeking to improve HIV treatment outcomes should assess and address experiences of GBV among this population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03525340.

Cost Analysis of Short Messaging Service and Peer Navigator Interventions for Linking and Retaining Adults Recently Diagnosed With HIV in Care in South Africa.

INTRODUCTION: Large proportions of people living with HIV (PLHIV) in sub-Saharan Africa are not linked to or retained in HIV care. There is a critical need for cost-effective interventions to improve engagement and retention in care and inform optimal allocation of resources. METHODS: We estimated costs associated with a short message service (SMS) plus peer navigation (SMS+PN) intervention; an SMS-only intervention; and standard of care (SOC), within the I-Care cluster-randomized trial to improve HIV care engagement for recently diagnosed PLHIV. We employed a uniform cost data-collection protocol to quantify resources used and associated costs for each intervention. RESULTS: Compared with SOC, the SMS+PN intervention cost $1284 ($828-$2859) more per additional patient linked to care within 30 days and $1904 ($1158-$5343) more per additional patient retained in care at 12 months, while improving linkage by 24% (95% CI: 11 to 36) and retention by 16% (95% CI: 6 to 26). By contrast, the SMS-only intervention cost $198 ($93-dominated) more per additional patient linked to care and $697 ($171-dominated) more per additional patient retained in care but was not significantly associated with improvements in linkage (12%; 95% CI: -1 to 25) or retention (3%; 95% CI: -7 to 14) compared with SOC. The efficiency of the SMS+PN intervention could be improved by 46%, to $690 more per additional patient linked and $1023 more per additional patient retained in care, if implemented within the Department of Health using more efficient distribution of staff resources. DISCUSSION: Findings suggest that scale-up of the SMS+PN intervention could benefit patients, improving care and health outcomes while being cost-effective.

Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.

Children born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability. We studied 379 neonates (54% male) born less than 30 weeks GA who had DNA methylation measured at neonatal intensive care unit discharge along with 3-year follow-up data. Cumulative prenatal risk was calculated from 24 risk factors obtained from maternal report and medical record and epigenome-wide neonatal DNA methylation was assayed from buccal swabs. At 3-year follow-up, child cognitive ability was assessed using the Bayley Scales of Infant and Toddler Development (third edition). Cumulative prenatal risk and DNA methylation at two cytosine-phosphate-guanines (CpGs) were uniquely associated with child cognitive ability. Using high-dimensional mediation analysis, we also identified differential methylation of 309 CpGs that mediated the association between cumulative prenatal risk and child cognitive ability. Many of the associated CpGs were located in genes (TNS3, TRAPPC4, MAD1L1, APBB2, DIP2C, TRAPPC9, DRD2) that have previously been associated with prenatal exposures and/or neurodevelopmental phenotypes. Our findings suggest a role for both prenatal risk factors and DNA methylation in explaining outcomes for children born preterm and suggest we should further study DNA methylation as a potential mechanism underlying the association between prenatal risk and child neurodevelopment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Compelling evidence from meta-epidemiological studies demonstrates overestimation of effects in randomized trials that fail to optimize randomization and blind patients and outcome assessors.

OBJECTIVES: To investigate the impact of potential risk of bias elements on effect estimates in randomized trials. STUDY DESIGN AND SETTING: We conducted a systematic survey of meta-epidemiological studies examining the influence of potential risk of bias elements on effect estimates in randomized trials. We included only meta-epidemiological studies that either preserved the clustering of trials within meta-analyses (compared effect estimates between trials with and without the potential risk of bias element within each meta-analysis, then combined across meta-analyses; between-trial comparisons), or preserved the clustering of substudies within trials (compared effect estimates between substudies with and without the element, then combined across trials; within-trial comparisons). Separately for studies based on between- and within-trial comparisons, we extracted ratios of odds ratios (RORs) from each study and combined them using a random-effects model. We made overall inferences and assessed certainty of evidence based on Grading of Recommendations, Assessment, development, and Evaluation and Instrument to assess the Credibility of Effect Modification Analyses. RESULTS: Forty-one meta-epidemiological studies (34 of between-, 7 of within-trial comparisons) proved eligible. Inadequate random sequence generation (ROR 0.94, 95% confidence interval [CI] 0.90-0.97) and allocation concealment (ROR 0.92, 95% CI 0.88-0.97) probably lead to effect overestimation (moderate certainty). Lack of patients blinding probably overestimates effects for patient-reported outcomes (ROR 0.36, 95% CI 0.28-0.48; moderate certainty). Lack of blinding of outcome assessors results in effect overestimation for subjective outcomes (ROR 0.69, 95% CI 0.51-0.93; high certainty). The impact of patients or outcome assessors blinding on other outcomes, and the impact of blinding of health-care providers, data collectors, or data analysts, remain uncertain. Trials stopped early for benefit probably overestimate effects (moderate certainty). Trials with imbalanced cointerventions may overestimate effects, while trials with missing outcome data may underestimate effects (low certainty). Influence of baseline imbalance, compliance, selective reporting, and intention-to-treat analysis remain uncertain. CONCLUSION: Failure to ensure random sequence generation or adequate allocation concealment probably results in modest overestimates of effects. Lack of patients blinding probably leads to substantial overestimates of effects for patient-reported outcomes. Lack of blinding of outcome assessors results in substantial effect overestimation for subjective outcomes. For other elements, though evidence for consistent systematic overestimate of effect remains limited, failure to implement these safeguards may still introduce important bias.

Anticipated Stigma and Social Barriers to Communication Between Transgender Women Newly Diagnosed with HIV and Health Care Providers: A Mediation Analysis.

Purpose: We assessed whether anticipated stigma (i.e., fear of public mistreatment due to gender identity) impacts communication between transgender women (TGW) living with HIV and health care providers. Methods: This is a secondary analysis of baseline data from Trans Amigas, a study conducted in Brazil, 2018. The study population consisted of TGW living with HIV, older than 18 years, residing in the São Paulo metropolitan area. We used multivariable logistic regression (α = 0.05), mediation, and bootstrapping for the analysis. Results: One hundred and thirteen participants completed the study. Fear of public mistreatment had an adjusted odds ratio (aOR) of 7.42 (p = 0.003) for difficulty reporting new symptoms to providers. Concerning fear of public mistreatment, we found that unemployment had an aOR of 3.62 (p = 0.036); sex work, an aOR of 2.95 (p = 0.041); and issues related to name change in documents, an aOR of 2.71 (p = 0.033). For the indirect effect on difficulty reporting new symptoms, mediated by fear of public mistreatment, unemployment had an aOR of 1.52 (confidence interval [CI] = 0.88-2.24); sex work, an aOR of 1.48 (CI = 0.81-2.52); and name change issues, an aOR of 1.47 (CI = 0.96-2.43). Conclusions: Anticipated stigma was associated with communication difficulties between TGW living with HIV and providers. Our data suggest that structural factors associated with anticipated stigma could indirectly impact on difficulty reporting new symptoms. These findings indicate the importance of considering social contexts that intersect with individual experiences when analyzing communication barriers between providers and patients, and the need to strengthen social policies for TGW in Brazil. Clinical Trial Registration number: R34MH112177.

Two-Year Autism Risk Screening and 3-Year Developmental Outcomes in Very Preterm Infants.

Importance: Use of the Modified Checklist for Autism in Toddlers, Revised With Follow-Up, a 2-stage parent-report autism risk screening tool, has been questioned due to reports of poor sensitivity and specificity. How this measure captures developmental delays for very preterm infants may provide support for continued use in pediatric care settings. Objective: To determine whether autism risk screening with the 2-stage parent-report autism risk screening tool at age 2 years is associated with behavioral and developmental outcomes at age 3 in very preterm infants. Design, Setting, and Participants: Neonatal Neurobehavior and Outcomes for Very Preterm Infants was a longitudinal, multisite cohort study. Enrollment occurred April 2014 to June 2016, and analyses were conducted from November 2022 to May 2023. Data were collected across 9 university-affiliated neonatal intensive care units (NICUs). Inclusion criteria were infants born less than 30 weeks' gestational age, a parent who could read and speak English and/or Spanish, and residence within 3 hours of the NICU and follow-up clinic. Exposures: Prematurity and use of the 2-stage parent-report autism risk screening tool at age 2 years. Main Outcomes and Measures: Outcomes include cognitive, language, motor composites on Bayley Scales for Infant and Toddler Development, third edition (Bayley-III) and internalizing, externalizing, total problems, and pervasive developmental disorder (PDD) subscale on the Child Behavior Checklist (CBCL) at age 3 years. Generalized estimating equations tested associations between the 2-stage parent-report autism risk screening tool and outcomes, adjusting for covariates. Results: A total of 467 children (mean [SD] gestational age, 27.1 [1.8] weeks; 243 male [52%]) were screened with the 2-stage parent-report autism risk screening tool at age 2 years, and outcome data at age 3 years were included in analyses. Mean (SD) maternal age at birth was 29 (6) years. A total of 51 children (10.9%) screened positive on the 2-stage parent-report autism risk screening tool at age 2 years. Children with positive screening results were more likely to have Bayley-III composites of 84 or less on cognitive (adjusted odds ratio [aOR], 4.03; 95% CI, 1.65-9.81), language (aOR, 5.38; 95% CI, 2.43-11.93), and motor (aOR, 4.74; 95% CI, 2.19-10.25) composites and more likely to have CBCL scores of 64 or higher on internalizing (aOR, 4.83; 95% CI, 1.88-12.44), externalizing (aOR, 2.69; 95% CI, 1.09-6.61), and PDD (aOR, 3.77; 95% CI, 1.72-8.28) scales. Conclusions and Relevance: Results suggest that the 2-stage parent-report autism risk screening tool administered at age 2 years was a meaningful screen for developmental delays in very preterm infants, with serious delays detected at age 3 years.

Agreement Between Two Behavioral Rating Scales in Preschoolers Born Very Preterm.

OBJECTIVE: Broadband parent rating scales are commonly used to assess behavioral problems in children. Multiple rating scales are available, yet agreement between them is not well-understood. The objective of this study was to evaluate agreement between the Behavior Assessment System for Children, Third Edition (BASC-3), and Child Behavior Checklist 1.5 to 5 years (CBCL) in a sample of children born very preterm. METHOD: We assessed 73 children born < 30 weeks' gestational age whose caregivers completed the BASC-3 and CBCL at age 4. We examined correlations, within-person differences, and agreement in clinical categorization for all corresponding subscales and composites. RESULTS: Comparable subscales on the BASC-3 and CBCL were significantly correlated, albeit to differing magnitudes. Subscales indexing hyperactivity and attention problems were the most comparable across the 2 measures, evidenced by strong correlations and few to no differences in mean T-scores. Composite scores indexing internalizing, externalizing, and total problems were also strongly correlated, and there were no differences in the mean T-scores for externalizing or total problems across measures. Agreement in clinical classifications were weak to moderate, though again, the highest agreement was found for hyperactivity, attention, externalizing, and total problems. CONCLUSION: Agreement between BASC-3 and CBCL subscales was weak to moderate, with the exception of subscales related to attention and hyperactivity, as well as composite scores indicating overall behavior problems. Researchers and clinicians should consider these discrepancies when interpreting the results of behavior rating scales with preschool children because conclusions could differ based on the assessment that is used.

A guaranteed income intervention to improve the health and financial well-being of low-income black emerging adults: study protocol for the Black Economic Equity Movement randomized controlled crossover trial.

Background: Economic inequity systematically affects Black emerging adults (BEA), aged 18-24, and their healthy trajectory into adulthood. Guaranteed income (GI)-temporary, unconditional cash payments-is gaining traction as a policy solution to address the inequitable distribution of resources sewn by decades of structural racism and disinvestment. GI provides recipients with security, time, and support to enable their transition into adulthood and shows promise for improving mental and physical health outcomes. To date, few GI pilots have targeted emerging adults. The BEEM trial seeks to determine whether providing GI to BEA improves financial wellbeing, mental and physical health as a means to address health disparities. Methods/design: Using a randomized controlled crossover trial design, 300 low-income BEA from San Francisco and Oakland, California, are randomized to receive a $500/month GI either during the first 12-months of follow-up (Phase I) or during the second 12-months of a total of 24-months follow-up (Phase II). All participants are offered enrollment in optional peer discussion groups and financial mentoring to bolster financial capability. Primary intention-to-treat analyzes will evaluate the impact of GI at 12 months among Phase I GI recipients compared to waitlist arm participants using Generalized Estimating Equations (GEE). Primary outcomes include: (a) financial well-being (investing in education/training); (b) mental health status (depressive symptoms); and (c) unmet need for mental health and sexual and reproductive health services. Secondary analyzes will examine effects of optional financial capability components using GEE with causal inference methods to adjust for differences across sub-strata. We will also explore the degree to which GI impacts dissipate after payments end. Study outcomes will be collected via surveys every 3 months throughout the study. A nested longitudinal qualitative cohort of 36 participants will further clarify how GI impacts these outcomes. We also discuss how anti-racism praxis guided the intervention design, evaluation design, and implementation. Discussion: Findings will provide the first experimental evidence of whether targeted GI paired with complementary financial programming improves the financial well-being, mental health, and unmet health service needs of urban BEA. Results will contribute timely evidence for utilizing GI as a policy tool to reduce health disparities. Clinical trial registration: https://clinicaltrials.gov, identifier NCT05609188.

Epigenetic age acceleration, neonatal morbidities, and neurobehavioral profiles in infants born very preterm.

Epigenetic age acceleration is a risk factor for chronic diseases of ageing and may reflect aspects of biological ageing. However, few studies have examined epigenetic ageing during the early neonatal period in preterm infants, who are at heightened risk of developmental problems. We examined relationships between neonatal age acceleration, neonatal morbidities, and neurobehavioral domains among very preterm (<30 weeks gestation) infants to characterize whether infants with early morbidities or different neurobehavioral characteristics had accelerated or decelerated epigenetic ageing. This study uses data from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, restricted to infants with data on variables assessed (n = 519). We used generalized estimating equations to test for differences in age acceleration associated with severe neonatal medical morbidities and neurobehavioral characteristics. We found that infants with neonatal morbidities, in particular, bronchopulmonary dysplasia (BPD), had accelerated epigenetic age - and some evidence that infants with hypertonicity and asymmetric reflexes had increased and decreased age acceleration, respectively. Adjustment for gestational age attenuated some associations, suggesting that the relationships observed may be driven by the duration of gestation. Our most robust finding shows that very preterm infants with neonatal morbidities (BPD in particular) exhibit age acceleration, but most neonatal neurobehavioral characteristics and morbidities are not associated with early life age acceleration. Lower gestational age at birth may be an upstream factor driving these associations.

Understanding the effects of universal test and treat on longitudinal HIV care outcomes among South African youth: a retrospective cohort study.

INTRODUCTION: Little is known about the effects of universal test and treat (UTT) policies on HIV care outcomes among youth living with HIV (YLHIV). Moreover, there is a paucity of information regarding when YLHIV are most susceptible to disengagement from care under the newest treatment guidelines. The longitudinal HIV care continuum is an underutilized tool that can provide a holistic understanding of population-level HIV care trajectories and be used to compare treatment outcomes across groups. We aimed to explore effects of the UTT policy on longitudinal outcomes among South African YLHIV and identify temporally precise opportunities for re-engaging this priority population in the UTT era. METHODS: Using medical record data, we conducted a retrospective cohort study among youth aged 18-24 diagnosed with HIV from August 2015-December 2018 in nine health care facilities in South Africa. We used Fine and Gray sub-distribution proportional hazards models to characterize longitudinal care continuum outcomes in the population overall and stratified by treatment era of diagnosis. We estimated the proportion of individuals in each stage of the continuum over time and the restricted mean time spent in each stage in the first year following diagnosis. Sub-group estimates were compared using differences. RESULTS: A total of 420 YLHIV were included. By day 365 following diagnosis, just 23% of individuals had no 90-or-more-day lapse in care and were virally suppressed. Those diagnosed in the UTT era spent less time as ART-naïve (mean difference=-19.3 days; 95% CI: -27.7, -10.9) and more time virally suppressed (mean difference = 17.7; 95% CI: 1.0, 34.4) compared to those diagnosed pre-UTT. Most individuals who were diagnosed in the UTT era and experienced a 90-or-more-day lapse in care disengaged between diagnosis and linkage to care or ART initiation and viral suppression. CONCLUSIONS: Implementation of UTT yielded modest improvements in time spent on ART and virally suppressed among South African YLHIV- however, meeting UNAIDS' 95-95-95 targets remains a challenge. Retention in care and re-engagement interventions that can be implemented between diagnosis and linkage to care and between ART initiation and viral suppression (e.g., longitudinal counseling) may be particularly important to improving care outcomes among South African YLHIV in the UTT era.

Multiplexed microfluidic screening of bacterial chemotaxis.

Microorganism sensing of and responding to ambient chemical gradients regulates a myriad of microbial processes that are fundamental to ecosystem function and human health and disease. The development of efficient, high-throughput screening tools for microbial chemotaxis is essential to disentangling the roles of diverse chemical compounds and concentrations that control cell nutrient uptake, chemorepulsion from toxins, and microbial pathogenesis. Here, we present a novel microfluidic multiplexed chemotaxis device (MCD) which uses serial dilution to simultaneously perform six parallel bacterial chemotaxis assays that span five orders of magnitude in chemostimulant concentration on a single chip. We first validated the dilution and gradient generation performance of the MCD, and then compared the measured chemotactic response of an established bacterial chemotaxis system (Vibrio alginolyticus) to a standard microfluidic assay. Next, the MCD's versatility was assessed by quantifying the chemotactic responses of different bacteria (Psuedoalteromonas haloplanktis, Escherichia coli) to different chemoattractants and chemorepellents. The MCD vastly accelerates the chemotactic screening process, which is critical to deciphering the complex sea of chemical stimuli underlying microbial responses.

Many microorganisms such as bacteria swim to explore their fluid habitats, which range from the human digestive system to the oceans. They can detect minute traces of food, toxins and other chemicals in their environment, and ­ through a process called chemotaxis ­ respond by swimming towards or away from them. Chemical concentrations naturally decrease with distance away from their source, forming gradients. By sensing these chemical gradients, and adjusting their swimming direction accordingly, cells can locate nutrients and other resources in harsh environments as well as avoid toxins and potential predators. Over the past 20 years, laboratory devices that manipulate minute volumes of fluid ­ known as microfluidics devices ­ have been indispensable for studying chemotaxis. They enable researchers to generate gradients of chemicals in carefully designed networks of microscopic channels, controlling the conditions that swimming cells are exposed to and mimicking their natural habitats. However, large-scale studies of chemotaxis have been limited by the sheer range of chemicals that are present at different levels in natural environments. Conventional microfluidic devices often compromise between distinguishing how individual cells behave, precise control over the chemical gradient, or the ability to execute multiple assays at the same time. Here, Stehnach et al. designed a microfluidic device called the Multiplexed Chemotaxis Device. The device generates five streams of precise dilutions of a chemical and then uses these streams ­ alongside a control stream lacking the chemical ­ to measure chemotaxis in six different conditions at the same time. The device was tested using a well-studied bacterium, Vibrio alginolyticus, which is commonly found in marine environments. The device reliably examined the chemotaxis response of the population to various chemicals, was able to carry out multiple assays more rapidly than conventional devices, and can be easily applied to study the response of individual bacteria under the same conditions. The Multiplexed Chemotaxis Device is relatively easy to manufacture using standard methods and therefore has the potential to be used for large-scale chemotaxis studies. In the future, it may be useful for screening new drugs to treat bacterial infections and to help identify food sources for communities of microbes living in marine environments.

PrEP knowledge, acceptability, and implementation in Ghana: Perspectives of HIV service providers and MSM, trans women, and gender diverse individuals living with HIV.

Pre-exposure prophylaxis (PrEP) could help reduce HIV incidence among cis men, trans women, and gender diverse individuals assigned male at birth who have sex with men (MSM, trans women, and GDSM) in Ghana, a group that bears a high HIV burden. Our study examined PrEP knowledge and acceptability, and barriers and facilitators to its uptake and implementation through qualitative interviews with 32 MSM, trans women, and GDSM clients living with HIV, 14 service providers (SPs), and four key informants (KIs) in Accra, Ghana. We interviewed participants about their PrEP knowledge, whether MSM would take PrEP, and what factors would make it easy/difficult to uptake or implement PrEP. Interview transcripts were analyzed using thematic analysis. There was high acceptability of PrEP use and implementation among MSM, trans women, GDSM, and SPs/KIs in Ghana. MSM, trans women, and GDSM interest in, access to, and use of PrEP were shaped by intersectional HIV and anti-gay stigma; PrEP affordability, acceptability, and ease of use (e.g., consumption and side effects); sexual preferences (e.g., condomless sex vs. condom use), and HIV risk perception. Concerns raised about barriers and facilitators of PrEP use and implementation ranged from medical concerns (e.g., STIs; drug resistance); social behavioral concerns (e.g., stigma, risk compensation, adherence issues); and structural barriers (e.g., cost/affordability, govern commitment, monitoring systems, policy guidance). Targeted education on PrEP and proper use of it is needed to generate demand and dispel worries of side effects among MSM, trans women, and GDSM. Free, confidential, and easy access to PrEP must be supported by health systems strengthening, clear prescription guidelines, and anti-stigma training for providers.

Depression and HIV Care-seeking Behaviors in a Population-based Sample in North West Province, South Africa.

Depression is associated with key HIV-related prevention and treatment behaviors in sub-Saharan Africa. We aimed to identify the association of depressive symptoms with HIV testing, linkage to care, and ART adherence among a representative sample of 18-49 year-olds in a high prevalence, rural area of South Africa. Utilizing logistic regression models (N = 1044), depressive symptoms were inversely associated with reported ever HIV testing (AOR 0.92, 95% CI 0.85-0.99; p = 0.04) and ART adherence (AOR 0.82, 95% CI: 0.73-0.91; p < 0.01) among women. For men, depressive symptoms were positively associated with linkage to care (AOR: 1.21, 95% CI: 1.09-1.34; p < 0.01). Depression may adversely impact ART adherence for HIV-positive women and reduce the likelihood of HIV testing for women not aware of their HIV status which, in settings with high HIV prevalence, carries severe consequences. For HIV-positive men, findings suggest that depression may encourage help-seeking behavior, thereby impacting their health system interactions. These findings underscore the need for health-care settings to factor mental health, such as depression, into their programs to address health-related outcomes, particularly for women.

RESUMEN: La depresión está asociada con conductas clave de prevención y tratamiento relacionadas con el VIH en África subsahariana. Nuestro objetivo fue identificar la asociación de los síntomas depresivos con los resultados relacionados con el VIH entre una muestra representativa de personas de 18 a 49 años en Sudáfrica. Utilizando modelos de regresión logística (N = 1044), los síntomas depresivos se asociaron inversamente con los que se informaron que habían probado de VIH alguna vez (AOR 0,92, IC del 95%: 0,85 a 0,99; p = 0,04) y la adherencia al TAR (AOR 0,82, IC del 95%: 0,73 a 0,91; p < 0,01) entre las mujeres. Para los hombres, los síntomas depresivos se asociaron positivamente con la vinculación con cuidado (AOR: 1,21, IC del 95%: 1,09­1,34; p < 0,01). La depresión puede tener un impacto adverso en la adherencia al TAR para las mujeres VIH-positivas y reducir la probabilidad de que las mujeres se hagan la prueba del VIH. Para los hombres VIH-positivos, los resultados sugieren que la depresión fomente una conducta de búsqueda de ayuda, afectando así sus interacciones con el sistema de salud. Estos resultados subrayan la necesidad de que los que proveen servicios médicos tengan en cuenta la salud mental en sus programas que abordan los resultados relacionados con la salud.

Neurobehavioral and Medical Correlates of Autism Screening: 2-Year Outcomes for Infants Born Very Preterm.

OBJECTIVE: To identify neonatal characteristics and 2-year neurodevelopmental outcomes associated with positive screening for risk of autism. STUDY DESIGN: Nine university-affiliated neonatal intensive care units (NICUs) enrolled infants born at <30 weeks of gestation. Infants underwent the NICU Network Neurobehavioral Scale examination before discharge and the Bayley Scales of Infant and Toddler Development, Third Edition, the Child Behavior Checklist, and the Modified Checklist for Autism in Toddlers, revised with follow-up (M-CHAT-R/F) at 2 years of corrected age. Generalized estimating equations examined associations between M-CHAT-R/F, neurobehavioral test results, and neonatal medical morbidities. RESULTS: At 2 years of corrected age, data were available for 466 of 744 enrolled infants without cerebral palsy. Infants with hypoaroused NICU Network Neurobehavioral Scale profiles were more likely to screen M-CHAT-R/F-positive (OR 2.76, 95% CI 1.38-5.54). Infants with ≥2 medical morbidities also were more likely to screen positive (OR 2.65, 95% CI 1.27-5.54). Children with positive M-CHAT-R/F scores had lower Bayley Scales of Infant and Toddler Development, Third Edition, Cognitive (t [451] = 5.43, P < .001, d = 0.82), Language (t [53.49] = 7.82, P < .001, d = 1.18), and Motor (t [451] = 7.98, P < .001, d = 1.21) composite scores and significantly greater Child Behavior Checklist Internalizing (t [457] -6.19, P < .001, d = -0.93) and Externalizing (t [57.87] = -5.62, P < .001, d = -0.84) scores. CONCLUSIONS: Positive M-CHAT-R/F screens at 2 years of corrected age were associated with neonatal medical morbidities and neurobehavioral examinations as well as toddler developmental and behavioral outcomes. These findings demonstrate the potential utility of the M-CHAT-R/F as a global developmental screener in infants born very preterm, regardless of whether there is a later autism diagnosis.

Barriers and facilitators of the return-to-school process affecting adolescent recipients of allogeneic hematopoietic cell transplantation: A qualitative interview study of caregivers.

BACKGROUND: Adolescent hematopoietic cell transplant (HCT) recipients remain out of school for a prolonged period of time; navigating their return to school after completion of therapy can be challenging for caregivers. METHODS: Between August 2020 and June 2021, we conducted individual semi-structured interviews of 19 caregivers of adolescent HCT recipients (10-18 years of age at HCT; 1-7 years post HCT) to understand the challenges faced at the time of their child's return to in-person school post HCT. Conventional content analysis was used to analyze interview transcripts, and thematic analysis was used to identify and organize emerging themes. RESULTS: Three themes emerged from the caregivers' experiences. First, caregivers reported facing several challenges related to lack of communication between their child's healthcare and school teams, which was burdensome for them. Second, some caregivers reported receiving support from school and healthcare professionals, as well as their child's peers, which helped reduce the burden of return to school. Caregivers also reported providing motivational, emotional, and spiritual support to patients. Lastly, caregivers made several recommendations regarding the need for better communication between family, healthcare professionals, and school professionals and availability of supportive care such as mental health counseling and neuropsychological testing. Notably, the need for a return-to-school navigator emerged as a key finding from our analysis. CONCLUSIONS: Caregivers of adolescent HCT recipients face several challenges supporting their children's return to school post HCT, which are related to lack of communication between patients' healthcare and school teams. While some reported receiving support from school and healthcare professionals and their child's peers, the need to coordinate the return-to-school process was burdensome for several caregivers. Additional work is needed to optimize support for HCT recipients and their caregivers during their return-to-school process to minimize burden. Our study findings have the potential to serve as a framework for developing and testing supportive care interventions to improve the return-to-school experience of HCT survivors and ultimately their quality of life.

Transcriptomic analysis of cave, surface, and hybrid samples of the isopod Asellus aquaticus and identification of chromosomal location of candidate genes for cave phenotype evolution.

BACKGROUND: Transcriptomic methods can be used to elucidate genes and pathways responsible for phenotypic differences between populations. Asellus aquaticus is a freshwater isopod crustacean with surface- and cave-dwelling ecomorphs that differ greatly in multiple phenotypes including pigmentation and eye size. Multiple genetic resources have been generated for this species, but the genes and pathways responsible for cave-specific characteristics have not yet been identified. Our goal was to generate transcriptomic resources in tandem with taking advantage of the species' ability to interbreed and generate hybrid individuals. RESULTS: We generated transcriptomes of the Rakov Skocjan surface population and the Rak Channel of Planina Cave population that combined Illumina short-read assemblies and PacBio Iso-seq long-read sequences. We investigated differential expression at two different embryonic time points as well as allele-specific expression of F1 hybrids between cave and surface individuals. RNAseq of F2 hybrids, as well as genotyping of a backcross, allowed for positional information of multiple candidate genes from the differential expression and allele-specific analyses. CONCLUSIONS: As expected, genes involved in phototransduction and ommochrome synthesis were under-expressed in the cave samples as compared to the surface samples. Allele-specific expression analysis of F1 hybrids identified genes with cave-biased (cave allele has higher mRNA levels than the surface allele) and surface-biased expression (surface allele has higher mRNA levels than the cave allele). RNAseq of F2 hybrids allowed for multiple genes to be placed to previously mapped genomic regions responsible for eye and pigmentation phenotypes. In the future, these transcriptomic resources will guide prioritization of candidates for functional analysis.

Obesity alters monocyte developmental trajectories to enhance metastasis.

Obesity is characterized by chronic systemic inflammation and enhances cancer metastasis and mortality. Obesity promotes breast cancer metastasis to lung in a neutrophil-dependent manner; however, the upstream regulatory mechanisms of this process remain unknown. Here, we show that obesity-induced monocytes underlie neutrophil activation and breast cancer lung metastasis. Using mass cytometry, obesity favors the expansion of myeloid lineages while restricting lymphoid cells within the peripheral blood. RNA sequencing and flow cytometry revealed that obesity-associated monocytes resemble professional antigen-presenting cells due to a shift in their development and exhibit enhanced MHCII expression and CXCL2 production. Monocyte induction of the CXCL2-CXCR2 axis underlies neutrophil activation and release of neutrophil extracellular traps to promote metastasis, and enhancement of this signaling axis is observed in lung metastases from obese cancer patients. Our findings provide mechanistic insight into the relationship between obesity and cancer by broadening our understanding of the interactive role that myeloid cells play in this process.