Key Populations Research Articles

Analysis of people newly diagnosed with HIV and intervention measures in Chongqing

This study aim to understand the characteristics of people newly diagnosed with HIV and intervention measures in Chongqing from 2010 to 2023 and determine more effective intervention measures for different key populations. The Spearman analysis method and multiple linear regression models were used to determine more effective intervention measures for different populations. The results showed that expanding tests had a good effect for both people attending STI clinics and MSM on detecting people newly diagnosed with HIV. Distributing condoms could effectively reduce the risk of HIV infection for FSW and peer education could effectively reduce the risk of HIV infection for MSM. Providing service packages for people attending STI clinics could help to reduce the risk of HIV infection. The study finds that more effective general intervention measures should be adopted for different key populations to facilitate more effective detection of individuals with HIV and reduce the risk of HIV infection, thereby effectively controlling the spread of HIV.

Usage of post-exposure prophylaxis and its impact on risk behaviors among men who have sex with men in Qingdao, China

BackgroundMen who have sex with men (MSM) are key populations for HIV infection. Post-exposure prophylaxis (PEP) has been confirmed to be an effective measure for preventing HIV transmission. This study aimed to investigate the usage of PEP among MSM in Qingdao and its associated factors, analyze the impact of PEP usage on risk behaviors, and offer insights for HIV prevention.MethodsBetween April and August 2021, a cross-sectional survey was conducted in Qingdao, relying on local community-based organizations (CBOs) and employing a snowball sampling method to recruit eligible MSM. We gathered sociodemographic information, behavioral data, and PEP usage details from the participants. The analysis of factors associated with PEP utilization among MSM was performed using a logistic regression model. Subsequently, a follow-up visit was conducted six months later, collecting behavioral information from the participants. Generalized estimating equations fitting Poisson regression were utilized to analyze behavioral changes during the follow-up for PEP users and non-PEP users.ResultsA total of 602 MSM were enrolled in this study, with a median age of 30.0 years. Among them, 140 individuals used PEP in the last 6 months, resulting in a usage rate of 23.3% (140/602). Factors associated with PEP usage included monthly income ≥ 5000 RMB (aOR = 2.092, 95%CI: 1.366–3.203) and engaging in group sex ≥ 3 times in the last 6 months (aOR = 1.844, 95%CI: 1.067–3.189). In the follow-up survey, 467 individuals participated, comprising 112 PEP users and 355 non-PEP users. Compared to the baseline, the proportion of non-PEP users with Rush Popper usage frequency ≥ 1 time/week increased from 19.3% to 34.4% during follow-up (RR = 1.671, 95%CI: 1.302–2.146), and the proportion of those engaging in unprotected anal intercourse in the past 6 months increased from 95.5% to 98.6% (RR = 1.029, 95%CI: 1.004–1.056). However, the risk behaviors of PEP users exhibited no significant changes during the study period (P > 0.05).ConclusionsHigher frequency of group sex and higher monthly income emerged as facilitating factors for PEP usage among MSM in Qingdao. Beyond its efficacy in preventing HIV infection, PEP may also play a role in managing the occurrence of risk behaviors among MSM. Consequently, there is a pressing need to intensify efforts to promote PEP uptake among MSM as a strategy to control the spread of HIV.

Theory-Based Social Media Intervention for Nonmedical Use of Prescription Opioids in Young Adults: Protocol for a Randomized Controlled Trial.

The nonmedical use of prescription opioids (NMUPO) in young adults in the United States is concerning and is robustly influenced by many psychosocial factors. Given the advantages of flexibility, wide coverage, and real-time responses and assessment, using social media appears to be a promising and innovative approach to delivering psychosocial intervention to young adults. However, few theory-based social media interventions are available for NMUPO targeting this at-risk population. Guided by the information-motivation-behavioral skills model, the proposed research aims to address critical gaps by theoretically exploring psychosocial content associated with NMUPO among young adults via formative assessment. These findings will then be used to develop and evaluate the feasibility and preliminary efficacy of a peer-led social media intervention to reduce NMUPO among young adults. The proposed study will comprise serial research activities. First, formative research will be conducted through semistructured interviews among 30 young adults engaged in NMUPO. Qualitative data will be synthesized using a pragmatic approach for identifying psychosocial content associated with NMUPO. Second, qualitative findings will be used for developing a peer-led social media intervention to reduce NMUPO among young adults by integrating promising psychotherapy principles and incorporating them with well-trained recovery coaches. Third, the social media intervention will be evaluated through a 12-week randomized controlled trial among 70 young adults (n=35, 50% in the intervention group and control group) engaged in NMUPO via mixed methods, including pre- and postintervention surveys, social media paradata (eg, time-series reactions to posts) collection, and ecological momentary assessment during the intervention. The control group will not receive an intervention but will complete the pre- and postintervention surveys. The primary outcomes will be feasibility, usability, and acceptability, while the secondary outcomes will be psychosocial and behavioral measures, such as past-3-month NMUPO, intention, psychological distress, self-efficacy, resilience, and coping strategies. The proposed study was funded in May 2024. Social media campaigns have received responses from a total of 379 individuals, with 24 (6.3%) identified as eligible. As of February 10, 2025, we have completed formative interviews with 8 eligible participants. The proposed study will be one of the first efforts to develop and deliver a theory-based peer-led intervention on social media, incorporating empirical findings on the psychosocial mechanism of NMUPO. The findings of the proposed study will provide valuable insights into opioid risk reduction for young adults through an innovative approach. If the tested trial is found to be feasible, the proposed study will contribute to future scaled-up and fully powered psychosocial interventions among young adults and other key populations at risk for NMUPO. ClincialTrials.gov NCT06469749; https://clinicaltrials.gov/study/NCT06469749. DERR1-10.2196/65847.

Misclassification of HIV infection status among serologically diverse populations in Nigeria: implications for test and treat program

BackgroundIn 2015, the World Health Organization (WHO) launched the Test and Treat policy which supports antiretroviral treatment for all people with HIV, irrespective of CD4 count or clinical stage. This was adopted in 2016 in Nigeria. This policy resulted in scaleup of HIV testing strategies and differentiated models of care including community-based ART. This study evaluated the HIV testing algorithm and assessed the rates of misclassification of HIV status among newly diagnosed clients.MethodsBetween February and August 2018, whole blood samples were collected from clients newly diagnosed with HIV in Lagos and Benue states. HIV status wasconfirmed with rapid tests using the serial algorithm during outreach sessions for both key populations and general populations. HIV positivity was confirmed using GenScreen™ HIV1/2.O Antibody only ELISA test (BioRad, USA). Optical density (OD) for each sample was measured with the use of Emax microplate reader set at endpoint 450 wavelength. Based on manufacturer’s algorithm, sample OD and calculated cut-off value ratio, an OD < 1.0 was interpreted as negative and > 1.0, positive. Concordance between rapid test algorithm result and ELISA was used to estimate the proportion of samples that were misclassified.ResultsA total of 788 samples were collected from newly diagnosed clients across 4 sites in Lagos and 3 sites in Benue. Samples were collected from 212 and 178 key populations (KPs) clients in Lagos and Benue, respectively, and from 206 and 192 general population (GPs) clients in Lagos and Benue, respectively. Mean OD was 3.75 (IQR:3.70–3.81) with a standard deviation of 0.13. There was a 100% concordance between rapid test and ELISA results and no misclassification identified.ConclusionWe identified no instances of misclassification of positive HIV status suggesting that all clients who have been placed on treatment truly had HIV infection. The 100% concordance rate recorded from all the sites may be attributable to the maturity of the HIV program in Nigerian with a concomitant standard quality assurance system for both clinical and outreach testing services. This finding supports the implementation of the Test and Treat policy that Nigeria has adopted. Scale up of Test and Treat and community ART is thus recommended to increase access to treatment.

Isolation of adipose stromal cells from blood using a two-step microfluidic platform ASCfinder

Mesenchymal stromal cells (MSCs) hold significant promise for their therapeutic potential and their possible role as disease biomarkers. While evidence suggests the presence of circulating Adipose-derived MSC (ASC) in peripheral blood (PB), isolating them is particularly challenging due to their low abundance, size variability, and incomplete characterization of their native immunophenotype in PB. Consequently, the relationship between ASC frequency in blood and various physiological or pathological conditions has been underexplored. In this study, we introduce ASC-Finder, a label-free isolation method specifically designed for adipose stromal cells (ASCs), a key MSC population. ASC-Finder integrates two independent modules: a size-dependent hydrodynamic filtration unit for sorting erythrocytes directly from PB and a negative enrichment module based on immunological markers to deplete remaining leukocytes. The device enabled removal of 99.98% of erythrocytes while achieving high recovery rates of spiked ASCs (> 81%) at rare-event concentrations (< 100 ASC/mL blood). Remarkably, ASC-Finder operates without clogging, even after multiple runs with donor blood samples. Crucially, our method bypasses the need for harsh lysis, centrifugation, or dilution buffers, preserving both cell integrity and phenotype—key factors for the discovery of novel cellular events. This work represents a significant advancement in the direct enrichment of circulating ASCs from whole PB without cell lysis, offering a crucial step toward investigating the characterization and role of blood-circulating ASCs.

The Involvement of MDSCs-Bacteria Crosstalk in Colitis as a Predisposing Factor for Colitis-Associated Colorectal Cancer

Inflammatory Bowel Disease (IBD), composed of Crohn's Disease (CD) and Ulcerative Colitis (UC), represents a chronic inflammatory condition that is associated, in some cases, with a predisposition of the host to Colitis-Associated Colorectal Cancer (CAC). Both IBD and CAC are characterized by immune system dysregulation and changes in intestinal microbiota composition (dysbiosis). The dysbiotic bacteria invade the intestinal tissue and are found to interact with diverse immune cells of which one key population is represented by Myeloid-Derived Suppressor Cells (MDSCs). MDSCs are a heterogeneous population of immature myeloid cells that, under normal conditions, give rise to immune cells from the myeloid lineage. However, under pathologies associated with chronic inflammation, these cells become highly polarized with enhanced suppressive activity, suppressing both the innate and adaptive immune systems by different routes. Our general aim is to better understand the involvement of MDSC-Bacteria crosstalk in colitis as a predisposing factor for CAC development. Herein, we demonstrate that IBD is characterized by elevated levels of MDSCs with enhanced suppressive activities, which can promote progression to CAC by inducing persistent immunosuppression and a proinflammatory environment in the colon during the IBD stage. In the intestines of IBD individuals, we found that MDSCs can often be seen in close proximity to tissue-invading bacteria, resulting in a polarization of these cells toward a highly suppressive and proinflammatory phenotype. Suppression mediated by the MDSCs is linked to the secretion of proinflammatory cytokines, nitric oxide, the arrest of T cell proliferation, and downregulated levels of CD247, a key signaling molecule expressed by T cells. Since MDSCs play a major role in the dysregulation of the immune system, different combinatorial therapeutic strategies to recuperate the host’s health and regress the disease were tested, aiming at targeting the MDSCs. To this end, we tested different metabolites and identified a potent metabolite inhibiting the bacteria-induced MDSCs polarization. The effects of this metabolite on MDSCs are currently under investigation, using proteomics analysis through the exploration of the downstream mechanism. These studies will help discover novel pathways that mediate the immunosuppression induced by MDSC upon their interaction with bacteria, towards the development of specific anti-MDSC therapeutic modalities. Our long-run aims are to alleviate intestinal inflammation by manipulating MDSC-induced immunosuppression, combat bacteria-induced MDSC polarization, and study the underlying mechanisms of unique metabolites as MDSC inhibitors.

Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers

Diabetic foot ulcers (DFU) are a common and severe complication among diabetic patients, posing a significant burden on patients’ quality of life and healthcare systems due to their high incidence, amputation rates, and mortality. This study utilized single-cell RNA sequencing technology to deeply analyze the cellular heterogeneity of the skin on the feet ofDFU patients and the transcriptomic characteristics of endothelial cells, aiming to identify key cell populations and genes associated with the healing and progression of DFU. The study found that endothelial cells from DFU patients exhibited significant transcriptomic differences under various conditions, particularly in signaling pathways related to inflammatory responses and angiogenesis. Through trajectory analysis and cell communication research, we revealed the key role of endothelial cell subsets in the development of DFU and identified multiple important gene modules associated with the progression of DFU. Notably, the promoting effect of the SH3BGRL3 gene on endothelial cell proliferation, migration, and angiogenic capabilities under high glucose conditions was experimentally verified, providing a new potential target and theoretical basis for the treatment of DFU. This study not only enhances the understanding of the pathogenesis ofDFU but also provides a scientific basis for the development ofnew therapeutic strategies.

Epidemiological characteristics and spatiotemporal distribution of hepatitis C in southeast coastal areas of China from 2015 to 2022

ObjectiveThe purpose of this study was to analyze the epidemiological characteristics and spatial-temporal distribution characteristics of hepatitis C in Fujian Province, China, from 2015 to 2022, and to provide reference for the risk identification, early warning and prevention and control measures of hepatitis C in Fujian Province.MethodsThe incidence data of hepatitis C in Fujian Province from 2015 to 2022 were collected from the China Information System for Disease Control and Prevention. Descriptive epidemiology method and JRP 4.9.1.0 software were used to analyze the epidemiological characteristics of hepatitis C in Fujian Province from 2015 to 2022. ArcGIS 10.8 software was used for spatial autocorrelation analysis of the reported incidence of hepatitis C, and SaTScan 10.1.3 software was used for spatio-temporal scanning analysis.ResultsA total of 18,712 cases of hepatitis C were reported in Fujian Province from 2015 to 2022, and the annual reported incidence showed a decreasing trend (AAPC =-10.4, P < 0.001). Males were more affected, accounting for 55.7% (n = 10,429) of all reported hepatitis C cases compared to 44.3% (n = 8,283) for females. Among all age groups, the number of cases in people aged 40–60 was the largest, accounting for 43.2%. Autocorrelation analysis showed that the reported cases of hepatitis C from 2015 to 2022 were clustered, and the global Moran´s I values were all greater than 0 (P < 0.001). Local autocorrelation analysis showed that the high-high concentration area of hepatitis C incidence was relatively fixed and concentrated in the Putian city. The spatial and temporal scanning analysis detected one largest possible agglomeration area, Xiuyu District of Putian city, and two type II agglomeration areas were mainly distributed in economically developed cities along the coastal line.ConclusionThe reported incidence of hepatitis C in Fujian province showed a downward trend from 2015 to 2022, and there were obvious epidemic characteristics and spatial-temporal clustering of hepatitis C. Attention should be paid not only to the key population of 40–60 years old males in rural areas and the key gathering areas in Putian City, but also to the incidence of hepatitis C in southeast coastal areas.

HIV Incidence and Associated Risk Factors Among Young Men Who Have Sex With Men in Tianjin, China: Retrospective Cohort Study.

Young men who have sex with men (YMSM) have a higher risk of HIV infection. However, evidence of HIV incidence from large cohort studies is limited in this key population, particularly among Chinese YMSM. This study aimed to investigate the HIV incidence and associated risk factors among YMSM aged 16-24 years in Tianjin, China. We conducted a retrospective cohort study among men who have sex with men aged 16-24 years from October 2017 to December 2022 through the largest local nongovernmental organization serving men who have sex with men in Tianjin. Participants who responded to the investigations at least twice during the study period were included. They completed questionnaires on demographic information, sexual behaviors, psychoactive substance use, and sexually transmitted infection status. Simultaneously, their blood samples were collected for HIV testing. HIV incidence was calculated by dividing the sum of observed HIV seroconversions by the observed person-years (PYs). A Cox proportional hazards regression model was used to identify risk factors associated with HIV incidence. A total of 1367 HIV-negative YMSM were included in the cohort, among whom 62 seroconversions occurred, contributing 2384.2 observed PYs; the total incidence was 2.6 (95% CI 2.0-3.2) per 100 PYs. The segmented HIV incidence rates were 3 (95% CI 1.5-4.5), 2.4 (95% CI 1.5-3.3), and 2.7 (95% CI 1.5-3.9) per 100 PYs for 2017-2018, 2019-2020, and 2021-2022, respectively. Compared to YMSM who had been followed up fewer than three times, those followed up three or more times had a relatively lower risk of HIV infection (Adjusted hazard ratio [AHR] 0.553, 95% CI 0.325-0.941). YMSM who preferred finding sexual partners offline had a higher risk of HIV infection compared to those who preferred finding sexual partners online (AHR 2.207, 95% CI 1.198-4.066). Compared to YMSM without syphilis, those infected with syphilis had an increased risk of HIV infection (AHR 2.234, 95% CI 1.137-4.391). Additionally, YMSM who used psychoactive substances had a higher risk of HIV infection compared to those who did not use such substances (AHR 2.467, 95% CI 1.408-4.321). Our study complements data on HIV incidence among YMSM in large cities across China. Syphilis infection and the use of psychoactive substances were risk factors associated with HIV occurrence, demonstrating an urgent need for tailored prevention and control interventions for this key population.

Evaluation of differentiated service delivery models on HIV treatment retention among key populations in Nigeria: a prospective cohort analysis

IntroductionDifferentiated Service Delivery models (DSD) that cater to the needs of key populations (KP) have shown promise in providing KP-sensitive and KP-tailored care and treatment services. We evaluated the effect of two DSD models on linkage to and retention in treatment in Nigeria.MethodsBetween December 2017 and June 2018, newly-diagnosed men who have sex with men (MSM) and female sex workers (FSWs) were enrolled into treatment through two DSD models and followed prospectively for one year. Model 1 was a fully integrated one-stop-shop (OSS) while model 2 was a hybrid HIV prevention and treatment site (DIC). Retention was estimated from drug pick-up records and was defined as being on treatment within 90 days one-year post ART initiation. Cox regression was used to identify the independent effect of the DSD models on retention while probability of being retained in treatment at 1-year was estimated with Kaplan-Meier product limit.ResultsA total of 605 newly-diagnosed clients were enrolled into the study (340 in OSS and 265 in DIC; 342 were FSWs, while 263 were MSM). Median age was 26 years for MSM and 30 years for FSWs. Among those linked to treatment, retention was higher in the OSS than in DIC (63% vs. 48%; p = 0.002). Among those not retained, mean days to be lost-to-follow up (LFTU) was 60 days. Controlling for educational level, population type and age, clients who received treatment in M2 were 6 times more likely not to be retained in treatment at the end of 1 year (Hazard ratio 5.89; 95% CI: 1.04–33.16). The Kaplan Meier estimates of the probability of being retained in 6 months, 9 months and 12 months was 0.97, 0.92, 0.80 for the DIC and 1.00, 0.96, 0.91 for the OSS.ConclusionLinkage to treatment was suboptimal across both models with less than 90% of newly-diagnosed positives initiated on treatment and suggests that facilitated linkage is required to achieve at least 95%. Though retention was higher in the OSS model, both models had an alarmingly short time frame for LTFU and thus intensive monitoring during this phase of treatment is recommended irrespective of the type of DSD. Addressing these gaps will improve service delivery by one stop shops for HIV care and treatment.

Optimal control strategies supported by system dynamics modelling: a study on hookworm disease in China

BackgroundHookworm disease remains a global health issue. In China, it persists with a 0.67% infection rate and uneven distribution in 2021. Optimized control strategies are needed. This study aims to optimize intervention strategies for hookworm disease in China.MethodsStructural analysis and parameter estimation were conducted using system dynamics theory. Key variables were identified via the Delphi method, leading to the creation of a causal loop diagram (CLD) and stock flow chart (SFC). Based on the SFC, parameter estimation and quantitative relationships were established and the model was validated. A cost-effectiveness model was then integrated into the intervention mechanism model. Various intervention measures were tested in the model to determine their cost-effectiveness ratio (CER) and effectiveness. Generalized linear models were constructed from simulation data, accounting for the impact of survey sites. The results were used to develop an optimized strategy for hookworm disease control.ResultsIn comparing drug treatment methods, whole population deworming (WPD) and key population deworming (KPD) showed lower CERs than examination and voluntarily deworming (EVD), saving 384.79–504.64 CNY and 354.35–506.21 CNY per infection reduced, respectively (P < 0.001). For WPD or KPD alone, CER decreased with increased drug coverage. For examination and deworming (ED) and EVD, CER was highest at 30% coverage for a 1-year intervention, but at 90% coverage for 2–5 years (P < 0.05). WPD, ED, and EVD had higher infection reduction rates than KPD, with ratios of 0.14–0.25, 0.10–0.19, and 0.08–0.17, respectively, over 1–5 years (P < 0.001). Continuous health education over 1–5 years showed that increasing coverage from a 10% baseline led to enhancing cost-effectiveness and intervention outcomes.ConclusionsIn high-endemic areas (infection rate ≥ 20%) in China, prioritize WPD for better cost-effectiveness and outcomes. In medium-endemic areas (5% ≤ infection rate < 20%) where WPD isn't feasible, use ED for cost-effectiveness and KPD for infection reduction, based on local needs. In low-endemic areas (infection rate < 5%), encourage voluntary examination and treatment due to limited cost-effectiveness of mass treatment. Combining drug treatment with extensive health education can enhance long-term control effect. This strategy can guide control efforts for hookworm diseases in China.Clinical trial number: Not applicable.Graphical

Impact of the COVID-19 Pandemic on Social Support Networks of Gay and Bisexual Men with HIV in New York City.

The COVID-19 pandemic, and the ensuing social policies enacted to control viral transmission of SARS-CoV-2, has had a significant impact on social support networks. For people living with HIV (PWH), including gay, bisexual, and other men who have sex with men (GBMSM), social support networks serve additional purposes in the self-management of HIV care and psychosocial health. Given the broad-reaching effects of the pandemic, characterizing its impact on specific dimensions of social support networks remains a prime area of investigation. We used egocentric social network data from an on-going longitudinal study of GBMSM with HIV, living in New York City (NYC), to examine changes in the structural, interactional, and functional characteristics of their social support networks from pre- to post-start of the pandemic. We analyzed data from 146 GBMSM who reported a total of 164 social support network members. We found that the average size of social support member networks increased over time, of which 57% and 25% provided companionship and confidant support, respectively. Follow-up questions about how often guidance, tangible, and emotional support was provided (if needed) suggest the quality of support decreased over time. At follow-up, nearly half (49%) of network members were friends, the vast majority (89%) were aware of GBMSM's HIV status, and most (74%) were also living within NYC. Characterizing the changes in social support networks over the course of the COVID-19 pandemic can help identify areas of need and resilience, especially for key populations such as GBMSM with HIV.

Exploring HIV self-testing as an early detection strategy among female sex workers in Waliso town, Ethiopia: a community based cross sectional study

BackgroundThe burden of HIV infection among key population like female sex workers (FSW) is higher and challenges the prevention and control of the virus compared to other population groups. HIV self-testing allows people to test themselves discreetly and conveniently and may provide opportunities to people not currently reached by existing HIV testing and counseling services. Hence, this study aimed to assess the magnitude of HIV Self-Testing (HIVST) and associated factors among Female sex workers in Waliso Town in Central Ethiopia.MethodA community-based Cross-sectional study was conducted from 1 October–November 30, 2023, among female sex workers using snowball sampling. A total of 400 participants were included in the study. Data was collected using pre-tested, structured self-administered, and interviewer-administered questionnaires using face-to-face interviews. A binary logistic regression model was fitted using SPSS version 26 to identify factors associated with HIV self-testing. Adjusted Odds Ratio (AOR), 95% confidence interval, and a p-value < 0.05 was used to judge the statistically significant variables.ResultsThe prevalence of HIV self-testing among female sex workers in Waliso town was found to be 37% (95% CI: 32, 42). Education status (attended high school and above) (AOR = 7.62[95% CI 2.55,24.67], marital status (divorced) (AOR = 2.1[95% CI 1.23,3.6], those whose both parents dead (AOR = 2.72[95% CI 1.4,5.28] and before sex whether they asked their partner test status (AOR = 0.17[95% CI 0.07,0.37] were statistically significant.ConclusionThis study revealed that HIV self-tests among female sex workers were lower than the 95% national target. Education status, marital status, parent`s living status and knowing the partner HIV status before sex were found to be predictors of HIV self-test. Our findings underscore the need to develop evidence-based strategies to improve HIV testing uptake by FSWs and improve community-based services.

Airway basal stem cell-derived extracellular vesicles modulate proliferation, migration and collagen deposition of fibroblasts

BackgroundHuman bronchial epithelial cell-derived extracellular vesicles have demonstrated the ability to attenuate fibroblasts activation. However, the specific key effector cell populations mediating this inhibitory effect remain unidentified. Airway basal stem cells (BSCs), which serve as progenitor cells for bronchial epithelial cells, play a critical role in fibrotic remodeling processes and possess significant therapeutic potential. This study aimed to characterize BSC-derived extracellular vesicles (BSC-EVs) and investigate their regulatory influence on fibroblasts behavior.MethodsAirway BSCs were collected through bronchoscopic brushing and differential centrifugation. Fibroblasts were subsequently treated with BSC-EVs at various concentrations to evaluate their dose- and time-dependent effects in vitro. The proteomic composition of BSC-EVs was analyzed using four-dimensional data-independent acquisition quantitative mass spectrometry (4D-DIA). Moreover, a bleomycin-induced pulmonary fibrosis model was established to evaluate the safety and preliminary efficacy of BSC-EVs.ResultsWe successfully isolated and identified BSC-EVs, which expressed the nucleus-specific marker TP63, indicative of BSCs, but lacked the BSC marker KRT5. Our findings demonstrated that BSC-EVs enhanced fibroblasts proliferation and migration in a dose-dependent manner. Importantly, BSC-EVs significantly attenuated fibroblasts activation and promoted fibroblasts senescence. Utilizing 4D-DIA quantitative proteomics, we revealed that BSC-EVs modulate extracellular matrix remodeling processes and regulate the expression of key proteins, including collagen I/III and matrix metalloproteinases. Animal models utilizing intratracheal administration of BSC-EVs demonstrate efficient reduction of collagen deposition.ConclusionThis study offers an extensive characterization of BSC-EVs, adhering to the guidelines set forth by MISEV2023. The findings underscore the significant therapeutic potential of BSC-EVs in the management of fibrotic diseases.

Trends in Mental and Behavioral Health Risks in Adolescents: 1999-2021.

To identify distinct profiles of adolescent mental and behavioral health risks and variation over cohorts and demographic strata from 1999 through 2021. We expected increased mental health risks and decreased behavioral health risks. We analyzed repeated, cross-sectional, nationally representative samples of high school students from the 1991-2021 national Youth Risk Behavior Survey (N = 178 658) using latent class analysis. Adolescents self-reported mental and behavioral health risk behaviors, including internalizing (depressive symptoms, suicidality), substance use (alcohol, marijuana use), sexual risk behaviors (number of sexual partners, effective birth control), and violence (weapons carriage, fighting). We identified 5 distinct profiles. The largest group, Low Everything (48% of adolescents), grew notably in prevalence from 1999 to 2021. The smallest, High Internalizing (9% of adolescents), also grew. High Sex (20%), High Everything (13%), and High Substance Use (10%) all decreased, with all trajectories strengthening between 2019 and 2021 during the COVID-19 pandemic. Younger adolescents predominated in the Low Everything and High Internalizing profiles, and older adolescents predominated in the High Sex and High Everything profiles. Females were more prevalent in the High Internalizing and High Sex profiles, and males were more prevalent in the High Everything and High Substance Use profiles. White adolescents were overrepresented in the High Substance Use profile, and youth of color were overrepresented in the other profiles. Results showing decreasing proportions of adolescents reporting comorbid mental and behavioral health risks or behavioral health risks only, but increases in mental health problems only, help to identify and target key populations for prevention and treatment efforts.

Analysis of HIV-1 subtypes and drug resistance mutations in people who inject drugs in Aizawl and nearby districts of Mizoram, India

ABSTRACT Over the last decade, there has been a steady increase in HIV-1 prevalence in Mizoram, India. Importantly, this increase in HIV-1 prevalence is not only limited to the key population groups such as female sex workers (FSWs) or people who inject drugs (PWID), and has been witnessed in general population as well. Injecting drug use has long been one of the key drivers of HIV-1 epidemic across the north-eastern states of India. In this study, using HIV-1 pol gene region sequences from Aizawl and adjoining districts, we examined the HIV-1 subtypes, recombinant forms, drug resistance mutations and also the spatiotemporal dynamics of the potential unique recombinant forms. In our dataset, the dominant subtype was HIV-1 subtype C (94.91%). We could also identify the presence of CRF01_AE (1.69%) and BC recombinant forms (3.39%). Drug resistance mutation analysis revealed that resistance against non-nucleoside reverse transcriptase inhibitors was most common in the sequences having any resistance mutations. Evolutionary analysis of unique BC recombinants estimated the most recent common ancestor of these sequences around 2004–2005 and them having an ancestry of United States of America (USA) origin.

Phylogenetic analysis and transmission networks highlight the role of older adults in the transmission of HIV-1 in northern Zhejiang, China

BackgroundIn China, human immunodeficiency virus (HIV) poses a significant challenge to older heterosexual adults. This study explored the transmission dynamics of HIV infection among older adults in northern Zhejiang Province, China using phylogenetic analysis and transmission networks.MethodsHIV pol sequences without any antiretroviral therapy were obtained from newly diagnosed HIV-positive patients in Huzhou between 2017 and 2022. Pairwise genetic distances between sequences were calculated using HIV Trace based on the Tamura-Nei 93 method. The transmission network was constructed using Cytoscape v3.9.1. The effective reproductive number (Re) of each large cluster was estimated using the birth-death skyline model in BEAST v2.4.2. Multivariate logistic regression was performed to identify factors associated with clustering using R v4.4.3 software.ResultsA total of 931 HIV pol sequences were successfully obtained, of which CRF07_BC (51.7%, 481/931) and CRF01_AE (27.5%, 256/931) were the predominant subtypes. The proportion of CRF07_BC increased from 43.5% in 2017 to 59.8% in 2022, whereas that of CRF01_AE decreased from 33.3% in 2017 to 19.5% in 2022. In total, 448 individuals formed 110 putative transmission networks with a clustering rate of 48.1%, ranging from 2 to 83 sequences per network. Four large clusters were identified, with a higher proportion of individuals aged ≥ 50 years (49.0%) compared to that in small/ medium clusters (35.5%) and non-clustered cases (26.1%). Multivariable logistic regression showed that clustering was associated with age ≥ 50 years (adjusted odds ratio [aOR] = 2.125, 95% confidence interval [CI]: 1.251–3.632), registered households in Huzhou (aOR: 1.677, 95% CI: 1.252–2.249), and CRF07_BC subtype (aOR: 2.119, 95% CI: 1.542–2.924). Only one of the four large transmission clusters had a Re > 1, with a high proportion (63.0%, 29/46) of male older adults exposed through commercial sexual contact.ConclusionsThe subtype of CRF07_BC was the predominant subtype locally, showing an increasing trend over time. Molecular transmission network analysis and multivariate logistic regression revealed that older adults play a key role in local HIV-1 transmission. Public health services should target this key population to curb the spread of HIV-1.

Sexual Violence and the Increased Risk of HIV among MSM in Nigeria.

Gay men and other men who have sex with men (MSM) are disproportionately affected by HIV and prone to sexual violence. While the association between HIV and sexual violence is well documented, the evidence is not conclusive from the few available studies among MSM in sub-Saharan Africa. The objective of this study was to estimate the prevalence of sexual violence and its association with HIV among MSM in Nigeria. The study was a secondary data analysis of the 2020 Integrated Biological & Behavioral Surveillance Survey (IBBSS) conducted among key populations in Nigeria's six geopolitical zones. Sexual violence was operationalized as self-reported forced sex by any person in the past 12 months. We performed weighted descriptive statistics and logistic regression analysis. The prevalence of sexual violence in the 4,324 MSM included in the analysis was 16.4% (95%CI = 15.3-17.5%). The highest prevalence was among MSM who reported injection drug use (49.0%, 95% CI = 41.7-56.6%), followed by those who engaged in transactional sex (29.6%, 95%CI = 27.0-32.2%). Among MSM who reported sexual violence, 36.1% (95%CI = 32.6-39.7%) tested HIV positive compared with 23.2% (95% CI: 21.8-24.6) in those who did not. After controlling for sociodemographic and behavioral characteristics, MSM who had been victims of sexual violence had higher odds of testing HIV positive (aOR = 1.87, 95%CI = 1.53-2.29). Sexual violence is prevalent and associated with HIV among MSM in Nigeria. Our findings further support the call to address sexual violence in this key population through the integration of preventive and care interventions into existing HIV programmes.

The Mpox Response Among Key Populations at High Risk of or Living with HIV in Rwanda: Leveraging the Successful National HIV Control Program for More Impactful Interventions.

Mpox, an emerging zoonotic infectious disease, presents a significant public health threat, especially among high-risk groups like female sex workers and men who have sex with men. This commentary reviews and summarizes Rwanda's response to mpox, focusing on its intersection with HIV. Rwanda has adopted an integrated strategy to tackle both mpox and HIV by leveraging lessons and experience from the country's success in the management of HIV and COVID-19, enhancing community engagement and health outcomes. To ensure long-term resilience, Rwanda must continue to invest in surveillance and research, expand vaccination efforts, address stigma, and foster regional impactful partnerships. Investing in fostering scientific and operational research will generate invaluable evidence that could lead to the implementation of evidence-based policymaking and cost-effective interventions.

Single-cell spatial transcriptomics unravels cell states and ecosystems associated with clinical response to immunotherapy

BackgroundThe tumor microenvironment (TME) is a complex and dynamic ecosystem that is known to influence responses to immunotherapy. We leveraged single-cell spatial transcriptomics to systematically dissect the intricate complexity of...