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Children of key population individuals (CPK) often face the same stigma and discrimination as their parents, limiting their access to HIV services. The Meeting Targets and Maintaining Epidemic Control project analyzed pediatric HIV testing data from project-supported sites to better understand risk among CKP and improve comprehensive prevention, testing, and treatment for KP families. We conducted a retrospective analysis of routine program data collected October 1, 2021-September 30, 2022, in project-supported sites in Burundi, Côte d'Ivoire, Democratic Republic of Congo, Tanzania, and Togo. We compared HIV case finding (defined as the percentage of children diagnosed with HIV among those who were tested) and treatment initiation (defined as the percentage of children diagnosed with HIV who were initiated on antiretroviral therapy) data for children <15 years disaggregated by index versus non-index testing and CKP versus children of non-KP individuals (non-CKP). A total of 5,651 children were tested (n = 2,974 index testing; n = 2,677 non-index testing). Of those diagnosed with HIV, 33% (181/541) were CKP, with case finding 17% (181 positive/1,070 tested) among CKP and 8% among non-CKP (360 positive/4,581 tested). Almost half of CKP diagnosed were ages 1-4 years. Among the 2,974 (53%) reached through index testing, overall case finding was higher among CKP (17%; 178 positive/1,052 tested) than non-CKP (11%; 219 positive/1,922 tested). Treatment initiation was 97% among CKP and 94% among non-CKP. CKP were identified primarily through index testing which, although considered a priority strategy to identify children at high risk, has not been widely used within KP family networks. Most CKP reached were children of female sex workers, but those of other KPs should also be prioritized. KP-focused programs have often excluded children, but the case-finding approaches in the project's KP programs were effective in reaching CKP. Comprehensive, family-centered KP programming is needed that includes family planning, prevention of vertical transmission, early infant diagnosis, and other maternal and child health services to reduce the impact of HIV on families and achieve an HIV-free generation.

Background Men who have sex with men (MSM) are consistently burdened by HIV at higher levels than other adults. While HIV prevention programs for MSM are growing in coverage and quality, HIV incidence remains high. In response, pre-exposure prophylaxis (PrEP) was introduced in 2019 to support HIV risk reduction among MSM in Cameroon. Understanding how PrEP initiation programs will change the HIV prevalence among MSM in Cameroon is important to developing effective programs. Methods This study uses a mathematical model to simulate population-level HIV transmission among MSM in the cities of Yaoundé and Douala, Cameroon. PrEP is incorporated into the model at rates that equal 25%, 50%, or 75% coverage after twenty years to assess the potential effects on HIV prevalence among MSM, requiring annual initiation rates of 2.5%, 6.8%, and 17.2% for Yaoundé and 2.2%, 5.6%, and 13.4% for Douala, respectively. The data utilized for this model are from a cross sectional study which recruited MSM through respondent-driven sampling of MSM in two major cities in Cameroon: Yaoundé and Douala. Results The model estimated an HIV prevalence of 43.2% among MSM, annual HIV diagnoses of 300 per 10,000 MSM and antiretroviral therapy (ART) coverage of 53.9% in Yaoundé. In Douala, estimated prevalence is 26.5% among MSM, 167 per 10,000 MSM annual diagnoses and ART coverage of 72.0%. Standalone PrEP interventions aimed at 50% coverage at the end of a 20-year program would reduce the prevalence from 43.2% to 35.4% in Yaoundé and from 26.5 to 20.1% in Douala. Combining PrEP with a 10% increase in HIV testing would decrease the number of MSM living with HIV and unaware of their status from 9.8 to 6.0% in Yaoundé and from 8.7 to 4.6% in Douala. Conclusions PrEP would be beneficial in reducing prevalence even at varying initiation and coverage levels. Combination of PrEP and increased HIV testing further decreased the number of undiagnosed MSM. This study supports the utility of implementing PrEP as part of comprehensive HIV prevention programming among MSM in Cameroon.

Addiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking. While habits are not inherently permanent or maladaptive, continued use of habits under conditions that should encourage goal-directed control makes them maladaptive and inflexible. We trained male and female Sprague Dawley rats on a seeking-taking chained schedule of cocaine self-administration (2 h/day). We then exposed them to 4 days of punishment testing, in which footshock (0.4 mA, 0.3 s) was delivered randomly on one-third of trials, immediately following completion of seeking and prior to extension of the taking lever. Before and after punishment testing (4 days pre-punishment and ≥4 days post-punishment), we assessed whether cocaine seeking was goal-directed or habitual using outcome devaluation via cocaine satiety. We found that punishment resistance was associated with continued use of habits, whereas punishment sensitivity was associated with increased goal-directed control. Although punishment resistance was not predicted by habitual responding pre-punishment, it was associated with habitual responding post-punishment. In parallel studies of food self-administration, we similarly observed that punishment resistance was associated with habitual responding post-punishment but not pre-punishment. These findings indicate that punishment resistance is related to habits that have become inflexible and persist under conditions that should encourage a transition to goal-directed behavior.Addiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking. While habits are not inherently permanent or maladaptive, continued use of habits under conditions that should encourage goal-directed control makes them maladaptive and inflexible. We trained male and female Sprague Dawley rats on a seeking-taking chained schedule of cocaine self-administration (2 h/day). We then exposed them to 4 days of punishment testing, in which footshock (0.4 mA, 0.3 s) was delivered randomly on one-third of trials, immediately following completion of seeking and prior to extension of the taking lever. Before and after punishment testing (4 days pre-punishment and ≥4 days post-punishment), we assessed whether cocaine seeking was goal-directed or habitual using outcome devaluation via cocaine satiety. We found that punishment resistance was associated with continued use of habits, whereas punishment sensitivity was associated with increased goal-directed control. Although punishment resistance was not predicted by habitual responding pre-punishment, it was associated with habitual responding post-punishment. In parallel studies of food self-administration, we similarly observed that punishment resistance was associated with habitual responding post-punishment but not pre-punishment. These findings indicate that punishment resistance is related to habits that have become inflexible and persist under conditions that should encourage a transition to goal-directed behavior.

Background: migraine can negatively affect students' health, well-being, and physical, mental, and cognitive functions. Aims: This study aims to (i) compare the health-related QoL of students with and without migraines, (ii) assess the association between higher QoL scores and the general characteristics of the students, and (iii) evaluate the predictors of higher QoL. Methods: A cross-sectional study was conducted over four months between November 2019 and April 2020, targeting 1095 students from the public university campus faculties. Data were collected using a validated tool (SF-8) through face-to-face interviews performed by four pharmacy students. Results: Cases had significantly lower scores in all the physical domains compared to controls, with an overall total score of 62.0 (16.7) compared to 73.1 (18.4) (pO.OOl). Similarly, lower overall scores for the mental domains were noted for cases (61.3 (16.7)). Caffeine consumption affected mental scores, where 71.9% of non-consmners had significantly higher scores than others (54.5%; p=0.015). Moreover, the higher the academic satisfaction, the better the QoL, with 61.2% of students who reported high satisfaction having higher scores in the mental domains compared to only 34.2% of those reporting low academic satisfaction (p=0.008). On the other hand, 62.6% of male students without migraine had significantly higher PC scores than females (48.2%; p<0.001), and those in their last academic years had substantially higher PC scores compared to those in their first two years (p=0.004). Cigarette and waterpipe smokers had lower PC scores among controls (p=0.042 and 0.012, respectively), and around 60% of those practicing sports had higher PC and MC scores (pO.OOl). Conclusion: Migraine adversely affected students on both physical and psychological aspects, translated by lower QoL scores. The predictors of a better QoL should be considered when developing treatment plans and supporting those affected by this condition.

Our brains constantly filter incoming sounds to understand our environment. While extensively studied in adults, how this ability develops across childhood remains unclear. We recorded intracranial brain activity from 54 participants aged 4-21 while they watched movie clips containing simultaneous speech and music. We used deep neural networks to separate the mixed audio into isolated speech and music streams, then built encoding models to determine which stream best predicted neural responses in the auditory cortex. Although participants heard only the original mixture with no instruction to attend to either stream, higher-order auditory regions including the superior temporal gyrus (STG), superior temporal sulcus (STS) and middle temporal gyrus (MTG), responded preferentially to speech. This speech-bias strengthened with age in STG, suggesting that this region progressively sharpens its representation of socially relevant sound across development. These findings indicate that speech prioritization in the developing brain emerges automatically, without directed attention.

Road traffic injuries (RTIs) are a growing public health problem requiring urgent attention in Cameroon where emergency medical services (EMS) are underdeveloped. In other countries, training laypersons to provide prehospital care has been shown to improve injury outcomes, but requires buy-in from the persons being trained to provide care. To inform development of a lay first responder (LFR) program in Cameroon, this study aimed to assess the willingness of community members and associated factors to provide prehospital care for RTIs along the N3 highway, a road linking Cameroon's two largest cities, known to have high incidence of RTIs. We conducted a cross-sectional survey of community members living along the N3 highway, between June 18th and August 16th, 2024. Health district officials and community leaders identified N3 communities across 11 health districts with high rates of RTI. Purposeful sampling was performed in each community to assess exposure to injury and willingness to participate in prehospital care. Trained research assistants verbally administered a structured questionnaire to each consenting household representative; data collected included socio-demographic characteristics, injury exposure, first aid knowledge and attitudes, and willingness to provide prehospital care to victims of RTIs. Associations between demographic factors and willingness to provide prehospital care were assessed using multivariable logistic regression. Data were analyzed using IBM-SPSS version 26.0 and statistical significance was set at p < 0.05. A total of 449 adult community members were surveyed. Most [268 (59.7%)) respondents were male with a median age of 33 years (interquartile range: 26-40). The majority, 333 (74.6%) community members were willing to provide care to injured victims. However, a third [167 (37.2%)] had adequate knowledge (scored ≥ 80%) of first aid and only 23 (5%) had been trained in first aid. Factors independently associated with willingness to provide prehospital care included having adequate first aid knowledge (adjusted odd ratio (aOR) = 1.69, 95% confidence interval (CI): 1.01-2.81, p = 0.046), primary education (aOR=4.20, 95% CI: 1.19-4.81, p = 0.026) and secondary education (aOR=4.70, 95% CI: 1.34-16.53, p = 0.016) compared to respondents with no formal education, prior witness of RTI (aOR=1.68, 95% CI: 1.055-2.68, p = 0.028), being aged between 30 and 40 years (aOR=1.82, 95% CI: 1.06-3.14, p = 0.031) and community members being able to call dedicated phone numbers to report RTIs (aOR=3.11, 95% CI: 1.28-7.54, p = 0.012). Most community members living in injury exposed-communities reported willingness to participate in prehospital care. However, first-aid knowledge is currently lacking in these communities. LFR training is needed in these communities to enable willing community members to contribute to prehospital efforts for RTIs along this road network.

BackgroundMerkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti–programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab.MethodsIn a cohort of this single-arm, phase 2 trial (JAVELIN Merkel 200), patients with mMCC and disease progression after prior chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate (ORR) by independent review per Response Evaluation Criteria in Solid Tumors V.1.1. Other assessments included duration of response, progression-free survival, overall survival (OS), safety and biomarker analyses.ResultsAs of 14 September 2018, 88 patients had been followed up for a median of 40.8 months (range 36.4–49.7 months). The ORR was 33.0% (95% CI 23.3% to 43.8%), including a complete response in 11.4% (10 patients), and the median duration of response was 40.5 months (95% CI 18.0 months to not estimable). As of 2 May 2019 (≥44 months of follow-up), the median OS was 12.6 months (95% CI 7.5 to 17.1 months) and the 42-month OS rate was 31% (95% CI 22% to 41%). Of long-term survivors (OS >36 months) evaluable for PD-L1 expression status (n=22), 81.8% had PD-L1+ tumors. In exploratory biomarker analyses, high tumor mutational burden (≥2 non-synonymous somatic variants per megabase) and high major histocompatibility complex class I expression (30% of tumors with highest expression) were associated with trends for improved ORR and OS. In long-term safety assessments (≥36 months of follow-up), no new or unexpected adverse events were reported, and no treatment-related deaths occurred.ConclusionsAvelumab showed continued durable responses and meaningful long-term survival outcomes in patients with mMCC, reinforcing avelumab as a standard-of-care treatment option for this disease.Trial registration number NCT02155647

BackgroundAvelumab (anti-programmed death ligand 1 (PD-L1)) is approved in multiple countries for the treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. We report efficacy and safety data and exploratory biomarker analyses from a cohort of patients with mMCC treated with first-line avelumab in a phase II trial.MethodsPatients with treatment-naive mMCC received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was durable response, defined as objective response (complete or partial response; assessed by independent review) lasting ≥6 months. Additional assessments included progression-free survival (PFS), overall survival (OS), safety, and biomarker analyses.ResultsIn 116 patients treated with avelumab, median follow-up was 21.2 months (range: 14.9–36.6). Thirty-five patients had a response lasting ≥6 months, giving a durable response rate of 30.2% (95% CI: 22.0% to 39.4%). The objective response rate was 39.7% (95% CI: 30.7% to 49.2%). Median PFS was 4.1 months (95% CI: 1.4 to 6.1) and median OS was 20.3 months (95% CI: 12.4 to not estimable). Response rates were numerically higher in patients with PD-L1+ tumors, Merkel cell polyomavirus (MCPyV)-negative tumors, and tumors with increased intratumoral CD8+ T-cell density. Exploratory analyses did not identify a biomarker that could reliably predict a response to first-line treatment with avelumab; however, a novel gene expression signature to identify the presence of MCPyV+ tumors was derived. Treatment-related adverse events (any grade) occurred in 94 (81.0%) patients, including grade 3/4 events in 21 (18.1%) patients; no treatment-related deaths occurred.ConclusionIn patients with mMCC, first-line treatment with avelumab led to responses in 40% and durable responses in 30%, and was associated with a low rate of grade 3/4 treatment-related adverse events.

Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In humans, ZGA is induced by DUX4, a pioneer factor that drives expression of downstream germline-specific genes and retroelements. Here we show that herpesviruses from all subfamilies, papillomaviruses and Merkel cell polyomavirus actively induce DUX4 expression to promote viral transcription and replication. Analysis of single-cell sequencing data sets from patients shows that viral DUX4 activation is of relevance in vivo. Herpes-simplex virus 1 (HSV-1) immediate early proteins directly induce expression of DUX4 and its target genes, which mimics zygotic genome activation. Upon HSV-1 infection, DUX4 directly binds to the viral genome and promotes viral transcription. DUX4 is functionally required for infection, since genetic depletion by CRISPR/Cas9 as well as degradation of DUX4 by nanobody constructs abrogates HSV-1 replication. Our results show that DNA viruses including herpesviruses mimic an embryonic-like transcriptional program that prevents epigenetic silencing of the viral genome and facilitates herpesviral gene expression. Neugebauer et al. show activation of the usually silenced embryonic factor DUX4 by herpesviruses in vitro and in patients, and demonstrate that depletion of DUX4 by nanobody degraders abrogates viral replication.