Summary Carcinoma associated fibroblasts (CAFs) that express α-smooth-muscle-actin (αSMA) contribute to cancer progression, but their precise origin and role is unclear. Using mouse models of inflammation-induced gastric cancer, we show that at least 20% of CAFs originate from bone marrow (BM) and derive from mesenchymal stem cells (MSCs). αSMA+ myofibroblasts (MF) are niche cells normally present in BM and increase markedly during cancer progression. MSC-derived CAFs that are recruited to the dysplastic stomach express IL-6, Wnt5α and BMP4, show DNA-hypomethylation, and promote tumor growth. Moreover, CAFs are generated from MSCs and are recruited to the tumor in TGF-β- and SDF-1α-dependent manner. Carcinogenesis therefore involves expansion and relocation of BM-niche cells to the tumor to create a niche to sustain cancer progression.

As demonstrated during the SARS-CoV-2 pandemic, detecting and tracking the emergence and spread of pathogen variants is an important component of monitoring infectious disease outbreaks. Pathogen genome sequencing has emerged as the primary tool for variant characterization, so it is important to consider the number of sequences needed when designing surveillance programs or studies, both to ensure accurate conclusions and to optimize use of limited resources. However, current approaches to calculating sample size for variant monitoring often do not account for the biological and logistical processes that can bias which infections are detected and which samples are ultimately selected for sequencing. In this manuscript, we introduce a framework that models the full process from infection detection to variant characterization and demonstrate how to use this framework to calculate appropriate sample sizes for sequencing-based surveillance studies. We consider both cross-sectional and continuous sampling, and we have implemented our method in a publicly available tool that allows users to estimate necessary sample sizes given a specific aim (e.g., variant detection or measuring variant prevalence) and sampling method. Our framework is designed to be easy to use, while also flexible enough to be adapted to other pathogens and surveillance scenarios.

Little is known about disparities in depression prevalence, treatment, and remission by psychiatric comorbidities and substance use among persons living with HIV (PLWH). We conducted a crosssectional analysis in a large cohort of PLWH in routine care and analyzed conditional probabilities of having an indication for depression treatment, receiving treatment, receiving indicated treatment adjustments, and achieving remission, stratified by alcohol use, illicit drug use, and panic symptoms. Overall, 34.7% (95% CI: 33.9-35.5%) of participants had an indication for depression treatment and of these, 55.3% (53.8-56.8%) were receiving antidepressants. Among patients receiving antidepressants, 33.0% (31.1-34.9%) had evidence of remitted depression. In a subsample of sites with antidepressant dosage data, only 8.8% (6.7-11.5%) of patients received an indicated treatment adjustment. Current drug users (45.8%, 95% CI: 43.6-48.1%) and patients reporting full symptoms of panic disorder (75.0%, 95% CI: 72.9-77.1%) were most likely to have

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BackgroundIn Malawi’s PMTCT Option B+ program, HIV-infected pregnant women who are already receiving ART are continued on their current therapy regimen without testing for treatment failure at the first antenatal care (ANC) visit. HIV RNA screening at ANC may identify women with treatment failure and ensure that viral suppression is maintained throughout the pregnancy.MethodsWe conducted a cross-sectional study of HIV-infected pregnant women who had been receiving ART for at least 6 months at the first ANC visit under the PMTCT Option B+ program at Bwaila Hospital in Lilongwe, Malawi from June 2015 to December 2017. Poisson regression models with robust variance were used to investigate the predictors of ART treatment failure defined as viral load ≥1000 copies/ml.ResultsThe median age of 864 women tested for ART failure was 31.1 years (interquartile range: 26.9–34.5). The prevalence of treatment failure was 7.6% (95% confidence interval (CI): 6.0–9.6). CD4 cell count (adjusted prevalence ratio (aPR) = 0.57; 95% CI: 0.50–0.65) was strongly associated with treatment failure.ConclusionThe low prevalence of treatment failure among women presenting for their first ANC in urban Malawi demonstrates success of Option B+ in maintaining viral suppression and suggests progress towards the last 90% of the UNAIDS 90-90-90 targets. Women failing on ART should be identified early for adherence counseling and may require switching to an alternative ART regimen.

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Objectives Malawi's Option B+ universal antiretroviral therapy (ART) program for pregnant and breastfeeding women does not include routine laboratory monitoring. We report safety outcomes of pregnant women who initiated ART through Option B+. Methods We analysed 12‐month data from an observational cohort study on Option B+ among women newly initiating tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) at a government antenatal clinic in Lilongwe, Malawi. Proportions of women engaged in care, incidence of DAIDS grade ≥ 2 laboratory toxicity, grade ≥ 3 adverse events (AEs), viral suppression (<1000 copies/mL), birth outcomes and infant HIV infections are reported. Results At ART initiation, participants (n = 299) had a median age of 26 years (IQR 22–30), median CD4 count of 352 cells/μl (IQR 231–520) and 94% were in WHO Stage 1. We noted 76 incident DAIDS Grade ≥ 2 laboratory results among 58 women, most commonly elevated liver function tests (n = 30 events) and low haemoglobin (n = 27). No women had elevated creatinine. Clinical AEs (n = 45) were predominantly infectious diseases and Grade 3. Five participants (2%) discontinued TDF/3TC/EFV due to virologic failure (3) or toxicity (2). Twelve months after ART initiation, most women were engaged in care (89%) and had HIV RNA < 1000 copies/ml (90%). 8% of pregnancies resulted in preterm birth, 9% were low birthweight (<2500 g), and 2% resulted in infant HIV infection at 6 weeks post‐delivery. Conclusion Most women remained on ART and were virally suppressed 12 months after starting Option B+. Few infants contracted HIV perinatally. While some women experienced adverse laboratory events, clinical symptom monitoring is likely reasonable.