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BACKGROUND: Yellow fever virus (YFV) infections are a major global disease concern with high mortality in humans, and as such it is critical to identify clinical correlates of disease severity. While nonstructural protein 1 (NS1) of the related dengue virus is implicated in contributing to vascular leak, little is known about the role of YFV NS1 in severe YF and mechanisms of vascular dysfunction in YFV infections. METHODS: Using serum samples from laboratory-confirmed YF patients with severe (n = 39) or non-severe (n = 18) disease in a well-defined hospital observational cohort in Brazil, plus samples from healthy uninfected controls (n = 11), we investigated factors associated with disease severity and endothelial dysfunction. FINDINGS: We found significantly increased levels of NS1, as well as syndecan-1, a marker of vascular leak, in serum from severe YF as compared to non-severe YF or control groups. We also showed that hyperpermeability of endothelial cell monolayers treated with serum from severe YF patients was significantly higher compared to non-severe YF and control groups, as measured by transendothelial electrical resistance (TEER). Further, we demonstrated that YFV NS1 induces shedding of syndecan-1 from the surface of human endothelial cells. Notably, YFV NS1 serum levels significantly correlated with syndecan-1 serum levels, TEER values, and signs of disease severity. Syndecan-1 levels also significantly correlated with clinical laboratory parameters of disease severity, viral load, hospitalization, and death. INTERPRETATION: This study provides further evidence for endothelial dysfunction as a mechanism of YF pathogenesis in humans and suggests serum quantification of YFV NS1 and syndecan-1 as valuable tools for disease diagnosis and/or prognosis. FUNDING: This work was supported by the US NIH and FAPESP.

: Introduction: Community‐based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre‐exposure prophylaxis (PrEP). Within individuals, one can assess exposure and outcome variables repeatedly and with increased certainty regarding temporal ordering. This cohort study examined the association of several risk factors with subsequent HIV seroconversion. Methods: We report data from a 4‐year study (2017−2022) of 6059 HIV seronegative sexual and gender minority individuals who have sex with men who had indications for‐, but were not using‐, PrEP at enrolment. Participants completed repeat exposure assessments and self‐collection of biospecimens for HIV testing. We examined the roles of race and ethnicity, socio‐economic status, methamphetamine use and PrEP uptake over the course of follow‐up in relation to HIV seroconversion. Results: Over 4 years, 303 of the participants seroconverted across 18,421 person‐years (incidence rate = 1.64 [95% CI: 1.59−1.70] per 100 person‐years). In multivariable discrete‐time survival analysis, factors independently associated with elevated HIV seroconversion risk included being Black/African American (adjusted risk ratio [aRR]: 2.44, 1.79−3.28), Hispanic/Latinx (1.53, 1.19−1.96), housing instability (1.58, 1.22−2.05) and past year methamphetamine use (3.82, 2.74−5.33). Conversely, time since study enrolment (24 vs. 12 months, 0.67, 0.51−0.87; 36 months, 0.60, 0.45−0.80; 48 months, 0.48, 0.35−0.66) and higher education (master's degree or higher vs. less than or equal to high school, 0.36, 0.17−0.66) were associated with reduced seroconversion risk. Compared to non‐PrEP users in the past 2 years without a current clinical indication, those who started PrEP but then discontinued had higher seroconversion risk, irrespective of clinical indication (3.23, 1.74−6.46) or lack thereof (4.30, 1.85−9.88). However, those who initiated PrEP in the past year (0.14, 0.04−0.39) or persistently used PrEP in the past 2 years (0.33, 0.14−0.74) had a lower risk of seroconversion. Of all HIV seroconversions observed during follow‐up assessments (12, 24, 36 and 48 months), methamphetamine was reported in the 12 months prior 128 (42.2%) times (overall). Conclusions: Interventions that acknowledge race and ethnicity, economic variables such as education and housing instability, and methamphetamine use are critically needed. Not only are interventions to engage individuals in PrEP care needed, but those that retain them, and re‐engage those who may fall out of care are essential, given the exceptionally high risk of seroconversion in these groups., INTRODUCTION Sexual minority individuals represent 2−5% of the United States, yet account for more than two‐thirds of new HIV acquisitions [1−4]. Meanwhile, gender minority individuals (transgender [trans] men and trans [...]

Background The mechanisms that mediate immune protection in individuals with subclinical (SC) or asymptomatic infection with Leishmania braziliensis are largely unknown. Neutrophils (polymorphonuclear leukocytes [PMNs]) have been implicated in progressive symptomatic cutaneous leishmaniasis (CL), but their potential participation in maintenance of subclinical infection is unexplored. The aim of this study was to compare the phenotypic and functional profiles of PMNs in individuals with SC infection versus patients with symptomatic CL due to L braziliensis. Methods Subjects were recruited in the endemic region of Corte de Pedra, Bahia, Brazil. Surface markers to define activation status were characterized by flow cytometry. Functional responses of PMNs including phagocytic capacity, production of oxidative species, and oxidative killing of intracellular parasites were studied in vitro. Results PMNs from individuals with SC infection displayed a more activated phenotype and greater ability to control the infection than PMNs from patients with CL. In contrast, PMNs from patients with CL exhibited higher expression of HLA-DR and higher production of oxidative species than PMNs from subjects with SC infection. Conclusions PMNs from individuals with SC infection can control the infection more efficiently than PMNs from patients with CL, despite the lower production of oxidants. Our observations suggest that L braziliensis may evade microbicidal mechanisms of PMNs from patients with CL, contributing to parasite dissemination and the establishment of disease. [ABSTRACT FROM AUTHOR]

Introduction: Efforts to improve pre-exposure prophylaxis (PrEP) uptake among gay men, transgender women, and Black cisgender women are evident across the United States, responding to epidemiologic data showing a disproportionate HIV burden in these communities. However, transgender men and other transmasculine people who have sex with men (TMSM)--those assigned female at birth who identify otherwise and have sex with cisgender men--are often excluded from these statistics. This community has unique vulnerabilities and prevention needs. National HIV prevention and planning has yet to include transgender men as a group with increased vulnerability to HIV seroconversion. This study follows a cohort of TMSM to characterize PrEP use longitudinally. Methods: Using data from a prospective US national cohort of TMSM not on PrEP, we analyzed annual PrEP uptake, discontinuation, and other HIV prevention measures over 24 months. We also used generalized estimating equations modeling to assess demographic, healthcare access, gender-affirming, and behavioral factors associated with PrEP uptake over time. Results: Our cohort of 196 TMSM was demographic and regionally diverse. 29% of our sample reported uptake of PrEP in 24 months, with about one-third of users discontinuing within 1 year. Health insurance, having had lower surgery, used post-exposure prophylaxis, or recently having a sexually transmitted infection were associated with increased odds of PrEP use. Conclusion: We found low uptake of PrEP and high discontinuation rates in a US national sample of TMSM over 24 months, despite significant need for HIV prevention. It is vital to increase efforts and investments to support this neglected community. [ABSTRACT FROM AUTHOR]

The article "Still Flying: Reply to 'Not a Flying Start after All?' by Lillebø et al." published in the Journal of Political Economy analyzes the long-term impacts of the 1977 Norwegian maternity leave reform on children. Lillebø et al. raised objections to the analysis, highlighting missed details of the reform, a coding error, and objections to the empirical work. The authors acknowledge the importance of the corrections made by Lillebø et al. and present new estimates of the reform's impact, addressing errors and providing a more accurate interpretation of the results. The research design used in the original paper was reevaluated in light of new information, leading to similar estimates of the reform's impact on children's outcomes. [Extracted from the article]

Recommendation of new varieties is supported by value for cultivation and use (Valor de Cultivo e Uso [VCU]) trials. For a more reliable recommendation, it is necessary to identify methodologies that make better use of the genotype‐by‐environment interaction (GEI). The methodology proposed by Dias et al. is an alternative to take advantage of the GEI; it considers concepts of Bayesian models and probability methods of adaptation and stability analysis in a single model, classifying the genotypes regarding possible success based on a defined selection intensity. Thus, the aim of the present study was to explore the use of Bayesian probabilistic method for the purpose of recommend common bean (Phaseolus vulgaris L.) varieties. To that end, we used grain yield data from 15 genotypes of common bean evaluated in 42 environments distributed over different crop seasons, years, and locations in regard to VCU trials conducted from 2016 to 2018. Under a predefined selection intensity of 30%, the genotypes with greater marginal probability of superior performance were G01, G14, G07, G11, and G02. The genotypes with greater marginal probability of superior stability were G06, G07, G04, G03, and G12. Considering the joint probability of superior performance and yield stability, the genotypes G07, G14, G01, G11, and G04 stand out. Therefore, the use of the Bayesian probabilistic method showed promise in recommendation of common bean varieties. Core Ideas: Reliable recommendations of common bean varieties can be obtained from probabilist Bayesian models.High‐performance and stable common bean varieties were identified for tropical conditions.Probability methods can minimize risk in decision‐making for broad and specific variety recommendation. Plain Language Summary: Recommendation of varieties is supported by multi‐environment trials (MET). In MET, in addition to genetic and environmental effects, there is an interaction between these (GEI). According to the study of Dias et al., the methodology to take advantage of the GEI is based in Bayesian probabilistic models. Thus, the aim of the present study was to explore the use of Bayesian probabilistic method proposed by Dias et al. for recommending common bean (Phaseolus vulgaris L.) varieties. To that end, we used grain yield data from 15 genotypes of common bean evaluated in 42 environments. Under a predefined selection intensity of 30%, the genotypes with greater joint probability of superior performance and yield stability were G07, G14, G01, G11 and G04. The use of the Bayesian probabilistic method showed promise in recommendation common bean varieties. [ABSTRACT FROM AUTHOR]