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Recurrent urogenital infections such as bacterial vaginosis, vulvovaginal candidiasis, and urinary tract infections have a high prevalence and pronounced psychosocial impact. However, no review has compared the psychosocial impacts across infection types. This narrative review discusses the impact of common recurrent urogenital infections on psychosocial aspects, including quality of life, stress, mental health, sexual health, work productivity, race and ethnicity, and satisfaction of medical care. Validated questionnaires show that women with recurrent vulvovaginal candidiasis and urinary tract infections have decreased scores on all aspects of quality of life. Those with recurrent vulvovaginal candidiasis and urinary tract infections show lower mental health scores compared to the general population, with increased risk of anxiety and depression. Recurrent urogenital infections affect sexual relationships and intimacy, including avoidance due to symptoms or as a method of prevention. Recurrent infections also increase medical cost and negatively affect work productivity, leading to a combined estimated cost of over US$13 billion per year. There are clear effects of racial inequality involving minority populations that affect diagnosis, treatment, prevalence, and reporting of recurrent urogenital infections. Satisfactory medical treatment improves quality of life and mental health in those suffering from these conditions. Research evaluating psychosocial aspects of recurrent urogenital infections is variable and is not comparable across vulvovaginal conditions. Even so, psychosocial factors are important in understanding contribution and consequence of urogenital infections. Education, awareness, normalization, community support, and access to care can help to alleviate the negative implications of recurrent urogenital infections.

Background. Hepatitis C virus (HCV) nucleic acid amplification test (NAAT)–positive donors have increased the organ pool. Direct-acting antivirals (DAAs) have led to high rates of treatment success and sustained virologic response (SVR) in recipients with donor-derived HCV infection without significant adverse effects, although variability remains in the timing and duration of antivirals. Methods. This retrospective study analyzed all adult HCV-NAAT–negative transplant recipients who received an organ from HCV-NAAT–positive donors from November 24, 2018, to March 31, 2022, at Duke University Medical Center with protocolized delay of DAA initiation until after hospital discharge, with at least 180-d follow-up on all patients. Transplant and HCV-related outcomes were analyzed. Results. Two hundred eleven transplants (111 kidneys, 41 livers, 34 hearts, and 25 lungs) were performed from HCV-NAAT–positive donors to HCV-NAAT–negative recipients. Ninety percent of recipients became viremic within 7 d posttransplant. Ninety-nine percent of recipients were initiated on pangenotypic DAAs in the outpatient setting a median of 52 d posttransplant, most commonly with 12-wk courses of sofosbuvir–velpatasvir (lungs) and glecaprevir–pibrentasvir (heart, kidney, and liver). Ninety-seven percent of recipients had SVR after a first-line DAA; all ultimately achieved SVR at 12 wk after subsequent treatment courses. The median peak HCV RNA for all organ systems was 2 436 512 IU/mL; the median time from antiviral to undetectable RNA was 48 d, although differences were noted between organ groups. No patient deaths or graft losses were directly attributable to HCV infection. Conclusions. One hundred percent of transplant recipients of HCV-NAAT–positive organs ultimately developed SVR without significant adverse effects when HCV antivirals were initiated in the outpatient setting after transplant hospitalization, suggesting that this real-world treatment pathway is a viable option.

Although weak lensing (WL) is a powerful method to estimate a galaxy cluster mass without any dynamical assumptions, a model bias can arise when the cluster density profile departs from the assumed model profile. In a merging system, the bias is expected to become most severe because the constituent halos undergo significant structural changes. In this study, we investigate WL mass bias in binary cluster mergers using a suite of idealized hydrodynamical simulations. Realistic WL shear catalogs are generated by matching the source galaxy properties, such as intrinsic shape dispersion, measurement noise, source densities, etc., to those from Subaru and Hubble Space Telescope observations. We find that, with the typical mass–concentration ( M – c ) relation and the Navarro–Frenk–White profile, the halo mass bias depends on the time since the first pericenter passage and increases with the mass of the companion cluster. The time evolution of the mass bias is similar to that of the concentration, indicating that, to first order, the mass bias is modulated by the concentration change. For a collision between two ∼10 ^15 M _⊙ clusters, the maximum bias amounts to ∼60%. This suggests that previous WL studies may have significantly overestimated the mass of the clusters in some of the most massive mergers. Finally, we apply our results to three merger cases: A2034, MACS J1752.0 + 4440, and ZwCl 1856.8 + 6616, and report their mass biases at the observed epoch, as well as their pre-merger masses, utilizing their merger shock locations as tracers of the merger phases.

We report here the discovery and optimization of a novel T cell retargeting anti-GUCY2C x anti-CD3ε bispecific antibody for the treatment of solid tumors. Using a combination of hybridoma, phage display and rational design protein engineering, we have developed a fully humanized and manufacturable CD3 bispecific antibody that demonstrates favorable pharmacokinetic properties and potent in vivo efficacy. Anti-GUCY2C and anti-CD3ε antibodies derived from mouse hybridomas were first humanized into well-behaved human variable region frameworks with full retention of binding and T-cell mediated cytotoxic activity. To address potential manufacturability concerns, multiple approaches were taken in parallel to optimize and de-risk the two antibody variable regions. These approaches included structure-guided rational mutagenesis and phage display-based optimization, focusing on improving stability, reducing polyreactivity and self-association potential, removing chemical liabilities and proteolytic cleavage sites, and de-risking immunogenicity. Employing rapid library construction methods as well as automated phage display and high-throughput protein production workflows enabled efficient generation of an optimized bispecific antibody with desirable manufacturability properties, high stability, and low nonspecific binding. Proteolytic cleavage and deamidation in complementarity-determining regions were also successfully addressed. Collectively, these improvements translated to a molecule with potent single-agent in vivo efficacy in a tumor cell line adoptive transfer model and a cynomolgus monkey pharmacokinetic profile (half-life>4.5 days) suitable for clinical development. Clinical evaluation of PF-07062119 is ongoing.

Ankylosing spondylitis (AS) is a progressive disease in which chronic inflammation can lead to extensive new bone formation throughout the spine. At present, few measures of the activity or extent of the disease are available. In this study, we sought to determine whether markers of cartilage synthesis and degradation could provide such quantitative measures.Serum samples from 23 patients receiving infliximab treatment for AS were obtained at baseline and at weeks 2, 6, 14, and 22. Patients were stratified with respect to joint involvement and baseline levels of inflammatory markers, and responders were defined according to the Assessments in Ankylosing Spondylitis 20% criteria. Serial measurements of interferon‐γ, tumor necrosis factor α, transforming growth factor β (TGFβ), interleukin‐10 (IL‐10), and IL‐1 were done at each time point. The following biomarkers were measured by enzyme‐linked immunosorbent assay: the proteoglycan aggrecan 846 epitope, a marker of cartilage turnover; C‐propeptide of type II collagen (CPII), a biosynthesis marker; and the Col2‐3/4long mono (C2C) and Col2‐3/4short (C1–2C) neoepitopes, reflecting collagen cleavage of type II collagen and type I/type II collagen, respectively.At baseline, patients with AS demonstrated significant elevations in serum levels of CPII, the 846 epitope, and the CPII‐to‐C2C (CPII:C2C) ratio (but not C2C or C1–2C) compared with normal controls. Of the biomarkers examined, only CPII:C2C showed a correlation with the C‐reactive protein (CRP) level. Among the biomarker–cytokine relationships, TGFβ demonstrated a trend toward a positive correlation with the 846 epitope.In AS, elevated serum levels of CPII and the 846 epitope may be related to biosynthetic turnover of hyaline cartilage and the intervertebral discs but may also reflect progressive bone formation as a result of endochondral ossification. The correlation of the CPII:C2C ratio with CRP suggests that the CPII:C2C ratio might prove to be a useful marker of disease activity in AS. [ABSTRACT FROM AUTHOR]