Allostatic Load Mediates Associations Between Race and Ethnicity and Hypertensive Disorders of Pregnancy.

Objective: To evaluate whether chronic stress exposure, measured by allostatic load (a biological measure of chronic stress embodiment, including stressors exacerbated by structural inequities [eg, structural racism]) and patient-reported perceived stress in the first trimester of pregnancy, mediates the association between self-identified race and ethnicity and hypertensive disorders of pregnancy (HDP).

Methods: This was a secondary analysis of data from nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a large prospective cohort study. We evaluated self-identified race and ethnicity as an independent variable (non-Hispanic Black, Hispanic, Asian, non-Hispanic White), and our outcome of interest was HDP (ie, gestational hypertension, preeclampsia or eclampsia).

"To Err is Human: Lessons from Prolapse Studies to Identify and Strategies to Reduce Data Errors".

Objective: The aim of this manuscript is to describe the quality improvement auditing process developed by the Pelvic Floor Disorders Network of the Eunice Kennedy Shriver NICHD for assessing the primary outcome of pelvic organ prolapse quantification (POP-Q) measurements in their prolapse research trials and provide the reader with the most iterative POP-Q form.

Methods: We reviewed the Pelvic Floor Disorders Network steering committee minutes, data coordinating center audit reports, and the case report forms for studies related to prolapse and summarized findings.

Results: Errors found were related to data entry and documentation of pelvic organ prolapse quantification data with sign errors and inaccurate Ba/Bp point assessments being most common.

The chemotherapy-induced senescence-associated secretome promotes cell detachment and metastatic dissemination through metabolic reprogramming.

Cellular senescence, characterized by a stable cell cycle arrest, is a well-documented consequence of several widely used chemotherapeutics that has context-dependent roles in cancer. Although senescent cells are non-proliferative, they remain biologically active and secrete a complex and diverse array of factors collectively known as the senescence-associated secretome (SAS), which exerts pro-tumorigenic effects. Here, we aimed to mechanistically investigate how the SAS contributes to metastatic dissemination of high grade serous ovarian cancer (HGSOC) using standard-of-care cisplatin as a senescence inducer.

Contraceptive Efficacy and Comparative Side Effects of a Mini Copper Intrauterine Device.

Background: Intrauterine devices (IUDs) are highly effective, yet acceptability and continuation differ by user and device characteristics. We evaluated the efficacy of the NTCu380 Mini, a 380-mm copper IUD available in Europe and Canada, and compared safety and continuation with the TCu380A IUD, the 380-mm copper IUD available in the United States.

Methods: We randomly assigned participants between 16 and 40 years of age in a 4:1 ratio to the NTCu380 Mini or TCu380A and assessed over 37 months.

A Report on Testicular Tissue Cryopreservation for Fertility Preservation in Children: Confirmation of Germ Cell Preservation and Few Surgical Complications.

Background: Testicular tissue cryopreservation (TTC) is an experimental method for fertility preservation in pediatric patients facing a fertility threatening treatment regimen or diagnosis. TTC requires a surgical procedure for the removal of testicular tissue, advanced tissue processing capabilities, and long-term tissue storage at a cryopreservation facility. The goal of this work is to evaluate the surgical and pathologic outcomes of patients enrolled in an ongoing clinical protocol for fertility preservation in children.

Periurethral versus intravaginal application of vaginal estrogen for the prevention of urinary tract infections in postmenopausal women: Design of a randomized non-inferiority trial.

Background: Recurrent urinary tract infections (UTIs) disproportionately affect older women. Vaginal estrogen is the only non-antibiotic therapy with a Grade A recommendation for the prevention of UTIs in postmenopausal women, but it is associated with a high rate of non-adherence due to reported difficulties with vaginal application and concerns about exogenous hormone exposure. To alleviate these challenges, some women apply estrogen cream periurethrally, although evidence supporting this approach is lacking.

Association of catechol-O-methyltransferase genetic polymorphism with neuromodulation treatment response in women with fecal or urinary incontinence.

Background: Prior studies have failed to demonstrate clinical or statistical difference in fecal incontinence (FI) symptom improvement with neuromodulation by percutaneous tibial nerve stimulation vs sham. The results of these studies may be indicative of a placebo or sham effect and led us to investigate possible genetic biomarkers of placebo response among women with FI.

Objective: To evaluate the relationship between response to percutaneous tibial nerve stimulation or sham and genetic polymorphisms associated with placebo response in women with FI.

All-cause mortality and neighborhood social vulnerability among women with ovarian cancer.

Objective: Neighborhood-level social determinants of health (N-SDoH) impact cancer survival. However, the relationship between N-SDoH and epithelial ovarian cancer (EOC) survival remains understudied.

Methods: We used data on all Pennsylvania residents diagnosed with EOC from 2000 to 2023 throughout the University of Pittsburgh Medical Center to assess the impact of N-SDoH on survival.

T cell signatures associated with reduced Chlamydia trachomatis reinfection in a highly exposed cohort.

Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection globally. Understanding natural immunity to CT will inform vaccine design. This study aimed to profile immune cells and associated functional features in CT-infected women and determine immune profiles associated with reduced risk of ascended endometrial CT infection and CT reinfection.

Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer.

Purpose: We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes.

Experimental Design: We conducted a two-center prospective study of patients with newly diagnosed EOC (N = 188).

Identification of the MRTFA/SRF pathway as a critical regulator of quiescence in cancer.

Chemoresistance is a major driver of cancer deaths. One understudied mechanism of chemoresistance is quiescence. We used single cell culture to identify, retrieve, and RNA-Seq profile primary quiescent ovarian cancer cells (qOvCa).

Association of neighborhood social vulnerability with ovarian cancer survival.

Objective: Social determinants of health (SDOH) impact cancer outcomes. The CDC Social Vulnerability Index (SVI) integrates scores for four neighborhood-based SDOH domains (socioeconomic status, household characteristics, minority status, and housing type/transportation) to assess neighborhood social vulnerability (NSV). While NSV has been associated with overall cancer mortality and lung, breast, colon, and endometrial cancer-specific mortality, the relationship between NSV as defined by the SVI and ovarian cancer outcomes remains unknown.

Clinical Outcomes Associated With a Remote Postpartum Hypertension Monitoring Program.

Objective: To evaluate differences in health care utilization and guideline adherence for postpartum individuals with hypertensive disorders of pregnancy (HDP) who are engaged in a remote monitoring program, compared with usual care.

Methods: This was a retrospective cohort study of postpartum individuals with HDP who delivered between March 2019 and June 2023 at a single institution. The primary exposure was enrollment in a remote hypertension management program that relies on patient home blood pressure (BP) measurement and centralized nursing team management.

Phase I and Randomized Phase II Study of Ruxolitinib With Frontline Neoadjuvant Therapy in Advanced Ovarian Cancer: An NRG Oncology Group Study.

Purpose: The interleukin-6/Janus kinase (JAK)/signal transducers and activators of transcription 3 axis is a reported driver of chemotherapy resistance. We hypothesized that adding the JAK1/2 inhibitor ruxolitinib to standard chemotherapy would be tolerable and improve progression-free survival (PFS) in patients with ovarian cancer in the upfront setting.

Materials And Methods: Patients with ovarian/fallopian tube/primary peritoneal carcinoma recommended for neoadjuvant chemotherapy were eligible.

Research autopsy programmes in oncology: shared experience from 14 centres across the world.

While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research.

Transcriptional metabolic reprogramming implements meiotic fate decision in mouse testicular germ cells.

Nutrient starvation drives yeast meiosis, whereas retinoic acid (RA) is required for mammalian meiosis through its germline target Stra8. Here, by using single-cell transcriptomic analysis of wild-type and Stra8-deficient juvenile mouse germ cells, our data show that the expression of nutrient transporter genes, including Slc7a5, Slc38a2, and Slc2a1, is downregulated in germ cells during meiotic initiation, and this process requires Stra8, which binds to these genes and induces their H3K27 deacetylation. Consequently, Stra8-deficient germ cells sustain glutamine and glucose uptake in response to RA and exhibit hyperactive mTORC1/protein kinase A (PKA) activities.

Acceptability of Single-dose Clindamycin Gel for Bacterial Vaginosis: A Randomized Controlled Trial.

Purpose: The goal of this study was to assess the acceptability of a single-dose bioadhesive 2% clindamycin vaginal gel for bacterial vaginosis (BV).

Methods: This double-blind, placebo-controlled, randomized study compared a new clindamycin gel with placebo gel (2:1 ratio). The primary objective was efficacy; secondary objectives were safety and acceptability.

RET signaling in breast cancer therapeutic resistance and metastasis.

RET, a single-pass receptor tyrosine kinase encoded on human chromosome 10, is well known to the field of developmental biology for its role in the ontogenesis of the central and enteric nervous systems and the kidney. In adults, RET alterations have been characterized as drivers of non-small cell lung cancer and multiple neuroendocrine neoplasms. In breast cancer, RET signaling networks have been shown to influence diverse functions including tumor development, metastasis, and therapeutic resistance.

Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip.

Necrotizing enterocolitis (NEC) is a deadly gastrointestinal disease of premature infants that is associated with an exaggerated inflammatory response, dysbiosis of the gut microbiome, decreased epithelial cell proliferation, and gut barrier disruption. We describe an in vitro model of the human neonatal small intestinal epithelium (Neonatal-Intestine-on-a-Chip) that mimics key features of intestinal physiology. This model utilizes intestinal enteroids grown from surgically harvested intestinal tissue from premature infants and cocultured with human intestinal microvascular endothelial cells within a microfluidic device.

Quiescent Ovarian Cancer Cells Secrete Follistatin to Induce Chemotherapy Resistance in Surrounding Cells in Response to Chemotherapy.

Purpose: We recently reported that the transcription factor NFATC4, in response to chemotherapy, drives cellular quiescence to increase ovarian cancer chemoresistance. The goal of this work was to better understand the mechanisms of NFATC4-driven ovarian cancer chemoresistance.

Experimental Design: We used RNA sequencing to identify NFATC4-mediated differential gene expression.

Monoclonal Antibodies for Treatment of SARS-CoV-2 Infection During Pregnancy : A Cohort Study.

Background: Monoclonal antibody (mAb) treatment decreases hospitalization and death in high-risk outpatients with mild to moderate COVID-19. However, no studies have evaluated adverse events and effectiveness of mAbs in pregnant persons compared with no mAb treatment.

Objective: To determine the frequency of drug-related adverse events and obstetric-associated safety outcomes after treatment with mAb compared with no mAb treatment of pregnant persons, and the association between mAb treatment and a composite of 28-day COVID-19-related hospital admission or emergency department (ED) visit, COVID-19-associated delivery, or mortality.

Glucocorticoid induced loss of oestrogen receptor alpha gene methylation and restoration of sensitivity to fulvestrant in triple negative breast cancer.

The response to psychological stress can differ depending on the type and duration of the stressor. Acute stress can facilitate a "fight or flight response" and aid survival, whereas chronic long-term stress with the persistent release of stress hormones such as cortisol has been shown to be detrimental to health. We are now beginning to understand how this stress hormone response impacts important processes such as DNA repair and cell proliferation processes in breast cancer.