Macropinocytosis controls metabolic stress-driven CAF subtype identity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) tumors are deficient in glutamine, an amino acid that tumor cells and CAFs use to sustain their fitness. In PDAC, both cell types stimulate macropinocytosis as an adaptive response to glutamine depletion. CAFs play a critical role in sculpting the tumor microenvironment, yet how adaptations to metabolic stress impact the stromal architecture remains elusive.

Comparing endometrial biopsy results with hysteroscopic pathology in women presenting with abnormal and postmenopausal uterine bleeding.

Objective: To compare pathology results after office-based blind endometrial biopsy and pathology results from hysteroscopy in women presenting with abnormal uterine bleeding (AUB).

Methods: A retrospective cohort study of biologic women presenting with AUB at a tertiary care referral care center. Patients were included if they underwent evaluation with blind endometrial biopsy performed in the office followed by hysteroscopy within one year.

PSGL-1 attenuates early TCR signaling to suppress CD8 T cell progenitor differentiation and elicit terminal CD8 T cell exhaustion.

PSGL-1 (P-selectin glycoprotein-1) is a T cell-intrinsic checkpoint regulator of exhaustion with an unknown mechanism of action. Here, we show that PSGL-1 acts upstream of PD-1 and requires co-ligation with the T cell receptor (TCR) to attenuate activation of mouse and human CD8 T cells and drive terminal T cell exhaustion. PSGL-1 directly restrains TCR signaling via Zap70 and maintains expression of the Zap70 inhibitor Sts-1.

Ubiquitin Ligases Siah1a/2 Control Alveolar Macrophage Functions to Limit Carcinogen-Induced Lung Adenocarcinoma.

Unlabelled: Cellular components of the tumor microenvironment, including myeloid cells, play important roles in the progression of lung adenocarcinoma (LUAD) and its response to therapy. Here, we characterize the function of the ubiquitin ligases Siah1a/2 in regulating the differentiation and activity of alveolar macrophages (AM) and assess the implication of Siah1a/2 control of AMs for carcinogen-induced LUAD. Macrophage-specific genetic ablation of Siah1a/2 promoted accumulation of AMs with an immature phenotype and increased expression of protumorigenic and pro-inflammatory Stat3 and β-catenin gene signatures.

The Impact of Fertility Goals on Long-term Quality of Life in Reproductive-aged Women Who Underwent Myomectomy versus Hysterectomy for Uterine Fibroids.

Study Objective: The objective of this study is to compare quality of life (QOL) for myomectomy with hysterectomy 1 to 5 years after surgical management for fibroids. This study evaluated the difference in QOL in a population of women of reproductive age, including those who desire fertility.

Design: A retrospective cohort study.

Resolving the conflicts around Par2 opposing roles in regeneration by comparing immune-mediated and toxic-induced injuries.

Background: Different factors may lead to hepatitis. Among which are liver inflammation and poisoning. We chose two hepatitis models, typical for these two underlying causes.

Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials.

Background: Uterine fibroids are common non-cancerous neoplasm that cause heavy menstrual bleeding and other signs. Linzagolix is an oral gonadotropin-releasing hormone receptor antagonist taken once per day that dose-dependently suppresses gonadal steroids and might reduce uterine-fibroid-associated signs. Two phase 3 trials were conducted to confirm the efficacy and safety of linzagolix at full-suppression (200 mg) and partial-suppression (100 mg) doses with or without hormonal add-back therapy (1 mg oestradiol and 0·5 mg norethisterone acetate) compared with placebo for the treatment of symptomatic uterine fibroids.

Induction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities.

Immune suppressive factors of the tumor microenvironment (TME) undermine viability and exhaust the activities of the intratumoral cytotoxic CD8 + T lymphocytes (CTL) thereby evading anti-tumor immunity and decreasing the benefits of immune therapies. To counteract this suppression and improve the efficacy of therapeutic regimens, it is important to identify and understand the critical regulators within CD8 + T cells that respond to TME stress and tumor-derived factors. Here we investigated the regulation and importance of activating transcription factor-4 (ATF4) in CTL using a novel Atf4 mouse model lacking ATF4 specifically in CD8 + cells.

Faith Community Nurses Making a Difference for Older African Americans in a Pandemic.

During and after COVID-19, African Americans experienced a disparate amount of social isolation and loneliness and subsequent increases in morbidity and mortality. Faith community nurses are equipped to assist community providers, health practitioners, and local officials in addressing gaps in older African Americans' financial, social, physical, and spiritual needs during social distancing.

Implementation of Office Hysteroscopy for the Evaluation and Treatment of Intrauterine Pathology.

Hysteroscopy provides a minimally invasive strategy to evaluate intrauterine pathology and manage conditions such as abnormal uterine bleeding, infertility, intrauterine adhesions, müllerian anomalies, and intrauterine foreign bodies. Increasing access to hysteroscopy procedures in the office has the potential to improve patient care by minimizing financial and logistical barriers, aiding in streamlined diagnosis and treatment planning, and potentially averting unnecessary operative procedures and anesthesia. Office hysteroscopy refers to procedures performed in outpatient settings where pain management involves no medications, oral nonsedating medications, local anesthetic agents, or oral or inhaled conscious sedation.

A Call-to-Action for Clinicians to Implement Evidence-Based Best Practices When Caring for Women with Uterine Fibroids.

Uterine fibroids are common benign tumors that occur in up to 80% of women. Approximately half of the women affected experience considerable physical, psychological, and economic burdens and impact on quality of life due to symptoms such as heavy menstrual bleeding, pelvic pain, and infertility. Several medical and surgical options are available to treat uterine fibroids; however, healthcare providers may benefit from practical guidance in the development of individualized treatment plans based on a personalized approach.

Racial and ethnic disparities in surgical care for endometriosis across the United States.

Background: Despite an estimated 10% prevalence of endometriosis among reproductive-age women, surgical population-based data are limited.

Objective: We sought to investigate racial and ethnic disparities in surgical interventions and complications among patients undergoing endometriosis surgery across the United States.

Study Design: We performed a retrospective cohort study of American College of Surgeons National Surgical Quality Improvement Program data from 2010 to 2018 identifying International Classification of Diseases, Ninth/Tenth Revision codes for endometriosis We compared procedures, surgical routes (laparoscopy vs laparotomy), and 30-day postoperative complications by race and ethnicity.

MicroRNA-139 Expression Is Dispensable for the Generation of Influenza-Specific CD8 T Cell Responses.

MicroRNAs (miRNAs/miRs) are small, endogenous noncoding RNAs that are important post-transcriptional regulators with clear roles in the development of the immune system and immune responses. Using miRNA microarray profiling, we characterized the expression profile of naive and in vivo generated murine effector antiviral CD8 T cells. We observed that out of 362 measurable mature miRNAs, 120 were differentially expressed by at least 2-fold in influenza-specific effector CD8 CTLs compared with naive CD8 T cells.

International Consensus Statement for Recommended Terminology Describing Hysteroscopic Procedures.

Objective: To develop a consensus statement of recommended terminology to use for describing different aspects of hysteroscopic procedures that can be uniformly used in clinical practice and research.

Design: Open forum discussion followed by online video meetings.

Setting: International community of hysteroscopy experts PATIENTS: Not applicable.

Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids.

To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons.

Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis.

Objective: To determine if coexisting adenomyosis limits the efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy in reducing heavy menstrual bleeding in women with uterine fibroids.

Design: Pooled analysis of two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids [UF]-1 and UF-2).

Setting: A total of 153 gynecological clinical care settings in the United States and Canada.

A most vulnerable population: Black men.

Black men disproportionately experience the worst health outcomes among U.S. populations.

PSGL-1 Is a T Cell Intrinsic Inhibitor That Regulates Effector and Memory Differentiation and Responses During Viral Infection.

Effective T cell differentiation during acute virus infections leads to the generation of effector T cells that mediate viral clearance, as well as memory T cells that confer protection against subsequent reinfection. While inhibitory immune checkpoints have been shown to promote T cell dysfunction during chronic virus infections and in tumors, their roles in fine tuning the differentiation and responses of effector and memory T cells are only just beginning to be appreciated. We previously identified PSGL-1 as a fundamental regulator of T cell exhaustion that sustains expression of several inhibitory receptors, including PD-1.

Uterine Fibroids in Black Women: A Race-Stratified Subgroup Analysis of Treatment Outcomes After Laparoscopic Radiofrequency Ablation.

The disease and treatment burden of uterine fibroids (UF) in Black women is substantially greater compared with other racial groups, with higher rates of complications and poorer outcomes with both hysterectomy and myomectomy. The inequities in the access Black women have to minimally invasive routes of surgery contribute to their burden of illness. Laparoscopic radiofrequency ablation (LAP-RFA) is a minimally invasive, safe, and effective uterine-sparing treatment option.