Determinants of Racial and Ethnic Differences in Maternal Cardiovascular Health in Early Pregnancy.

Background: Suboptimal cardiovascular health (CVH) in pregnancy is associated with adverse maternal and offspring outcomes. To guide public health efforts to reduce disparities in maternal CVH, we determined the contribution of individual- and neighborhood-level factors to racial and ethnic differences in early pregnancy CVH.

Methods: We included nulliparous individuals with singleton pregnancies who self-identified as Hispanic, non-Hispanic Black (NHB), or non-Hispanic White (NHW) and participated in the nuMoM2b cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be).

Association of SARS-CoV-2 Infection during pregnancy with placental weight and histopathologic lesions.

Introduction: The reported gross and histopathologic changes in the placenta associated with SARS-CoV-2 infection are heterogeneous. We sought to summarize placental histopathologic findings from pregnancies affected by SARS-CoV-2 infection according to timing of infection and symptom severity.

Methods: We conducted a retrospective cohort study of patients with SARS-CoV-2 infection during pregnancy who had deliveries at Mayo Clinic, Rochester, Minnesota, from April 2020 through June 2021.

WEE1 confers resistance to KRAS inhibitors in non-small cell lung cancer.

KRAS inhibitors sotorasib and adagrasib have been approved for the treatment of KRAS-mutant non-small cell lung cancer (NSCLC). However, the efficacy of single-agent treatments is limited, presumably due to multiple resistance mechanisms. To overcome these therapeutic limitations, combination strategies that potentiate the antitumor efficacy of KRAS inhibitors must be developed.

Placental Pathology and Blood Pressure at Age 7: A Longitudinal Discordant Twin Analysis.

Background: Evidence suggests that the intrauterine environment shapes offspring cardiovascular disease risk. Although placental dysfunction may be an important pathophysiologic pathway, numerous parental and pregnancy characteristics that influence offspring blood pressure are strong confounders of the mechanistic role of the placenta in observational analyses of singletons. Therefore, we leverage twin- and sibling-based comparison designs to determine whether placental pathology is associated with offspring blood pressure at age 7 while mitigating major sources of confounding.

Clinical Potential of Novel Microbial Therapeutic LP51 Based on Xerosis-Microbiome Index.

Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis.

Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications.

While triple-negative breast cancer (TNBC) is known to be heterogeneous at the genomic and transcriptomic levels, spatial information on tumor organization and cell composition is still lacking. Here, we investigate TNBC tumor architecture including its microenvironment using spatial transcriptomics on a series of 92 patients. We perform an in-depth characterization of tumor and stroma organization and composition using an integrative approach combining histomorphological and spatial transcriptomics.

IL-4 drives exhaustion of CD8 CART cells.

Durable response to chimeric antigen receptor T (CART) cell therapy remains limited in part due to CART cell exhaustion. Here, we investigate the regulation of CART cell exhaustion with three independent approaches including: a genome-wide CRISPR knockout screen using an in vitro model for exhaustion, RNA and ATAC sequencing on baseline and exhausted CART cells, and RNA and ATAC sequencing on pre-infusion CART cell products from responders and non-responders in the ZUMA-1 clinical trial. Each of these approaches identify interleukin (IL)-4 as a regulator of CART cell dysfunction.

Design of a Phase 3, Global, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn.

Objective:  Nipocalimab is a neonatal fragment crystallizable (Fc) receptor (FcRn)-blocking monoclonal antibody that inhibits placental immunoglobulin G (IgG) transfer and lowers circulating maternal IgG levels. In an open-label, single-arm, phase 2 study, nipocalimab demonstrated evidence of safety and efficacy that support further investigation in a pivotal phase 3 trial of recurrent hemolytic disease of the fetus and newborn (HDFN). The phase 3 AZALEA study aims to evaluate the efficacy and safety of nipocalimab in a larger population at risk for severe HDFN, defined as HDFN associated with poor fetal outcomes or neonatal death.

An explorative analysis on the optimal cryo-passes and freezing time of the ultrathin cryoprobe in endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy.

EBUS-guided transbronchial mediastinal cryobiopsy (TBMC) has emerged as a promising biopsy tool for diagnosing hilar and mediastinal pathologies. However, several fundamental technical aspects of TBMC remain unexplored. This study aims to determine the optimal number of cryo-passes and freezing time of the ultrathin cryoprobe in EBUS-TBMC concerning specimen size and procedural diagnostic yield.

Integrative single-cell RNA-seq and spatial transcriptomics analyses reveal diverse apoptosis-related gene expression profiles in EGFR-mutated lung cancer.

In EGFR-mutated lung cancer, the duration of response to tyrosine kinase inhibitors (TKIs) is limited by the development of acquired drug resistance. Despite the crucial role played by apoptosis-related genes in tumor cell survival, how their expression changes as resistance to EGFR-TKIs emerges remains unclear. Here, we conduct a comprehensive analysis of apoptosis-related genes, including BCL-2 and IAP family members, using single-cell RNA sequence (scRNA-seq) and spatial transcriptomics (ST).

Co-targeting SOS1 enhances the antitumor effects of KRAS inhibitors by addressing intrinsic and acquired resistance.

Combination approaches are needed to strengthen and extend the clinical response to KRAS inhibitors (KRASi). Here, we assessed the antitumor responses of KRAS mutant lung and colorectal cancer models to combination treatment with a SOS1 inhibitor (SOS1i), BI-3406, plus the KRAS inhibitor, adagrasib. We found that responses to BI-3406 plus adagrasib were stronger than to adagrasib alone, comparable to adagrasib with SHP2 (SHP2i) or EGFR inhibitors and correlated with stronger suppression of RAS-MAPK signaling.

scL-2PAM: A Novel Countermeasure That Ameliorates Neuroinflammation and Neuronal Losses in Mice Exposed to an Anticholinesterase Organophosphate.

Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.

Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer.

The advent of targeted therapies revolutionized treatments of advanced oncogene-driven non-small cell lung cancer (NSCLC). Nonetheless, despite initial dramatic responses, development of drug resistance is inevitable. Although mechanisms underlying acquired resistance, such as on-target mutations, bypass pathways, or lineage transformation, have been described, overcoming drug resistance remains challenging.

Zolbetuximab plus chemotherapy for locally advanced unresectable or metastatic stomach or gastroesophageal junction cancers: a plain language summary.

What Is This Summary About?: This is a summary of two articles. The first article is about a clinical trial called SPOTLIGHT and it was published in the medical journal in in April of 2023. The second article is about a clinical trial called GLOW and it was published in the medical journal in July of 2023.

Pharmacological inhibition of the LIF/LIFR autocrine loop reveals vulnerability of ovarian cancer cells to ferroptosis.

Of all gynecologic cancers, epithelial-ovarian cancer (OCa) stands out with the highest mortality rates. Despite all efforts, 90% of individuals who receive standard surgical and cytotoxic therapy experience disease recurrence. The precise mechanism by which leukemia inhibitory factor (LIF) and its receptor (LIFR) contribute to the progression of OCa remains unknown.

Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs.

Pyoderma Gangrenosum of the Genitalia, Anus, and Perineum: Two Case Reports and a Review of Published Cases.

Pyoderma gangrenosum is an inflammatory skin disease that presents with rapidly progressive ulcers with violaceous, undermined borders. Despite most commonly affecting the lower extremities, pyoderma gangrenosum can rarely present in the genital, anal, and perineal regions. We describe 2 cases and report a review of published cases.

Multiparameter immunoprofiling for the diagnosis and differentiation of progressive versus nonprogressive nontuberculous mycobacterial lung disease-A pilot study.

Clinical prediction of nontuberculous mycobacteria lung disease (NTM-LD) progression remains challenging. We aimed to evaluate antigen-specific immunoprofiling utilizing flow cytometry (FC) of activation-induced markers (AIM) and IFN-γ enzyme-linked immune absorbent spot assay (ELISpot) accurately identifies patients with NTM-LD, and differentiate those with progressive from nonprogressive NTM-LD. A Prospective, single-center, and laboratory technician-blinded pilot study was conducted to evaluate the FC and ELISpot based immunoprofiling in patients with NTM-LD (n = 18) and controls (n = 22).