First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.

Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.

Mitigating Membrane Biofouling in Protein Production with Zwitterionic Peptides.

Biofouling on polymeric membranes poses a significant challenge in protein production and separation processes. We report here on the use of zwitterionic peptides composed of alternating lysine (K) and glutamic acid (E) residues to reduce biomolecular fouling on gold substrates and polymeric membranes within a protein production-mimicking environment. Our findings demonstrate that both gold chips and polymeric membranes functionalized with longer sequence zwitterionic peptides, along with a hydrophilic linker, exhibit superior antifouling performance across various protein-rich environments.

Biomimetic Anisotropic-Functionalized Platelet-Membrane-Coated Polymeric Particles for Targeted Drug Delivery to Human Breast Cancer Cells.

Biomimetic particles that can replicate aspects of natural biological cell function are useful for advanced biological engineering applications. Engineering such particles requires mimicking the chemical complexity of the surface of biological cells, and this can be achieved by coating synthetic particles with naturally derived cell membranes. Past research has demonstrated the feasibility of utilizing cell membrane coatings from a variety of cell types to achieve extended blood circulation half-life.

TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond.

While most Tripartite motif (TRIM) family proteins are E3 ubiquitin ligases, some members have functions beyond the regulation of ubiquitination, impacting normal physiological processes and disease progression. TRIM29, an important member of the TRIM family, exerts a predominant influence on cancer growth, epithelial-to-mesenchymal transition, stemness and metastatic progression by directly potentiating multiple canonical oncogenic pathways. The cancer-promoting effect of TRIM29 is also evident in metabolic interventions and interference with the efficacy of cancer therapeutics.

Liquid biopsy to identify Barrett's oesophagus, dysplasia and oesophageal adenocarcinoma: the multicentre study.

Background: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE).

Objective: To develop and test a blood-based assay for EAC and BE.

Design: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia () was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries (NCT06381583) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE.

Integrating immunotherapy with conventional treatment regime for breast cancer patients- an amalgamation of armamentarium.

Immunotherapy stands as the frontrunner in treatment strategies imparting efficient remission in various types of cancer. In fact, emerging breakthroughs with immune checkpoint inhibitors (ICI) in a spectrum of cancers have evoked interest in research related to the potential effects of immunotherapy in breast cancer patients. A major challenge with breast cancer is the molecular heterogeneity that limits the efficacy of many therapeutic regimes.

Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma.

Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers.

Cigarette Smoking, Mental Health, Depression, Maryland Behavioral Risk Factor Surveillance System Survey, 2020.

Background: Smoking cessation is linked to improved mental health that encompasses the overall well-being and psychological functioning of an individual.

Objective: Examine relationships between smoking, mental health, and social connectedness among adults in Maryland, US in 2020.

Methodology: This cross-sectional study used data from the Maryland 2020 Behavioral Risk Factor Surveillance System Survey of adults during the onset of COVID-19.

Obesity, dysbiosis and inflammation: interactions that modulate the efficacy of immunotherapy.

Recent years have seen an outstanding growth in the understanding of connections between diet-induced obesity, dysbiosis and alterations in the tumor microenvironment. Now we appreciate that gut dysbiosis can exert important effects in distant target tissues via specific microbes and metabolites. Multiple studies have examined how diet-induced obese state is associated with gut dysbiosis and how gut microbes direct various physiological processes that help maintain obese state in a bidirectional crosstalk.

What Is the Value of Palliative Care for Inpatients With Cancer?

@ramsedhom and colleagues highlight the opportunity of palliative care to bend the cost (and value) curve in cancer. Enhanced, early, and expanded access to PC offers benefits to inpatients with cancer and cost savings to health systems and payors.

Detection of diffusely abnormal white matter in multiple sclerosis on multiparametric brain MRI using semi-supervised deep learning.

In addition to focal lesions, diffusely abnormal white matter (DAWM) is seen on brain MRI of multiple sclerosis (MS) patients and may represent early or distinct disease processes. The role of MRI-observed DAWM is understudied due to a lack of automated assessment methods. Supervised deep learning (DL) methods are highly capable in this domain, but require large sets of labeled data.

Moderators of Intervention Efficacy in the Pathways to Wellness Trial of Survivorship Education and Mindfulness Meditation for Younger Breast Cancer Survivors.

Purpose: Depression is associated with poor outcomes in breast cancer survivors (BCSs), with higher prevalence among younger women. The Pathways to Wellness (PTW; ClinicalTrials.gov identifier: NCT03025139) randomized controlled trial (RCT) demonstrated beneficial effects of two behavioral interventions (survivorship education [SE] and mindful awareness practices [MAPs]) on depressive symptoms in younger BCS.

Survivorship Care for People Affected by Advanced or Metastatic Cancer: MASCC-ASCO Standards and Practice Recommendations.

Purpose: People with advanced or metastatic cancer and their caregivers may have different care goals and face unique challenges compared with those with early-stage disease or those nearing the end of life. These Multinational Association for Supportive Care in Cancer (MASCC)-ASCO standards and practice recommendations seek to establish consistent provision of quality survivorship care for people affected by advanced or metastatic cancer.

Methods: A MASCC-ASCO expert panel was formed.

Survivorship care for people affected by advanced or metastatic cancer: MASCC-ASCO standards and practice recommendations.

Purpose: People with advanced or metastatic cancer and their caregivers may have different care goals and face unique challenges compared to those with early-stage disease or those nearing the end-of-life. These MASCC-ASCO standards and practice recommendations seek to establish consistent provision of quality survivorship care for people affected by advanced or metastatic cancer.

Methods: An expert panel comprising MASCC and ASCO members was formed.

Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort.

Background: There are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations.

Objective: We sought to identify metabolites unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort, the Boston Birth Cohort.

Methods: Mass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (n = 811).

Targeting PRMT9-mediated arginine methylation suppresses cancer stem cell maintenance and elicits cGAS-mediated anticancer immunity.

Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein arginine N-methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia stem cells (LSCs) from patients with acute myeloid leukemia (AML), eliminates disease via cancer-intrinsic mechanisms and cancer-extrinsic type I interferon (IFN)-associated immunity. PRMT9 ablation in AML cells decreased the arginine methylation of regulators of RNA translation and the DNA damage response, suppressing cell survival.