Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

CT Predictors of Angiolymphatic Invasion in Non-Small Cell Lung Cancer 30 mm or Smaller.

Background Angiolymphatic invasion (ALI) is an important prognostic indicator in non-small cell lung cancer (NSCLC). However, few studies focus on radiologic features for predicting ALI in patients with early-stage NSCLCs 30 mm or smaller. Purpose To identify radiologic features for predicting ALI in NSCLCs 30 mm or smaller in maximum diameter.

Pulsed Field Ablation of Paroxysmal Supraventricular Tachycardia: A Prospective Multicenter Single-Arm Study in China.

Background: Pulsed field ablation (PFA) has gained attention in cardiac electrophysiology, but data on its application to paroxysmal supraventricular tachycardia are limited. This study aimed to assess the feasibility and safety of PFA and its combination with radiofrequency ablation for treating paroxysmal supraventricular tachycardia.

Methods: A prospective, multicenter, single-arm study was conducted across 8 centers in China.

Age-related decline in CD8 tissue resident memory T cells compromises antitumor immunity.

Aging compromises antitumor immunity, but the underlying mechanisms remain elusive. Here, we report that aging impairs the generation of CD8 tissue resident memory T (T) cells in nonlymphoid tissues in mice, thus compromising the antitumor activity of aged CD8 T cells, which we also observed in human lung adenocarcinoma. We further identified that the apoptosis regulator BFAR was highly enriched in aged CD8 T cells, in which BFAR suppressed cytokine-induced JAK2 signaling by activating JAK2 deubiquitination, thereby limiting downstream STAT1-mediated T reprogramming.

Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial.

The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. A greater understanding of biomarkers predictive of response to Enco+Cetux±Bini treatment is of clinical relevance. In this prespecified, exploratory biomarker analysis of the BEACON CRC study, we characterize genomic and transcriptomic correlates of clinical outcomes and acquired resistance mechanisms through integrated clinical and molecular analysis, including whole-exome and -transcriptome tissue sequencing and circulating tumor DNA genomic profiling.

Comparison of Short-term and Long-term Outcomes after Different Reconstructions between Totally Laparoscopic Distal Gastrectomy and Laparoscopic-assisted Distal Gastrectomy for Gastric Cancer: a Retrospective Analysis at a High-volume Center.

The short-term and long-term outcomes of laparoscopic-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) have been subject to controversy with various reconstruction techniques of Billroth-I, Billroth-II, Roux-en-Y, and Uncut. This study aims to compare the short-term and long-term outcomes of LADG and TLDG as well as the outcomes of different anastomoses. This study enrolled patients with gastric cancer at the First Affiliated Hospital of Nanjing Medical University (NMUH) between 2017 and 2021.

Leveraging cfDNA fragmentomic features in a stacked ensemble model for early detection of esophageal squamous cell carcinoma.

In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness.

Distinct dynamics of parental 5-hydroxymethylcytosine during human preimplantation development regulate early lineage gene expression.

The conversion of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes represents a significant epigenetic modification, yet its role in early human embryos remains largely unknown. Here we showed that the early human embryo inherited a significant amount of 5hmCs from an oocyte, which unexpectedly underwent de novo hydroxymethylation during its growth. Furthermore, the generation of 5hmC in the paternal genome after fertilization roughly followed the maternal pattern, which was linked to DNA methylation dynamics and regions of sustained methylation.

A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia.

Background: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells.

Methods: We conducted a phase 1-2, open-label study to evaluate the safety and efficacy of CM313 in adult patients with ITP.

Decoding 2.3 million ECGs: interpretable deep learning for advancing cardiovascular diagnosis and mortality risk stratification.

Aims: Electrocardiogram (ECG) is widely considered the primary test for evaluating cardiovascular diseases. However, the use of artificial intelligence (AI) to advance these medical practices and learn new clinical insights from ECGs remains largely unexplored. We hypothesize that AI models with a specific design can provide fine-grained interpretation of ECGs to advance cardiovascular diagnosis, stratify mortality risks, and identify new clinically useful information.

Tissue distribution and retention drives efficacy of rapidly clearing VHL-based PROTACs.

Background: Proteolysis-targeting chimeras (PROTACs) are being developed for therapeutic use. However, they have poor pharmacokinetic profiles and their tissue distribution kinetics are not known.

Methods: A typical von Hippel-Lindau tumor suppressor (VHL)-PROTAC C-A947 (BRM degrader)-was synthesized and its tissue distribution kinetics was studied by quantitative whole-body autoradiography (QWBA) and tissue excision in rats following IV dosing.

Overexpressed Trophoblast Glycoprotein Contributes to Preeclampsia Development by Inducing Abnormal Trophoblast Migration and Invasion Toward the Uterine Spiral Artery.

Background: Preeclampsia is a significant pregnancy disorder with an unknown cause, mainly attributed to impaired spiral arterial remodeling.

Methods: Using RNA sequencing, we identified key genes in placental tissues from healthy individuals and preeclampsia patients. Placenta and plasma samples from pregnant women were collected to detect the expression of TPBG (trophoblast glycoprotein).

Clinical and Genomic Landscape of RAS Mutations in Gynecologic Cancers.

Purpose: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.

Experimental Design: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan-Meier method, and multivariable analysis was performed using the Cox proportional hazard model.

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses.

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production.

Assessment of Right Atrial Function Measured with Cardiac MRI Feature Tracking for Predicting Outcomes in Patients with Dilated Cardiomyopathy.

Background Right atrial (RA) function strain is increasingly acknowledged as an important predictor of adverse events in patients with diverse cardiovascular conditions. However, the prognostic value of RA strain in patients with dilated cardiomyopathy (DCM) remains uncertain. Purpose To evaluate the prognostic value of RA strain derived from cardiac MRI (CMR) feature tracking (FT) in patients with DCM.

The Addition of Resveratrol-Loaded Emulsions to Yogurts: Physicochemical Characterization, In Vitro Bioaccessibility and NMR-Based Nutritional Profiles.

In this study, resveratrol-loaded nano-emulsions were added to yogurts, improving the physicochemical properties and functional factors and realizing the development of nutrient-fortified yogurt. Yogurts added with free resveratrol (Y-R), resveratrol-loaded emulsions stabilized by sodium caseinate (Y-NN), decaglycerol monooleate (Y-DN), and sodium caseinate-decaglycerol monooleate (Y-DND) were evaluated for their physicochemical properties, including pH, titratable acidity, syneresis, and textural parameters, with 5-day intervals for 15-day storage. The resveratrol retention rate was analyzed in the Y-R, Y-NN, Y-DN, and Y-NDN groups during 15 days of storage.

Evaluation of the drug-drug interaction potential of brigatinib using a physiologically-based pharmacokinetic modeling approach.

Brigatinib is an oral anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive metastatic non-small cell lung cancer. In vitro studies indicated that brigatinib is primarily metabolized by CYP2C8 and CYP3A4 and inhibits P-gp, BCRP, OCT1, MATE1, and MATE2K. Clinical drug-drug interaction (DDI) studies with the strong CYP3A inhibitor itraconazole or the strong CYP3A inducer rifampin demonstrated that CYP3A-mediated metabolism was the primary contributor to overall brigatinib clearance in humans.

A comparison of pregnancy outcomes and congenital malformations in offspring between patients undergoing intracytoplasmic sperm injection and conventional in vitro fertilization: a retrospective cohort study.

Objective: To explore whether intracytoplasmic sperm injection (ICSI) would increase the malformation risk in fetuses and live births compared with conventional in vitro fertilization (IVF).

Design: Retrospective cohort study.

Patient(s): Data were collected from couples who underwent conventional IVF or ICSI from January 2009 to December 2019 at the Center for Reproductive Medicine of Peking University Third Hospital in the People's Republic of China.

CT Predictors of Visceral Pleural Invasion in Patients with Non-Small Cell Lung Cancers 30 mm or Smaller.

Background CT-defined visceral pleural invasion (VPI) is an important indicator of prognosis for non-small cell lung cancer (NSCLC). However, there is a lack of studies focused on small subpleural NSCLCs (≤30 mm). Purpose To identify CT features predictive of VPI in patients with subpleural NSCLCs 30 mm or smaller.

Breast Multiparametric MRI for Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer: The BMMR2 Challenge.

Purpose To describe the design, conduct, and results of the Breast Multiparametric MRI for prediction of neoadjuvant chemotherapy Response (BMMR2) challenge. Materials and Methods The BMMR2 computational challenge opened on May 28, 2021, and closed on December 21, 2021. The goal of the challenge was to identify image-based markers derived from multiparametric breast MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, along with clinical data for predicting pathologic complete response (pCR) following neoadjuvant treatment.