Nivolumab combination therapies in patients with advanced gastric and gastroesophageal junction cancer: the phase II FRACTION gastric cancer study.

Background: Nivolumab-based therapies are efficacious with acceptable safety in patients with gastric cancer (GC) and gastroesophageal junction cancer (GEJC). Novel nivolumab-based combination immunotherapies may offer enhanced efficacy in these indications. FRACTION-GC was a signal-seeking, randomized, open-label, phase II adaptive-design trial assessing efficacy and safety of nivolumab in combination with ipilimumab [cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody], relatlimab (lymphocyte-activation gene 3 antibody), or IDO1i (BMS986205, an indoleamine-2,3-dioxygenase-1 inhibitor) in patients with unresectable, advanced/metastatic GC/GEJC.

Protocol for generating and characterizing a nasal epithelial model using imaging with application for respiratory viruses.

Air-liquid interface (ALI) culture can differentiate airway epithelial cells to recapitulate the respiratory tract in vitro. Here, we present a protocol for isolating and culturing nasal epithelial cells from turbinate tissues for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We describe steps to overcome challenges of imaging fragile cultures, detect the production of mucus, and quantify intracellular virus post-SARS-CoV-2 infection.

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator's Consortium Registry Analysis.

Introduction: Osimertinib is now a standard first-line (1L) therapy for EGFR-mutated (EGFRm) advanced NSCLC. We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC.

Methods: Patients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator's Consortium were included; demographic and clinical data including treatment patterns were described.

Machine learning based prediction model for bile leak following hepatectomy for liver cancer.

Objective: We sought to develop a machine learning (ML) preoperative model to predict bile leak following hepatectomy for primary and secondary liver cancer.

Methods: An eXtreme Gradient Boosting (XGBoost) model was developed to predict post-hepatectomy bile leak using data from the ACS-NSQIP database. The model was externally validated using data from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) multi-institutional databases.

Structural basis for catalysis and selectivity of phospholipid synthesis by eukaryotic choline-phosphotransferase.

Phospholipids are the most abundant component in lipid membranes and are essential for the structural and functional integrity of the cell. In eukaryotic cells, phospholipids are primarily synthesized de novo through the Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group of cytidine-5'-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) that use 1,2-diacylglycerol (DAG) and CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC) or phosphatidylethanolamine (PE) that are the main phospholipids in eukaryotic cells.

Perioperative Changes in Serum Transaminases Levels Predicts Long-Term Survival Following Liver Resection of Hepatocellular Carcinoma.

Background: We sought to define whether and how hepatic ischemia/reperfusion (I/R) as manifested by perioperative aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) levels impact long-term outcomes after curative-intent resection of hepatocellular carcinoma (HCC).

Patients And Methods: Intrasplenic injection of HCC cells was used to establish a murine model of HCC recurrence with versus without I/R injury. Patients who underwent curative resection for HCC were identified from a multi-institutional derivative cohort (DC) and separate external validation (VC) cohort.

Constitutive androstane receptor (CAR) functions as a tumor suppressor via regulating stemness in liver cancer.

Constitutive androstane receptor (CAR) is a xenosensor that is almost exclusively expressed in the liver. Studies in rodents suggest an oncogenic role for CAR in liver cancer, but its role in human liver cancer is unclear. We aimed to investigate the functional roles of CAR in human liver cancer with a focus on the liver cancer stem cells.

Effect of a multimodal continuing professional development initiative on HIV testing in primary care in British Columbia, Canada.

Introduction: Many persons are unaware of HIV infection until they present in an advanced stage of the disease. Diagnosing HIV infection in its earliest stages reduces morbidity and mortality and contributes to improved public health. Increased testing for HIV is critical for prevention, and primary care providers play an essential role in early HIV screening.

Predictors of failure of conservative management of cholecystitis: a systematic review of the literature.

Objectives: While emergency cholecystectomy is the preferred treatment for acute cholecystitis, conservative management can be used as a bridge to definitive surgical management in situations where emergency surgical services are limited. The objective of this systematic review is to identify factors associated with conservative management failure as defined as either failed resolution of symptoms on initial presentation, or the recurrence of symptoms whilst awaiting an elective cholecystectomy. This study aims to allow clinicians to make evidence-based recommendations for conservative versus operative management.

Percutaneous transhepatic biliary intervention for the management of recurrent cholangitis secondary to intrahepatic biliary stones after hepaticojejunostomy.

Recurrent cholangitis, intrahepatic stones and biliary and anastomotic strictures are common complications after Roux-en-Y hepaticojejunostomy. The surgically altered anatomy makes management of these complications with endoscopic retrograde cholangiopancreatography technically difficult. We present a case of recurrent cholangitis in a 25-year-old woman with a prior hepaticojejunostomy.

The quantum gravity seeds for laws of nature.

We discuss the challenges that the standard (Humean and non-Humean) accounts of laws face within the framework of quantum gravity where space and time may not be fundamental. This paper identifies core (meta)physical features that cut across a number of quantum gravity approaches and formalisms and that provide seeds for articulating updated conceptions that could account for QG laws not involving any spatio-temporal notions. To this aim, we will in particular highlight the constitutive roles of quantum entanglement, quantum transition amplitudes and quantum causal histories.

Effects of temperature on physiology, transcription, and toxin production of the harmful benthic dinoflagellate Gambierdiscus belizeanus.

Benthic dinoflagellates constitute a group of microalgae that inhabit the ocean floor, adhering to substrates such as coral, seagrasses, and sand. Certain species within this group have the potential to produce toxins. Ocean warming could increase the occurrence of harmful benthic dinoflagellate blooms, which pose a significant threat to coastal ecosystems in tropical and subtropical regions.

Alternative splicing of transcript mediates the response of circadian clocks to temperature changes.

Circadian clocks respond to temperature changes over the calendar year, allowing organisms to adjust their daily biological rhythms to optimize health and fitness. In , seasonal adaptations are regulated by temperature-sensitive alternative splicing (AS) of () and () genes that encode key transcriptional repressors of clock gene expression. Although () gene encodes the critical activator of circadian gene expression, AS of its transcripts and its potential role in temperature regulation of clock function have not been explored.

Analyzing the interaction between time to surgery and tumor burden score in hepatocellular carcinoma.

Background: The effect of "time to surgery (TTS)" on outcomes for curative-intent hepatectomy of hepatocellular carcinoma (HCC) remains debated. The interaction between tumor burden score (TBS) and TTS remains unclear. We sought to evaluate the effects of TBS and TTS on long-term HCC outcomes.

Determining Line of Therapy from Real-World Data in Non-Small Cell Lung Cancer.

Introduction: Determining lines of therapy (LOT) using real-world data is crucial to inform clinical decisions and support clinical research. Existing rules for determining LOT in patients with metastatic non-small cell lung cancer (mNSCLC) do not incorporate the growing number of targeted therapies used in treatment today. Therefore, we propose rules for determining LOT from real-world data of patients with mNSCLC treated with targeted therapies.

Machine learning prediction of early recurrence after surgery for gallbladder cancer.

Background: Gallbladder cancer is often associated with poor prognosis, especially when patients experience early recurrence after surgery. Machine learning may improve prediction accuracy by analysing complex non-linear relationships. The aim of this study was to develop and evaluate a machine learning model to predict early recurrence risk after resection of gallbladder cancer.

Various CVD-grown ZnO nanostructures for nanodevices and interdisciplinary applications.

This work presents a simple chemical vapour deposition (CVD) method to grow ZnO nanostructures. By annealing Zn powder under atmospheric pressure conditions, we collected nanocrystals with various morphologies, including rods, pencils, sheets, combs, tetrapods, and multilegs. Raman scattering study reveals that the samples are monophasic with a hexagonal structure, and fall into the 6 space group.

Fecal Microbiome Composition Correlates with Pathologic Complete Response in Patients with Operable Esophageal Cancer Treated with Combined Chemoradiotherapy and Immunotherapy.

: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer.

Cardioprotective Efficacy of Sevoflurane in Patients With Rheumatic Heart Disease Undergoing Heart Valve Surgery Under Cardiopulmonary Bypass.

Objectives: In this study, we investigated whether cardioprotective properties of sevoflurane were expressed in patients with rheumatic heart disease undergoing heart valve surgery under cardiopulmonary bypass (CPB).

Methods: Fifty patients with rheumatic heart disease undergoing heart valve surgery under CPB were randomly assigned to receive total anesthesia with sevoflurane or propofol during surgery. Except for this, anesthetic and surgical management was the same in all patients.

Multidisciplinary protocol to reduce surgical readmissions in Australia: American College of Surgeons National Surgical Quality Improvement Program.

Introduction: Unplanned readmissions in general surgery are an important quality indicator of patient care and are associated with increased costs to healthcare services. This study aims to implement a multidisciplinary protocol in a single institution in a tertiary referral hospital to monitor and reduce unplanned readmission rates.

Methods: A prospective cohort study using an institution-based protocol was conducted over an 18-month period including patients undergoing a general surgical procedure.

Advocacy Skill Development in Public Health Education Curriculum: A Pilot Study.

The National Commission for Health Education Credentialing (NCHEC) released updated Responsibilities and Competencies for Health Education Specialists based on the 2020 HESPA II. For the first time, advocacy is a standalone area of responsibility (Area V: Advocacy) for health education specialists. Although this is exciting for the field of health education, there is limited consensus on how to effectively teach advocacy or what content and skills to include.