Outcomes of patients treated with venetoclax plus azacitidine versus azacitidine alone stratified by advanced age and acute myeloid leukemia composite model.

Venetoclax plus azacitidine is recognized as standard of care for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). However, some patients may still not be treated with venetoclax combinations due to frailty concerns. We evaluated efficacy and safety of venetoclax plus azacitidine vs.

The surgical burden score: a novel continuous metric to predict postoperative complications after hepatectomy for hepatocellular carcinoma.

Background: No validated model incorporates surgical parameters for complication risk in hepatocellular carcinoma (HCC) resection. We evaluated a novel Surgical Burden Score (SBS), integrating adjusted blood loss (aBL; mL/kg) and operative time (hours) via a Pythagorean formula, and developed an SBS-based model to predict complications.

Methods: Patients undergoing curative-intent hepatectomy for HCC(2000-2023) were identified from an international database.

Modifying inhibitor specificity for homologous enzymes by machine learning.

Selective inhibitors are essential for targeted therapeutics and for probing enzyme functions in various biological systems. The two main challenges in identifying such protein-based inhibitors lie in the extensive experimental effort required, including the generation of large libraries, and in tailoring the selectivity of inhibitors to enzymes with homologous structures. To address these challenges, machine learning (ML) is being used to improve protein design by training on targeted libraries and identifying key interface mutations that enhance affinity and specificity.

Implementing a PREcision meDICine Thoracic (PREDICT) service using in-house reflex testing in a large academic-community practice.

Background: Broad genomic testing is necessary to treat stage IV non-small cell lung cancer (NSCLC) patients. We describe a NSCLC precision medicine service at an academic-community practice and provide model-based estimates of the impact of a similar intervention.

Research Question: Will implementation of a precision medicine service increase NSCLC next-generation sequencing (NGS) rates, improve testing turnaround times (TAT), and increase rates of actionable genomic alterations (AGAs)?

Study Design And Methods: PREDICT (PREcision meDICine Thoracic) consisted of: 1) system-wide reflex testing of stage IV NSCLC patients by in-house solid tumor NGS focused assay and PD-L1 testing, 2) navigator, 3) molecular tumor board (MTB), 4) integrated information portal (OncoTracker) for real-time updates on samples processing, results, and treatment recommendations by the MTB.

Comparison of Underlying Risk of Developing and Dying from Lung Cancer in Screened Populations.

Background: Trial participants are typically healthier than the general population. Differences in underlying characteristics between the population undergoing lung cancer screening (LCS) and LCS trial participants may alter the benefits of LCS.

Research Question: Does the risk of developing and dying from lung cancer differ between trial participants and the general population?

Study Design And Methods: Using data from the i) North Carolina Lung Screening Registry (NCLSR), ii) 2022 Center for Disease Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS) Lung Cancer Screening Module, and iii) National Lung Screening Trial (NLST), we estimated the 5-year probability of developing and dying from lung cancer if not screened using publicly available macros.

Coalescing single-cell genomes and transcriptomes to decode breast cancer progression.

Understanding epithelial lineages of breast cancer and genotype-phenotype relationships requires direct measurements of the genome and transcriptome of the same single cells at scale. To achieve this, we developed wellDR-seq, a high-genomic-resolution, high-throughput method to simultaneously profile the genome and transcriptome of thousands of single cells. We profiled 33,646 single cells from 12 estrogen-receptor-positive breast cancers and identified ancestral subclones in multiple patients that showed a luminal hormone-responsive lineage, indicating a potential cell of origin.

Craving for opioid and cannabis use among adults with chronic pain: Insights from a 30-day ecological momentary assessment study.

Background: Craving is an aversive state and risk factor for progression to nonmedical substance use. The aims of this secondary analysis of Ecological Momentary Assessment (EMA) data were 1) to test whether craving was elevated on days of co-use of opioids and cannabis, and 2) to examine pain, pain catastrophizing, affect, and stress as risk factors for current and next-moment craving, among patients with chronic pain.

Methods: Adults with chronic pain (N = 46) who used both opioids and cannabis were recruited online and completed a 30-day EMA study, consisting of four momentary surveys per day that assessed opioids and cannabis craving, use, pain and pain catastrophizing, affect, and stress.

An Olive Oil-Based High-Fat Diet Promotes Obesity-Driven Metastasis of Triple-Negative Breast Cancer.

Obesity is strongly associated with triple-negative breast cancer (TNBC). A better understanding of the molecular mechanisms driving obesity-induced TNBC progression could facilitate development of precision dietary intervention strategies. Here, we used murine models of obesity induced by different high-fat diets (HFDs) to examine their impact on TNBC progression.

Treatment of Locally Advanced and Metastatic Salivary Gland Cancer: A 10-year Experience of an Oncology Center in Portugal.

Introduction: Scientific evidence regarding salivary gland cancer systemic treatment is limited and the therapeutic approach to locally advanced or metastatic disease is mainly based on consensus. This study aimed to evaluate treatment patterns and outcomes in patients with advanced salivary gland cancer.

Methods: We conducted a retrospective cohort study in a comprehensive cancer center in Portugal, including adult patients diagnosed with primary malignant salivary gland tumors between 2012 and 2021.

Protocol for genome-wide DNA replication timing analysis using click chemistry-based biotinylation.

DNA replication timing (RT) is the cell-type-specific order by which different genomic regions are replicated during the S phase. Here, we present a biotinylation-based version of Repli-seq (BioRepli-seq) to determine genome-wide RT through next-generation sequencing. We detail steps for nucleotide analog pulse labeling, DNA content-based cell sorting, click chemistry-based biotinylation, DNA fragmentation, and on-bead sequencing library generation.

[Frailty in oncogeriatrics].

Frailty is a common geriatric syndrome in older patients with cancer. It affects prognosis and treatment tolerance in various ways. Frailty and cancer share several common risk factors, which are reflected in the hallmarks of aging.

Exposing the Risk: Identifying Perspectives on Skin Cancer Awareness and Prevention Opportunities Among Hispanic Outdoor Workers.

Introduction: Hispanics are over-represented in outdoor occupations; therefore they face an elevated risk of skin cancer. However, there is limited research examining these workers' self-risk perceptions and sun-protective behaviors. This study explores Hispanic outdoor workers' knowledge, attitudes, barriers, and facilitators for engaging in sun-protective behaviors to inform a culturally-tailored intervention.

Cancer-related cognitive impairment: a review of National Institutes of Health‑Funded grants (2017-2024).

Purpose: Cancer-related cognitive impairment (CRCI) adversely affects cancer survivors' academic, occupational, and psychosocial functioning. Analyzing the National Institutes of Health (NIH) portfolio of funded research provides insight into current efforts, trends, and gaps in CRCI research.

Methods: We queried the internal NIH iSearch database to identify awards focused on CRCI.

A framework to mine laser microdissection-based omics data and uncover regulators of pancreatic cancer heterogeneity.

Background: Pancreatic ductal adenocarcinoma (PDAC), the most common and aggressive form of pancreatic cancer, exhibits profound intratumor morphological heterogeneity, complicating the elucidation of the underlying molecular mechanisms driving its progression.

Results: We present and validate an optimized framework for RNA sequencing (RNA-seq) of multiple spatially resolved laser micro-dissected tumor areas (LMD-seq), along with methodological and analytical details to maximize reproducibility and data mining. This approach enhances sensitivity in detecting lowly expressed genes, outperforming single-cell RNA-seq methods, particularly in identifying rare tumor cell populations and transcriptional programs with low expression.

Glucocorticoid Receptor Signaling Mediates Resistance to Therapy in Matrix Rigidity-Induced Dormant Brain Metastatic Breast Cancer Spheroids.

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality in females. Approximately 20-30% of patients with advanced breast cancer develop brain metastasis. Often, brain metastatic breast cancer (BMBC) exhibits a nonproliferative (dormant) phenotype and therapy resistance due to the unfavorable organ microenvironment.

A robust Bayesian dose optimization design with backfill and randomization for phase I/II clinical trials.

The integration of backfill cohorts into Phase I clinical trials has garnered increasing interest within the clinical community, particularly following the "Project Optimus" initiative by the U.S. Food and Drug Administration, as detailed in their final guidance of August 2024.

Comfort With Sharing Food Insecurity Risk for Clinical Care Among Individuals With and Without a Cancer History: Findings From a National Survey.

Introduction: Food insecurity negatively affects timely access to care, treatment adherence, quality of life, and survival among cancer survivors. There is limited knowledge about cancer survivors' comfort with sharing food insecurity risk for clinical care on a national scale. This study aims to assess comfort with sharing food insecurity risk for clinical care among adults with and without a cancer history and to identify factors that may be associated with comfort for sharing food insecurity risk.

Elevated FDG uptake in non-tumorous lung regions does not predict immune checkpoint inhibitor-related pneumonitis in lung cancer patients.

Background: Predictors for checkpoint inhibitor-related pneumonitis (cinrPneumonitis) are desperately needed. This study aimed to investigate the pretreatment standardized uptake value (SUV) on [F]FDG-PET/CT of non-tumorous lung tissue as a predictive imaging marker for the development of cinrPneumonitis in 239 patients with lung cancer.

Methods: All patients with lung cancer receiving [F]Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) prior to immune checkpoint inhibitor (ICI) therapy were included and retrospectively analyzed.

Genetic and Cellular Architecture of Breast Cancer Risk in Multi-Ancestry Studies of 159,297 Cases and 212,102 Controls.

Breast cancer genome-wide association studies (GWAS) have identified over 200 independent genome-wide significant susceptibility markers. However, most studies have focused on one or two ancestral groups. We examined breast cancer genetic architecture using GWAS summary statistics from African (AFR), East Asian (EAS), European (EUR) and Hispanic/Latina (H/L) samples, totaling 159,297 cases and 212,102 controls, comprising the largest multi-ancestry study of breast cancer to date.

Peripheral immune patterns enable robust cross-platform prediction of ALS onset and progression.

Amyotrophic lateral sclerosis (ALS) progression rates vary dramatically between patients, yet the basis of this heterogeneity remains elusive, with no prognostic biomarkers existing to guide clinical decisions or stratify patients for therapeutic trials. Here, we identify a network of coordinated immune cell types, which exhibit differential disruption across progression groups. Using mass cytometry (CyTOF) to profile 2.

An Efficient Lasso Framework for Admixture-Aware Polygenic Scores.

Polygenic scores (PGS) have promising clinical applications for risk stratification, disease screening, and personalized medicine. However, most PGS are trained on predominantly European ancestry cohorts and have limited portability to external populations. While cross-population PGS methods have demonstrated greater generalizability than single-ancestry PGS, they fail to properly account for individuals with recent admixture between continental ancestry groups.