Evaluation of multiple breast cancer polygenic risk score panels in women of Latin American heritage.

Background: A substantial portion of the genetic predisposition for breast cancer is explained by multiple common genetic variants of relatively small effect. A subset of these variants, which have been identified mostly in individuals of European and Asian ancestry, have been combined to construct a polygenic risk score (PRS) to predict breast cancer risk, but the prediction accuracy of existing PRSs in Hispanic/Latinx individuals (H/L) remain relatively low. We assessed the performance of several existing PRS panels with and without addition of H/L specific variants among self-reported H/L women.

CD33-CD123 IF-THEN Gating Reduces Toxicity while Enhancing the Specificity and Memory Phenotype of AML-Targeting CAR-T Cells.

Our study demonstrates the use of "IF-THEN" SynNotch-gated CAR-T cells targeting CD33 and CD123 in AML reduces off-tumor toxicity. This strategy enhances T-cell phenotype, improves expansion, preserves HSPCs, and mitigates cytokine release syndrome-addressing critical limitations of existing AML CAR-T therapies.

Specialized Infrared Camera-Computer System (SPY) Imaging for Monitoring the Restoration of Nipple Sensation in Patients Undergoing Breast Reduction.

Introduction Symptomatic mammary hypertrophy (SMH) refers to excessive breast weight exceeding 3% of total body weight, impacting not only the breast but also the nipples and areola. Breast reduction surgery (BRS) has a complication that adversely affects the nipple-areolar complex (NAC) sensation. The purpose of this study was to estimate the degree to which the specialized infrared camera-computer system (SPY) may predict postoperative sensation of the NAC following BRS.

Quadrant darkfield for label-free imaging of intracellular puncta.

Significance: Imaging changes in subcellular structure is critical to understanding cell behavior but labeling can be impractical for some specimens and may induce artifacts. Although darkfield microscopy can reveal internal cell structures, it often produces strong signals at cell edges that obscure intracellular details. By optically eliminating the edge signal from darkfield images, we can resolve and quantify changes to cell structure without labeling.

Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study.

Background: Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma.

Methods: This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients.

Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies.

Patients And Methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed.

Molecular Features of Diffuse Large B-Cell Lymphoma Associated With Primary Treatment Resistance.

Diffuse large B-cell lymphoma (DLBCL) patients that fail to achieve a complete metabolic response with frontline immunochemotherapy have a poor prognosis. Genomic profiling has led to a broader understanding of the molecular drivers in DLBCL, but it is unknown how well current classifiers identify patients that will experience primary treatment resistance (PTR). Using whole exome and RNA sequencing data from newly diagnosed DLBCL patients, we evaluated the genomic landscape of PTR and compared it to that of non-PTR DLBCL.

Draft genome of a human gut-derived sp. that ameliorates colitis and colitis-associated sociability deficits in mice.

is a genus of anaerobic, gram-positive bacteria commonly found in mammalian gastrointestinal tracts. Yet, how variations among different strains can impact host health is poorly understood. We present a sp.

Outcomes with loncastuximab tesirine following CAR T-cell therapy in patients with relapsed or refractory diffuse large B-cell lymphoma.

The efficacy of loncastuximab tesirine (lonca) following chimeric antigen receptor T-cell therapy (CAR-T) progression/failure is unknown. Hence, we sought to examine real-world use and outcomes of lonca following CAR-T in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the USA. In this retrospective study, we included adults (age ≥ 18 years) with R/R DLBCL who received lonca monotherapy as third- (3 L) or fourth line (4 L) treatment after progressing on second line (2 L) or 3 L CAR-T, respectively.

: Integrative Module Analysis for Multi-omics Data.

Summary: The integration of metabolomics with other omics ("multi-omics") offers complementary insights into disease biology. However, this integration remains challenging due to the fragmented landscape of current methodologies, which often require programming experience or bioinformatics expertise. Moreover, existing approaches are limited in their ability to accommodate unidentified metabolites, resulting in the exclusion of a significant portion of data from untargeted metabolomics experiments.

Mating and ecdysone signaling modify growth, metabolism, and digestive efficiency in the female gut.

Adaptive changes in organ size and physiology occur in most adult animals, but how these changes are regulated is not well understood. Previous research found that mating in females drives not only increases in gut size and stem cell proliferation but also alters feeding behavior, intestinal gene expression, and whole-body lipid storage, suggesting altered gut metabolism. Here, we show that mating dramatically alters female gut metabolism and digestive function.

Disparities in childhood leukemia survival for Asian, Native Hawaiian, and Pacific Islanders in the United States.

While some previous studies disaggregated the Asian, Native Hawaiian, and Pacific Islander (ANHPI) population to investigate survival for childhood leukemia, further studies are needed to understand the differences between subpopulations. The aim of our study was to estimate 5-year relative survival for patients with childhood leukemia and to investigate disparities in prognostic factors with disaggregation of the ANHPI population. We used the Surveillance, Epidemiology, and End Results Program 17 database and included 1881 ANHPI patients with childhood leukemia and 8772 non-Hispanic White (NHW) patients with childhood leukemia.

Associations Between Dietary Patterns and Quality of Life in a Longitudinal Cohort of Colorectal Cancer Survivors.

Purpose: To characterize dietary patterns and examine associations with cross-sectional and longitudinal changes in quality of life (QOL) over approximately one year after colorectal cancer (CRC) diagnosis.

Methods: The ColoCare Study is an international, multi-center, prospective cohort study of newly diagnosed CRC survivors of any stage. A subset of participants with CRC in the United States completed patient-reported outcome measures at 6- and 12-months post-enrollment, including the Food Frequency Questionnaire (FFQ) and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

CRIPTO's multifaceted role in driving aggressive prostate cancer unveiled by in vivo, organoid, and patient data.

CRIPTO (or CR-1 or TDGF1) is a protein that plays an active role in tumor initiation and progression. We have confirmed that increased expression of CRIPTO is associated with clinical and prostate-specific antigen (PSA) progression in human prostate tissues. Our approach involved gaining insight into the role of CRIPTO signaling in castration-resistant Nkx3.

Localized hepatocellular carcinoma: Is liver-directed therapy alone as efficacious as surgical resection?

Objective: Studies of the efficacy of nonsurgical methods of liver-directed therapy (percutaneous microwave or radiofrequency ablation, transarterial bland embolization, chemoembolization, and/or radioembolization) in the treatment of hepatocellular cancer lack contemporaneous comparative surgical cohorts. The role of these methods of liver-directed therapy as destination treatment in hepatocellular cancer is not well defined.

Methods: We queried our institutional registry for patients undergoing resection or liver-directed therapy alone for clinical stage I to IVa hepatocellular cancer between 2012 and 2022.

Parameterization of beta distributions for bias parameters of binary exposure misclassification in probabilistic bias analysis.

To account for misclassification of dichotomous variables using probabilistic bias analysis, beta distributions are often assigned to bias parameters (e.g., PPV and NPV) based on data from an internal validation substudy.