Meiotic DNA break resection and recombination rely on chromatin remodeler Fun30.

DNA double-strand breaks (DSBs) are nucleolytically processed to generate single-stranded DNA for homologous recombination. In Saccharomyces cerevisiae meiosis, this resection involves nicking by the Mre11-Rad50-Xrs2 complex (MRX), then exonucleolytic digestion by Exo1. Chromatin remodeling at meiotic DSBs is thought necessary for resection, but the remodeling enzyme was unknown.

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.

A qualitative study of attitudes and perceptions of smoking cessation medication among patients with cancer.

Purpose: Among patients with cancer, tobacco use remains high. Nearly half who report smoking at diagnosis continue to smoke following diagnosis, and use of smoking cessation medication remains low. This study explores attitudes, barriers, and preferences for smoking cessation medication among patients enrolled in a tobacco treatment trial in the context of cancer care.

A proof-of-concept study to investigate the radiolabelling of human mesenchymal and hematopoietic stem cells with [Zr]Zr-Df-Bz-NCS.

Background: The transplantation of hematopoietic stem and progenitor cells (HSPCs) or mesenchymal stromal/stem cells (MSCs) for the treatment of a wide variety of diseases has been studied extensively. A challenge with cell-based therapies is that migration to and retention at the target site is often difficult to monitor and quantify. Zirconium-89 (Zr) is a positron-emitting radionuclide with a half-life of 3.

Does enhanced meaning after meaning-centered group psychotherapy mediate a reduction in depressive symptoms in cancer survivors? A mediation analysis in the context of a randomized controlled trial.

Purpose: After meaning-centered group psychotherapy for cancer survivors (MCGP-CS), depressive symptoms tend to decrease. An enhanced sense of meaning may play a mediating role in this decrease. The aim of this study was to assess whether personal meaning mediates the relationship between MCGP-CS and depressive symptoms.

The pentameric chloride channel BEST1 is activated by extracellular GABA.

Bestrophin 1 (BEST1) is chloride channel expressed in the eye, central nervous system (CNS), and other tissues in the body. A link between BEST1 and the principal inhibitory neurotransmitter γ-aminobutyric acid (GABA) has been proposed. The most appreciated receptors for extracellular GABA are the GABA G-protein coupled receptors and the pentameric GABA chloride channels, both of which have fundamental roles in the CNS.

Reconstitution of SPO11-dependent double-strand break formation.

Homologous meiotic recombination starts with DNA double-strand breaks (DSBs) generated by SPO11 protein. SPO11 is critical for meiosis in most species but the DSBs it makes are also dangerous because of their mutagenic and gametocidal potential, so cells must foster SPO11's beneficial functions while minimizing its risks. SPO11 mechanism and regulation remain poorly understood.

Genotype-immunophenotype relationships in -mutant AML clonal evolution uncovered by single cell multiomic analysis.

Acute myeloid leukemia (AML) is a multi-clonal disease, existing as a milieu of clones with unique but related genotypes as initiating clones acquire subsequent mutations. However, bulk sequencing cannot fully capture AML clonal architecture or the clonal evolution that occurs as patients undergo therapy. To interrogate clonal evolution, we performed simultaneous single cell molecular profiling and immunophenotyping on 43 samples from 32 -mutant AML patients at different stages of disease.

Predictors of Recurrence in Nonmetastatic Appendiceal Epithelial Cancers: An Updated Single-Center Experience Over 25 Years.

Background: Appendiceal epithelial tumors are rare and encompass a broad set of adenocarcinoma histologies, including mucinous (mAC), colonic-type (cAC), and goblet cell (GCA) adenocarcinomas. It has previously been reported that nodal disease predicted recurrence in patients with nonmetastatic appendiceal adenocarcinomas, supporting diagnostic laparoscopy with right hemicolectomy for staging and assessment for risk of recurrence. In this update, we sought to identify predictors of nodal disease on initial diagnostic pathology in nonmetastatic adenocarcinomas.

Fungal symbiont transmitted by free-living mice promotes type 2 immunity.

The gut mycobiota is crucial for intestinal homeostasis and immune function. Yet its variability and inconsistent fungal colonization of laboratory mice hinders the study of the evolutionary and immune processes that underpin commensalism. Here, we show that Kazachstania pintolopesii is a fungal commensal in wild urban and rural mice, with an exceptional ability to colonize the mouse gastrointestinal tract and dominate the gut mycobiome.

Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes.

The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved.

Locoregional Therapies for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Importance: Several locoregional therapies (LRTs) for nonmetastatic hepatocellular carcinoma (HCC) are available; however, a global comparison of the relative efficacy of each is needed.

Objective: To conduct a systematic review and direct, pairwise meta-analytic comparison of all identified randomized clinical trials evaluating the treatment of nonmetastatic HCC.

Data Sources: A comprehensive search of PubMed and the proceedings of the American Society of Clinical Oncology and American Society for Radiation Oncology annual meetings from January 1, 2010, to November 1, 2023, was performed.

Adjuvant chemotherapy in T1a/bN0 breast cancer with a high 21-gene recurrence score (> 25): a 10-year follow-up in a real-world cohort.

Background: In ER + /HER2- early breast cancer (BC), 21-Gene Recurrence Score (RS) > 25 indicates high-risk of distant-recurrence and predicts benefit from adjuvant chemotherapy (aCT) regardless of tumor-size. However, T1a/b (≤ 1 cm) node-negative (N0) tumors, regarded as of low risk of recurrence, were under-represented in the RS trials. We therefore aimed to investigate the benefit of aCT in patients with T1a/bN0 BC, RS > 25, where clinical and genomic risk indicators are discordant.

Comprehensive genomic analysis reveals molecular heterogeneity in pediatric ALK-positive anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL (ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA sequencing, and DNA methylation profiling.

Trends in enforcement of National Comprehensive Cancer Network financial conflict of interest policy.

Background: The National Comprehensive Cancer Network (NCCN) financial conflict of interest (FCOI) policy sets dollar maximums for panelists, but violations may occur.

Methods: We studied NCCN Guidelines panelists for the 20 most prevalent cancers, 2013-2022. We included panelists with at least 1 full calendar year of service ("current panelists") and those who began service during the study period ("new panelists"); NCCN FCOI policy limits ($20 000 from any single company or $50 000 across all companies) apply to both groups.

The Utility of BSND Immunohistochemistry in the Differential Diagnosis of Oncocytic and Warthin-like Mucoepidermoid Carcinoma of Salivary Gland.

Purpose: BSND is a chloride channel subunit that is expressed in the normal salivary gland. We aimed to validate the utility of BSND immunohistochemistry in the differential diagnosis of oncocytic salivary gland neoplasms.

Methods: BSND immunohistochemistry was performed in a retrospective cohort of 93 salivary gland lesions, enriched with tumors with oncocytic features and histologic variants of mucoepidermoid carcinoma (MEC).

D2 Lymphadenectomy for Gastric Cancer: Advancements and Technical Considerations.

Lymphadenectomy (LND) is a crucial component of the curative surgical treatment of gastric cancer (GC). The LND serves to both accurately stage the disease and offer therapeutic benefits. At the time of "curative-intent" gastrectomy, D2 LND is the optimal treatment for patients with locally advanced GC due to its survival benefits and acceptable morbidity.

The lives of cells, recorded.

A paradigm for biology is emerging in which cells can be genetically programmed to write their histories into their own genomes. These records can subsequently be read, and the cellular histories reconstructed, which for each cell could include a record of its lineage relationships, extrinsic influences, internal states and physical locations, over time. DNA recording has the potential to transform the way that we study developmental and disease processes.

Esophagectomy may have a role in stage IV esophageal adenocarcinoma.

Objective: We sought to determine whether aggressive local treatment provides a benefit in patients with stage IV esophageal adenocarcinoma and to determine factors associated with survival.

Methods: Patients with clinical stage IV esophageal adenocarcinoma at diagnosis who underwent esophagectomy from 2010 to 2023 were identified from our prospectively maintained database. Clinicopathologic and demographic characteristics were compared among patients by stage.