Leveraging chromatin packing domains to target chemoevasion .

Cancer cells exhibit a remarkable resilience to cytotoxic stress, often adapting through transcriptional changes linked to alterations in chromatin structure. In several types of cancer, these adaptations involve epigenetic modifications and restructuring of topologically associating domains (TADs). However, the underlying principles by which chromatin architecture facilitates such adaptability across different cancers remain poorly understood.

Notes from the Field: Enhanced Surveillance for Raccoon Rabies Virus Variant and Vaccination of Wildlife for Management - Omaha, Nebraska, October 2023-July 2024.

On September 28, 2023, a kitten aged approximately 6 weeks found in Omaha, Nebraska, had test results positive for rabies at the Nebraska Veterinary Diagnostic Center (NVDC) after dying with neurologic signs and having bitten and scratched its caretakers. Preliminary investigation identified 10 exposed persons for whom postexposure prophylaxis (PEP) was recommended. Subsequent variant-typing by NVDC yielded a presumptive positive result for the Eastern raccoon rabies virus variant (RRVV), which CDC confirmed on October 6.

A Comparison of Postoperative Outcomes Between Supine and Lateral Patient Positioning in Total Hip Arthroplasty Using the Anterior-Based Muscle Sparing Surgical Approach.

Background: To determine any differences in clinical outcomes between patients in the supine vs the lateral position during anterior-based muscle sparing (ABMS) total hip arthroplasty (THA).

Methods: A retrospective review was performed of 368 patients undergoing THA via the ABMS approach (201 lateral vs 167 supine position) at our institution (2015-2019) with a minimum follow-up of 12 months. Inclusion criteria were all patients undergoing primary THA.

Three-color single-molecule localization microscopy in chromatin.

Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets like chromatin. Chromatin exhibits a hierarchical organization with structural compartments and domains at different length scales, from nanometers to micrometers. Single molecule localization microscopy (SMLM) methods, such as STORM, are essential for studying chromatin at the supra-nucleosome level due to their ability to target epigenetic marks that determine chromatin organization.

T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed.