Dominant-negative mutations potentiated by the HSF1-regulated proteostasis network.

Protein mutational landscapes are sculpted by the impacts of the resulting amino acid substitutions on the protein's stability and folding or aggregation kinetics. These properties can, in turn, be modulated by the composition and activities of the cellular proteostasis network. Heat shock factor 1 (HSF1) is the master regulator of the cytosolic and nuclear proteostasis networks, dynamically tuning the expression of cytosolic and nuclear chaperones and quality control factors to meet demand.

NCCN Guidelines® Insights: Management of Immunotherapy-Related Toxicities, Version 2.2024.

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell-engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

Prevention and Treatment of Cancer-Related Infections, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

There is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy.

Oncology Survivorship Care Clinics: Design and Implementation of Survivorship Care Delivery Systems at NCCN Member Institutions.

Background: It is estimated that there are >18 million cancer survivors in the United States, and there is a growing number of survivorship programs across the country to care for these individuals. There is a clear need for survivorship care; however, evidence is still emerging on how to best operationalize the guidance from nationally recognized organizations and clinical practice guidelines.

Methods: The NCCN Best Practices Committee (BPC) recently conducted a survey to better understand survivorship clinics at NCCN Member Institutions.

A platform for mapping reactive cysteines within the immunopeptidome.

The major histocompatibility complex class I antigen presentation pathways play pivotal roles in orchestrating immune responses. Recent studies have begun to explore the therapeutic potential of cysteines within the immunopeptidome, such as the use of covalent ligands to generate haptenated peptide neoepitopes for immunotherapy. In this work, we report a platform for mapping reactive cysteines on MHC-I-bound peptide antigens.

A Genomic Language Model for Chimera Artifact Detection in Nanopore Direct RNA Sequencing.

Chimera artifacts in nanopore direct RNA sequencing (dRNA-seq) can significantly distort transcriptome analyses, yet their detection and removal remain challenging due to limitations in existing basecalling models. We present DeepChopper, a genomic language model that precisely identifies and removes adapter sequences from base-called dRNA-seq long reads at single-base resolution, operating independently of raw signal or alignment information to effectively eliminate chimeric read artifacts. By removing these artifacts, DeepChopper substantially improves the accuracy of critical downstream analyses, such as transcript annotation and gene fusion detection, thereby enhancing the reliability and utility of nanopore dRNA-seq for transcriptomics research.

An integrated view of the structure and function of the human 4D nucleome.

The dynamic three-dimensional (3D) organization of the human genome (the "4D Nucleome") is closely linked to genome function. Here, we integrate a wide variety of genomic data generated by the 4D Nucleome Project to provide a detailed view of human 3D genome organization in widely used embryonic stem cells (H1-hESCs) and immortalized fibroblasts (HFFc6). We provide extensive benchmarking of 3D genome mapping assays and integrate these diverse datasets to annotate spatial genomic features across scales.

Comparative efficacy of lisocabtagene maraleucel in the PILOT study second-line chemotherapy regimens in the real world.

This study assessed the comparative efficacy of lisocabtagene maraleucel (liso-cel) in PILOT (NCT03483103), an open-label, phase II study, versus conventional second-line (2L) chemotherapy regimens in the real world administered to patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who were not intended for hematopoietic stem cell transplantation (HSCT). The liso-cel-treated cohort (n=61) was based on patients who received liso-cel in the PILOT study. The conventional chemotherapy cohort included patients who met PILOT eligibility criteria and received conventional 2L chemotherapy in the real-world clinical setting (n=273).

The heat shock factor code: Specifying a diversity of transcriptional regulatory programs broadly promoting stress resilience.

The heat shock factor (HSF) family of transcription factors drives gene expression programs that maintain cytosolic protein homeostasis (proteostasis) in response to a vast array of physiological and exogenous stressors. The importance of HSF function has been demonstrated in numerous physiological and pathological contexts. Evidence accumulating over the last two decades has revealed that the regulatory programs driven by the HSF family can vary dramatically depending on the context in which it is activated.

Narrative review of lifestyle interventions in breast cancer survivors: current evidence and future directions.

Background: In 8 females, 1 will be diagnosed with breast cancer in their lifetime. Although medical advances have increased the likelihood of survival, up to 90% of females will gain weight during and after treatment increasing the risk of breast cancer recurrence and obesity-related comorbidities in survivorship. Behavioral lifestyle interventions focused on diet with or without physical activity can provide breast cancer survivors nonpharmacological options to decrease weight gain and cardiometabolic risk.

Post-operative care for patients following surgical treatment of lymphedema.

Surgical treatments are promising for the treatment of lymphedema. It is important for patients, healthcare providers, and lymphedema community to understand that surgical treatments currently are not a cure for lymphedema but have provided promising options for patients. Post-operative care for patients following surgical treatment of lymphedema is vital to optimize and sustain patient outcomes.