Association of oropharyngeal cancer recurrence with tumor-intrinsic and immune-mediated sequelae of reduced genomic instability.

Background: Limited understanding of the biology predisposing certain human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) to relapse impedes therapeutic personalization. We aimed to identify molecular traits that distinguish recurrence-prone tumors.

Methods: 50 HPV+ OPSCCs that later recurred (cases) and 50 non-recurrent controls matched for stage, therapy, and smoking history were RNA-sequenced.

Role of inflammasomes and neuroinflammation in epilepsy.

Epilepsy is a brain disorder characterized by recurrent seizures, which are brief episodes of abnormal electrical activity in the brain and involuntary movement that can lead to physical injury and loss of consciousness. Seizures are canonically accompanied by increased inflammatory cytokine production that promotes neuroinflammation, brain pathology, and seizure propagation. Understanding the source of pro-inflammatory cytokines which promote seizure pathogenesis could be a gateway to precision epilepsy drug design.

Management of Dry Mouth Toxicity Following Lu-PSMA-617 Radioligand Therapy.

Treatment options for patients with metastatic castration-resistant prostate cancer include the use of radioligand therapy with Lu-PSMA-617. Although Lu-PSMA-617 can selectively target prostate cancer cells, salivary glands express PSMA on the apical lumen of the acinar epithelium. Xerostomia resulting from the use of radioligand therapy is common.

Differential T cell accumulation within intracranial and subcutaneous melanomas is associated with differences in intratumoral myeloid cells.

Patients with metastatic brain melanomas (MBM) experience shorter-lasting survival than patients with extracranial metastases, and this is associated with a higher fraction of dysfunctional CD8 T cells. The goal of this study was to understand the underlying cause of T cell dysfunction in MBM. To accomplish this, we compared murine B16 melanomas implanted intracranially (IC) or subcutaneously (SC).

Caspase-1 in Cx3cr1-expressing cells drives an IL-18-dependent T cell response that promotes parasite control during acute Toxoplasma gondii infection.

Inflammasome activation is a robust innate immune mechanism that promotes inflammatory responses through the release of alarmins and leaderless cytokines, including IL-1α, IL-1β, and IL-18. Various stimuli, including infectious agents and cellular stress, cause inflammasomes to assemble and activate caspase-1. Then, caspase-1 cleaves targets that lead to pore formation and leaderless cytokine activation and release.

Ambulation in patients with peripheral veno-arterial extracorporeal membrane oxygenation and concomitant femoral intra-aortic balloon pump support.

Introduction: The mobilization and ambulation of patients with severe cardiogenic shock supported with peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO) and concomitant femoral intra-aortic balloon pump (IABP) support is not well-described. This technical paper describes an ambulation protocol to prevent deconditioning in this critically ill patient population.

Methods: A protocol for the ambulation of patients with pVA-ECMO and concomitant IABP support was created in December 2022 and implemented at a single center.

Definitive Radiation Therapy is a Viable Treatment for Locally Advanced Basal Cell Carcinoma Otherwise Requiring Radical or Disfiguring Resection.

Purpose: Standard treatment for basal cell carcinoma (BCC) is surgical resection. However, a subset of locally advanced BCCs may be unresectable, or surgery would result in unacceptable functional or cosmetic defects. Outcomes after definitive radiation therapy for locally advanced BCC in the contemporary era are not well established.

Circulating tumor tissue modified viral (TTMV)-HPV DNA in Recurrent, metastatic HPV-driven oropharyngeal cancer.

Background: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Testing for plasma tumor tissue modified viral (TTMV)-HPV DNA has emerged as a biomarker strategy for post-treatment surveillance to identify recurrent disease. We aimed to understand the prognostic and predictive potential of TTMV-HPV DNA when monitoring patients who had developed recurrent or metastatic (R/M) HPV+OPSCC.

Oligomeric amyloid beta prevents myelination in a clusterin-dependent manner.

Background: White matter loss is a well-documented phenomenon in Alzheimer's disease (AD) patients that has been recognized for decades. However, the underlying reasons for the failure of oligodendrocyte progenitor cells (OPCs) to repair myelin deficits in these patients remain elusive. A single nucleotide polymorphism (SNP) in Clusterin has been identified as a risk factor for late-onset Alzheimer's disease and linked to a decrease in white matter integrity in healthy adults, but its specific role in oligodendrocyte function and myelin maintenance in Alzheimer's disease pathology remains unclear.

Factors Associated With and Characteristics of Patients Receiving Proton Therapy at the End of Life.

Purpose: To identify the characteristics, indications, and toxicities among patients receiving proton beam therapy (PBT) in the final year of life at an academic medical center.

Materials And Methods: A retrospective review of patients who received PBT within the final 12 months of life was performed. Electronic medical records were reviewed for patient and treatment details from 2010 to 2019.

Microglia pack a toolbox for life.

After decades of being overlooked, a recent wave of studies have explored the roles of microglia in brain health and disease. Microglia perform important physiological functions to set up and maintain proper neural network functions, as well as orchestrate responses to toxic stimuli to limit harm. Many microglial transcriptional programs, extracellular sensing molecules, and functional outputs are seen throughout life.

Multicenter Evaluation of Radiation and Immune Checkpoint Inhibitor Therapy in Mucosal Melanoma and Review of Recent Literature.

Purpose: Optimal integration of local therapy and systemic immune therapy for patients with mucosal melanoma (MM) is uncertain. We evaluated treatment patterns and outcomes following radiation therapy (RT) in combination with immune checkpoint inhibition (ICI) in MM.

Methods And Materials: Thirty-seven patients with localized (n = 32, 87%) or node-positive (n = 5, 14%) MM were treated across 4 institutions with RT to the primary tumor with or without oncologic resection (n = 28, 76%) and ICI from 2012 to 2020.

NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC.

Corrigendum: Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

[This corrects the article DOI: 10.3389/fmed.2023.

Structural and functional damage to neuronal nuclei caused by extracellular tau oligomers.

Introduction: Neuronal nuclei are normally smoothly surfaced. In Alzheimer's disease (AD) and other tauopathies, though, they often develop invaginations. We investigated mechanisms and functional consequences of neuronal nuclear invagination in tauopathies.

Generation and characterization of ultrabroadband polarization-frequency hyperentangled photons.

We generate ultrabroadband photon pairs entangled in both polarization and frequency bins through an all-waveguided Sagnac source covering the entire optical C- and L-bands (1530-1625 nm). We perform comprehensive characterization of high-fidelity states in multiple dense wavelength-division multiplexed channels, achieving full tomography of effective four-qubit systems. Additionally, leveraging the inherent high dimensionality of frequency encoding and our electro-optic measurement approach, we demonstrate the scalability of our system to higher dimensions, reconstructing states in a 36-dimensional Hilbert space consisting of two polarization qubits and two frequency-bin qutrits.

A multicenter real-world analysis of risk factors, therapeutics, and outcomes of patients with metastatic basal cell carcinoma.

Background: Metastatic basal cell carcinoma (mBCC) is rare and there are limited data regarding patient and tumor risk factors, optimal treatments, and disease prognosis.

Objective: To assess patient and tumor characteristics, therapeutics, and outcomes of mBCC stratified by location of metastasis.

Methods: Retrospective cohort study of 53 patients with mBCC treated at 4 large academic centers in Boston, Massachusetts; Philadelphia, Pennsylvania; and Cleveland, Ohio between January 1, 2005 and December 31, 2021.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise.

Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

Background: Clinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions.