Comprehensive characterization of the transcriptional landscape in Alzheimer's disease (AD) brains.

Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts, encompassing 33,321 long ncRNAs, 92,897 enhancer RNAs, 53,763 alternative polyadenylation events, and 900,221 A-to-I RNA editing events.

Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function.

Metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy.

Same-day molecular testing for targetable mutations in solid tumor cytopathology-The next frontier of the rapid on-site evaluation.

Introduction: This study aimed to assess the feasibility of implementing the Idylla system, an ultra-rapid, cartridge-based assay, as an extension of rapid on-site evaluation (ROSE) in cytology. The authors conducted a pilot validation study on specimens from non-small cell lung carcinoma, thyroid carcinoma, and melanoma, evaluating four assays designed to detect alterations in KRAS, EGFR, BRAF, gene fusions, and expression imbalances in ALK, ROS1, RET, NTRK1/2/3, and MET exon 14 skipping transcripts. They investigated the feasibility of providing accurate biomarker molecular testing results in a cytopathology laboratory within hours of specimen collection.

Outcomes of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation.

Patients with multiple myeloma (MM) without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous hematopoietic stem cell transplantation (autoHCT) are limited. To evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. Single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013 and 2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization, defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification.

Rise in Minimally Invasive Surgery for Colorectal Cancer Is Associated With Adoption of Robotic Surgery.

Background: Minimally invasive surgery is associated with improved short-term outcomes and similar long-term oncologic outcomes for colorectal cancer patients compared with open surgery. Although the robotic approach has ergonomic and technical benefits, how it has impacted utilization of traditional laparoscopic surgery and minimally invasive surgery overall is unclear.

Objective: Describe trends in open, robotic, and laparoscopic approaches for colorectal cancer resections and examine factors associated with minimally invasive surgery.

Virus Protein-Specific Immune Responses in Selective Depletion of Lymphocyte Populations Using Monoclonal Antibodies in Bolivian Squirrel Monkeys ().

The increasing use of immune suppressive monoclonal antibodies in the treatment of organ transplant recipients and patients with oncologic, neurological, and autoimmune diseases can lead to serious morbidity and mortality from the reactivation of viral agents that persist in humans. The squirrel monkey polyomaviruses are naturally found in Bolivian squirrel monkeys (SQM) and may be a useful model for the study of polyomavirus-associated pathogenesis and experimental treatment and prevention strategies. Two diverse groups of squirrel monkeys were given, a single dose of an anti-B cell antibody (rituximab) resulting in complete depletion of B cells (CD20+), while an anti-CD8 monoclonal antibody (7 pt-3F9) resulted in a transient depletion of CD8+ lymphocytes compared with control animals (group with no infusion with either of the monoclonal antibodies).

Melanoma toolkit for early detection for primary care clinicians: a 1-year follow-up on outcomes.

Introduction: Primary care providers or clinicians (PCPs) have the potential to assist dermatologists in screening patients at risk for skin cancer, but require training to appropriately identify higher-risk patients, perform skin checks, recognize and biopsy concerning lesions, interpret pathology results, document the exam, and bill for the service. Very few validated dermatology training programs exist for PCPs and those that are available focus primarily on one emphasis area, which results in variable efficacy and single-topic limited scope.

Methods: We have created a free, online, continuing education program (Melanoma Toolkit for Early Detection, MTED) that allows learners to choose from a variety of multimedia tools (image recognition, videos, written material, in-person seminars, self-tests, etc.

Quality of Cancer Recurrence Data in the National Cancer Database: A Reappraisal of Reporting Readiness.

Background: This study evaluated the quality of cancer recurrence data in the National Cancer Database (NCDB) to determine if missingness and reporting consistency have improved enough to support national research.

Methods: This multi-methods study included NCDB analyses and a cancer registry staff survey. Trends in recurrence data missingness from 2004 to 2021 and multivariable analyses of factors associated with missingness from 2017 to 2021 were evaluated for 4,568,927 patients with non-metastatic cancer.

Primary gastric T-cell lymphoma presenting with perforation: a case report and review of the literature.

Primary gastric T-cell lymphomas (PGTL) are exceedingly rare with an estimated incidence of 0.0091 per 100,000 person-years, affecting mainly elderly males. PGTL can present with a variety of gastrointestinal symptoms, but patients only rarely present with perforation.

Biliary complications of surgical procedures: what the radiologist needs to know.

Post-surgical biliary complications increase morbidity, mortality, and healthcare utilization. Early detection and management of biliary complications is thus of great clinical importance. Even though the overall risk for biliary complications is low after laparoscopic cholecystectomy, post-cholecystectomy biliary complications are frequently encountered in clinical practice as laparoscopic cholecystectomy is the most common surgical procedure performed in the United States.

NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

A sample size analysis of a mathematical model of longitudinal tumor volume and progression-free survival for Bayesian individual dynamic predictions in recurrent high-grade glioma.

Patients with recurrent high-grade glioma (rHGG) have a poor prognosis with median progression-free survival (PFS) of <7 months. Responses to treatment are heterogenous, suggesting a clinical need for prognostic models. Bayesian data analysis can exploit individual patient follow-up imaging studies to adaptively predict the risk of progression.

Precision medicine for patients with salivary gland neoplasms: Determining the feasibility of implementing a next-generation sequencing-based RNA assay in a hospital laboratory.

Objective: Diagnosing neoplasms of the salivary gland is challenging, as morphologic features of these tumors are complex, and well-defined diagnostic categories have overlapping features. Many salivary gland neoplasms are associated with recurrent genetic alterations. The utilization of RNA-based targeted next-generation sequencing (NGS) panels for the detection of cancer-driving translocations and mutations is emerging in the clinical laboratory.

Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3.

Background: Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.

Methods: We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases.

Phase 1b/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance.

Defining an Undergraduate Radiation Oncology Microclerkship via the Delphi Method.

Purpose: Many medical students in the U.S. lack formal exposure to radiation oncology (RO).

Ossification patterns of the C1 (atlas) and C2 (axis) vertebrae children.

Purpose: This retrospective study aimed to assess ossification patterns and synchondrosis fusion timelines of the C1 and C2 vertebrae in pediatric age group, to help differentiate injuries from normal variations and serve as a guide when evaluating incompletely fused synchondrosis.

Materials And Methods: The study analyzed 432 CT examinations of children aged 0-72 months, conducted at a single institution between January 2010 and January 2018. The focus was assessment of the visibility and fusion of the three ossification centers and three synchondroses of the atlas, and six ossification centers and four synchondroses of the axis, based on age.

The Utility of Interferon-γ Release Assays in the Diagnosis of Tuberculosis in Patients With Cancer.

Background: Patients with cancer are at elevated risk for tuberculosis (TB) reactivation. Diagnosis of latent TB infection and TB disease remains challenging in this patient population despite the advent of interferon-γ release assays (IGRA).

Methods: We retrospectively reviewed medical records of all patients with cancer who had IGRA testing (QuantiFERON-TB [QFT-TB] or T-SPOT.

Improved Control of Triple-Negative Breast Cancer Tumor and Metastasis with a pH-Sensitive Hyaluronic Acid Nanocarrier for Doxorubicin Delivery.

Polymer based nanoformulations offer substantial prospects for efficacious chemotherapy delivery. Here, we developed a pH-responsive polymeric nanoparticle based on acidosis-triggered breakdown of boronic ester linkers. A biocompatible hyaluronic acid (HA) matrix served as a substrate for carrying a doxorubicin (DOX) prodrug which also possesses natural affinity for CD44 cells.

Peritoneal Cancer Index Correlates with Radiographic Assessment of Colorectal Carcinomatosis.

Background: The Peritoneal Cancer Index (PCI), calculated intraoperatively, has previously yielded mixed results when correlated with computed tomography. This study aimed to quantify variation in this scoring method comparing radiologists' and surgeons' radiologic PCI (rPCI) assessment.

Methods: The rPCI of 104 patients treated at a single institution for peritoneal carcinomatosis was calculated by an abdominal radiologist and a surgeon.