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. We sought to evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. This was a 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.

Real-time CBCT imaging and motion tracking via a single arbitrarily-angled x-ray projection by a joint dynamic reconstruction and motion estimation (DREME) framework.

Real-time cone-beam computed tomography (CBCT) provides instantaneous visualization of patient anatomy for image guidance, motion tracking, and online treatment adaptation in radiotherapy. While many real-time imaging and motion tracking methods leveraged patient-specific prior information to alleviate under-sampling challenges and meet the temporal constraint (<500 ms), the prior information can be outdated and introduce biases, thus compromising the imaging and motion tracking accuracy. To address this challenge, we developed a frameworkynamicconstruction andotionstimation (DREME) for real-time CBCT imaging and motion estimation, without relying on patient-specific prior knowledge.

Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer.

Purpose: In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy.

Methods: In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS).

Cardiovascular Disease and Breast Cancer Stage at Diagnosis.

Importance: Cardiovascular disease (CVD) and cancer are the leading causes of mortality in the US. Large-scale population-based and mechanistic studies support a direct effect of CVD on accelerated tumor growth and spread, specifically in breast cancer.

Objective: To assess whether individuals presenting with advanced breast cancers are more likely to have prevalent CVD compared with those with early-stage breast cancers at the time of diagnosis.

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).

Inhibition of nitric oxide synthase transforms carotid occlusion-mediated benign oligemia into large cerebral infarction.

It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia in mice, yet leads to various outcomes (asymptomatic-to-death) in humans. We hypothesized that inhibition of nitric oxide synthase (NOS) both transforms UCAO-mediated oligemia into full infarction and expands pre-existing infarction. Using 900 mice, we i) investigated stroke-related effects of UCAO with/without intraperitoneal administration of the NOS inhibitor (NOSi) N-nitro-L-arginine methyl ester (L-NAME, 400 mg/kg); ii) examined the rescue effect of the NO-donor, molsidomine (200 mg/kg at 30 minutes); and iii) tested the impact of antiplatelet medications.

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.

Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis.

Background: The impact of steroid-sparing immunosuppressive agents (SSIAs) for immune-related adverse events (irAEs) on tumor outcome is not well-known. This systematic review evaluates tumor outcomes for corticosteroid (CS) monotherapy versus CS with SSIA (CS-SSIA) for irAE treatment with a focus on melanoma.

Methods: Search was conducted through 1/5/23 using PubMed, Embase, Cochrane CENTRAL, and Web of Science.

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.