Increased translation driven by non-canonical EZH2 creates a synthetic vulnerability in enzalutamide-resistant prostate cancer.

Overcoming resistance to therapy is a major challenge in castration-resistant prostate cancer (CRPC). Lineage plasticity towards a neuroendocrine phenotype enables CRPC to adapt and survive targeted therapies. However, the molecular mechanisms of epigenetic reprogramming during this process are still poorly understood.

Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity.

Purpose Of Review: To review the evidence and describe the biological plausibility for the benefits of inhibiting cholesteryl ester transfer protein (CETP) on multiple organ systems through modification of lipoprotein metabolism.

Recent Findings: Results from observational studies, Mendelian randomization analyses, and randomized clinical trials support the potential of CETP inhibition to reduce atherosclerotic cardiovascular disease (ASCVD) risk through a reduction of apolipoprotein B-containing lipoproteins. In contrast, raising high-density lipoprotein (HDL) particles, as previously hypothesized, did not contribute to ASCVD risk reduction.

Raman spectroscopy for monitoring free sulfhydryl formation during monoclonal antibody manufacturing.

During production, harvested cell culture fluid (HCCF) can degrade due to reductases breaking interchain disulfide bonds, forming low molecular weight (LMW) impurities that contain free sulfhydryl and high molecular weight (HMW) impurities through disulfide shuffling. Thus, detecting and quantifying the free sulfhydryl increase in HCCF is critical. Herein, Raman spectroscopy is implemented as a process analytical technology, and multivariate data analysis is applied to characterize and quantify sulfhydryl formation in HCCF with disulfide-containing indicator molecules.

A multi-center, clinical analysis of IDH-mutant gliomas, WHO Grade 4: implications for prognosis and clinical trial design.

Purpose: Mutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival.

Obicetrapib exhibits favorable physiochemical and pharmacokinetic properties compared to previous cholesteryl ester transfer protein inhibitors: An integrated summary of results from non-human primate studies and clinical trials.

Anacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor previously under development, exhibited an usually extended terminal half-life and large food effect and accumulated in adipose tissue. Other CETP inhibitors have not shown such effects. Obicetrapib, a potent selective CETP inhibitor, is undergoing Phase III clinical development.

Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide.

Background: Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.

Effects of Ionic Liquids on the Nucleofugality of Dimethyl Sulfide.

The nucleofugality of dimethyl sulfide was measured in solvent mixtures containing ionic liquids. The first-order rate constants of the solvolysis of sulfonium salts were determined in mixtures containing different proportions of 1-butyl-3-methylimidazolium (trifluoromethanesulfonyl)imide in ethanol, representing the first report on the solvolysis of a charged species in an ionic liquid. Temperature-dependent kinetic studies allowed determination of activation parameters and rationalization of observed solvent effects in different ionic liquid mixtures.

Overcoming Barriers: A Comprehensive Review of Chronic Pain Management and Accessibility Challenges in Rural America.

In the United States (U.S.), chronic pain poses substantial challenges in rural areas where access to effective pain management can be limited.

Widespread Neuroanatomical Integration and Distinct Electrophysiological Properties of Glioma-Innervating Neurons.

Unlabelled: Gliomas are the most common malignant primary brain tumors and are often associated with severe neurological deficits and mortality. Unlike many cancers, gliomas rarely metastasize outside the brain, indicating a possible dependency on unique features of brain microenvironment. Synapses between neurons and glioma cells exist, suggesting that glioma cells rely on neuronal inputs and synaptic signaling for proliferation.

Supportive Workplace Wellness Cultures and Mattering Are Associated With Less Burnout and Mental Health Issues in Nurse Managers.

Objective: The aims of this study were to describe burnout, mental health, and healthy lifestyle behaviors of nurses in a managerial role and assess associations among workplace culture factors (perceived culture, mattering, support, and staff shortages) with burnout, mental health outcomes, and healthy lifestyle behaviors.

Background: Nurse managers foster unit-based wellness cultures, yet burnout and mental health problems adversely impact the culture and well-being of staff.

Methods: A cross-sectional, descriptive correlational design was used.

A Randomized, Parallel, Open-Label, Single-Dose and Multiple-Dose Clinical Trial to Investigate the Pharmacokinetic, Pharmacodynamic, and Safety Profiles of Obicetrapib in Healthy Participants in China.

Obicetrapib is a selective cholesteryl ester transfer protein (CETP) inhibitor. Previous research has demonstrated similar pharmacokinetic (PK) responses to single doses of obicetrapib between Japanese and White males, but the PK responses have not been established in Chinese individuals. The purpose of this randomized, parallel, open-label trial was to characterize the PK and pharmacodynamic (PD; CETP activity and plasma lipids) responses and safety of single doses (5, 10, or 25 mg; N = 36) and multiple doses (10 mg for 14 days; N = 12) of obicetrapib in healthy Chinese individuals.

Biomedical literature mining: graph kernel-based learning for gene-gene interaction extraction.

The supervised machine learning method is often used for biomedical relationship extraction. The disadvantage is that it requires much time and money to manually establish an annotated dataset. Based on distant supervision, the knowledge base is combined with the corpus, thus, the training corpus can be automatically annotated.

Decoding RNA Metabolism by RNA-linked CRISPR Screening in Human Cells.

RNAs undergo a complex choreography of metabolic processes in human cells that are regulated by thousands of RNA-associated proteins. While the effects of individual RNA-associated proteins on RNA metabolism have been extensively characterized, the full complement of regulators for most RNA metabolic events remain unknown. Here we present a massively parallel RNA-linked CRISPR (ReLiC) screening approach to measure the responses of diverse RNA metabolic events to knockout of 2,092 human genes encoding all known RNA-associated proteins.

Comparative analysis of genetic risk scores for predicting biochemical recurrence in prostate cancer patients after radical prostatectomy.

Background: In recent years, Genome-Wide Association Studies (GWAS) has identified risk variants related to complex diseases, but most genetic variants have less impact on phenotypes. To solve the above problems, methods that can use variants with low genetic effects, such as genetic risk score (GRS), have been developed to predict disease risk.

Methods: As the GRS model with the most incredible prediction power for complex diseases has not been determined, our study used simulation data and prostate cancer data to explore the disease prediction power of three GRS models, including the simple count genetic risk score (SC-GRS), the direct logistic regression genetic risk score (DL-GRS), and the explained variance weighted GRS based on directed logistic regression (EVDL-GRS).

Patterns of chemotherapy use with primary radiotherapy for localized bladder cancer in patients 65 or older.

Introduction: Bladder preservation with concurrent chemoradiotherapy after maximum transurethral resection of bladder tumor is an alternative to radical cystectomy in select patients with muscle invasive bladder cancer (MIBC). Concurrent administration of radio-sensitizing chemotherapy and radiation therapy (RT) has been shown to have superior disease control compared with RT alone and can often be administered with modest added toxicity. We sought to describe national patterns of chemotherapy use.

Predicting Risks of Dry Eye Disease Development Using a Genome-Wide Polygenic Risk Score Model.

Purpose: The purpose of this study was to conduct a large-scale genome-wide association study (GWAS) and construct a polygenic risk score (PRS) for risk stratification in patients with dry eye disease (DED) using the Taiwan Biobank (TWB) databases.

Methods: This retrospective case-control study involved 40,112 subjects of Han Chinese ancestry, sourced from the publicly available TWB. Cases were patients with DED (n = 14,185), and controls were individuals without DED (n = 25,927).