Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease-A Review.

The coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro-inflammatory cytokines and excessive oxidative stress in these regions.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2025.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide criteria for selecting individuals for screening and offer recommendations for evaluating and managing lung nodules detected during initial and subsequent annual screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Small protein ERSP encoded by LINC02870 promotes triple negative breast cancer progression via IRE1α/XBP1s activation.

Clinical treatment options for triple-negative breast cancer (TNBC) are currently limited to chemotherapy because of a lack of effective therapeutic targets. Recent evidence suggests that long noncoding RNAs (lncRNAs) encode bioactive peptides or proteins, thereby playing noncanonical yet significant roles in regulating cellular processes. However, the potential of lncRNA-translated products in cancer progression remains largely unknown.

Design and implementation of an action plan for justice, equity, diversity, and inclusion within the Clinical Genome Resource.

How might members of a large, multi-institutional research and resource consortium foster justice, equity, diversity, and inclusion as central to its mission, goals, governance, and culture? These four principles, often referred to as JEDI, can be aspirational-but to be operationalized, they must be supported by concrete actions, investments, and a persistent long-term commitment to the principles themselves, which often requires self-reflection and course correction. We present here the iterative design process implemented across the Clinical Genome Resource (ClinGen) that led to the development of an action plan to operationalize JEDI principles across three major domains, with specific deliverables and commitments dedicated to each. Active involvement of consortium leadership, buy-in from its members at all levels, and support from NIH program staff at pivotal stages were essential to the success of this effort.

Trastuzumab Plus Pertuzumab Versus Cetuximab Plus Irinotecan in Patients With Wild-Type, HER2-Positive, Metastatic Colorectal Cancer (S1613): A Randomized Phase II Trial.

Purpose: overexpression/amplification in wild-type (WT) metastatic colorectal cancer (mCRC; human epidermal growth factor receptor 2 [HER2]-positive mCRC) appears to be associated with limited benefit from anti-EGFR antibodies and promising responses to dual-HER2 inhibition; however, comparative efficacy has not been investigated. We conducted a randomized phase II trial to evaluate efficacy and safety of dual-HER2 inhibition against standard-of-care anti-EGFR antibody-based therapy as second/third-line treatment in HER2-positive mCRC.

Methods: Patients with -WT mCRC after central confirmation of HER2 positivity (immunohistochemistry 3+ or 2+ and in situ hybridization amplified [HER2/CEP17 ratio >2.

Stage at diagnosis and cancer-specific survival for stomach, lung, colorectal, and bladder cancers among Armenians in California.

Objective: To observe stage at diagnosis and cancer-specific survival for common cancers among Armenians in California.

Methods: We used the Armenian Surname List and birthplace information in the California Cancer Registry to identify Armenians with stomach, lung, colorectal, and bladder cancers diagnosed during 1988-2019. We used multivariable logistic regression models to calculate odds of late-stage diagnoses among Armenian and non-Armenian, non-Hispanic White patients and examine the association of sociodemographic factors with late-stage diagnoses among the Armenian patient population.

oncogenic variants as prognostic factors in individuals with glioblastoma: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis investigated the relationship between somatic oncogenic variants and prognosis, specifically with overall survival (OS) and progression-free survival (PFS) in patients diagnosed with supratentorial glioblastoma.

Methods: We included longitudinal studies and clinical trials involving a minimum of 40 adult participants diagnosed with supratentorial glioblastoma, wherein the status of variants was assessed. We conducted searches in multiple databases.

Bridging genomics' greatest challenge: The diversity gap.

Achieving diverse representation in biomedical data is critical for healthcare equity. Failure to do so perpetuates health disparities and exacerbates biases that may harm patients with underrepresented ancestral backgrounds. We present a quantitative assessment of representation in datasets used across human genomics, including genome-wide association studies (GWASs), pharmacogenomics, clinical trials, and direct-to-consumer (DTC) genetic testing.

Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology.

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing.

NCCN Guidelines® Insights: Survivorship, Version 2.2024.

The NCCN Guidelines for Survivorship include recommendations for screening, evaluation, and treatment of psychosocial and physical problems resulting from adult-onset cancer and its treatment. They also include recommendations to promote healthy behaviors and immunizations in survivors and provide a framework for care coordination. These NCCN Guidelines Insights summarize the panel's current recommendations regarding sexual health and fertility.

The TRIM37 variant rs57141087 contributes to triple-negative breast cancer outcomes in Black women.

Triple-negative breast cancer (TNBC) disproportionately affects younger Black women, who show more aggressive phenotypes and poorer outcomes than women of other racial identities. While the impact of socioenvironmental inequities within and beyond health systems is well documented, the genetic influence in TNBC-associated racial disparities remains elusive. Here, we report that cancer-free breast tissue from Black women expresses TRIM37 at a significantly higher level relative to White women.

Metabolomic Profiling and Machine Learning Models for Tumor Classification in Patients with Recurrent IDH-Wild-Type Glioblastoma: A Prospective Study.

Background/objectives: The recurrence of glioblastoma is an inevitable event in this disease's course. In this study, we sought to identify the metabolomic signature in patients with recurrent glioblastomas undergoing surgery and radiation therapy.

Methods: Blood samples collected prospectively from six patients with recurrent IDH-wildtype glioblastoma who underwent one surgery at diagnosis and a second surgery at relapse were analyzed using untargeted gas chromatography-time-of-flight mass spectrometry to measure metabolite abundance.

Rapid curing dynamics of PEG-thiol-ene resins allow facile 3D bioprinting and in-air cell-laden microgel fabrication.

Thiol-norbornene photoclick hydrogels are highly efficient in tissue engineering applications due to their fast gelation, cytocompatibility, and tunability. In this work, we utilized the advantageous features of polyethylene glycol (PEG)-thiol-ene resins to enable fabrication of complex and heterogeneous tissue scaffolds using 3D bioprinting and in-air drop encapsulation techniques. We demonstrated that photoclickable PEG-thiol-ene resins could be tuned by varying the ratio of PEG-dithiol to PEG norbornene to generate a wide range of mechanical stiffness (0.

-Active Soluble Epoxide Hydrolase-Targeting PROTACs with Improved Potency and Stability.

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme involved in fatty acid metabolism and a promising drug target. We previously reported first-generation sEH proteolysis-targeting chimeras (PROTACs) with limited degradation potency and low aqueous and metabolic stability. Herein, we report the development of next-generation sEH PROTAC molecules with improved stability and degradation potency.

Metabolic Risk Factors and Survival in Patients with Glioblastoma.

Background: Metabolic syndrome increases the risk of developing various systemic cancers. The prevalence of metabolic syndrome in newly diagnosed glioblastoma patients is unknown. Further, there have been contradictory reports about how metabolic syndrome affects clinical outcomes.

Paclitaxel loaded Capmul MCM and tristearin based nanostructured lipid carriers (NLCs) for glioblastoma treatment: screening of formulation components by quality by design (QbD) approach.

Paclitaxel (PTX), a naturally occurring diterpenoid isolated from Taxus brevifolia, is a first-line drug for the treatment of glioblastoma; however, it suffers from the disadvantages of poor water solubility and nonspecific biodistribution, which cause serious side effects in the human body. The marketed formulation suffers from serious side effects, such as allergic reactions, neutropenia, and neuropathy, which require safe and effective formulations of PTX. In the present study, PTX was entrapped in a solid-liquid lipid mixture with the aid of a surfactant using a modified solvent evaporation technique.

The Impact of Social Determinants of Health on Peripheral T Cell Lymphoma Outcomes: Treatment Center-Type Emerges as a Powerful Prognostic Indicator.

Background: Prognostic models in peripheral T cell lymphoma (PTCL) have identified biological factors including age, performance status, LDH, and BM involvement as prognostic for survival. The association of social determinants of health (SDH), on PTCL outcomes remains unexplored.

Methods: To evaluate the impact of actionable SDH on PTCL mortality across race groups, we conducted a retrospective cohort study that included all White, Hispanic, Asian/Pacific Islander (PI) and Black adult patients with nodal PTCLs , diagnosed 2000-2020, in California.

PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells.

Olaparib, a PARP inhibitor, is effective against various cancers, including prostate cancer. However, resistance to olaparib poses a significant challenge. This study uncovers that mitochondrial alterations and PINK1 gene overexpression contribute to this resistance in prostate cancer cells.

First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies.

Purpose: Preclinical data indicate that fianlimab (antilymphocyte activation gene-3) plus cemiplimab (anti-PD-1) enhances antitumor activity. Here, we report prespecified final analyses of the dose-escalation part of a first-in-human, phase 1 study (NCT03005782) of fianlimab as monotherapy and in combination with cemiplimab in patients with advanced malignancies.

Patients And Methods: Adult patients received 1 to 40 mg/kg of fianlimab plus 350 mg of cemiplimab every 3 weeks (Q3W) across various dose-escalation schedules.

Looking Beyond the Surface: Olutasidenib and Ivosidenib for Treatment of mIDH1 Acute Myeloid Leukemia.

Mutations in isocitrate dehydrogenase-1 (IDH1) are recurrent in several malignancies and prevalent in acute myeloid leukemia (AML). Olutasidenib and ivosidenib are inhibitors that target mutant IDH1 (mIDH1) and are FDA approved for the treatment of patients with mIDH1 AML. Olutasidenib and ivosidenib were identified through unique molecular screens and thus are structurally very different molecules.