Molecular Testing for the World Health Organization Classification of Central Nervous System Tumors: A Review.

Importance: Molecular techniques, including next-generation sequencing, genomic copy number profiling, fusion transcript detection, and genomic DNA methylation arrays, are now indispensable tools for the workup of central nervous system (CNS) tumors. Yet there remains a great deal of heterogeneity in using such biomarker testing across institutions and hospital systems. This is in large part because there is a persistent reluctance among third-party payers to cover molecular testing.

Does cognitive intra-individual variability predict change in everyday functioning performance in women with and without HIV in the Women's Interagency HIV Study?

This study examined the association between cognitive intra-individual variability (IIV), a non-mean-based indicator of underlying neuropathology, and self-reported everyday functioning of 1,086 women with HIV (WWH) and 494 socio-demographically similar women without HIV (WWoH). Objective cognitive performance across seven domains and the self-rated Lawton & Brody scale of Instrumental Activities of Daily Living (IADL) were assessed among participants of the Women's Interagency HIV Study. Two types of cognitive IIV were calculated by taking the standard deviation across seven cognitive domains to calculate dispersion: 1) intra-individual standard deviation (denoted as IIV) and 2) coefficient of variation (denoted as IIV).

Quantitative Systems Pharmacology Modeling in Immuno-Oncology: Hypothesis Testing, Dose Optimization, and Efficacy Prediction.

Despite an increasing number of clinical trials, cancer is one of the leading causes of death worldwide in the past decade. Among all complex diseases, clinical trials in oncology have among the lowest success rates, in part due to the high intra- and inter-tumoral heterogeneity. There are more than a thousand cancer drugs and treatment combinations being investigated in ongoing clinical trials for various cancer subtypes, germline mutations, metastasis, etc.

To Acquire or Not to Acquire: Evaluating Compressive Sensing for Raman Spectroscopy in Biology.

Raman spectroscopy has revolutionized the field of chemical biology by providing detailed chemical and compositional information with minimal sample preparation. Despite its advantages, the technique suffers from low throughput due to the weak Raman effect, necessitating long acquisition times and expensive equipment. This limitation is particularly acute in time-sensitive applications like bioprocess monitoring and dynamic studies.

Implementation of Universal Germline Genetic Testing Into Standard of Care for Patients With Prostate Cancer: The Time Is Now.

Indications for and implications of germline genetic testing (GGT) in patients with prostate cancer have expanded over the past decade, particularly related to precision therapies and management. GGT has become the standard of care for many cancers such as breast, ovarian, colorectal, pancreatic, and metastatic prostate cancer, and it is imperative that patients be offered timely and equitable access to testing as it can inform patient-physician shared decision making for management of the current cancer as well as anticipatory guidance for disease progression. Additionally, GGT guides screening for and prevention of secondary malignancies for the patient and cascade testing for at-risk family members.

Management of translocation carcinomas of the kidney.

Microphthalmia-associated transcription factor family translocation renal cell carcinoma (MiT-tRCC) stands out as a rare subtype of kidney cancer with distinct biological features compared to other kidney cancer subtypes. It encompasses TFE3-rearranged RCC (also known as Xp11 translocation RCC) and TFE-rearranged translocations RCC, although multiple new fusion partners were identified. Traditionally thought to primarily affect children and young adults, more cases of MiT-tRCC are being identified in adults.

If it is a solid tumor target, then it may be a hematologic cancer target: Bridging the great divide.

Tumor-agnostic US Food and Drug Administration approvals are transforming oncology. They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAF mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms.

Dynamic modulation of IRE1α-XBP1 signaling by adenovirus.

The abundant production of foreign proteins and nucleic acids during viral infection elicits a variety of stress responses in host cells. Viral proteins that accumulate in the endoplasmic reticulum (ER) can trigger the unfolded protein response (UPR), a coordinated signaling program that culminates in the expression of downstream genes that collectively restore protein homeostasis. The model pathogen adenovirus serotype 5 (HAdV5) activates the UPR via the signaling axis formed by inositol-requiring enzyme type 1 (IRE1α) and the X-box binding protein 1 (XBP1), a transcription factor required for immune function.

Three-Year Overall Survival With Nivolumab Plus Relatlimab in Advanced Melanoma From RELATIVITY-047.

Nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), along with a clinically meaningful, but not statistically significant improvement in overall survival (OS) and a numerically higher objective response rate (ORR) compared with nivolumab in the RELATIVITY-047 trial (ClinicalTrials.gov identifier: NCT03470922). We report updated descriptive efficacy and safety results from RELATIVITY-047 with a median follow-up of 33.

Sex-specific associations between cerebrospinal fluid inflammatory biomarkers and cognition in antiretroviral-naïve people with HIV in rural Uganda.

Globally, people with HIV (PWH) experience a broad spectrum of cognitive impairment that can be noted both before and after initiation of antiretroviral therapy (ART). Sex differences in immune function have been implicated in differential cognitive outcomes. Here, we report sex differences in cerebrospinal fluid (CSF) markers in relation to cognitive performance in a subset of ART-naïve PWH participating in the Rakai Neurology Cohort Study.

Intracranial Nanogel Pellets Carrying Temozolomide and Paclitaxel for Adjuvant Brain Cancer Therapy.

Glioblastoma multiforme is the most frequently diagnosed primary malignant brain tumor. Despite multimodal therapy with surgical resection, radiation therapy, and chemotherapy, recurrence of the tumor is almost always guaranteed due to the infiltrative nature of the disease. Moreover, the blood brain barrier imparts an additional layer of complexity by impeding the delivery of therapeutic agents to the tumor, hence limiting the efficacy of systemically delivered drugs.

π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

Establishment and analysis of a prognostic model of pancreatic ductal adenocarcinomas based on nerve-cancer crosstalk-related genes.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a five-year survival rate of 13%, the lowest among all malignant tumors. The work aims to use bioinformatics methods to mine Nerve-cancer crosstalk-related genes (NCCGs) in pancreatic cancer and evaluate their correlation with tumor stage and prognosis, thereby providing a new direction of development and experimental basis for pancreatic cancer treatment. This study included 185 individuals with PDAC from the TCGA database, together with clinical and RNA sequencing data.

TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond.

While most Tripartite motif (TRIM) family proteins are E3 ubiquitin ligases, some members have functions beyond the regulation of ubiquitination, impacting normal physiological processes and disease progression. TRIM29, an important member of the TRIM family, exerts a predominant influence on cancer growth, epithelial-to-mesenchymal transition, stemness and metastatic progression by directly potentiating multiple canonical oncogenic pathways. The cancer-promoting effect of TRIM29 is also evident in metabolic interventions and interference with the efficacy of cancer therapeutics.

Personalized Medicine: Leave no Patient Behind; Report From the 2024 Coffey-Holden Prostate Cancer Academy Meeting.

Introduction: The 11th Annual 2024 Coffey - Holden Prostate Cancer Academy (CHPCA) Meeting, was themed "Personalized Medicine: Leave No Patient Behind," and was held from June 20 to 23, 2024 at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA.

Methods: The CHPCA Meeting is an academy-styled annual conference organized by the Prostate Cancer Foundation, to focus discussion on the most critical emerging research that have the greatest potential to advance knowledge of prostate cancer biology and treatment. The 2024 CHPCA Meeting was attended by 75 academic investigators and included 37 talks across 8 sessions.

Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes.

Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated in the heart, lung, kidney, and liver, but not mediastinal lymph nodes.

LUCAT1-Mediated Competing Endogenous RNA (ceRNA) Network in Triple-Negative Breast Cancer.

Breast cancer is a heterogeneous disease comprising multiple molecularly distinct subtypes with varied prevalence, prognostics, and treatment strategies. Among them, triple-negative breast cancer, though the least prevalent, is the most aggressive subtype, with limited therapeutic options. Recent emergence of competing endogenous RNA (ceRNA) networks has highlighted how long noncoding RNAs (lncRNAs), microRNAs (miRs), and mRNA orchestrate a complex interplay meticulously modulating mRNA functionality.

Brain Metastasis in Pediatric Patients with Osteosarcoma.

Background: Brain metastases in pediatric osteosarcoma are infrequent but associated with a dire prognosis.

Methods: This retrospective study examined six pediatric patients at Johns Hopkins Hospital who developed brain metastases from osteosarcoma between April 2015 and November 2023.

Results: Median survival post-brain metastasis was 2.

Cytoskeletal activation of NHE1 regulates mechanosensitive cell volume adaptation and proliferation.

Mammalian cells rapidly respond to environmental changes by altering transmembrane water and ion fluxes, changing cell volume. Contractile forces generated by actomyosin have been proposed to mechanically regulate cell volume. However, our findings reveal a different mechanism in adherent cells, where elevated actomyosin activity increases cell volume in normal-like cells (NIH 3T3 and others) through interaction with the sodium-hydrogen exchanger isoform 1 (NHE1).

Multiplex digital profiling of DNA methylation heterogeneity for sensitive and cost-effective cancer detection in low-volume liquid biopsies.

Molecular alterations in cancerous tissues exhibit intercellular genetic and epigenetic heterogeneity, complicating the performance of diagnostic assays, particularly for early cancer detection. Conventional liquid biopsy methods have limited sensitivity and/or ability to assess epigenetic heterogeneity of rare epiallelic variants cost-effectively. We report an approach, named REM-DREAMing (Ratiometric-Encoded Multiplex Discrimination of Rare EpiAlleles by Melt), which leverages a digital microfluidic platform that incorporates a ratiometric fluorescence multiplex detection scheme and precise digital high-resolution melt analysis to enable low-cost, parallelized analysis of heterogeneous methylation patterns on a molecule-by-molecule basis for the detection of cancer in liquid biopsies.

Phase 2 Trial of Veliparib, Local Irradiation and Temozolomide in Patients with Newly Diagnosed High-Grade Glioma: A Children's Oncology Group Study.

Background: The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy.

Methods: We conducted a single-arm, non-randomized phase 2 clinical trial to determine whether treatment with veliparib and radiotherapy, followed by veliparib and temozolomide, improves progression-free survival in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations compared to patient level data from historical cohorts with closely matching clinical and molecular features.