Systematic characterization of cell type-specific master metabolic regulators in Alzheimer's disease.

Alzheimer's disease (AD) exhibits metabolic heterogeneity; yet, the consequences on metabolic dynamics in a cell-type-specific manner and the underlying metabolite-sensor network basis remain unclear. Here, we show that neurons exhibit a striking decrease in energy and lipid-related metabolic activity, contrasted by an increase in microglial metabolism associated with neuroinflammation. To identify brain cell-type specific master metabolic regulators underlying the metabolic alterations of AD, we introduce scFUMES (ingle ell nctional tabolite-ensor), an algorithm integrating single-cell RNA sequencing, interactomics (protein-protein interactions), genomics, transcriptomics, and metabolomics from large human brain biobanks.

The emerging role of biomaterial applications in cerebral lymphatic surgical interventions: A narrative review.

The cerebral lymphatic system plays a critical role in central nervous system (CNS) homeostasis through fluid regulation, toxin clearance, and immune modulation. Recent discoveries in the glial-lymphatic (glymphatic) and meningeal lymphatic systems have demonstrated their involvement in a spectrum of CNS pathologies such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), traumatic brain injury (TBI), stroke, and cancers. This review summarizes current understanding of the cerebral lymphatic system's mechanisms and their contribution to CNS health.

Dual probe ligation in situ hybridization with rolling-circle amplification for high-plex spatial transcriptomics.

New biological insights are increasingly dependent upon a deeper understanding of tissue architectures. Critical to such studies are spatial transcriptomics technologies, especially those amenable to analysis of the most widely available human tissue type, formalin-fixed and paraffin-embedded (FFPE) clinical specimens. Here we build on our previous oligonucleotide probe ligation-based approach to accurately analyze FFPE mRNA, which suffers from variable levels of degradation.

Study design and methods for the physical activity index (PAI) feasibility pilot trial for breast and colon cancer survivors in North Carolina.

The majority of the 18 million US adults with cancer history ("survivors") do not meet recommendations for obtaining regular physical activity (PA) or limiting sedentary behavior in their daily lives. Breast cancer survivors (BCS) and colon cancer survivors (CCS) are particularly at risk of insufficient PA and excessive sedentary behavior (i.e.

Molecular Characteristics, Heterogeneity, Plasticity, and Cell of Origin of Neuroendocrine Bladder Cancer.

Neuroendocrine bladder cancer (NEBC) is a rare but highly aggressive cancer, representing approximately 1% of urinary bladder cancer. The most common NEBC is small cell bladder cancer (SCBC), characterized by high rates of recurrence, chemotherapy resistance, and early mortality. SCBC is histologically identical to small cell lung cancer (SCLC) but remains significantly understudied.

Influence of preprocessing of stimulated Raman scattering images on the performance of deep neural networks for detecting cancer tissue.

Background: Images obtained from stimulated Raman scattering can be used to identify histomorphologically relevant information intraoperatively. In order to leverage deep learning algorithms for distinguishing tumoral and non-tumoral tissue, data preprocessing remains a crucial task and may affect the classification performance. To date, the effect of different preprocessing techniques on deep learning algorithm performance is unclear.

Open-Label, Phase II Trial of Extracellular Regulated Kinase Inhibition Alone and in Combination With Autophagy Inhibition in Patients With Metastatic Pancreatic Cancer.

Purpose: Oncogenic mutations in Kirsten rat sarcoma virus are present in over 90% of pancreatic ductal adenocarcinomas (PDACs). Preclinical data suggest that PDAC cells treated with inhibitors of the mitogen-activated protein kinase pathway demonstrate elevated autophagic flux. In this study, we evaluate the clinical efficacy of combining LY3214996 (extracellular regulated kinase inhibitor) with hydroxychloroquine (HCQ; autophagy inhibitor) in patients with metastatic PDAC.

Genetic variation in the FMO and GSTO gene clusters impacts arsenic metabolism in humans.

Background: In Bangladesh, > 50 million individuals are chronically exposed to inorganic arsenic (iAs) through drinking water, increasing risk for cancer and other iAs-related diseases. Previous studies show that individuals' ability to metabolize and eliminate iAs, and their risk of toxicity, is influenced by genetic variation in the AS3MT and FTCD gene regions.

Methods: To identify additional loci influencing arsenic metabolism, we used data from Bangladeshi individuals to conduct genome-wide association analyses of the relative abundances of arsenic species measured in both urine (n = 6,540) and blood (n = 976).

Anaplastic Large Cell Lymphoma of the Breast by Race and Ethnicity.

Importance: The incidence rate of primary breast anaplastic large cell lymphoma (ALCL), a complication associated with breast implants, is rapidly rising in the US. Comprehensive studies on the racial and ethnic epidemiologic characteristics of ALCL in the US are lacking, despite evidence of worldwide geographic variability.

Objective: To characterize the incidence rates of breast ALCL by race and ethnicity in the US.

Micrometastasis and Isolated Tumor Cells in Oral Squamous Cell Carcinoma: Refining Nodal Staging with Emerging Technologies.

Purpose: Cervical lymph node metastasis significantly influence prognosis in oral squamous cell carcinoma (OSCC), guiding staging, treatment decisions, and overall survival. Sentinel lymph node biopsy (SLNB) offers a minimally invasive approach for early detection of subclinical nodal metastasis, including micrometastases (0.2-2 mm) and isolated tumor cells (ITCs, < 0.

Gonadotropin trajectories among postmenopausal women not using hormone therapy.

Objective: While evidence suggests that gonadotropins may play an important role in aging-related changes in body composition and health outcomes, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) patterns have not been well characterized in older women. We characterized patterns of FSH and LH change over time after menopause.

Methods: In a sample of 291 postmenopausal women from the Women's Health Initiative OsteoPerio study who were not using hormone therapy, we estimated FSH and LH trajectories over a 20-year period using group-based trajectory modeling.

External Radiotherapy in Mozambique: Report of the First Five Years of Activity of the Radiotherapy Service of the Maputo Central Hospital.

Background: A Radiotherapy Service (RS) started working in the Maputo Central Hospital (MCH), Mozambique, in August 2019. Here we describe its first 5 years of activity.

Methods: A total of 810 patients who underwent external radiotherapy between August 2019 and December 2023 were considered for the analysis.

The plasma proteome and breast cancer risk.

Background: Plasma proteins may serve as biomarkers for breast cancer. This study aimed to characterize the blood proteomic signatures of women with a higher risk of breast cancer due to their family history.

Methods: We conducted a nested case-control study (median followup: 9.

RACK1 attenuates pancreatic tumorigenesis by suppressing acinar-to-ductal metaplasia through inflammatory signaling modulation.

Purpose: Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal malignancies with limited early diagnostic and therapeutic options. Although receptor for activated C kinase 1 (RACK1) is an evolutionarily conserved scaffold protein, its functional role and mechanistic involvement in PDA pathogenesis remain elusive.

Methods: Using multimodal approaches including: (1) genetically engineered mouse models of pancreatitis and carcinogenesis, (2) patient-derived PDA tissues with matched normal specimens, (3) primary acinar cell 3D cultures, and (4) orthogonal gain/loss-of-function assays in PDA cell lines, we systematically investigated RACK1's spatiotemporal expression patterns and functional impacts.

Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia.

Acute myeloid leukaemia (AML) remains a challenging haematological malignancy, with most patients developing resistance to standard-of-care (SOC) treatments. This resistance is often attributed to the overexpression of anti-apoptotic BCL-2 family proteins, which regulate the intrinsic apoptotic pathway by inhibiting pro-apoptotic effector proteins such as BAX and BAK. AML cells exploit this imbalance to evade apoptosis and sustain survival, necessitating the development of novel therapeutic strategies.

Supercharged NK cells: a unique population of NK cells capable of differentiating stem cells and lysis of MHC class I high differentiated tumors.

This study highlights the significance of supercharged NK (sNK) cells in inducing the lysis and differentiation of tumors at much higher levels compared to primary activated NK cells. sNK cells-induced higher release of growth factors, cytokines, and chemokines when compared to primary activated NK cells. When we used a similar level of IFN-γ from primary activated NK cells and sNK cells, the IFN-γ secreted from sNK cells exhibited greater potential to induce differentiation in both oral and pancreatic tumors.

Oncological outcomes and organ preservation after brachytherapy for penile carcinoma: A multicentric retrospective study by the Brachytherapy Group of the French Society for Radiation Oncology.

Introduction: Penile cancer is a rare malignancy with significant implications for patients' quality of life due to the sensitivity of the affected organ. While partial or total penectomy remains the standard treatment, its functional and psychological sequelae are significant. Brachytherapy is an effective alternative to penectomy offering penile preservation and good local control.

Association of Patient Comorbidities with Treatment Regret Among Patients with Localized Prostate Cancer - Results from a Population-Based Cohort.

Objectives: Decision regret is a well-established, negative outcome in prostate cancer. We hypothesized that baseline comorbidities, which impact treatment tolerability, are associated with regret.

Materials And Methods: In a prospective, population-based cohort of prostate cancer patients, patient-reported regret was assessed at 12 months after treatment using a validated measure.

Rapid in vitro and computer-aided method for assessing synergistic interactions between NSAIDs and analgesics.

Pain is a complex phenomenon that plays a significant role in various diseases, influencing both the physical and psychological well-being of individuals. In clinical practice, combining nonsteroidal anti-inflammatory drugs (NSAIDs) with analgesics, such as paracetamol or metamizole, has become a widely adopted strategy to manage pain. Although the synergistic effects of combining NSAIDs with analgesics are well recognized in clinical practice, this approach is primarily based on empirical clinical experience.

Dietary vitamin D and gastric cancer risk within the stomach cancer pooling (stop) project.

Purpose: The evidence regarding the role of vitamin D on gastric cancer (GC) is controversial. Within the Stomach cancer Pooling (StoP) Project, a global consortium of epidemiological studies on GC, we aimed to evaluate the relationship between dietary vitamin D and GC risk.

Methods: Five case-control studies were included in the analysis, accounting for 1875 cases and 5899 controls.

Multiplexed Single-Molecule Detection of Nucleic Acid Biomarkers with a Distance-Tuned Single FRET Pair.

Biomarkers have gained tremendous attention in recent years, as they offer reliable detection of diseases such as cancers and other health conditions. However, with the recent realization that one biomarker can be associated with more than one disease (cross-talk), there is a significant shift toward simultaneous monitoring of more than one biomarker to increase the accuracy of diagnosis. Despite a sizable effort made over the last several years, multiplexing using the common techniques including surface-enhanced Raman spectroscopy (SERS), microarrays, RT-qPCR, nanostring, fluorescence, and others requires target amplification, target labeling, or the use of additional probes/actuators, and hence, these requirements complicate the experiments and data analyses.