Daily sleep and physical activity from accelerometry in adults: Temporal associations and lag effects.

Objectives: Insufficient sleep is linked to various health issues, while physical activity is a protective measure against chronic diseases. Despite the importance of sleep and physical activity for supporting public health, there remains scant research investigating daily and cumulative associations between objectively measured physical activity and sleep. Understanding the associations of physical activity and sleep behaviors over multiple days may inform the efficacy of interventions to synergistically support both behaviors.

Validation of Clinical Dynamic Contrast-Enhanced Magnetic Resonance Imaging Perfusion Modeling and Neoadjuvant Chemotherapy Response Prediction in Breast Cancer Using FDG and Cu-DOTA-Trastuzumab Positron Emission Tomography Studies.

Purpose: Perfusion modeling presents significant opportunities for imaging biomarker development in breast cancer but has historically been held back by the need for data beyond the clinical standard of care (SoC) and uncertainty in the interpretability of results. We aimed to design a perfusion model applicable to breast cancer SoC dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series with results stable to low temporal resolution imaging, comparable with published results using full-resolution DCE-MRI, and correlative with orthogonal imaging modalities indicative of biophysical markers.

Methods: Subsampled high-temporal-resolution DCE-MRI series were run through our perfusion model and resulting fits were compared for consistency.

DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets.

Introduction: Type 1 diabetic human islet β-cells are deficient in double C 2 like domain beta (DOC2b) protein. Further, DOC2b protects against cytokine-induced pancreatic islet β-cell stress and apoptosis. However, the mechanisms underpinning the protective effects of DOC2b remain unknown.

Single Extracellular VEsicle Nanoscopy-Universal Protocol (SEVEN-UP): Accessible Imaging Platform for Quantitative Characterization of Single Extracellular Vesicles.

Extracellular vesicles (EVs), membrane-encapsulated nanoparticles shed from all cells, are tightly involved in critical cellular functions. Moreover, EVs have recently emerged as exciting therapeutic modalities, delivery vectors, and biomarker sources. However, EVs are difficult to characterize, because they are typically small and heterogeneous in size, origin, and molecular content.

Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression.

Prostate cancer (PCa) remains a critical global health challenge, with high mortality rates and significant heterogeneity, particularly in advanced stages. While early-stage PCa is often manageable with conventional treatments, metastatic PCa is notoriously resistant, highlighting an urgent need for precise biomarkers and innovative therapeutic strategies. This review focuses on the dualistic roles of sirtuins, a family of NAD+-dependent histone deacetylases, dissecting their unique contributions to tumor suppression or progression in PCa depending on the cellular context.

Human iPSC-derived microglial cells protect neurons from neurodegeneration in long-term cultured adhesion brain organoids.

Brain organoid models have greatly facilitated our understanding of human brain development and disease. However, key brain cell types, such as microglia, are lacking in most brain organoid models. Because microglia have been shown to play important roles in brain development and pathologies, attempts have been made to add microglia to brain organoids through co-culture.

Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML.

BMT CTN 1506 ("MORPHO"; NCT02997202) was a randomized phase 3 study of gilteritinib compared to placebo as maintenance therapy after hematopoietic stem cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary endpoint was to determine the impact on survival of pre- and/or post-HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD.

Phosphoproteomic Profiling Reveals mTOR Signaling in Sustaining Macrophage Phagocytosis of Cancer Cells.

: Macrophage-mediated cancer cell phagocytosis has demonstrated considerable therapeutic potential. While the initiation of phagocytosis, facilitated by interactions between cancer cell surface signals and macrophage receptors, has been characterized, the mechanisms underlying its sustentation and attenuation post-initiation remain poorly understood. : Through comprehensive phosphoproteomic profiling, we interrogated the temporal evolution of the phosphorylation profiles within macrophages during cancer cell phagocytosis.

Multi-omics analysis of long-term cultured human islets.

β-cell dysfunction in pancreatic islets, characterized as either the loss of β-cell mass or the resistance of β-cell to glucose, is the leading cause of progression to diabetes. Islet transplantation became a promising approach to replenish functional β-cell mass. However, not much known about changes in islets used for transplantation after isolation.

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency.

Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. We discovered that SLC25A13 loss causes accumulation of glycerol-3-phosphate (G3P), which activates carbohydrate response element binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol, and to transcribe key genes of lipogenesis.

The Hallmarks of Predictive Oncology.

As the field of artificial intelligence evolves rapidly, these hallmarks are intended to capture fundamental, complementary concepts necessary for the progress and timely adoption of predictive modeling in precision oncology. Through these hallmarks, we hope to establish standards and guidelines that enable the symbiotic development of artificial intelligence and precision oncology.

Targeting CEA in metastatic triple negative breast cancer with image-guided radiation followed by Fab-mediated chimeric antigen receptor (CAR) T-cell therapy.

Introduction: Although CAR-T cell therapy has limited efficacy against solid tumors, it has been hypothesized that prior treatment with Image-Guided Radiation Therapy (IGRT) would increase CAR-T cell tumor infiltration, leading to improved antigen specific expansion of CAR-T cells.

Methods: To test this hypothesis in a metastatic triple negative breast cancer (TNBC) model, we engineered two anti-CEA single-chain Fab (scFab) CAR-T cells with signaling domains from CD28zeta and 4-1BBzeta, and tested them and .

Results: The anti-CEA scFab CAR-T cells generated from three different human donors demonstrated robust expression, expansion, and lysis of only CEA-positive TNBC cells, with the CD28z-CAR-T cells showing the highest cytotoxicity.

Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer.

Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemotherapy resistance significantly limits its efficacy, posing a major clinical challenge. Moreover, heterogeneity of resistance mechanisms across cancer types complicates the development of universally effective diagnostic and therapeutic approaches.

Tofacitinib Mitigates the Increased SARS-CoV-2 Infection Susceptibility Caused by an IBD Risk Variant in the PTPN2 Gene.

Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, triggered a global pandemic with severe medical and socioeconomic consequences. While fatality rates are higher among the elderly and those with underlying comorbidities, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases.

Prospective pooled analyses of ambient ultraviolet radiation levels and risk of non-Hodgkin lymphoma and multiple myeloma.

Case-control studies of sun exposure and ultraviolet radiation (UVR) have consistently reported inverse associations with non-Hodgkin lymphoma (NHL) risk, but prospective studies have yielded mixed results. Few studies have explored these exposures in relation to multiple myeloma (MM) risk. To further evaluate these associations with NHL and MM risk and identify etiologically relevant exposure timing, we pooled data on 566,693 individuals from 6 United States (U.

AOH1996 targets mitochondrial dynamics and metabolism in leukemic stem cells via mitochondrial PCNA inhibition.

Cytoplasmic proliferating cell nuclear antigen (PCNA) is highly expressed in acute myeloid leukemia (AML) cells, supporting oxidative metabolism and leukemia stem cell (LSC) growth. We report on AOH1996 (AOH), an oral compound targeting cancer-associated PCNA, which shows significant antileukemic activity. AOH inhibited growth in AML cell lines and primary CD34 + CD38 - blasts (LSC-enriched) in vitro while sparing normal hematopoietic stem cells (HSCs).

Epigenetic alterations and memory: key players in the development/progression of chronic kidney disease promoted by acute kidney injury and diabetes.

Chronic kidney disease (CKD) is a highly prevalent global public health issue and can progress to renal failure. Survivors of acute kidney injury (AKI) have an increased risk of progressing to CKD by 8.8-fold and kidney failure by 3.

Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.

Cell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, a cell signaling-focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression.

Current state and future prospects of spatial biology in colorectal cancer.

Over the past century, colorectal cancer (CRC) has become one of the most devastating cancers impacting the human population. To gain a deeper understanding of the molecular mechanisms driving this solid tumor, researchers have increasingly turned their attention to the tumor microenvironment (TME). Spatial transcriptomics and proteomics have emerged as a particularly powerful technology for deciphering the complexity of CRC tumors, given that the TME and its spatial organization are critical determinants of disease progression and treatment response.

Estimates of walking prevalence and volume for U.S. cancer survivors and those without cancer: overall, by sex, and by race and ethnicity.

Purpose: This paper estimated overall, by sex, and by race and ethnicity walking behaviors in the cancer survivor population, where prevalence is not known, compared to those without cancer.

Methods: Data from the 2015 and 2020 National Health Interview Survey (n = 54,542) were used to estimate walking behaviors. Multivariable logistic regression models estimated walking behavior prevalence with predictive margins and volume of weekly minutes overall and stratified by sex and race/ethnicity.

Potential Role of EBI3 in Gastric Cancer and Its Inductive Effects on T Cell Exhaustion.

Background: Immunotherapy has achieved effective antitumor activity in advanced GC patients. However, the rate of response to ICI therapy is disappointing, T cell exhaustion may contribute to this phenomenon. EBI3 is an emerging immunosuppressive factor, and the association between EBI3 and T cell exhaustion is not clear.

Association between cardiovascular health and perceived quality of life in ethnically diverse adults: insights from the Community of Mine study using the American Heart Association's Life's Simple 7.

Purpose: The association between cardiovascular health (CVH) with perceived quality of life (PQoL) and variations by sex and Hispanic ethnicity is not well understood.

Methods: This study included 583 participants (42% Hispanic, 56% female, mean age 59 years). Linear regression modeled the covariate-adjusted associations between CVH, using the combined 7 components of Life's Simple 7 (LS7; ideal and intermediate, compared to poor), and PQoL (total and physical, social, and cognitive health domains).

YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies.

Long-term durable remission in patients with B cell malignancies following chimeric antigen receptor (CAR)-T cell immunotherapy remains unsatisfactory, often due to antigen escape. Malignant B cell transformation and oncogenic growth relies on efficient ATP synthesis, although the underlying mechanisms remain unclear. Here, we report that YTHDF2 facilitates energy supply and antigen escape in B cell malignancies, and its overexpression alone is sufficient to cause B cell transformation and tumorigenesis.