Effect of Personalized Risk Messages on Uptake of Colorectal Cancer Screening : A Randomized Controlled Trial.

Background: Providing personalized risk information to patients and their providers could improve colorectal cancer (CRC) screening.

Objective: To determine whether providing information on patient risk for advanced colorectal neoplasia (ACN; which includes CRC and advanced precancerous lesions) to patients and providers affects screening uptake, and to identify effect moderators.

Design: Randomized controlled trial (2 × 2 factorial design).

Tumor-derived EBI3 promotes CD8+ T cell exhaustion via STAT4-IL-10/CCL5 in gastric cancer.

Combination chemotherapy and immunotherapy are effective against advanced gastric cancer (GC). However, T cell exhaustion in the tumor microenvironment may decrease the immune response and compromise the effectiveness of immunotherapy. Herein, we report the potential role of EBI3 in promoting T cell exhaustion and its mechanism in GC, showing high expression of EBI3 in GC.

Circulating Tumor DNA Profiling Reveals Genomic Evolution in Recurrent Gastric or Gastroesophageal Junction Cancer.

Background: Recurrent gastric or gastroesophageal junction cancers have poor prognoses and limited treatment options. While archival tumor tissue is commonly used for genomic profiling, it may not reflect molecular changes at recurrence.

Objective: We aimed to assess the utility of a circulating tumor DNA analysis in identifying actionable genomic alterations at recurrence and compare findings with archival primary tumor profiles.

Chemomechanical regulation of growing tissues from a thermodynamically-consistent framework and its application to tumor spheroid growth.

It is widely recognized that reciprocal interactions between cells and their microenvironment, via mechanical forces and biochemical signaling pathways, regulate cell behaviors during normal development, homeostasis and disease progression such as cancer. However, how exactly cells and tissues regulate growth in response to chemical and mechanical cues is still not clear. Here, we propose a framework for the chemomechanical regulation of growth based on thermodynamics of continua and growth-elasticity to predict growth patterns.

Immunotherapy in the Treatment of Undifferentiated Pleomorphic Sarcoma and Myxofibrosarcoma.

Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are among the most common adult soft tissue sarcoma (STS) subtypes. Due to their high genetic complexity, heterogeneity, and lack of specific genetic alterations, no consistent molecular targets for targeted therapy have been identified for UPS and MFS. Recently, immune checkpoint inhibition (ICI) has emerged as a promising treatment modality for UPS and MFS.

Prevalence of Financial Hardship and Health-Related Social Needs in Pediatric Oncology: A Practice-Level Analysis of Systematic Screening.

Background: Screening for financial hardship and health-related social needs (HRSN) in pediatric oncology is recommended, yet practices vary widely, and standardized implementation remains limited. We implemented systematic screening in a pediatric oncology clinic in New York City.

Procedure: We evaluated the implementation of financial hardship (two items) and HRSN (difficulty affording food, housing, transportation, eight items) screening in outpatient pediatric oncology clinic.

Modeling the Effects of Combination Immunotherapy on Triple-Negative Breast Cancer in Syngeneic Mice from PET Imaging of CD4+ and CD8+ Cells.

We propose a system of ordinary differential equations to model the mouse immune response of two key immune cell types (CD4+ and CD8+ cells) to an established triple-negative breast cancer tumor while being treated with immunotherapy drugs of anti-PD-1 and anti-CTLA-4 immune checkpoint inhibitors. The model incorporates longitudinal positron emission tomography image data from a series of experiments where immunotherapy treatment was given in combination or separately. Control data optimization estimates the immune-tumor response of a general mouse burdened with breast cancer.

AI-driven WHO 2021 classification of gliomas based only on H&E-stained slides.

Background: The WHO 2021 classification criteria for adult diffuse glioma integrate histology with molecular profiling for conclusive diagnosis. Since molecular profiling can be expensive and time-consuming, often necessitating outsourcing or leading to the 'not otherwise specified (NOS) label', this study develops an AI-driven WHO 2021 classification of gliomas solely from H&E whole-slide images (WSIs).

Methods: Our pipeline is based on a multi-institutional dataset reclassified per WHO 2021 guidelines.

Trio exome sequencing of an optic nerve hypoplasia cohort reveals evidence for polygenic architecture.

Background: Optic nerve hypoplasia (ONH), the leading congenital cause of permanent blindness, is characterized by a retinal ganglion cell (RGC) deficit at birth and frequently associated neurologic and endocrine abnormalities. Multifactorial developmental events are hypothesized to underlie ONH; however, environmental influences are unclear, and genetic causes are under-investigated.

Methods: To identify monogenic, disease-causing variants among ONH patients, exomes from 34 ONH subjects and their parents were sequenced and rare variants identified.

Clinical and molecular characterization of patients with juvenile myelomonocytic leukaemia.

Juvenile myelomonocytic leukaemia (JMML) is a rare haematological malignancy caused by mutations in the Ras signalling pathway. Next-generation sequencing (NGS) and DNA methylation profiling used for diagnostic and risk stratification purposes are now standard of care in Europe and the United States for patients with JMML. To better understand how implementing these types of technologies would impact the treatment of JMML patients in different settings, molecular profiling was performed on 81 patients treated for JMML in Egypt from 2009 to 2022.

In-bacteria arginylation assay.

ATE1 is an enzyme that catalyzes the post-translational arginylation of proteins by transferring arginine to acidic residues, such as aspartate and glutamate, located at the N-terminus or on side chains. This modification plays important roles in regulating protein stability and function. The mechanisms underlying substrate and site selection by ATE1 remain unclear.

Recombinant expression, purification, and characterization of human ATE1 arginyltransferase.

This chapter presents a straightforward method for expressing and purifying recombinant human Arginyl-tRNA-protein transferase 1 (ATE1) from E. coli. ATE1 is an enzyme that catalyzes the transfer of arginine from arginyl-tRNA to the N-terminal or internal Asp or Glu residues of the substrate proteins, a process that regulates protein turnover or function.

Comparing and optimizing protein extraction methods with different lysis buffers for the analyses of human fecal microbiome via metaproteomics approach.

Metaproteomic analysis offers critical insights into gut microbiome function; however, efficient microbial protein extraction from fecal samples remains challenging due to the complexity of different types of bacterial cell walls in the microbiome. In this study, we systematically compared three representative detergent-based lysis buffers (sodium dodecyl sulfate_urea, dodecyl β-D-maltoside_urea, sodium dodecyl sulfate_ dodecyl β-D-maltoside_urea) for metaproteomics sample preparation. After multiple levels of analyses, we identified SDS_DDM_urea as the most efficient option for extracting diverse microbial proteins, peptides, and identifying microbial species.

High-grade endometrioid carcinomas with pilomatrix-like features lacking CTNNB1 Mutations: Clinicopathologic characteristics and novel molecular events.

Context: Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) represents a recently described, aggressive variant of endometrial carcinoma. Prior reports have linked PiMHEC with CTNNB1 exon 3 mutations and abnormal nuclear β-catenin expression.

Objective: We aimed to expand the understanding a potential subclassification of PiMHEC by analyzing three new cases that lack CTNNB1 mutations and β-catenin nuclear accumulation.

Investigating the role of UBASH3B in cancer: structural relevance, physiological functions, and therapeutic possibilities.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally and presents a persistent clinical challenge due to the limited availability of effective targeted therapeutics. Recent studies have identified the ubiquitin-associated and SH3 domain-containing B (UBASH3B), a tyrosine phosphatase, as a key oncogenic player in HNSCC pathogenesis. Elevated UBASH3B expression correlates with poor clinical outcomes in HNSCC patients.

Neutrophil-specific targeting of STAT3 impairs tumor progression via the expansion of cytotoxic CD8 T cells.

Neutrophils have emerged as key players in tumor progression and are often associated with poor prognosis. Despite ongoing efforts to target neutrophil functions in cancer, therapeutic success has been limited. In this study, we addressed the possibility of blocking STAT3 signaling in neutrophils as a targeted therapeutic intervention in cancer.

Real-world costs, treatment patterns, and clinical outcomes associated with treatments for advanced anaplastic lymphoma kinase-positive non-small cell lung cancer.

Background: Alectinib, brigatinib, and lorlatinib are all preferred first-line (1L) therapies for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in National Comprehensive Cancer Network (NCCN) guidelines. Although clinical trials have demonstrated their efficacy, real-world evidence on treatment patterns, costs, and outcomes may help differentiate these therapies and inform optimal 1L treatment selection in the absence of head-to-head comparisons.

Objective: To evaluate real-world outcomes for patients with ALK+ NSCLC receiving 1L ALK tyrosine kinase inhibitors (TKIs), focusing on drug acquisition costs, health care utilization, and clinical outcomes.

RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation.

Background: RANBP9 and RANBP10, also called Scorpins, are essential components of the C-terminal to LisH (CTLH) complex, an evolutionarily conserved poorly investigated multisubunit E3 ligase. Their role in non-small cell lung cancer (NSCLC) is unknown.

Methods: In this study, first we used stable loss-of function and overexpression inducible cell lines to investigate the ability of either RANBP9 or RANBP10 to form their own functional CTLH complex.

Carbon isotopic labelling of carboxylic acids enabled by organic photoredox-catalysed cyanation.

The application of molecular imaging has advanced personalized medicine and generated a profound impact on patient care. Positron emission tomography and magnetic resonance imaging are among the most widely used imaging modalities, often requiring the isotopic labelling of bioactive molecules to generate the desired imaging probes. Unfortunately, radiochemistry often limits the development of novel agents due to complicated syntheses and the incompatibility of complex molecules.

Constitutive metabolomic profile of a transgressive segregant of rice with superior salinity tolerance potentials due to unique morphological features and well-modulated growth.

Understanding the nature of non-parental phenotypes created by transgressive segregation is important in creating novel genetic recombinants that can withstand different environmental conditions for crop production. FL510, a transgressive salinity-tolerant rice genotype from a cross between IR29 (salt-sensitive) and Pokkali (salt-tolerant), has tolerance mechanisms active under control conditions and improves survival upon the onset of salinity. This study compares normal-state metabolomes and lipidomes of FL510 with its parents.

Comparative effectiveness of remote perioperative telemonitoring in cancer surgery: a randomized trial.

This randomized trial compared remote perioperative telemonitoring (RPM) care versus surgeon only care in patients with gastrointestinal (GI), genitourinary (GU), or gynecological (GYN) cancers (N = 293). The RPM care arm wore a wristband accelerometer and reported symptoms via a mobile application (app) before surgery and at days 7, 14, 30, 60, 90 post-discharge. Triage nurses telephoned patients when data deviated from predetermined thresholds.

Persistent Type I Interferon Signaling Impairs Innate Lymphoid Cells During HIV-1 Infection Under Suppressive ART.

Persistent type I interferon (IFN-I) signaling compromises adaptive anti-HIV-1 T cell immunity and promotes viral reservoir persistence, yet its effects on innate lymphoid cells during chronic infection remain unclear. Through integrated single-cell RNA sequencing and functional validation in HIV-1-infected humanized mice with combination antiretroviral therapy (cART) and IFN-I signaling blockade, we reveal IFN-I-induced dysfunction of natural killer (NK) cells and group 3 innate lymphoid cells (ILC3s). Mechanistically, the IFN-I-CD9 axis drives NK cells toward a decidual NK cell-like phenotype, impairing their cytotoxic activity.