Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine: Bringing next-generation precision oncology to patients.

The human genome project ushered in a genomic medicine era that was largely unimaginable three decades ago. Discoveries of druggable cancer drivers enabled biomarker-driven gene- and immune-targeted therapy and transformed cancer treatment. Minimizing treatment not expected to benefit, and toxicity-including financial and time-are important goals of modern oncology.

Changes of Pericoronary Adipose Tissue in Stable Heart Transplantation Recipients and Comparison with Controls.

Rationale And Objectives: Pericoronary adipose tissue (PCAT) is a key cardiovascular risk biomarker, yet its temporal changes after heart transplantation (HT) and comparison with controls remain unclear. This study investigates the temporal changes of PCAT in stable HT recipients and compares it to controls.

Materials And Methods: In this study, we analyzed 159 stable HT recipients alongside two control groups.

Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.

NR4A1 Acts as a Novel Regulator of Platelet Activation and Thrombus Formation.

Background: Mounting evidence indicates that nuclear receptors play a critical regulatory role in platelet pathophysiology and thrombotic disorders. Although NR4A (the nuclear receptor subfamily 4 group A) plays an important role in cardiovascular pathophysiology, the expression profile and biological function of NR4A member 1 (NR4A1) in platelets have never been reported.

Methods: We evaluated the functions and the underlying mechanisms of NR4A1 in platelet activation and thrombus formation using platelet-specific NR4A1-deficient mice and NR4A1-specific agonists.

On Finite Difference Jacobian Computation in Deformable Image Registration.

Producing spatial transformations that are diffeomorphic is a key goal in deformable image registration. As a diffeomorphic transformation should have positive Jacobian determinant everywhere, the number of voxels with has been used to test for diffeomorphism and also to measure the irregularity of the transformation. For digital transformations, is commonly approximated using a central difference, but this strategy can yield positive 's for transformations that are clearly not diffeomorphic-even at the voxel resolution level.

Deep Learning-Assisted Diagnosis of Malignant Cerebral Edema Following Endovascular Thrombectomy.

Background: Malignant cerebral edema (MCE) is a significant complication following endovascular thrombectomy (EVT) in the treatment of acute ischemic stroke. This study aimed to develop and validate a deep learning-assisted diagnosis model based on the hyperattenuated imaging marker (HIM), characterized by hyperattenuation on head non-contrast computed tomography immediately after thrombectomy, to facilitate radiologists in predicting MCE in patients receiving EVT.

Methods: This study included 271 patients, with 168 in the training cohort, 43 in the validation cohort, and 60 in the prospective internal test cohort.

Lysine vitcylation is a vitamin C-derived protein modification that enhances STAT1-mediated immune response.

Vitamin C (vitC) is essential for health and shows promise in treating diseases like cancer, yet its mechanisms remain elusive. Here, we report that vitC directly modifies lysine residues to form "vitcyl-lysine"-a process termed vitcylation. Vitcylation occurs in a dose-, pH-, and sequence-dependent manner in both cell-free systems and living cells.

High-density brush-shaped polymer lipids reduce anti-PEG antibody binding for repeated administration of mRNA therapeutics.

Messenger RNA lipid-nanoparticle-based therapies represent an emerging class of medicines for a variety of applications. However, anti-poly(ethylene glycol) (anti-PEG) antibodies generated by widely used PEGylated medicines and lipid nanoparticles hinder therapeutic efficacy upon repeated dosing. Here we report the chemical design, synthesis and optimization of high-density brush-shaped polymer lipids that reduce anti-PEG antibody binding to improve protein production consistency in repeated dosing.

Metabolic engineering to facilitate anti-tumor immunity.

Fructose consumption is elevated in western diets, but its impact on anti-tumor immunity is unclear. Fructose is metabolized in the liver and small intestine, where fructose transporters are highly expressed. Most tumors are unable to drive glycolytic flux using fructose, enriching fructose in the tumor microenvironment (TME).

Immune Checkpoint Blockade Response in Mucinous Tubular and Spindle Cell Carcinoma.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare kidney tumor which is usually characterized by indolent disease physiology. While several high-grade and sarcomatoid MTSCC tumors have been reported, the clinical experience with contemporary immune checkpoint blockade (ICB) combination therapies extrapolated from treatment paradigms of conventional renal cell carcinoma (RCC) remains limited. Here, we report two patients with metastatic MTSCC treated with first-line ipilimumab plus nivolumab therapy who both achieved great clinical benefit.

Development of Prompt Templates for Large Language Model-Driven Screening in Systematic Reviews.

Background: Systematic reviews (SRs) are hindered by the initial rigorous article screen, which delays access to reliable information synthesis.

Objective: To develop generic prompt templates for large language model (LLM)-driven abstract and full-text screening that can be adapted to different reviews.

Design: Diagnostic test accuracy.

Predicting Late Adverse Events in Uncomplicated Stanford Type B Aortic Dissection: Results From the ROADMAP Validation Study.

Background: Risk stratification is highly desirable in patients with uncomplicated Stanford type B aortic dissection but inadequately supported by evidence. We sought to validate externally a published prediction model for late adverse events (LAEs), consisting of 1 clinical (connective tissue disease) and 4 imaging variables: maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and number of identifiable intercostal arteries.

Methods: We assembled a retrospective multicenter cohort (ROADMAP [Registry of Aortic Diseases to Model Adverse Events and Progression]) of 401 patients with uncomplicated Stanford type B aortic dissection presenting to 1 of 8 aortic centers between 2001 and 2013, followed until 2020.

De-escalating Dual Antiplatelet Therapy to Ticagrelor Monotherapy in Acute Coronary Syndrome : A Systemic Review and Individual Patient Data Meta-Analysis of Randomized Clinical Trials.

Background: The role of transitioning from short dual antiplatelet therapy (DAPT) to potent P2Y12 inhibitor monotherapy in patients with acute coronary syndrome (ACS) undergoing drug-eluting stent (DES) implantation remains inconclusive.

Purpose: To compare the effects of de-escalating DAPT to ticagrelor monotherapy versus standard DAPT from randomized clinical trials in patients with ACS.

Data Sources: PubMed, EMBASE, Scopus, and ClinicalTrials.

Intrinsic electrical activity drives small-cell lung cancer progression.

Elevated or ectopic expression of neuronal receptors promotes tumour progression in many cancer types; neuroendocrine (NE) transformation of adenocarcinomas has also been associated with increased aggressiveness. Whether the defining neuronal feature, namely electrical excitability, exists in cancer cells and impacts cancer progression remains mostly unexplored. Small-cell lung cancer (SCLC) is an archetypal example of a highly aggressive NE cancer and comprises two major distinct subpopulations: NE cells and non-NE cells.

A molecular proximity sensor based on an engineered, dual-component guide RNA.

One of the goals of synthetic biology is to enable the design of arbitrary molecular circuits with programmable inputs and outputs. Such circuits bridge the properties of electronic and natural circuits, processing information in a predictable manner within living cells. Genome editing is a potentially powerful component of synthetic molecular circuits, whether for modulating the expression of a target gene or for stably recording information to genomic DNA.

Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups.

We conducted a multiancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry, 58,236 African ancestry, 23,546 Hispanic/Latino and 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (P ≤ 5 × 10) variants, 184 of which were novel.

Long-read sequencing of 945 Han individuals identifies structural variants associated with phenotypic diversity and disease susceptibility.

Genomic structural variants (SVs) are a major source of genetic diversity in humans. Here, through long-read sequencing of 945 Han Chinese genomes, we identify 111,288 SVs, including 24.56% unreported variants, many with predicted functional importance.

Cell-free epigenomes enhanced fragmentomics-based model for early detection of lung cancer.

Background: Lung cancer is a leading cause of cancer mortality, highlighting the need for innovative non-invasive early detection methods. Although cell-free DNA (cfDNA) analysis shows promise, its sensitivity in early-stage lung cancer patients remains a challenge. This study aimed to integrate insights from epigenetic modifications and fragmentomic features of cfDNA using machine learning to develop a more accurate lung cancer detection model.

Typhimurium persistently infects host via its effector SseJ-induced PHB2-mediated mitophagy.

Despite decades of research on effective methods to resist serovar Typhimurium (. Typhimurium) pathogenicity, the mechanisms of . Typhimurium-host interactions have not been fully determined.

Short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth.

Interleukin (IL)-18 functions primarily through its 18-kDa mature form produced from caspase-1 cleavage. However, IL-18 can also be processed by other proteases, leading to the generation of different fragments with less recognized functions. Here, we discover that, in cancer cells, caspase-3 cleavage of IL-18 generates a 15-kDa form of IL-18, referred to as short IL-18.

Awaiting insurance coverage: Medicaid enrollment and post-acute care use after traumatic injury.

Background: Lack of insurance after traumatic injury is associated with decreased use of postacute care and poor outcomes. Insurance linkage programs enroll eligible patients in Medicaid at the time of an unplanned admission. We hypothesized that Medicaid enrollment would be associated with increased use of postacute care, but also with prolonged hospital length of stay (LOS) while awaiting insurance authorization.

ROCK Inhibitor Enhances Resilience Against Metabolic Stress Through Increasing Bioenergetic Capacity in Corneal Endothelial Cells.

Purpose: To investigate the effect of Rho-associated protein kinase (ROCK) inhibitor Y27632 on bioenergetic capacity and resilience of corneal endothelial cells (CECs) under metabolic stress.

Methods: Bovine CECs (BCECs) were treated with Y27632 and subjected to bioenergetic profiling using the Seahorse XFp Analyzer. The effects on adenosine triphosphate (ATP) production through oxidative phosphorylation and glycolysis were measured.

Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation.

Background: Abelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown.

Methods: Patients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion.

Botulinum neurotoxins exploit host digestive proteases to boost their oral toxicity via activating OrfXs/P47.

Botulinum neurotoxins (BoNTs) rank among the most potent toxins and many of them are produced by bacteria carrying the orfX gene cluster that also encodes four nontoxic proteins (OrfX1, OrfX2, OrfX3 and P47). The orfX gene cluster is also found in the genomes of many non-BoNT-producing bacteria, often alongside genes encoding oral insecticidal toxins. However, the functions of these OrfXs and P47 remain elusive.