Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

Programmable Self-Assembly from Two-Dimensional Nanosheets to Spiral, Twisted and Branched Nanostructures.

Self-assembly of nanomaterials into hierarchical structure is of great interest to fabricate functional materials. However, programmable design of the assembled structures remains a great challenge. Herein, we reported a programmable self-assembly strategy to customize the assembled structure.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

Structural variation in the pangenome of wild and domesticated barley.

Pangenomes are collections of annotated genome sequences of multiple individuals of a species. The structural variants uncovered by these datasets are a major asset to genetic analysis in crop plants. Here we report a pangenome of barley comprising long-read sequence assemblies of 76 wild and domesticated genomes and short-read sequence data of 1,315 genotypes.

Spermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression.

It has been established that N-acetyltransferase (murine NAT1 (mNAT1) and human NAT2 (hNAT2)) mediates insulin sensitivity in type 2 diabetes. Here we show that mNAT1 deficiency leads to a decrease in cellular spermidine-a natural polyamine exhibiting health-protective and anti-ageing effects-but understanding of its mechanism is limited. We identify that mNAT1 and hNAT2 modulate a type of post-translational modification involving acetylated spermidine, which we name acetylhypusination, on receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-a key regulator of inflammation and cell death.

RSNA 2023 Abdominal Trauma AI Challenge: Review and Outcomes.

Purpose To evaluate the performance of the winning machine learning models from the 2023 RSNA Abdominal Trauma Detection AI Challenge. Materials and Methods The competition was hosted on Kaggle and took place between July 26 and October 15, 2023. The multicenter competition dataset consisted of 4274 abdominal trauma CT scans, in which solid organs (liver, spleen, and kidneys) were annotated as healthy, low-grade, or high-grade injury.

Smooth Muscle Ythdf2 Abrogation Ameliorates Pulmonary Vascular Remodeling by Regulating Myadm Transcript Stability.

Background: The N6-methyladenosine (mA) modification of RNA and its regulators have important roles in the pathogenesis of pulmonary hypertension (PH). (YTH N6-methyladenosine RNA binding protein 2) is best known for its role in degrading mA-modified mRNAs such as mRNA, which leads to alternative activation of macrophages in PH. Recent studies have also linked to the proliferation of pulmonary artery smooth muscle cells (PASMCs).

A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma.

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus.

Thermal Characterization and Preclinical Feasibility Verification of an Accessible, Carbon Dioxide-Based Cryotherapy System.

To investigate the potential of an affordable cryotherapy device for the accessible treatment of breast cancer, the performance of a novel carbon dioxide-based device was evaluated through both benchtop testing and an in vivo canine model. This novel device was quantitatively compared to a commercial device that utilizes argon gas as the cryogen. The thermal behavior of each device was characterized through calorimetry and by measuring the temperature profiles of iceballs generated in tissue phantoms.

Comparative physiological, biochemical, metabolomic, and transcriptomic analyses reveal the formation mechanism of heartwood for Acacia melanoxylon.

Acacia melanoxylon is well known as a valuable commercial tree species owing to its high-quality heartwood (HW) products. However, the metabolism and regulatory mechanism of heartwood during wood development remain largely unclear. In this study, both microscopic observation and content determination proved that total amount of starches decreased and phenolics and flavonoids increased gradually from sapwood (SW) to HW.

Learning Representations from Heart Sound: A Comparative Study on Shallow and Deep Models.

Leveraging the power of artificial intelligence to facilitate an automatic analysis and monitoring of heart sounds has increasingly attracted tremendous efforts in the past decade. Nevertheless, lacking on standard open-access database made it difficult to maintain a sustainable and comparable research before the first release of the PhysioNet CinC Challenge Dataset. However, inconsistent standards on data collection, annotation, and partition are still restraining a fair and efficient comparison between different works.

An atlas of epithelial cell states and plasticity in lung adenocarcinoma.

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers.

Improved Measurement of CP Violation Parameters in B_{s}^{0}→J/ψK^{+}K^{-} Decays in the Vicinity of the ϕ(1020) Resonance.

The decay-time-dependent CP asymmetry in B_{s}^{0}→J/ψ(→μ^{+}μ^{-})K^{+}K^{-} decays is measured using proton-proton collision data, corresponding to an integrated luminosity of 6  fb^{-1}, collected with the LHCb detector at a center-of-mass energy of 13 TeV. Using a sample of approximately 349 000 B_{s}^{0} signal decays with an invariant K^{+}K^{-} mass in the vicinity of the ϕ(1020) resonance, the CP-violating phase ϕ_{s} is measured, along with the difference in decay widths of the light and heavy mass eigenstates of the B_{s}^{0}-B[over ¯]_{s}^{0} system, ΔΓ_{s}, and the difference of the average B_{s}^{0} and B^{0} meson decay widths, Γ_{s}-Γ_{d}. The values obtained are ϕ_{s}=-0.

Neurotoxicity Profiling of Aluminum Salt-Based Nanoparticles as Adjuvants for Therapeutic Cancer Vaccine.

Therapeutic vaccines containing aluminum adjuvants have been widely used in the treatment of tumors due to their powerful immune-enhancing effects. However, the neurotoxicity of aluminum adjuvants with different physicochemical properties has not been completely elucidated. In this study, a library of engineered aluminum oxyhydroxide (EAO) and aluminum hydroxyphosphate (EAHP) nanoparticles was synthesized to determine their neurotoxicity in vitro.

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages.

Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type.

Mitral Annular Disjunction: Review of an Increasingly Recognized Mitral Valve Entity.

Mitral annular disjunction (MAD) refers to atrial displacement of the hinge point of the mitral valve annulus from the ventricular myocardium. MAD leads to paradoxical expansion of the annulus in systole and may often be associated with mitral valve prolapse (MVP), leaflet degeneration, myocardial and papillary muscle fibrosis, and, potentially, malignant cardiac arrhythmias. Patients with MAD and MVP may present similarly, and MAD is potentially the missing link in explaining why some patients with MVP experience adverse outcomes.

Clinical Outcomes of Deferred Lesions by IVUS Versus FFR-Guided Treatment Decision.

Background: There are limited data regarding the safety of deferral of percutaneous coronary intervention based on intravascular ultrasound (IVUS) findings. The current study sought to compare the prognosis between deferred lesions based on IVUS and fractional flow reserve (FFR)-guided treatment decision.

Methods: This study is a post hoc analysis of the FLAVOUR randomized trial (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients With Intermediate Stenosis) that compared 2-year clinical outcomes between IVUS- and FFR-guided treatment decision on intermediate coronary artery lesions using predefined criteria.

Precision Measurement of CP Violation in the Penguin-Mediated Decay B_{s}^{0}→ϕϕ.

A flavor-tagged time-dependent angular analysis of the decay B_{s}^{0}→ϕϕ is performed using pp collision data collected by the LHCb experiment at the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb^{-1}. The CP-violating phase and direct CP-violation parameter are measured to be ϕ_{s}^{ss[over ¯]s}=-0.042±0.

Anti-factor Xa level monitoring of low-molecular-weight heparin for prevention of venous thromboembolism in critically ill patients (AXaLPE): protocol of a randomised, open-label controlled clinical trial.

Introduction: Whether and when to monitor the amount of anti-factor Xa (aFXa) activity in critically ill patients with complex diseases to prevent venous thromboembolism (VTE) remain unclear. This study is a randomised controlled trial to investigate the effect of aFXa level monitoring on reducing VTE and to establish a new method for accurately preventing VTE in critically ill patients with low-molecular-weight heparin (LMWH).

Methods And Analysis: A randomised controlled trial is planned in two centres with a planned sample size of 858 participants.