Advanced electrocardiography heart age: a prognostic, explainable machine learning approach applicable to sinus and non-sinus rhythms.

Aims: An explainable advanced electrocardiography (A-ECG) Heart Age gap is the difference between A-ECG Heart Age and chronological age. This gap is an estimate of accelerated cardiovascular aging expressed in years of healthy human aging, and can intuitively communicate cardiovascular risk to the general population. However, existing A-ECG Heart Age requires sinus rhythm.

An automatic and real-time echocardiography quality scoring system based on deep learning to improve reproducible assessment of left ventricular ejection fraction.

Background: Echocardiography can conveniently, rapidly, and economically evaluate the structure and function of the heart, and has important value in the diagnosis and evaluation of cardiovascular diseases (CVDs). However, echocardiography still exhibits significant variability in image acquisition and diagnosis, with a heavy dependency on the operator's experience. Image quality affects disease diagnosis in the later stage, and even image quality assessment still has variability in human evaluation.

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.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

US-Guided Thermal Ablation for Secondary Hyperparathyroidism: A Prospective Multicenter Study.

Background Interest in microwave ablation (MWA) and radiofrequency ablation (RFA) use for treating secondary hyperparathyroidism (SHPT) is rising; however, ablation outcomes in patients with SHPT are not well characterized. Purpose To assess the response of parathyroid hormone (PTH), calcium, phosphorus, and alkaline phosphatase (ALP) levels to US-guided parathyroid MWA and RFA and the safety of these treatments in participants with SHPT. Materials and Methods This prospective multicenter cohort study, conducted from September 2017 to March 2022, included participants with SHPT.

An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

Macranthoidin B restrains the epithelial-mesenchymal transition through COX-2/PGE pathway in endometriosis.

Introduction: Macranthoidin B is one of the primary and unique triterpenoid saponin metabolites from Hand. -Mazz, which is used to treat endometriosis (EMS) in traditional Chinese medicine. However, the effect of macranthoidin B remains unknown in EMS.

Part 2: Drug Interactions Involving Cannabis Products in Persons Aged 18 and Over: A Summary of Published Case Reports and Analysis of the FDA Adverse Event Reporting System.

The increasing utilization of cannabis products combined with lack of data regarding potential cannabis-prescription drug interactions is concerning. This study aimed to review published case reports and FDA Adverse Event Reporting System (FAERS) spontaneous reports to assess cannabis-drug interactions in persons aged 18 and over. A literature search identified 20 case reports that were each assessed for drug interaction causality using the Drug Interaction Probability Scale.

Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection.

The Ebola filovirus (EBOV) poses a serious threat to global health and national security. Nanobodies, a type of single-domain antibody, have demonstrated promising therapeutic potential. We identified two anti-EBOV nanobodies, Nanosota-EB1 and Nanosota-EB2, which specifically target the EBOV glycoprotein (GP).

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

Sex Differences in Cardiovascular-Kidney-Metabolic Syndrome: 30-Year US Trends and Mortality Risks-Brief Report.

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remains unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and the long-term prognosis of CKM syndrome in the United States.

SGK1-Mediated Vascular Smooth Muscle Cell Phenotypic Transformation Promotes Thoracic Aortic Dissection Progression.

Background: The occurrence of thoracic aortic dissection (TAD) is closely related to the transformation of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. The role of SGK1 (serum- and glucocorticoid-regulated kinase 1) in VSMC phenotypic transformation and TAD occurrence is unclear.

Methods: Four-week-old male Sgk1 ( floxed) and Sgk1;Tagln (smooth muscle cell-specific knockout) mice were administered β-aminopropionitrile monofumarate for 4 weeks to model TAD.

Crystalline potassium boryl dithiolate and diselenolate.

Both the B-S and S-S bonds of 1,2,4,3,5-trithiadiborolane 1 could be cleaved by potassium graphite (KC) to give the first isolable boryl dithiolate DmpB(SK)3, whereas the reduction of 1,2,4-triselena-3,5-diborolane 2 with KC afforded the boryl diselenolate DmpB(SeK)(SeSeK) 4, showcasing the unprecedented structural authentication of ligand substituted diselenolate.

Spatially Resolved CRISPR Screen Sequencing via Perturb-DBiT.

Perturb-seq enabled the profiling of transcriptional effects of genetic perturbations in single cells but lacks the ability to examine the impact on tissue environments. We present Perturb-DBiT for simultaneous co-sequencing of spatial transcriptome and guide RNAs (gRNAs) on the same tissue section for in vivo CRISPR screen with genome-scale gRNA libraries, offering a comprehensive understanding of how genetic modifications affect cellular behavior and tissue architecture. This platform supports a variety of delivery vectors, gRNA library sizes, and tissue preparations, along with two distinct gRNA capture methods, making it adaptable to a wide range of experimental setups.

Efficacy and Safety of a Dedicated Device for Cerebral Venous Thrombectomy: A Pilot Randomized Clinical Trial.

Background: Lack of a dedicated thrombectomy device for cerebral venous thrombosis hinders the recanalization ability of endovascular treatment (EVT). Novel NiTi-braided stent retriever (Venous-TD) is a dedicated venous sinus thrombectomy device. This study aims to demonstrate the safety and efficacy of Venous-TD.

Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate.

Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic viruses due to their favorable properties. In this study, we identified a novel nanobody, Nanosota-9, which demonstrates high potency against a wide range of Omicron subvariants both in vitro and in a mouse model.

Seeking orderness out of the orderless movements: an up-to-date review of the biomechanics in clear aligners.

Introduction: Although with increasing popularity due to aesthetic appeal and comfort, clear aligners (CAs) are facing challenges in efficacy and predictability. Advancement in the underlying biomechanical field is crucial to addressing these challenges. This paper endeavors to provide a comprehensive framework for understanding the biomechanics of CA and enlightening biomechanics-based improvements on treatment strategies.

Anatase/TiO(B) homojunction nanosheets with a gold cocatalyst for direct photocatalytic coupling of methane to ethane.

An anatase/TiO(B) homojunction loaded with Au nanoparticles was synthesized, achieving a CH yield rate of 170 μmol g h in a flow photoreactor. The homojunction reduces TiO(B)'s strong oxidative ability, offering a more moderate environment for methane dehydrogenation, while Au aids in charge mitigation and methyl radical coupling. The catalyst highlights homojunction engineering and a ternary synergistic effect in photocatalytic CH coupling.

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.

In situ phase engineering during additive manufacturing enables high-performance soft-magnetic medium-entropy alloys.

Additive manufacturing (AM) shows promise as a method for producing soft-magnetic multicomponent alloys for use in electric motors and sustainable electromobility applications. However, the simultaneous achievement of a high saturation magnetic flux density (B) and a low coercivity (H) in AM soft-magnetic materials remains challenging. Herein, we present an approach that integrates an elemental powder mixture of FeCoNi with FeO nano-oxides, which is then subjected to laser powder bed fusion (LPBF) followed by high-temperature annealing to achieve an FCC-structured FeCoNi MEA/FeO composite.

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.

Novel Ratiometric Surface-Enhanced Raman Scattering (SERS) Biosensor for Ultrasensitive Quantitative Monitoring of Human Carboxylesterase-1 in Hepatocellular Carcinoma Cells Using Ag-Au Nanoflowers as SERS Substrate.

In this study, we developed ratiometric surface-enhanced Raman scattering (SERS) biosensors using Ag-Au alloy nanoflowers as SERS substrates, molecules having amide bonds and alkyne groups (Tag A) as Raman reporters, and sodium thiocyanate as an internal standard molecule (Tag B) for the sensitive detection of human carboxylesterase-1 (hCE1) in HepG-2 cells. The correlation between HepG-2 cell damage and hCE1 activity levels was investigated. Both Tag A's alkyne group and Tag B's cyanide group produced characteristic SERS signals in the Raman-silent region ( and , respectively).