Engaging dystonia networks with subthalamic stimulation.

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth.

High correlation between Ki-67 expression and a novel perfusion MRI biomarker diffusion-derived vessel density (DDVD) in endometrial carcinoma.

Objective: This study aimed to investigate the feasibility of diffusion-derived vessel density (DDVD) in characterizing tumor microvasculature in endometrial carcinoma (EC), and to explore the correlations with Ki-67 proliferation status and histological type based on DDVD values.

Methods: There were in total 81 EC patients. There were 64 cases of non-aggressive histological type, and 17 cases of aggressive histological type.

Anion modulation enhances the internal electric field of CuCoO to improve the catalysis in ammonia borane hydrolysis.

Ammonia borane (NHBH, AB) is considered a promising chemical hydrogen storage material. The development of efficient, stable, and economical catalysts for AB hydrolysis is essential for realizing the hydrogen energy economy. In this study, a series of p-p heterojunction catalysts, labeled M (P/S/Cl)-CuCoO, were fabricated using the high-temperature vapor phase method to achieve anionic interface gradient doping.

Large Language Model Ability to Translate CT and MRI Free-Text Radiology Reports Into Multiple Languages.

Background High-quality translations of radiology reports are essential for optimal patient care. Because of limited availability of human translators with medical expertise, large language models (LLMs) are a promising solution, but their ability to translate radiology reports remains largely unexplored. Purpose To evaluate the accuracy and quality of various LLMs in translating radiology reports across high-resource languages (English, Italian, French, German, and Chinese) and low-resource languages (Swedish, Turkish, Russian, Greek, and Thai).

Haematological setpoints are a stable and patient-specific deep phenotype.

The complete blood count (CBC) is an important screening tool for healthy adults and a common test at periodic exams. However, results are usually interpreted relative to one-size-fits-all reference intervals, undermining the precision medicine goal to tailor care for patients on the basis of their unique characteristics. Here we study thousands of diverse patients at an academic medical centre and show that routine CBC indices fluctuate around stable values or setpoints, and setpoints are patient-specific, with the typical healthy adult's nine CBC setpoints distinguishable as a group from those of 98% of other healthy adults, and setpoint differences persist for at least 20 years.

Enhancing hydride formation and transfer for catalytic hydrogenation via electron-deficient single-atom silver.

Metal hydrides are sensitive to HO and O, which reduces the atom efficiency of the hydride donors. Silver (Ag) is an inexpensive coinage metal; however, its lower activity compared to gold, platinum, and palladium limits its application in catalytic hydrogenation. Here, electron-deficient metallic single-atom Ag (AgSA) was loaded onto γ-AlO using a benzoquinone- and KNO- assisted photolysis approach.

Development and Application of High-Internal-Phase Water-in-Oil Emulsions Using Amphiphilic Nanoparticle-Based Emulsifiers.

High-internal-phase water-in-oil (W/O) emulsions generated in situ have garnered considerable attention as novel profile control systems. However, conventional emulsifiers are unreactive and poorly dispersed in water, necessitating large dosages and resulting in poor injectivity. In this study, we synthesized amphiphilic nanoparticles (SiO-NH-DAC NPs) containing amine and long-chain alkyl groups using a one-pot method and investigated the stabilized emulsion properties.

Nationwide, Couple-Based Genetic Carrier Screening.

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy.

Discovery of IRAK1/4/pan-FLT3 Kinase Inhibitors as Treatments for Acute Myeloid Leukemia.

We report the discovery of an imidazopyridine series of IRAK1/4/pan-FLT3 kinase inhibitors. Optimization of this series has produced compound which displays potent and selective inhibition of IRAK1, IRAK4, FLT3, and all mutant forms of FLT3, as well as good in vitro ADME and pharmacokinetic properties. In a mouse xenograft model of AML, produces survival prolongation equal to that of Gilteritinib, the leading marketed FLT3 inhibitor currently used to treat AML.

Tirzepatide for Obesity Treatment and Diabetes Prevention.

Background: Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes.

Luminescence Modulation in Boron-Cluster-Based Luminogens via Boron Isotope Effects.

Recent advances in luminescent materials highlight the significant impact of hydrogen isotope effects on improving optoelectronic properties. However, the research on the influence of the boron isotope effects on photophysical properties remains underdeveloped. This study focused on exploring the boron isotope effects in boron-cluster-based luminogens.

Designed endocytosis-inducing proteins degrade targets and amplify signals.

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by endogenous ligands. Therapeutic approaches such as lysosome-targeting chimaeras (LYTACs) and cytokine receptor-targeting chimeras (KineTACs) have used this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. Although powerful, these approaches can be limited by competition with native ligands and requirements for chemical modification that limit genetic encodability and can complicate manufacturing, and, more generally, there may be no native ligands that stimulate endocytosis through a given receptor.

Dative Bonding Activation Enables Precise Functionalization of the Remote B-H Bond of -Carborane Clusters.

The innovation of synthetic strategies for selective B-H functionalization is a pivotal objective in the realm of boron cluster chemistry. However, the precise, efficient, and rapid functionalization of a B-H bond of carboranes that is distant from the existing functional groups remains intractable owing to the limited approaches for site-selective control from the established methods. Herein, we report a dative bonding activation strategy for the selective functionalization of a nonclassical remote B-H site of -carboranes.

Spatial Confinement of Lithium Borohydride in Bimetallic CoNi-Doped Hollow Carbon Frameworks for Stable Hydrogen Storage.

While lithium borohydride is one of the most promising hydrogen storage materials due to its ultrahigh hydrogen storage density, high thermodynamic stability, kinetic barriers, and poor reversibility, it is far from being used in practical applications. Herein, we prepare a cubic hollow carbon dodecahedron uniformly modified with a bimetallic CoNi alloy (CoNi/NC) for preserving the stable catalytic effect of CoNi alloys toward reversible hydrogen storage. It is theoretically confirmed that bimetallic CoNi alloys effectively weaken the B-H bonds of LiBH by extending their average length to 1.

Site-specific template generative approach for retrosynthetic planning.

Retrosynthesis, the strategy of devising laboratory pathways by working backwards from the target compound, is crucial yet challenging. Enhancing retrosynthetic efficiency requires overcoming the vast complexity of chemical space, the limited known interconversions between molecules, and the challenges posed by limited experimental datasets. This study introduces generative machine learning methods for retrosynthetic planning.

Fermi Edge of Semimetallic Borophane Sheets and its Reduction by a Porous Structure.

Theoretically predicted materials are often synthesized in low yields, and unexpected relationships are often encountered between the target materials and byproducts. Recently, two-dimensional boron materials proposed on the basis of model simulations and first principles calculations and possessing abundant atomic structures have attracted considerable interest. Borophane or the hydrogen boride (HB) sheet has been predicted to be the Dirac nodal semimetal when it has a boron network of nonsymmorphic symmetry.

Aurora Kinase A Inhibition Potentiates Platinum and Radiation Cytotoxicity in Non-Small-Cell Lung Cancer Cells and Induces Expression of Alternative Immune Checkpoints.

Despite major advances in non-small-cell lung cancer (NSCLC) treatment, the five-year survival rates for patients with non-oncogene-driven tumors remain low, necessitating combinatory approaches to improve outcomes. Our prior high-throughput RNAi screening identified Aurora kinase A (AURKA) as a potential key player in cisplatin resistance. In this study, we investigated AURKA's role in platinum and radiation sensitivity in multiple NSCLC cell lines and xenograft mouse models, as well as its effect on immune checkpoints, including PD-L1, B7x, B7-H3, and HHLA2.

Precise Image-level Localization of Intracranial Hemorrhage on Head CT Scans with Deep Learning Models Trained on Study-level Labels.

Purpose To develop a highly generalizable weakly supervised model to automatically detect and localize image-level intracranial hemorrhage (ICH) by using study-level labels. Materials and Methods In this retrospective study, the proposed model was pretrained on the image-level Radiological Society of North America dataset and fine-tuned on a local dataset by using attention-based bidirectional long short-term memory networks. This local training dataset included 10 699 noncontrast head CT scans in 7469 patients, with ICH study-level labels extracted from radiology reports.

CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection.

Background: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

Methods: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months).

BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models.

The MCL1 gene is frequently amplified in cancer and codes for the antiapoptotic protein myeloid cell leukemia 1 (MCL1), which confers resistance to the current standard of care. Therefore, MCL1 is an attractive anticancer target. Here we describe BRD-810 as a potent and selective MCL1 inhibitor and its key design principle of rapid systemic clearance to potentially minimize area under the curve-driven toxicities associated with MCL1 inhibition.