Adjunctive PCSK9 Inhibitor Evolocumab in the Prevention of Early Neurological Deterioration in Non-cardiogenic Acute Ischemic Stroke: A Multicenter, Prospective, Randomized, Open-Label, Clinical Trial.

Background: Early neurological deterioration (END) is associated with a poor prognosis in acute ischemic stroke (AIS). Effectively lowering low-density lipoprotein cholesterol (LDL-C) can improve the stability of atherosclerotic plaque and reduce post-stroke inflammation, which may be an effective means to lower the incidence of END. The objective of this study was to determine the preventive effects of evolocumab on END in patients with non-cardiogenic AIS.

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.

ASGR1 Deficiency Inhibits Atherosclerosis in Western Diet-Fed Mice by Regulating Lipoprotein Metabolism and Promoting Cholesterol Efflux.

Background: Atherosclerosis is the most common cause of cardiovascular diseases. Clinical studies indicate that loss-of-function ASGR1 (asialoglycoprotein receptor 1) is significantly associated with lower plasma cholesterol levels and reduces cardiovascular disease risk. However, the effect of ASGR1 on atherosclerosis remains incompletely understood; whether inhibition of ASGR1 causes liver injury remains controversial.

Multistage protective anti-CelTOS monoclonal antibodies with cross-species sterile protection against malaria.

CelTOS is a malaria vaccine antigen that is conserved in Plasmodium and other apicomplexan parasites and plays a role in cell-traversal. The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes.

AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery.

Ionizable lipid nanoparticles (LNPs) are seeing widespread use in mRNA delivery, notably in SARS-CoV-2 mRNA vaccines. However, the expansion of mRNA therapies beyond COVID-19 is impeded by the absence of LNPs tailored for diverse cell types. In this study, we present the AI-Guided Ionizable Lipid Engineering (AGILE) platform, a synergistic combination of deep learning and combinatorial chemistry.

Ticking Brain: Circadian Rhythm as a New Target for Cerebroprotection.

Circadian rhythm is a master process observed in nearly every type of cell throughout the body, and it macroscopically regulates daily physiology. Recent clinical trials have revealed the effects of circadian variation on the incidence, pathophysiological processes, and prognosis of acute ischemic stroke. Furthermore, core clock genes, the cell-autonomous pacemakers of the circadian rhythm, affect the neurovascular unit-composing cells in a nonparallel manner after the same pathophysiological processes of ischemia/reperfusion.

Ultrasound and x-ray imageable poloxamer-based hydrogel for loco-regional therapy delivery in the liver.

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs).

Inulin-gel-based oral immunotherapy remodels the small intestinal microbiome and suppresses food allergy.

Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models.

Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs.

The efficacy and safety of PARP inhibitors in mCRPC with HRR mutation in second-line treatment: a systematic review and bayesian network meta-analysis.

Background: Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous recombination repair deficiency (HRD). However, it is unclear which PARPi is optimal in mCRPC patients with HRD in 2nd -line setting.

Method: We conducted a systematic review of trials regarding PARPi- based therapies on mCRPC in 2nd -line setting and performed a Bayesian network meta-analysis (NMA).

Indocyanine green near-infrared fluorescence-assisted video endoscopic inguinal lymph node dissection for rectal cancer: a single-center experience.

Background: This study aimed to investigate the safety and feasibility of indocyanine green near-infrared fluorescence (ICG-NIR) fluorescence-guided video-endoscopic inguinal lymphadenectomy (VEIL) for rectal cancer with inguinal lymph node metastasis (ILNM).

Methods: A retrospective analysis was conducted on 11 patients with rectal cancer who underwent ICG-NIR fluorescence-guided VEIL, assessing various parameters such as operation time, intraoperative bleeding, number of harvested lymph nodes, intraoperative and postoperative complications, and follow-up.

Results: Regarding surgical procedures for ILNM, unilateral surgery was performed in 7 cases (54.

Massively parallel in vivo Perturb-seq reveals cell-type-specific transcriptional networks in cortical development.

Leveraging AAVs' versatile tropism and labeling capacity, we expanded the scale of in vivo CRISPR screening with single-cell transcriptomic phenotyping across embryonic to adult brains and peripheral nervous systems. Through extensive tests of 86 vectors across AAV serotypes combined with a transposon system, we substantially amplified labeling efficacy and accelerated in vivo gene delivery from weeks to days. Our proof-of-principle in utero screen identified the pleiotropic effects of Foxg1, highlighting its tight regulation of distinct networks essential for cell fate specification of Layer 6 corticothalamic neurons.

Thermal Oxidative Aging and Service Life Prediction of Commercial Ethylene-Propylene-Diene Monomer Spacer Damping Composites for High-Voltage Transmission Lines.

The aging behavior and life prediction of rubber composites are crucial for ensuring high-voltage transmission line safety. In this study, commercially available ethylene-propylene-diene monomer (EPDM) spacer composites were chosen and investigated to elucidate the structure and performance changes under various aging conditions. The results showed an increased C=O peak intensity with increasing aging time, suggesting intensified oxidation of ethylene and propylene units.

The burden of mental disorders in Asian countries, 1990-2019: an analysis for the global burden of disease study 2019.

Mental disorders are the leading contributors to the globally nonfatal burden of disease. This study was aimed to estimate the burden of mental disorders in Asian countries. Based on GBD 2019, the prevalence and disability-adjusted life of years (DALYs) rates with 95% uncertainty intervals (UI) were estimated in Asian countries.

Complex causal association between genetically predicted 731 immunocyte phenotype and osteonecrosis: a bidirectional two-sample Mendelian randomization analysis.

Purpose: Previous studies have explored the role of immune cells on osteonecrosis. This Mendelian randomization (MR) study further assessed 731 immunocyte phenotypes on osteonecrosis, whether a causal relationship exists, and provides some evidence of causality.

Methods: The 731 immunocyte phenotypes and osteonecrosis data used in this study were obtained from their respective genome-wide association studies (GWAS).

A novel automatic segmentation method directly based on magnetic resonance imaging K-space data for auxiliary diagnosis of glioma.

Background: The use of segmentation architectures in medical imaging, particularly for glioma diagnosis, marks a significant advancement in the field. Traditional methods often rely on post-processed images; however, key details can be lost during the fast Fourier transformation (FFT) process. Given the limitations of these techniques, there is a growing interest in exploring more direct approaches.

Molecular complexity of intraductal carcinoma of the prostate.

Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies.