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.

CRISPR-Cas9 Gene Editing with Nexiguran Ziclumeran for ATTR Cardiomyopathy.

Background: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, often fatal disease. Nexiguran ziclumeran (nex-z) is an investigational therapy based on CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease) targeting the gene encoding transthyretin ().

Methods: In this phase 1, open-label trial, we administered a single intravenous infusion of nex-z to patients with ATTR-CM.

Targeting neutrophil serine proteases in bronchiectasis.

Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis. Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur.

Potent efficacy of an IgG-specific endoglycosidase against IgG-mediated pathologies.

Endo-β-N-acetylglucosaminidases (ENGases) that specifically hydrolyze the Asn297-linked glycan on immunoglobulin G (IgG) antibodies, the major molecular determinant of fragment crystallizable (Fc) γ receptor (FcγR) binding, are exceedingly rare. All previously characterized IgG-specific ENGases are multi-domain proteins secreted as an immune evasion strategy by Streptococcus pyogenes strains. Here, using in silico analysis and mass spectrometry techniques, we identified a family of single-domain ENGases secreted by pathogenic corynebacterial species that exhibit strict specificity for IgG antibodies.

Microwave versus Radiofrequency Ablation in Treating Predominantly Solid Benign Thyroid Nodules: A Randomized Controlled Trial.

Background Current guidelines recommend radiofrequency ablation (RFA) as the first-line treatment for benign thyroid nodules. Purpose To compare the efficacy and safety of microwave ablation (MWA) and RFA for the treatment of predominantly solid benign thyroid nodules. Materials and Methods This prospective, randomized, open-label, multicenter study was conducted from August 2019 to February 2023.

Disparities Between Clinical Trial Recruitment and Real-World Demographics in Macular Edema Secondary to Retinal Vein Occlusion.

Purpose: Clinical trial cohorts frequently differ demographically from the overall population receiving treatment for the condition under study. Our study describes the racial, ethnic, and gender composition of the cohorts of retinal vein occlusion (RVO) macular edema (ME) clinical trials and compares this to the racial, ethnic, and gender composition of patients undergoing treatment for ME secondary to RVO from the (Intelligent Research in Sight) IRIS Registry.

Design: Retrospective observational case series Subjects: Participants in RVO-ME clinical trials that met the following inclusion criteria: conducted in the United States of America, Phase III completed, data reported between January 1, 2000, and January 1, 2020, and demographic information reported with results.

Bronchiectasis in Asia: a review of current status and challenges.

Recent bronchiectasis studies from large-scale multinational, multicentre registries have demonstrated that the characteristics of the disease vary according to geographic region. However, most perspectives on bronchiectasis are dominated by data from Western countries. This review intends to provide an Asian perspective on the disease, focusing on the established registries in India, Korea and China.

EPAS1 Attenuates Atherosclerosis Initiation at Disturbed Flow Sites Through Endothelial Fatty Acid Uptake.

Background: Atherosclerotic plaques form unevenly due to disturbed blood flow, causing localized endothelial cell (EC) dysfunction. Obesity exacerbates this process, but the underlying molecular mechanisms are unclear. The transcription factor EPAS1 (HIF2A) has regulatory roles in endothelium, but its involvement in atherosclerosis remains unexplored.

Integrated clinical risk prediction of type 2 diabetes with a multifactorial polygenic risk score.

Combining information from multiple GWASs for a disease and its risk factors has proven a powerful approach for development of polygenic risk scores (PRSs). This may be particularly useful for type 2 diabetes (T2D), a highly polygenic and heterogeneous disease where the additional predictive value of a PRS is unclear. Here, we use a meta-scoring approach to develop a metaPRS for T2D that incorporated genome-wide associations from both European and non-European genetic ancestries and T2D risk factors.

Close-packed nitronyl nitroxide radicals by Au-S self-assembly: strong ferromagnetic coupling.

The study of the magnetism of tightly arranged nitronyl nitroxide (NN) radicals Au-S self-assembly is interesting. In this study, a series of radicals (S-NN, D-NN, BS-NN, BD-NN) along with two types of nanomaterials (S-NPs, D-NPs) were synthesized. NN was chosen for the magnetic units.

Comparative Performance of Common Fecal Immunochemical Tests : A Cross-Sectional Study.

Background: Despite widespread use of fecal immunochemical tests (FITs) for colorectal cancer (CRC) screening, data to guide test selection are limited.

Objective: To compare the performance characteristics of 5 commonly used FITs, using colonoscopy as the reference standard.

Design: Cross-sectional study.

PTEN Loss Shapes Macrophage Dynamics in High-Grade Serous Ovarian Carcinoma.

High-grade serous ovarian carcinoma (HGSC) remains a disease with poor prognosis that is unresponsive to current immune checkpoint inhibitors. Although PI3K pathway alterations, such as PTEN loss, are common in HGSC, attempts to target this pathway have been unsuccessful. We hypothesized that aberrant PI3K pathway activation may alter the HGSC immune microenvironment and present a targeting opportunity.

An acid-tolerant metal-organic framework for industrial CO electrolysis using a proton exchange membrane.

Industrial CO electrolysis via electrochemical CO reduction has achieved progress in alkaline solutions, while the same reaction in acidic solution remains challenging because of severe hydrogen evolution side reactions, acid corrosion, and low target product selectivity. Herein, an industrial acidic CO electrolysis to pure HCOOH system is realized in a proton-exchange-membrane electrolyzer using an acid-tolerant Bi-based metal-organic framework guided by a Pourbaix diagram. Significantly, the Faradaic efficiency of HCOOH synthesis reaches 95.

An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.

In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the cortical interneuron subtypes.

Succession characteristics of phytoplankton functional groups and ecological assessment in a cold spring-type urban lake, China.

Phytoplankton functional groups have been increasingly utilized in elucidating and predicting the response of phytoplankton species to environmental conditions and seasonal succession in various aquatic systems including lakes, rivers and reservoirs. However, it is still unclear whether the trait-based functional classification can be applied to spring-type lakes. To understand the temporal and spatial characteristics of phytoplankton functional groups and their responses to environmental factors in spring-type urban lake in northern China, an investigation was conducted in Daming Lake from May 2020 to September 2021.

Dupilumab: Mechanism of action, clinical, and translational science.

Allergic disease prevalence has increased globally with the subset of type 2 inflammatory diseases playing a substantial role. Type 2 inflammatory diseases may differ in clinical presentation, but they exhibit shared pathophysiology that is targeted by the unique pharmacology of dupilumab. Dupilumab binds to the interleukin (IL)-4 receptor alpha subunit (IL-4Rα) that blocks IL-4 and IL-13 signaling, two key drivers of type 2 inflammation.

Pharmacokinetics and pharmacodynamics of itepekimab in adults with moderate-to-severe atopic dermatitis: Results from two terminated phase II trials.

Interleukin-33 (IL-33) is a proinflammatory alarmin cytokine released by damaged epithelial tissue cells that initiates and amplifies both type 1 and type 2 inflammatory cascades. A role for IL-33 in atopic dermatitis (AD; a chronic, relapsing type 2 inflammatory disease of the skin) has been proposed. Itepekimab is a novel human IgG4P monoclonal antibody against IL-33, currently in clinical development for chronic obstructive pulmonary disease (COPD).

Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer.

Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes as top dependencies specific to POU2F3-positive SCLC.

Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma.

Background: The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown.

Methods: We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs.