Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial.

Background: Previous trials have failed to demonstrate the benefits of extracranial-intracranial (EC-IC) bypass surgery for patients with carotid or middle cerebral artery occlusion. However, little evidence has focused on the effect of age on prognosis. This study aimed to explore whether EC-IC bypass surgery can provide greater benefits than medical therapy alone in specific age groups.

Is Ablation Suitable For Small Renal Masses? A Meta-Analysis.

Rationale And Objectives: To compare perioperative and oncology outcomes of ablation and partial nephrectomy in small renal masses (SRMs).

Methods: We conduct this meta-analysis strictly according to the PRISMA standard, and the quality evaluation follows the AMSTAR standard. Four databases, Embase, PubMed, Cochrane Library, and Web of Science, were systematically searched.

Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

Background: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects.

Producing high-quantity and high-quality recombinant adeno-associated virus by low-cis triple transfection.

Recombinant adeno-associated virus (rAAV)-based gene therapy is entering clinical and commercial stages at an unprecedented pace. Triple transfection of HEK293 cells is currently the most widely used platform for rAAV manufacturing. Here, we develop low-cis triple transfection that decreases transgene plasmid use by 10- to 100-fold and overcomes several major limitations associated with standard triple transfection.

Association of Valproic Acid and Its Main Metabolites' Plasma Concentrations with Clinical Outcomes among Epilepsy Patients: A 10-Year Retrospective Study Based on Therapeutic Drug Monitoring.

Valproic acid (VPA) is a first-line antiepileptic drug with broad efficacy. Due to significant individual differences in its metabolism, therapeutic drug monitoring is commonly used. However, the recommended therapeutic range (50-100 μg/mL) is inadequate for predicting clinical outcomes.

Quartet DNA reference materials and datasets for comprehensively evaluating germline variant calling performance.

Background: Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome.

Non-canonical amino acid incorporation into AAV5 capsid enhances lung transduction in mice.

Gene therapy using recombinant adeno-associated virus (rAAV) relies on safe, efficient, and precise gene delivery that is largely dependent on the AAV capsid. The proteinaceous capsid is highly amenable to engineering using a variety of approaches, and most resulting capsids carry substitutions or insertions comprised of natural amino acids. Here, we incorporated a non-canonical amino acid (ncAA), Nε-2-azideoethyloxycarbonyl-L-lysine (also known as NAEK), into the AAV5 capsid using genetic code expansion, and serendipitously found that several NAEK-AAV5 vectors transduced various cell lines more efficiently than the parental rAAV5.

Dynamic Contrast-Enhanced MRI Assessing Antifibrotic Therapeutic Effects of Pancreatic Fibrosis with Curcumin - An Experimental Study at 11.7 T.

Rationale And Objectives: Pancreatic fibrosis is the hallmark of chronic pancreatitis (CP), which is associated with microcirculatory disturbance. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess the perfusion and permeability of the pancreas by providing information about microcirculation. We hypothesize that DCE-MRI parameters can be utilized to assess pancreatic fibrosis and may furthermore provide an opportunity to evaluate response to antifibrotic treatment with curcumin.

Lack of Incremental Prognostic Value of Pericoronary Adipose Tissue Computed Tomography Attenuation Beyond Coronary Artery Disease Reporting and Data System for Major Adverse Cardiovascular Events in Patients With Acute Chest Pain.

Background: Pericoronary adipose tissue (PCAT) and Coronary Artery Disease Reporting and Data System (CAD-RADS) category had prognostic values for major adverse cardiovascular events (MACEs). However, little is known about the difference between CAD-RADS and PCAT computed tomography (CT) attenuation for predicting MACEs. This study was to compare the prognostic value of PCAT and CAD-RADS for MACEs in patients with acute chest pain.

Selective permeation up a chemical potential gradient to enable an unusual solvent purification modality.

The need for energy-efficient recovery of organic solutes from aqueous streams is becoming more urgent as chemical manufacturing transitions toward nonconventional and bio-based feedstocks and processes. In addition to this, many aqueous waste streams contain recalcitrant organic contaminants, such as pharmaceuticals, industrial solvents, and personal care products, that must be removed prior to reuse. We observe that rigid carbon membrane materials can remove and concentrate organic contaminants via an unusual liquid-phase membrane permeation modality.

AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice.

Gene therapy is a potentially curative medicine for many currently untreatable diseases, and recombinant adeno-associated virus (rAAV) is the most successful gene delivery vehicle for in vivo applications. However, rAAV-based gene therapy suffers from several limitations, such as constrained DNA cargo size and toxicities caused by non-physiological expression of a transgene. Here we show that rAAV delivery of a suppressor tRNA (rAAV.

Efficient and Precise Processing of the Optimized Primary Artificial MicroRNA in a Huntingtin-Lowering Adeno-Associated Viral Gene Therapy and in Mice and Nonhuman Primates.

Huntington's disease is a fatal neurodegenerative disorder caused by an inherited mutation in the huntingtin () gene comprising an expanded cytosine-adenine-guanine (CAG) trinucleotide repeat sequence that results in a pathogenic huntingtin protein. Adeno-associated viral (AAV) gene therapy containing a primary artificial microRNA (pri-amiRNA) specifically targeting messenger RNA (mRNA) has the potential to provide long-lasting therapeutic benefit, through durable reduction of mutant expression after a single administration. The efficiency and precision of processing of the pri-amiRNA precursor to the mature guide (G) strand by transduced cells are critical for specific and potent mRNA lowering.

Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension.

Background: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear.

Methods: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes.

Optimizing Positivity Thresholds for a Risk-Adapted Screening Strategy in Colorectal Cancer Screening.

Introduction: Risk-adapted screening combining the Asia-Pacific Colorectal Screening score, fecal immunochemical test (FIT), and colonoscopy improved the yield of colorectal cancer screening than FIT. However, the optimal positivity thresholds of risk scoring and FIT of such a strategy warrant further investigation.

Methods: We included 3,407 participants aged 50-74 years undergoing colonoscopy from a colorectal cancer screening trial.

Iterative single-cell multi-omic integration using online learning.

Integrating large single-cell gene expression, chromatin accessibility and DNA methylation datasets requires general and scalable computational approaches. Here we describe online integrative non-negative matrix factorization (iNMF), an algorithm for integrating large, diverse and continually arriving single-cell datasets. Our approach scales to arbitrarily large numbers of cells using fixed memory, iteratively incorporates new datasets as they are generated and allows many users to simultaneously analyze a single copy of a large dataset by streaming it over the internet.

Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China: A Real-World Nationwide Registry.

Background And Purpose: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population.

Methods: We conducted a prospective registry of EVT at 111 centers in China.

Total mercury concentration in placental tissue, a good biomarker of prenatal mercury exposure, is associated with risk for neural tube defects in offspring.

Objective: To examine the role of total mercury (T-Hg) in placenta as a biomarker of prenatal mercury (Hg) exposure and determine the association between prenatal Hg exposure and risk for neural tube defects (NTDs) in offspring.

Methods: Total Hg concentrations in placental tissue were detected in 408 NTD cases and 593 healthy controls enrolled in Shanxi province in northern China. Methylmercury (MeHg) and T-Hg were also detected in the umbilical cord of 147 NTD cases and 140 healthy controls.

Comparison of the two up-to-date sequencing technologies for genome assembly: HiFi reads of Pacific Biosciences Sequel II system and ultralong reads of Oxford Nanopore.

Background: The availability of reference genomes has revolutionized the study of biology. Multiple competing technologies have been developed to improve the quality and robustness of genome assemblies during the past decade. The 2 widely used long-read sequencing providers-Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT)-have recently updated their platforms: PacBio enables high-throughput HiFi reads with base-level resolution of >99%, and ONT generated reads as long as 2 Mb.

Application of liver acquisition with volume acceleration enhanced sequence in improving the accuracy of reassessing organ-invasive rectal mucinous adenocarcinoma after chemoradiation.

Objectives: To explore the ability of liver acquisition with volume acceleration contrast-enhanced sequence (LAVA-ce) to improve the accuracy of reassessing adjacent organ involvement by rectal mucinous adenocarcinoma (MC) after neoadjuvant therapy (NAT).

Methods: This study retrospectively enrolled twenty-five patients with MC who underwent pre- and post-NAT MRI, were staged as T4b using pre-NAT T weighted imaging, received NAT and underwent radical resection. All MR images were divided into two schemes, T weighted plus diffusion weighted imaging (TD protocol) and plus LAVA-ce (TDL protocol).

Plasma Proteomics Identify Biomarkers and Pathogenesis of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis. However, little is known about the pathogenesis and biomarkers of COVID-19. Here, we profiled host responses to COVID-19 by performing plasma proteomics of a cohort of COVID-19 patients, including non-survivors and survivors recovered from mild or severe symptoms, and uncovered numerous COVID-19-associated alterations of plasma proteins.

Novel Acute Retinal Artery Ischemia and Reperfusion Model in Nonhuman Primates.

Background And Purpose: The retina, as an externally located neural tissue, offers unique advantages in investigating the effect of therapeutic intervention on the brain. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in nonhuman primates.

Methods: Acute retinal artery ischemia and reperfusion was induced by injecting an autologous clot into the ophthalmic artery of adult rhesus monkeys, and recanalization was achieved by focal thrombolysis with tPA (tissue-type plasminogen activator).

The Feasibility of Using a Smartphone Magnetometer for Assisting Needle Placement.

Minimally invasive surgical procedures often require needle insertion. For these procedures, efficacy greatly depends on precise needle placement. Many methods, such as optical tracking and electromagnetic tracking, have been applied to assist needle placement by tracking the real-time position information of the needle.

Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis.

Background and Purpose- Early use of antiplatelet drugs within 24 hours after intravenous thrombolysis (IVT) has always been a confusing clinical problem. The purpose of this study was to assess the safety and efficacy of early low-dose tirofiban treatment in patients with early neurological deterioration (END) within the first 24 hours after IVT. Methods- This was a retrospective analysis of prospectively collected data of 1764 consecutive patients with acute ischemic stroke treated with IVT between January 2017 and September 2018.