Sex-Based Differences in Endovascular Thrombectomy Outcomes for Large Ischemic Stroke: A SELECT2 Subanalysis.

Background: Several social and biological factors are shown to differentially affect stroke outcomes between men and women. We evaluated whether clinical outcomes and endovascular thrombectomy (EVT) treatment effects differed between the sexes in patients presenting with large ischemic stroke.

Methods: The SELECT2 trial (A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke) was a randomized controlled trial assessing the efficacy and safety of EVT in patients with large strokes across the United States, Canada, Europe, Australia, and New Zealand between October 2019 and September 2022.

A Comparison of Optical Coherence Tomography Angiography Metrics and Artifacts on Scans of Different Sizes in Diabetic Macular Ischemia.

Purpose: Changes in the foveal avascular zone (FAZ) metrics over time are key outcome measures for clinical trials in diabetic macular ischemia (DMI). However, artifacts and automatically delineated FAZ measurements may influence the results. We aimed to compare the artifact frequency and FAZ metrics on 3 × 3 versus 6 × 6 mm optical coherence tomography angiography (OCTA) macular scans in patients with DMI.

Identifying People at High Risk for Severe Aortic Stenosis: Aortic Valve Calcium Versus Lipoprotein(a) and Low-Density Lipoprotein Cholesterol.

Background: Aortic valve calcification (AVC), Lp(a) [lipoprotein(a)], and low-density lipoprotein cholesterol (LDL-C) are associated with severe aortic stenosis (AS). We aimed to determine which of these risk factors were most strongly associated with the risk of incident severe AS.

Methods: A total of 6792 participants from the MESA study (Multi-Ethnic Study of Atherosclerosis) had computed tomography-quantified AVC, Lp(a), and LDL-C values at MESA visit 1 (2000-2002).

Exposing the molecular heterogeneity of glycosylated biotherapeutics.

The heterogeneity inherent in today's biotherapeutics, especially as a result of heavy glycosylation, can affect a molecule's safety and efficacy. Characterizing this heterogeneity is crucial for drug development and quality assessment, but existing methods are limited in their ability to analyze intact glycoproteins or other heterogeneous biotherapeutics. Here, we present an approach to the molecular assessment of biotherapeutics that uses proton-transfer charge-reduction with gas-phase fractionation to analyze intact heterogeneous and/or glycosylated proteins by mass spectrometry.

Dense, Continuous Membrane Labeling and Expansion Microscopy Visualization of Ultrastructure in Tissues.

Lipid membranes are key to the nanoscale compartmentalization of biological systems, but fluorescent visualization of them in intact tissues, with nanoscale precision, is challenging to do with high labeling density. Here, we report ultrastructural membrane expansion microscopy (umExM), which combines a novel membrane label and optimized expansion microscopy protocol, to support dense labeling of membranes in tissues for nanoscale visualization. We validated the high signal-to-background ratio, and uniformity and continuity, of umExM membrane labeling in brain slices, which supported the imaging of membranes and proteins at a resolution of ~60 nm on a confocal microscope.

Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.

Background: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.

Methods: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed.

Risk Factors and Incidence of Serious Infections in Patients With Systemic Lupus Erythematosus Undergoing Rituximab Therapy.

Objective: To evaluate the risk and protective factors of serious infection (SI) in patients with systemic lupus erythematosus (SLE) within 180 days of rituximab (RTX) treatment.

Methods: Patients with SLE treated with RTX were analyzed. SI was defined as any infectious disease requiring hospitalization.

Topographic Correlation of Microperimetry With Structural Characteristics in Diabetic Macular Ischemia.

Purpose: This study aimed to determine the threshold for defining abnormal retinal sensitivity (RS) that correlates with structural changes in diabetic macular ischemia (DMI) patients with stable treated proliferative diabetic retinopathy (PDR).

Design: Prospective cross-sectional study.

Methods: In a single center, we recruited 85 eyes (67 patients) with stable treated PDR with best-corrected visual acuity (BCVA) ≥54 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent 20/80) and optical coherence tomography angiography evidence of DMI.

Coating-Free Culture Medium for Establishing and Maintaining Human Induced Pluripotent Stem Cells.

Cell expansion of human pluripotent stem cells (hPSCs) commonly depends on Matrigel as a coating matrix on two-dimensional (2D) culture plates and 3D microcarriers. However, the xenogenic Matrigel requires sophisticated quality-assurance processes to meet clinical requirements. In this study, we develop an innovative coating-free medium for expanding hPSCs.

Trial of Endovascular Thrombectomy for Large Ischemic Strokes.

Background: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations.

Methods: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging.

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.

Using performance frontiers to differentiate elective and capacity-based surgical services.

Background: Acute care surgery (ACS) model of care delivery has many benefits. However, since the ACS surgeon has limited control over the volume, timing, and complexity of cases, traditional metrics of operating room (OR) efficiency almost always measure ACS service as "inefficient." The current study examines an alternative method-performance fronts-of evaluating changes in efficiency and tests the following hypotheses: (1) in an institution with a robust ACS service, performance front methodology is superior to traditional metrics in evaluating OR throughput/efficiency, and (2) introduction of an ACS service with block time allocation will improve OR throughput/efficiency.

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals.

Reelin Depletion Protects Against Atherosclerosis by Decreasing Vascular Adhesion of Leukocytes.

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Genome-Wide Association Study Highlights as a Novel Locus for Lipoprotein(a) Levels-Brief Report.

Objective: Lp(a) (lipoprotein[a]) is an independent risk factor for cardiovascular diseases and plasma levels are primarily determined by variation at the locus. We performed a genome-wide association study in the UK Biobank to determine whether additional loci influence Lp(a) levels. Approach and Results: We included 293 274 White British individuals in the discovery analysis.

Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.

Background: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.

Methods: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption.

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries.

Hemoglobin β93 Cysteine Is Not Required for Export of Nitric Oxide Bioactivity From the Red Blood Cell.

Background: Nitrosation of a conserved cysteine residue at position 93 in the hemoglobin β chain (β93C) to form S-nitroso (SNO) hemoglobin (Hb) is claimed to be essential for export of nitric oxide (NO) bioactivity by the red blood cell (RBC) to mediate hypoxic vasodilation and cardioprotection.

Methods: To test this hypothesis, we used RBCs from mice in which the β93 cysteine had been replaced with alanine (β93A) in a number of ex vivo and in vivo models suitable for studying export of NO bioactivity.

Results: In an ex vivo model of cardiac ischemia/reperfusion injury, perfusion of a mouse heart with control RBCs (β93C) pretreated with an arginase inhibitor to facilitate export of RBC NO bioactivity improved cardiac recovery after ischemia/reperfusion injury, and the response was similar with β93A RBCs.

Author Correction: Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

The original version of this Article omitted the author Kuan Wang, who is from the 'College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan' and 'Nanyang Environment & Water Research Institute, Nanyang Technological University, Singapore 637141, Singapore.'Also, the author S.H.

Bone Morphogenetic Protein-6 Attenuates Type 1 Diabetes Mellitus-Associated Bone Loss.

Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM-induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow-derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non-T1DM donors and further identified a mechanism involving bone morphogenetic protein-6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells.

A Polymer-Based Extended Release System for Stable, Long-term Intracochlear Drug Delivery.

Objective: Investigate a new polymer-based drug coating suitability for safe intracochlear delivery and ability to maintain long-term physiologically active levels of the corticosteroid fluticasone propionate.

Study Design: In vitro dissolution study to evaluate release profiles of polymer-coated drug particles and in vivo studies using a guinea pig model to measure perilymph drug concentrations at specific time points after implantation with polymer-coated drug particles and evaluate their effect on hearing function.

Methods: Polymer-coated fluticasone propionate (FP) particles were surgically implanted in guinea pigs through the round window membrane into the cochlear scala tympani.

Lower emergency general surgery (EGS) mortality among hospitals with higher-quality trauma care.

Background: Patients undergoing emergency general surgery (EGS) procedures are up to eight times more likely to die than patients undergoing the same procedures electively. This excess mortality is often attributed to nonmodifiable patient factors including comorbidities and physiologic derangements at presentation, leaving few targets for quality improvement. Although the hospital-level traits that contribute to EGS outcomes are not well understood, we hypothesized that facilities with lower trauma mortality would have lower EGS mortality.