Endovascular versus Best Medical Treatment for Acute Carotid Occlusion BelOw Circle of Willis (ACOBOW): The ACOBOW Study.

Background Symptomatic acute occlusions of the internal carotid artery (ICA) below the circle of Willis can cause a variety of stroke symptoms, even if the major intracranial cerebral arteries remain patent; however, outcome and safety data are limited. Purpose To compare treatment effects and procedural safety of endovascular treatment (EVT) and best medical treatment (BMT) in patients with symptomatic acute occlusions of the ICA below the circle of Willis. Materials and Methods This retrospective, multicenter cohort study from 22 comprehensive stroke centers in Europe and Asia includes patients treated between January 1, 2008, and December 31, 2022.

Explainable deep learning and virtual evolution identifies antimicrobial peptides with activity against multidrug-resistant human pathogens.

Artificial intelligence (AI) is a promising approach to identify new antimicrobial compounds in diverse microbial species. Here we developed an AI-based, explainable deep learning model, EvoGradient, that predicts the potency of antimicrobial peptides (AMPs) and virtually modifies peptide sequences to produce more potent AMPs, akin to in silico directed evolution. We applied this model to peptides encoded in low-abundance human oral bacteria, resulting in the virtual evolution of 32 peptides into potent AMPs.

INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform.

Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume.

Ethnicity and Socioeconomic Disparities in Clinical Trial Participation for Ovarian Cancer: A Retrospective Observational Study in London.

Background: Ethnic and socioeconomic disparities in cancer outcomes are exacerbated by clinical trial underrepresentation. This study aims to identify inequalities in ethnicity and socioeconomic features among ovarian cancer clinical trial participants in two London cancer centres.

Methods: All ovarian cancer patients treated between 2017 and 2022 were included.

Long-term adherence to a wearable for continuous behavioural activity measuring in the SafeHeart implantable cardioverter defibrillator population.

Aims: Wearable health technologies are increasingly popular. Yet, wearable monitoring only works when devices are worn as intended, and adherence reporting lacks standardization. In this study, we aimed to explore the long-term adherence to a wrist-worn activity tracker in the prospective SafeHeart study and identify patient characteristics associated with adherence.

Deep behavioural representation learning reveals risk profiles for malignant ventricular arrhythmias.

We aimed to identify and characterise behavioural profiles in patients at high risk of SCD, by using deep representation learning of day-to-day behavioural recordings. We present a pipeline that employed unsupervised clustering on low-dimensional representations of behavioural time-series data learned by a convolutional residual variational neural network (ResNet-VAE). Data from the prospective, observational SafeHeart study conducted at two large tertiary university centers in the Netherlands and Denmark were used.

Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

Background: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone.

Novel OX40 and 4-1BB derived spacers enhance CD30 CAR activity and safety in CD30 positive lymphoma models.

The chimeric antigen receptor (CAR) derived from the CD30 specific murine antibody, HRS-3, has produced promising clinical efficacy with a favorable safety profile in the treatment of relapsed or refractory CD30-positive lymphomas. However, persistence of the autologous CAR-T cells was brief, and many patients relapsed a year after treatment. The lack of persistence may be attributed to the use of a wild-type immunoglobulin (Ig)G1 spacer that can associate with Fc receptors.

Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses.

Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links.

Experimental and Theoretical Study of the OH-Initiated Degradation of Piperidine under Simulated Atmospheric Conditions.

The OH-initiated photo-oxidation of piperidine and the photolysis of 1-nitrosopiperidine were investigated in a large atmospheric simulation chamber and in theoretical calculations based on CCSD(T*)-F12a/aug-cc-pVTZ//M062X/aug-cc-pVTZ quantum chemistry results and master equation modeling of the pivotal reaction steps. The rate coefficient for the reaction of piperidine with OH radicals was determined by the relative rate method to be = (1.19 ± 0.

Ocular Manifestations and Outcomes in Children With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Comparison With Adult Patients.

Purpose: To compare the clinical features and visual outcomes in children and adults with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Design: Retrospective comparative case series.

Methods: This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020.

Cardiovascular disease risk assessment using a deep-learning-based retinal biomarker: a comparison with existing risk scores.

Aims: This study aims to evaluate the ability of a deep-learning-based cardiovascular disease (CVD) retinal biomarker, Reti-CVD, to identify individuals with intermediate- and high-risk for CVD.

Methods And Results: We defined the intermediate- and high-risk groups according to Pooled Cohort Equation (PCE), QRISK3, and modified Framingham Risk Score (FRS). Reti-CVD's prediction was compared to the number of individuals identified as intermediate- and high-risk according to standard CVD risk assessment tools, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the results.

Pathogenesis of Tobacco-Associated Lung Adenocarcinoma Is Closely Coupled with Changes in the Gut and Lung Microbiomes.

Microbial dysbiosis has emerged as a modulator of oncogenesis and response to therapy, particularly in lung cancer. Here, we investigate the evolution of the gut and lung microbiomes following exposure to a tobacco carcinogen. We performed 16S rRNA-Seq of fecal and lung samples collected prior to and at several timepoints following (nicotine-specific nitrosamine ketone/NNK) exposure in mice that were previously shown to exhibit accelerated lung adenocarcinoma (LUAD) development following NNK exposure.

Pteropine Orthoreovirus, PRV7S (Sikamat Virus) Demonstrates Oncolysis in Nasopharyngeal Carcinoma Cell Lines.

Background: Oncolytic properties had been demonstrated in Mammalian Orthoreovirus (MRV) and Avian Orthorevirus (ARV). Besides MRV and ARV, Pteropine Orthoreovirus (PRV) is also categorized under the genus PRV7S (Sikamat virus) is an orthoreovirus isolated in Malaysia. Present study aims to investigate the oncolytic effects of PRV7S on ranges of nasopharyngeal carcinoma (NPC) cells through apoptosis in comparison to MRV3.

An anti-PD-1-GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy.

Costimulatory receptors such as glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) play key roles in regulating the effector functions of T cells. In human clinical trials, however, GITR agonist antibodies have shown limited therapeutic effect, which may be due to suboptimal receptor clustering-mediated signaling. To overcome this potential limitation, a rational protein engineering approach is needed to optimize GITR agonist-based immunotherapies.

Thrombectomy in Extensive Stroke May Not Be Beneficial and Is Associated With Increased Risk for Hemorrhage.

Background And Purpose: This study evaluates the benefit of endovascular treatment (EVT) for patients with extensive baseline stroke compared with best medical treatment.

Methods: This retrospective, multicenter study compares EVT and best medical treatment for computed tomography (CT)–based selection of patients with extensive baseline infarcts (Alberta Stroke Program Early CT Score ≤5) attributed to anterior circulation stroke. Patients were selected from the German Stroke Registry and 3 tertiary stroke centers.

Re-evaluating absent clinical success after adrenalectomy in unilateral primary aldosteronism.

Background: Adrenalectomy cures unilateral primary aldosteronism, and it improves or cures hypertension. However, a significant proportion of patients are classified with absent clinical success postsurgery, suggesting that surgery was ineffective.

Methods: We assessed all patients 6 to 12 months post-surgery for clinical outcomes using Primary Aldosteronism Surgical Outcomes (PASO), AVIS-2, and CONNsortium criteria.

Bifidobacteria-mediated immune system imprinting early in life.

Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host's immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies.

A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice.

A self-transcribing and replicating RNA (STARR)-based vaccine (LUNAR-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full-length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolongs SARS-CoV-2 spike glycoprotein expression.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.