Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences.

Evaluating the need for standardised disease manifestation categories in patients infected with the tick-borne encephalitis virus: A Delphi panel.

Categorization systems for tick-borne encephalitis virus (TBEV) infection lack consistency in classifying disease severity. To evaluate the need for a standard, consensus-based categorisation system for TBEV infection across subtypes, we gathered an expert panel of clinicians and scientists with diverse expertise in TBEV infection. Consensus was sought using the Delphi technique, which consisted of 2 web-based survey questionnaires and a final, virtual, consensus-building exercise.

Bereavement and type 1 diabetes in childhood: a register-based cohort study in Sweden.

Aims/hypothesis: The potential impact of childhood bereavement-a severe psychological stressor-on childhood type 1 diabetes development remains unclear. Here, we aimed to bridge this knowledge gap and assess whether bereavement characteristics influenced any impact.

Methods: We conducted a register-based cohort study encompassing 3,598,159 children born in Sweden between 1987 and 2020.

Diagnostic Performance of Clinical and Routine Laboratory Data in Acute Mesenteric Arterial Occlusion-An International Multicenter Study.

Background: There are no clinical or laboratory markers that can diagnose acute mesenteric ischemia (AMI) accurately. This study aimed to find differences in clinical and laboratory markers between arterial occlusive AMI and other acute abdominal diseases where AMI was initially suspected.

Methods: This was a post hoc study of an international prospective multicenter study where data on patients with suspected AMI were collected.

Cardiac biomarkers for detection of coronary artery disease in the community.

To investigate whether coronary artery disease (CAD) burden is associated with plasma levels of the myocardial biomarkers Troponin I (TropI) and NT-proBNP in a large population-based sample using a cross-sectional design. Coronary computerized tomography (CT) angiography was performed in 25,859 subjects without a history of atherosclerotic disease from SCAPIS study (age 50-65, 52% women). TropI and NT-proBNP were measured in plasma.

scTrends: A living review of commercial single-cell and spatial 'omic technologies.

Understanding the rapidly evolving landscape of single-cell and spatial omic technologies is crucial for advancing biomedical research and drug development. We provide a living review of both mature and emerging commercial platforms, highlighting key methodologies and trends shaping the field. This review spans from foundational single-cell technologies such as microfluidics and plate-based methods to newer approaches like combinatorial indexing; on the spatial side, we consider next-generation sequencing and imaging-based spatial transcriptomics.

Consensus Report on the Use of Continuous Glucose Monitoring in Chronic Kidney Disease and Diabetes.

This report represents the conclusions of 15 experts in nephrology and endocrinology, based on their knowledge of key studies and evidence in the field, on the role of continuous glucose monitors (CGMs) in patients with diabetes and chronic kidney disease (CKD), including those receiving dialysis. The experts discussed issues related to CGM accuracy, indications, education, clinical outcomes, quality of life, research gaps, and barriers to dissemination. Three main goals of management for patients with CKD and diabetes were identified: (1) greater use of CGMs for better glycemic monitoring and management, (2) further research evaluating the accuracy, feasibility, outcomes, and potential value of CGMs in patients with end-stage kidney disease (ESKD) on hemodialysis, and (3) equitable access to CGM technology for patients with CKD.

Incidence of SARS-CoV-2 Infection Among European Healthcare Workers and Effectiveness of the First Booster COVID-19 Vaccine, VEBIS HCW Observational Cohort Study, May 2021-May 2023.

European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up.

Outcomes of Mechanical Thrombectomy in Patients With Acute Basilar Artery Occlusion With Mild to Moderate Symptoms.

Background And Objectives: The benefit of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) with basilar artery occlusion (BAO) and a baseline National Institute of Health Stroke Scale (NIHSS) score <10 is unclear because this subpopulation has been substantially excluded from large clinical trials. The aim of our study was to determine whether MT ± IV thrombolysis (IVT) improves functional outcomes compared with IVT alone in patients with BAO and a NIHSS score <10.

Methods: We emulated a hypothetical trial including adult patients with BAO, a baseline NIHSS score <10, and prestroke modified Rankin scale (mRS) scores 0-2, comparing MT (±IVT) with IVT alone.

Device-Measured 24-Hour Movement Behaviors and Blood Pressure: A 6-Part Compositional Individual Participant Data Analysis in the ProPASS Consortium.

Background: Blood pressure (BP)-lowering effects of structured exercise are well-established. Effects of 24-hour movement behaviors captured in free-living settings have received less attention. This cross-sectional study investigated associations between a 24-hour behavior composition comprising 6 parts (sleeping, sedentary behavior, standing, slow walking, fast walking, and combined exercise-like activity [eg, running and cycling]) and systolic BP (SBP) and diastolic BP (DBP).

A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T proliferation and anti-tumor immunity in mice.

Current antibody-based immunotherapy depends on tumor antigen shedding for proper T cell priming. Here we select a novel human CD40 agonistic drug candidate and generate a bispecific antibody, herein named BiA9*2_HF, that allows for rapid antibody-peptide conjugate formation. The format is designed to facilitate peptide antigen delivery to CD40 expressing cells combined with simultaneous CD40 agonistic activity.

Vemurafenib inhibits the replication of diabetogenic enteroviruses in intestinal epithelial and pancreatic beta cells.

Enteroviruses, which infect via the gut, have been implicated in type 1 diabetes (T1D) development. Prolonged faecal shedding of enterovirus has been associated with islet autoimmunity. Additionally, enteroviral proteins and viral RNA have been detected in the pancreatic islets of individuals with recent-onset T1D, implicating their possible role in beta cell destruction.

Teamwork in Rural Emergency Health Care: A Simulation-Based Cross-over Study of Co-located and Distributed Teams.

Introduction: Despite the increasing use of distributed healthcare teams, performance evaluation is largely lacking. This study examined rural emergency health care in Sweden to determine the effect of teams being either co-located or distributed with remote physicians accessible via telemedicine.

Method: In this crossover study, 17 three-person teams were video recorded during co-located and distributed simulated scenarios.

The 75-Year Anniversary of the Department of Physiology and Pharmacology at Karolinska Institutet-Examples of Recent Accomplishments and Future Perspectives.

Karolinska Institutet is a medical university encompassing 21 departments distributed across three departmental or campus groups. Pharmacological research has a long and successful tradition at the institute with a multitude of seminal findings in the areas of neuronal control of vasodilatation, cardiovascular pharmacology, neuropsychopharmacology, receptor pharmacology, and pharmacogenomics that resulted in, among many other recognitions, two Nobel prizes in Physiology and Medicine, one in 1970 to Ulf von Euler for his discovery of the processes involved in storage, release, and inactivation of neurotransmitters and the other in 1982 to Sune Bergström and Bengt Samuelsson for their work on prostaglandins and the discovery of leukotrienes. Pharmacology at Karolinska Institutet has over the last decade been ranked globally among the top 10 according to the QS World University Ranking.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide.

Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety.

Background: Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non-psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder.

Methods: Individuals aged 15-65 with bipolar disorder were identified from Finnish national health registers in 1996-2018.

Multiplexed spatial mapping of chromatin features, transcriptome, and proteins in tissues.

The phenotypic and functional states of a cell are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome, and metabolome. Spatial omics approaches have enabled the capture of information from different molecular layers directly in the tissue context. However, current technologies are limited to map one to two modalities at the same time, providing an incomplete representation of cellular identity.