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.

Identification of cell type-specific cell-penetrating peptides through in vivo phage display leveraged by next generation sequencing.

Vascular anomalies (VA) refer to abnormal blood or lymphatic vessel architecture, most often as a result of dysregulated growth. Venous malformations (VM), a subgroup of VAs, are triggered by activating mutations in the Angiopoietin/TIE2-PI3K/AKT/mTOR signaling pathway with TIE2 L914F (gene name TEK) being one of the most frequent mutations in patients with VMs. Although systemic targeting of the overactivated pathway is possible, it would be a therapeutic advantage to restrict treatment to only the affected lesions.

Bulevirtide Monotherapy Is Safe and Well Tolerated in Chronic Hepatitis Delta: An Integrated Safety Analysis of Bulevirtide Clinical Trials at Week 48.

Background And Aims: The safety and tolerability of bulevirtide (BLV), a novel entry inhibitor of hepatitis delta virus, were evaluated in an integrated analysis of clinical trial results from patients with chronic hepatitis delta (CHD).

Methods: Week 48 on-treatment clinical and laboratory results from two Phase 2 trials (MYR203 [NCT02888106] and MYR204 [NCT03852433]) and one Phase 3 trial (MYR301 [NCT03852719]) were pooled (N = 269). Patients were grouped as follows: BLV 2 mg (n = 64), BLV 10 mg (n = 115), pegylated interferon-alfa (n = 39) and control (n = 51).

Optimized prime editing of the Alzheimer's disease-associated APOE4 mutation.

Gene editing strategies to safely and robustly modify the Alzheimer's disease-associated APOE4 isoform are still lacking. Prime editing (PE) enables the precise introduction of genetic variants with minimal unintended editing and without donor templates. However, it requires optimization for each target site and has not yet been applied to APOE4 gene editing.

Evaluating the Pathogenic Potential of IgE Targeting Cross-Reactive Carbohydrate Determinants in Dogs.

Cross-reactive carbohydrate determinants (CCDs) are complex N-glycans shared among allergens of plant, insect venom, and nematode origin. In allergic humans, IgE anti-CCD often develop and cause discrepancies between serological and skin tests. Overall, CCD-IgE are believed to be of low pathogenic relevance.

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.

Lower Surgical Volume Reduces the Odds of Performing Meniscus Repair for Tears During Primary Anterior Cruciate Ligament Reconstruction.

Purpose: To investigate the influence of surgical volume, and various patient-, injury-, and surgery-related factors, on meniscal treatment strategies in primary anterior cruciate ligament reconstruction (ACLR).

Methods: This retrospective cohort study analyzed patients with concomitant meniscal injuries undergoing primary ACLR, from 2008 to 2022, using data from the Swedish National Knee Ligament Registry. Surgeons and clinics were stratified by total caseload (cutoff: 50 ACLRs/surgeon, 500 ACLRs/clinic) and annual volume (cutoff: 29 ACLRs/year/surgeon, 56 ACLRs/year/clinic).

Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles.

Clinical implementation of therapeutic genome editing relies on efficient in vivo delivery and the safety of CRISPR-Cas tools. Previously, we identified PsCas9 as a Type II-B family enzyme capable of editing mouse liver genome upon adenoviral delivery without detectable off-targets and reduced chromosomal translocations. Yet, its efficacy remains insufficient with non-viral delivery, a common challenge for many Cas9 orthologues.

Design and cohort characteristics of TRACK, a prospective study of hyperkalaemia management decision-making.

Background: Guideline-recommended hyperkalaemia management includes dietary potassium (K) restriction, bicarbonate correction, diuretics and K binders with dose reduction of renin-angiotensin-aldosterone system inhibitors as a last resort. The extent to which these recommendations are implemented is uncertain, as real-world data on hyperkalaemia management are limited. The Tracking Treatment Pathways in Adult Patients with Hyperkalemia (TRACK) study is a multinational, prospective, longitudinal study that is being conducted to address this knowledge gap.

Validation of a Multiplex Molecular Macroarray for the Determination of Allergen-Specific IgE Sensitizations in Dogs.

Detecting IgE sensitizations in the serum of allergic dogs is commonly performed using allergen extracts, but these are difficult to standardize. This article details the development and validation of the Pet Allergy Xplorer (PAX; Nextmune, Stockholm, Sweden), the first multiplex macroarray for the detection of IgE sensitization in dogs using allergen extracts and molecular components; the PAX is derived from the Allergy Xplorer (ALEX; MacroArray Diagnostics, Vienna, Austria). The selection of allergens, cartridge processing, strategy for identifying and blocking IgE directed against cross-reactive carbohydrate determinants (CCDs), and the method used for determining the positivity threshold are described.

Subclassification of obesity for precision prediction of cardiometabolic diseases.

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000).

Nanomechanical Crystalline AlN Resonators with High Quality Factors for Quantum Optoelectromechanics.

High-quality factor (Q) mechanical resonators are crucial for applications where low noise and long coherence time are required, as mirror suspensions, quantum cavity optomechanical devices, or nanomechanical sensors. Tensile strain in the material enables the use of dissipation dilution and strain engineering techniques, which increase the mechanical quality factor. These techniques have been employed for high-Q mechanical resonators made from amorphous materials and, recently, from crystalline materials such as InGaP, SiC, and Si.

Anaemia and quality of life in chronic kidney disease: a consensus document from the European Anaemia of CKD Alliance.

Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events.

Development of Fewer Falls in MS-An Online, Theory-Based, Fall Prevention Self-Management Programme for People With Multiple Sclerosis.

Objective: The aim of this study was to describe the process used to develop a theory-based, online fall prevention self-management programme for ambulatory and non-ambulatory people with multiple sclerosis (pwMS).

Methods: The development process was guided by the Medical Research Council framework of complex interventions and began with a scoping review of the literature on self-management of falls in pwMS. Subsequent phases of development were performed through iterative and concurrent processes and were informed by the perspectives of pwMS and healthcare professionals with MS expertise.

Rise in fasting and dynamic glucagon levels in children and adolescents with obesity is moderate in subjects with impaired fasting glucose but accentuated in subjects with impaired glucose tolerance or type 2 diabetes.

Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG).

Materials And Methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.

Normoglycemia and physiological cortisone level maintain glucose homeostasis in a pancreas-liver microphysiological system.

Current research on metabolic disorders and diabetes relies on animal models because multi-organ diseases cannot be well studied with standard in vitro assays. Here, we have connected cell models of key metabolic organs, the pancreas and liver, on a microfluidic chip to enable diabetes research in a human-based in vitro system. Aided by mechanistic mathematical modeling, we demonstrate that hyperglycemia and high cortisone concentration induce glucose dysregulation in the pancreas-liver microphysiological system (MPS), mimicking a diabetic phenotype seen in patients with glucocorticoid-induced diabetes.

Male fertility restoration: in vivo and in vitro stem cell-based strategies using cryopreserved testis tissue: a scoping review.

Importance: Advances in the treatment of childhood cancer have significantly improved survival rates, with more than 80% of survivors reaching adulthood. However, gonadotoxic cancer treatments endanger future fertility, and prepubertal males have no option to preserve fertility by sperm cryopreservation. In addition, boys with cryptorchidism are at risk of compromised fertility in adulthood.

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

Introduction: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases.

Methods: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative.

Results: PVS was significantly associated with sEF (c = -0.

Cannabinoid 2 Receptor Activation Protects against Diabetic Cardiomyopathy through Inhibition of AGE/RAGE-Induced Oxidative Stress, Fibrosis, and Inflammasome Activation.

Oxidative stress, fibrosis, and inflammasome activation from advanced glycation end product (AGE)-receptor of advanced glycation end product (RAGE) interaction contribute to diabetic cardiomyopathy (DCM) formation and progression. Our study revealed the impact of -caryophyllene (BCP) on activating cannabinoid type 2 receptors (CB2Rs) against diabetic complication, mainly cardiomyopathy and investigated the underlying cell signaling pathways in mice. The murine model of DCM was developed by feeding a high-fat diet with streptozotocin injections.

Patient's Height and Sex Predict Graft Diameter: A Cohort Study of 4,519 Patients With Primary Anterior Cruciate Ligament Reconstruction Using Semitendinosus Autograft.

Purpose: To determine whether anthropometric measurements (height and weight), sex, age, and preinjury Tegner Activity Scale (TAS) were predictors of the quadrupled semitendinosus (ST) graft diameter in primary anterior cruciate ligament reconstruction.

Methods: A total of 4,519 patients who underwent primary anterior cruciate ligament reconstruction with a quadrupled ST autograft were included. Anthropometric measurements (height and weight), sex, age, and preinjury TAS were collected.

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD 'human proximity score' to define their metabolic relevance and ability to induce MASH-fibrosis.