The Effect of Inhaled Beta-2 Agonists on Heart Rate in Patients With Asthma: Sensor-Based Observational Study.

Background: Beta-2 agonists play an important role in the management of asthma. Inhaled long-acting beta-2 agonists (LABAs) and short-acting beta-2 agonists (SABAs) cause bronchodilation by stimulating adrenoceptors. These receptors are also present in cardiac cells and, as a side effect, could also be stimulated by inhaled beta-2 agonists.

Body Weight Gain Associated With Alectinib in Patients With ALK+ Non-Small Cell Lung Cancer: Pooled Analysis of Individual Patient Data From Four Prospective Clinical Trials.

Purpose: Weight gain is a known adverse event (AE) of alectinib. This study evaluates the progression of actual weight gain over time and explores its association with baseline characteristics.

Methods: A pooled analysis of individual patient data from four clinical trials (ALEX, J-ALEX, ALUR, and ML29453) was conducted.

Residual risk prediction in anticoagulated patients with atrial fibrillation using machine learning: A report from the GLORIA-AF registry phase II/III.

Background: Although oral anticoagulation decreases the risk of thromboembolism in patients with atrial fibrillation (AF), a residual risk of thrombotic events still exists. This study aimed to construct machine learning (ML) models to predict the residual risk in these patients.

Methods: Patients with newly diagnosed non-valvular AF were collected from the Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry.

Two Cases of Intraocular Undifferentiated Pleomorphic Sarcoma.

Introduction: Undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma, is a high-grade soft tissue sarcoma arising from mesenchymal stem cells. UPSs are rare and account for about 5% of all soft tissue sarcoma. UPSs arising in the head and neck are especially rare, comprising 1-3% of all UPSs.

Expert Opinions on Uveal Melanoma: Insights from the 58th Ophthalmic Oncology Group Meeting.

Introduction: Clear evidence for the best clinical management of uveal melanoma is lacking in some areas. Therefore, reports on expert opinions in the field can be valuable.

Methods: A questionnaire comprising 10 questions was distributed to potential participants of the 58th Ophthalmic Oncology Group Meeting in Stockholm, Sweden, in June 2024.

The Utility of Total Thrombus-Formation Analysis System (T-TAS) in the Thrombosis and Hemostasis Field: A Scoping Review.

Background: A wide variety of laboratory hemostasis tests is available, but the majority is plasma-based, static and unable to assess platelet function and fibrin formation simultaneously. The Total Thrombus-Formation Analysis System (T-TAS) is a microchip-based flow chamber system that simulates in vivo conditions for evaluating whole blood thrombogenicity.

Aim: A comprehensive overview of its applicability in different thrombosis and hemostasis related clinical situations is lacking and therefore this scoping review was performed.

History of antineutrophil cytoplasmic autoantibodies : Milestones in rheumatology.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are autoimmune inflammatory small-vessel disorders with potentially life-threatening organ manifestations. Recent disease definitions and classification criteria allow distinction between granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and non-granulomatous microscopic polyangiitis (MPA). The discovery of ANCA-autoantibodies directed against proteolytic enzymes of neutrophil granules-has enabled earlier diagnosis of AAV and paved the way to stage-adapted treatments.

Myeloid effector cells in cancer.

The role of myeloid cells in tumor immunity is multifaceted. While dendritic cells support T cell-mediated tumor control, the highly heterogenous populations of macrophages, neutrophils, and immature myeloid cells were generally considered immunosuppressive. This view has led to effective therapies reinvigorating tumor-reactive T cells; however, targeting the immunosuppressive effects of macrophages and neutrophils to boost the cancer immunity cycle was clinically less successful.

Office-Based Serial Intralesional Steroid Injections in Benign Subglottic Stenosis-First Results.

Objective: Serial intralesional steroid injections (SILSI) are increasingly used in the treatment of idiopathic subglottic stenosis (iSGS) and auto-immune related subglottic stenosis (SGS), which are both known for their high rate of recurrences. SILSI could potentially prolong the time to re-intervention. We evaluated the effects of adjuvant SILSI in iSGS and auto-immune related SGS-patients on time to reintervention and spirometry results.

The effect of sleep and shift work on the primary immune response to messenger RNA-based COVID-19 vaccination.

Shift work can cause circadian misalignment, which often results in sleeping problems and has been associated with immune dysfunction. To better understand the impact of shift work on a primary immune response to vaccination, we compared severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific humoral and cellular immune responses after one injection of the messenger RNA (mRNA)-1273 vaccine between day workers (n = 24) and night shift workers (n = 21). In addition, duration and quality of sleep were assessed for a period of 7 days around the time of vaccination using actigraphy and daily sleep diaries, and their relationship with immunogenicity of mRNA-1273 vaccination was studied.

Comparing the construct validity of measurement instruments for pain and stiffness in patients with axial spondyloartwhritis: cross-sectional analysis in the OASIS cohort.

Objectives: To compare the construct validity, including discrimination between known groups, of three pain and three morning stiffness (MS) measurement instruments.

Methods: Patients with radiographic axial spondyloarthritis with 8-year data from the Outcome in Ankylosing Spondylitis International Study cohort were assessed cross-sectionally. Three instruments for pain and three for MS, all self-reported and scored 0-10, were compared.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Precision genome editing using combinatorial viral vector delivery of CRISPR-Cas9 nucleases and donor DNA constructs.

Genome editing based on programmable nucleases and donor DNA constructs permits introducing specific base-pair changes and complete transgenes or live-cell reporter tags at predefined chromosomal positions. A crucial requirement for such versatile genome editing approaches is, however, the need to co-deliver in an effective, coordinated and non-cytotoxic manner all the required components into target cells. Here, adenoviral (AdV) and adeno-associated viral (AAV) vectors are investigated as delivery agents for, respectively, engineered CRISPR-Cas9 nucleases and donor DNA constructs prone to homologous recombination (HR) or homology-mediated end joining (HMEJ) processes.

Practical and statistical aspects of subgroup analyses in surgical neuro-oncology: A comprehensive review from the PIONEER Consortium.

Subgroup analyses are essential to generate new hypotheses or to estimate treatment effects in clinically meaningful subgroups of patients. They play an important role in taking the next step towards personalized surgical treatment for brain tumor patients. However, subgroup analyses must be used with consideration and care because they have significant potential risks.

The DETECTION project part 1: An international Delphi survey about diagnostics and treatment of anterior mediastinal cystic lesions.

Background: Differentiating benign anterior mediastinal cysts from malignancies is challenging in clinical practice. International guidelines on optimal diagnostics and treatment for anterior mediastinal cystic lesions are lacking. The first part of the DETECTION project focuses on possible heterogeneity in diagnostics and treatment of anterior mediastinal cystic lesions among international thoracic medical experts.

Sex-based differences in risk of revision for infection after hip, knee, shoulder, and ankle arthroplasty in osteoarthritis patients: a multinational registry study of 4,800,000 implants.

Background And Purpose:  We aimed to determine sex differences for periprosthetic joint infections after primary arthroplasty of the hip, knee, ankle, and shoulder in osteoarthritis patients in an international perspective.

Methods:  This is a multinational combined arthroplasty registry study. Each arthroplasty registry performed Cox-regression analysis of their data and reported the crude and adjusted hazard ratios (HR) with an a priori designed data form.

The Correlation Between Fear Avoidance Beliefs and Physical Activity in Unilateral Vestibulopathies.

Background And Purpose: In individuals with unilateral vestibulopathy (UVP), physical activity (PA) is recommended to stimulate central vestibular compensation. However, the presence of fear avoidance beliefs might negatively influence PA. The objectives of this study were to investigate the relationship between fear avoidance beliefs and PA and to compare PA levels between individuals with UVP in an acute/subacute vs chronic phase.

Pessary or cerclage (PC study) to prevent recurrent preterm birth: a non-inferiority, randomised controlled trial.

Background: Previous spontaneous preterm birth (sPTB) is a strong risk indicator for recurrent preterm birth (PTB). Cervical cerclage is an accepted intervention to prevent recurrent PTB in high risk patients. Cervical pessary might be a less invasive alternative.

Coronary angiography: a review of the state of the art and the evolution of angiography in cardio therapeutics.

Traditionally, coronary angiography was restricted to visual estimation of contrast-filled lumen in coronary obstructive diseases. Over the previous decades, considerable development has been made in quantitatively analyzing coronary angiography, significantly improving its accuracy and reproducibility.  Notably, the integration of artificial intelligence (AI) and machine learning into quantitative coronary angiography (QCA) holds promise for further enhancing diagnostic accuracy and predictive capabilities.

Cannabis combined with oxycodone for pain relief in fibromyalgia pain: a randomized clinical self-titration trial with focus on adverse events.

Objectives: We determined whether adding cannabis to oxycodone for chronic non-cancer pain management could reduce treatment-related adverse effects (AEs) while maintaining effective analgesia.

Methods: In this open-label study, fibromyalgia patients aged ≥18 years were randomized to receive 5 mg oxycodone tablets (max. four times/day), 150 mg of inhaled cannabis containing 6.

Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an excess of lipids, mainly triglycerides, in the liver and components of the metabolic syndrome, which can lead to cirrhosis and liver cancer. While there is solid epidemiological evidence that MASLD clusters with cardiometabolic disease, several leading genetic risk factors for MASLD do not increase the risk of cardiovascular disease, suggesting no causal relationship between MASLD and cardiometabolic derangement. In this work, we leveraged measurements of visceral adiposity identifying 27 previously unknown genetic loci associated with MASLD (n = 36,394), six replicated in four independent cohorts (n = 3,903).

DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (alloSCT) provides a curative treatment option for hematological malignancies. After HLA-matched alloSCT, donor-derived T cells recognize minor histocompatibility antigens (MiHAs), which are polymorphic peptides presented by HLA on patient cells. MiHAs are absent on donor cells due to genetic differences between patient and donor.

Site-Specific Glyco-Tagging of Native Proteins for the Development of Biologicals.

Glycosylation is an attractive approach to enhance biological properties of pharmaceutical proteins; however, the precise installation of glycans for structure-function studies remains challenging. Here, we describe a chemoenzymatic methodology for glyco-tagging of proteins by peptidoligase catalyzed modification of the -terminus of a protein with a synthetic glycopeptide ester having an -acetyl-glucosamine (GlcNAc) moiety to generate an -GlcNAc modified protein. The GlcNAc moiety can be elaborated into complex glycans by -glycosylation using well-defined sugar oxazolines and mutant forms of endo β--acetylglucosaminidases (ENGases).