Letermovir should be first-line cytomegalovirus prophylaxis in lung transplant recipients.

Universal cytomegalovirus (CMV) prophylaxis is recommended for at-risk lung transplant recipients. Valganciclovir is currently the preferred first-line agent. Valganciclovir-related myelosuppression, however, can lead to drug discontinuation or reduction in anti-metabolite immunosuppression.

Convergence of orphan quality control pathways at a ubiquitin chain-elongating ligase.

Unassembled and partially assembled subunits of multi-protein complexes have emerged as major quality control clients, particularly under conditions of imbalanced gene expression such as stress, aging, and aneuploidy. The factors and mechanisms that eliminate such orphan subunits to maintain protein homeostasis are incompletely defined. Here, we show that the UBR4-KCMF1 ubiquitin ligase complex is required for the efficient degradation of multiple unrelated orphan subunits from the chaperonin, proteasome cap, proteasome core, and a protein targeting complex.

Similar Survival Between Non-Western Immigrant Patients and Danish-Born Patients with Lymphoma: A Danish Population-Based Study.

Purpose: This nationwide Danish cohort study compared overall survival (OS) between non-Western immigrant patients and Danish-born patients with lymphoma in Denmark. Furthermore, differences in clinical and socioeconomic variables were compared, and mediators of OS differences were explored to explain possible outcome differences.

Patients And Methods: The study included a total of 540 non-Western patients and 16,294 Danish-born patients diagnosed with lymphoma in the period 2000-2020.

The long-term risk of immune-related conditions in survivors of diffuse large B-cell lymphoma: A Danish nationwide registry study.

Background: There is limited knowledge of the long-term effects on the immune system after treatment for diffuse large B-cell lymphoma (DLBCL).

Methods: This study included DLBCL patients from the Danish Lymphoma Registry who obtained complete remission (CR) after (R)-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-like immunochemotherapy. Each R CHOP-like treated patient was matched to five comparators from the Danish background population and furthermore compared to R CHOP-like treated patients.

2024 White paper on recent issues in bioanalysis: Impact of LDT in US and IVDR in EU; AI/ML for High Parameter Flow Cytometry; The rise of Olink Technology; CDx for AAV Gene Therapies; Integrative Bioanalysis by Multiple Platforms; Super Sensitive ADA/NAb LBA ( - Recommendations on Advanced Strategies for Biomarkers, IVD/CDx Assays (BAV), Cell Based Assays (CBA), and Ligand-Binding Assays (LBA) - Regulatory Agencies' Input on Biomarkers, IVD/CDx, and Biomarker Assay Validation).

The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Design of ()-3-(5-Thienyl)carboxamido-2-aminopropanoic Acid Derivatives as Novel NMDA Receptor Glycine Site Agonists: Variation in Molecular Geometry to Improve Potency and Augment GluN2 Subunit-Specific Activity.

NMDA receptor ligands have therapeutic potential in neurological and psychiatric disorders. We designed ()-3-(5-thienyl)carboxamido-2-aminopropanoic acid derivatives with nanomolar agonist potencies at NMDA receptor subtypes (GluN12/A-D). These compounds are superagonists at GluN1/2C compared to glycine and partial to full agonists at GluN1/2A and GluN1/2D but display functional antagonism at GluN1/2B due to low agonist efficacy.

A Clinical Care Pathway for Patients With Chronic Mechanical Low Back Pain Having Restorative Neurostimulation for Multifidus Muscle: Description, Patient Compliance, Clinical Outcomes, and Satisfaction in the First Two Years.

Objectives: Restorative neurostimulation for multifidus muscle is a novel therapy for chronic low back pain (CLBP). Optimal outcomes require interdisciplinary follow-up. We describe a clinical care pathway (CPW) for this therapy and report patient compliance, clinical outcomes, and patient satisfaction with the CPW.

Design, synthesis, and screening of an RNA optimized fluorinated fragment library.

Fragment-based screening is an efficient method for early-stage drug discovery. In this study, we aimed to create a fragment library optimized for producing high hit rates against RNA targets. RNA has historically been an underexplored target, but recent research suggests potential for optimizing small molecule libraries for RNA binding.

Descriptives and genetic correlates of eating disorder diagnostic transitions and presumed remission in the Danish registry.

Objective: Eating disorders (EDs) are serious psychiatric disorders with an estimated 3.3 million healthy life-years lost worldwide yearly. Understanding the course of illness, diagnostic transitions and remission, and their associated genetic correlates could inform both ED etiology and treatment.

Prevalence of thoracic degenerative MRI findings and association with pain and disability: a systematic review.

Objectives: To systematically review the literature on the prevalence of degenerative MRI findings in the thoracic spine and their association with pain and disability.

Materials And Methods: The Medline, EMBASE, CINAHL, and CENTRAL databases were searched. Two independent reviewers screened the articles, extracted the data, and assessed the risk of bias (RoB) using a modified version of the Hoy tool for articles on prevalence and QUADAS-2 for articles on associations.

Smoking as a Marker of Comorbid Vulnerability Among Persons with Probable Posttraumatic Stress Disorder Who Engage in Hazardous Drinking.

Persons with posttraumatic stress disorder (PTSD) compared to those without evince high rates of hazardous drinking, or patterns of alcohol consumption that increase the risk for harmful consequences. One potential marker of vulnerability for PTSD-hazardous drinking comorbidity may be smoking behavior. Individuals with PTSD have a higher prevalence of smoking and smoke at higher rates.

Impact of Trial Eligibility Criteria on Outcomes of 1183 Patients With Follicular Lymphoma Treated in the Real-World Setting.

The development of new first-line treatments for patients with follicular lymphoma (FL) is becoming increasingly challenging due to already excellent survival outcomes. The present study investigated the outcomes of patients with FL who underwent contemporary first-line therapies but would not have been eligible for inclusion in recent trials and explored how commonly used in/exclusion criteria impacted their survival outcomes. This study included adult patients diagnosed with FL in the period 2000-2018 registered in the Danish Lymphoma Registry.

Patterns of Medical Diagnoses Before and After a Diagnosis of Anorexia Nervosa: A Danish Nationwide Cohort Study.

Objective: This study investigates the overall pattern and timing of medical diagnoses up to 10 years before an anorexia nervosa (AN) diagnosis and explores differences before and after AN diagnosis aiming to improve early detection.

Method: In this nationwide population-based cohort study, we included all patients diagnosed with incident AN from 1987 to 2018 (n = 13,345) and a 1:10 age- and sex-matched general population comparison cohort, using Danish health registries. Using conditional logistic regression, we calculated odds ratios (ORs) of medical diagnoses up to 10 years before AN diagnosis.

Application of urinary peptide-biomarkers in trauma patients as a predictive tool for prognostic assessment, treatment and intervention timing.

Treatment of severely injured patients represents a major challenge, in part due to the unpredictable risk of major adverse events, including death. Preemptive personalized treatment aimed at preventing these events is a crucial objective of patient management; however, the currently available scoring systems provide only moderate guidance. Biomarkers from proteomics/peptidomics studies hold promise for improving the current situation, ultimately enabling precision medicine based on individual molecular profiles.

Donor C1 Group KIR-ligand inferiority is linked to increased mortality in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide.

Background Aims: In HLA-identical hematopoietic stem cell transplantation (HSCT), HLA-C1 group killer cell immunoglobulin-like receptor (KIR) ligands have been linked to graft-versus-host disease, whereas C2 homozygosity was associated with increased relapses. The differential impact of the recipients versus the donor's HLA-C KIR ligands cannot be determined in HLA-identical HSCT but may be elucidated in the haploidentical setting, in which HLA-C (including the HLA-C KIR ligand group) mismatching is frequently present.

Methods: We retrospectively investigated the effect of recipient versus donor C1 ligand content on survival and complications in post-transplant cyclophosphamide (PTCy)-based haploidentical HSCT (n = 170).

Electron-rich anilines as cleavable linkers for peptides.

We report the development of a new electron-rich aniline (ERA)-based cleavable linker. Anilines can be incorporated into peptides during SPPS and are stable to most reaction conditions. ERA-containing peptides can be cleaved rapidly in the presence of oxidants, such as DDQ, CAN, and NaIO, in 30 min at room temperature.

Maternal postpartum infection risk following induction of labor: A Danish national cohort study.

Introduction: Induction of labor is a common procedure, and in Denmark, approximately one in four vaginal deliveries are induced. The association between induction and maternal postpartum infections such as endometritis, surgical site infection after cesarean section, urinary tract infection, and sepsis has been sparsely investigated. Our objective was to investigate the association between induction of labor and risk of maternal postpartum infection and to identify potential risk factors for infection.

Persistence, severity and reactivity thresholds in fish allergic patients sensitized to parvalbumin.

Background: Fish allergy affects children and adults worldwide and there are transient and persistent phenotypes.

Objective: We aimed to analyze persistence, severity and reactivity thresholds in challenge-confirmed fish allergic patients sensitized to parvalbumin.

Methods: Patients 12-65 years-old reporting immediate reactions to fish, with fish skin prick test ≥5 mm and IgE to cod and carp β-parvalbumins ≥0.

Combinations of job demands are associated with increased risk of depression in clinical veterinary practice: a cross-sectional study.

Background: Veterinarians have a high prevalence of mental health disorders, such as depression. Previous research suggests that veterinarians are highly exposed to emotional demands at work and that these emotional demands are associated with adverse mental health outcomes. However, little is known about the consequences of the simultaneous exposure to emotional demands and other types of job demands in clinical veterinary practice.

Living a Cancer Surveillance Life: A Meta-Ethnographic Synthesis of Everyday Experiences and Ambivalences for Women Living With Hereditary Risk of Breast and/or Ovarian Cancer.

Objective: Women with or at risk of hereditary breast- and ovarian cancer (HBOC) often live a surveillance-focused life from young adulthood. As they navigate a life of heightened medical vigilance, or a "cancer surveillance life," we explore how women with HBOC, as well as their partners and families, experience this particular kind of living through a thorough literature review of existing qualitative research.

Methods: We performed Boolean searches in PubMed, EMBASE, EBSCOhost, PSYCHinfo, Scopus, and Web of Science from April-May 2022, identifying 506 relevant articles.

Efficacy and safety of a 72-h infusion of prostacyclin (1 ng/kg/min) in mechanically ventilated patients with pulmonary infection and endotheliopathy-protocol for the multicenter randomized, placebo-controlled, blinded, investigator-initiated COMBAT-ARF trial.

Background: Acute respiratory failure (ARF) is common in critically ill patients, and 50% of patients in intensive care units require mechanical ventilation [3, 4]. The COVID-19 pandemic revealed that COVID-19 infection induced ARF caused by damage to the microvascular pulmonary endothelium. In a randomized clinical trial, mechanically ventilated COVID-19 patients with severe endotheliopathy, as defined by soluble thrombomodulin (sTM) ≥ 4 ng/mL, were randomized to evaluate the effect of a 72-h infusion of low-dose prostacyclin 1 ng/kg/min or placebo.

Characterisation of GPR17-expressing oligodendrocyte precursors in human ischaemic lesions and correlation with reactive glial responses.

White matter damage and subsequent demyelination significantly contribute to long-term functional impairment after ischaemic stroke. Identifying novel pharmacological targets to restore myelin integrity by promoting the maturation of oligodendrocyte precursor cells (OPCs) into new myelinating oligodendrocytes may open new perspectives for ischaemic stroke treatment. In this respect, previous studies highlighted the role of the G protein-coupled membrane receptor 17 (GPR17) as a key regulator of OPC differentiation in experimental models of brain injury, including ischaemic stroke.

Evaluation of the clinical effect of a nationwide implementation of targeted routine antenatal anti-D prophylaxis in Denmark.

Background: In 2010, Denmark was the first country to implement a targeted routine antenatal anti-D prophylaxis (tRAADP) program, offering fetal RHD genotyping to all nonimmunized D negative pregnant women. The program represented a shift from only postnatal prophylaxis to a combined antenatal and postnatal prophylaxis. This study aimed to evaluate the clinical effect of tRAADP in Denmark.

Clinico-pathological characteristics and treatment outcome in non-small cell lung cancer in Greenland 2015-2020 - a comparison with the cohort from 2004 to 2010.

Background And Purpose: Lung cancer is the leading cause of cancer-related mortality in Greenland. Since 2004, medical treatment of lung cancer has been available in Greenland. However, both diagnostic work-up and treatment logistics are hampered by the lack of medical services in smaller settlements, the infrastructure, and extreme arctic weather conditions.