One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

Communicating scientific evidence: drugs for Alzheimer's disease as a case study.

This paper reviews the scientific evidence on new anti-amyloid monoclonal antibodies for treating Alzheimer's disease as a case study for improving scientific evidence communication. We introduce five guidelines condensed from the biomedical evidence literature but adapted to the short format of science communication in e.g.

ATM Expression and Activation in Ataxia Telangiectasia Patients with and without Class Switch Recombination Defects.

Background: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

Trimethylamine N-Oxide (TMAO) Plasma Levels in Patients with Different Stages of Chronic Kidney Disease.

Background: In patients with chronic kidney disease (CKD), trimethylamine n-oxide (TMAO) accumulation exacerbates inflammation and contributes to oxidative stress. These complications are putatively linked to the development of cardiovascular diseases. Despite the known associations, the variation in TMAO plasma levels across different CKD stages and dialysis modalities remains underexplored.

Somatic mutations and DNA methylation identify a subgroup of poor prognosis within lower-risk myelodysplastic syndromes.

Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and transcriptomic profiling has the potential to spotlight distinct LR-MDS categories on the basis of pathophysiological mechanisms. We performed a comprehensive study of somatic mutations and DNA methylation in a large and clinically well-annotated cohort of treatment-naive patients with LR-MDS at diagnosis from the EUMDS registry (ClinicalTrials.

First-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies.

Background: ATOR-1017 (evunzekibart) is a human agonistic immunoglobulin G4 antibody targeting the costimulatory receptor 4-1BB (CD137). ATOR-1017 activates T cells and natural killer cells in the tumor environment, leading to immune-mediated tumor cell death.

Methods: In this first-in-human, multicenter, phase I study, ATOR-1017 was administered intravenously every 21 days as a monotherapy to patients with advanced, unresectable solid tumors having received multiple standard-of-care treatments.

Structural elucidation of the O-antigen polysaccharide from shigatoxin-producing E. coli O179 using genetic information, NMR spectroscopy and the CASPER program.

The serological properties of the O-antigen polysaccharide region of the lipopolysaccharides are used to differentiate E. coli strains into serogroups. In this study, we report the structure elucidation of the O-specific chain of E.

Targeting CD84 protein on myeloid-derived suppressor cells as a novel immunotherapy in solid tumors.

Background And Objective: Myeloid-derived suppressor cells (MDSCs) are a crucial and diverse group of cells found in the tumor microenvironment (TME) that facilitate progression, invasion, and metastasis within solid tumors. CD84, a homophilic adhesion molecule expressed on MDSCs, plays a critical role in their accumulation and function within the TME. This study aims to investigate the protein-protein interactions of CD84 using molecular dynamics simulations and to explore potential therapeutic strategies targeting these interactions.

Exploring socio-economic inequalities in mental healthcare utilization in adults with self-reported psychological distress: a survey-registry linked cohort design.

Aims: Although individuals with lower socio-economic position (SEP) have a higher prevalence of mental health problems than others, there is no conclusive evidence on whether mental healthcare (MHC) is provided equitably. We investigated inequalities in MHC use among adults in Stockholm County (Sweden), and whether inequalities were moderated by self-reported psychological distress.

Methods: MHC use was examined in 31,433 individuals aged 18-64 years over a 6-month follow-up period, after responding to the General Health Questionnaire-12 (GHQ-12) in 2014 or the Kessler Six (K6) in 2021.

No difference in ACL revision rates between hamstring and patellar tendon autograft in patients with ACL-R and a concurrent meniscal injury irrespective of meniscal treatment.

Purpose: The aims of this study were to compare (1) the rate of anterior cruciate ligament (ACL) revision and (2) subjective knee function using the Knee injury and Osteoarthritis Outcome Score (KOOS) between isolated ACL reconstruction (ACL-R) and ACL-R and concurrent meniscal injury, based on graft selection and meniscal treatment.

Methods: Data from the Swedish National Knee Ligament Registry were extracted in November 2022 for patients who underwent primary ACL-R. Patients were divided into two main groups based on graft choice: hamstring tendon (HT) or patellar tendon (PT) autograft, with four meniscal sub-groups: no injury, resection, repair or left in situ.

Fear of childbirth and psychiatric disorders decrease the likelihood of subsequent births: a retrospective register-based cohort study.

Background: Mirroring other developed countries globally, the birth rate has decreased in Finland in recent years. The effects of a fear of childbirth (FOC) and psychiatric disorders on the likelihood of having more than one child remain relatively unstudied. This study aims to assess the influence of FOC, psychiatric disorders, and the mode of first delivery on the likelihood of the second birth among primiparous women.

Emotion regulation-based internet-delivered cognitive behavioural therapy for premenstrual dysphoric disorder: study protocol for a randomised controlled trial in Sweden.

Introduction: Premenstrual dysphoric disorder (PMDD) is a cyclic mood disorder affecting around 2%-5% of women of reproductive age. Pharmacological interventions exist, but many patients with PMDD experience residual symptoms, discontinue medications or refrain from them due to side effects. Thus, non-pharmacological treatments are needed as an alternative or additive treatment strategy.

Migrant Health Country Profile tool (MHCP-t) for transforming health data collection and surveillance in the Middle East and North African (MENA) region: tool development protocol with embedded process evaluation.

Introduction: The Middle East and North Africa (MENA) region is characterised by major health disparities and complex migration flows. Yet, because of a lack of epidemiological data, there is an urgent need to strengthen routine data collection around migrant health and to define key indicators towards migrant health monitoring. To address this problem, we aim to design and pilot test the Migrant Health Country Profile tool (MHCP-t) which can collate country-level data collection around migration health data, policies and healthcare provision.

Syn2Real: synthesis of CT image ring artifacts for deep learning-based correction.

We strive to overcome the challenges posed by ring artifacts in X-ray computed tomography (CT) by developing a novel approach for generating training data for deep learning-based methods. Training such networks require large, high quality, datasets that are often generated in the data domain, time-consuming and expensive. Our objective is to develop a technique for synthesizing realistic ring artifacts directly in the image domain, enabling scalable production of training data without relying on specific imaging system physics.

Mortality in Autoimmune Liver Disease in Sweden: A Population-Based Cohort Study of 9,654 Patients.

Background/aims: Epidemiological data on mortality in autoimmune liver diseases (AILDs) are scarce. We examined all-cause and cancer-related mortality in individuals with AILD from Sweden.

Methods: We identified 9654 individuals with AILD (3342 with autoimmune hepatitis (AIH), 3751 with primary biliary cholangitis (PBC), and 2561 with primary sclerosing cholangitis (PSC)) using national Swedish registries between 2001 and 2020.

Universal Hydrogel Carrier Enhances Bone Graft Success: Preclinical and Clinical Evaluation.

Orthopedic, maxillofacial, and complex dentoalveolar bone grafting procedures that require donor-site bone harvesting can be associated with post-surgical complications. There has been widespread adoption of exogenously sourced particulate bone graft materials (BGM) for bone regenerative procedures; however, the particulate nature of these materials may lead to compromised healing outcomes, mainly attributed to structural collapse of the BGM, prolonged tissue healing. In this study, a fully synthetic thermoresponsive hydrogel-based universal carrier matrix (TX) that forms flowable and shapable putties with different BGMs while spatially preserving the particles in a 3D scaffold at the implantation site is introduced.

Current practices in prevention, screening, and treatment of diabetes in kidney transplant recipients: European survey highlights from the ERA DESCARTES Working Group.

Background: Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there are few data on prevention, optimal screening, and treatment strategies.

Methods: The European Renal Association's DESCARTES working group distributed a web-based survey to European transplant centres to gather information on risk assessment, screening procedures, and management practices for preventing and treating PTDM in kidney transplant recipients.

Results: Answers were obtained from 121/241 transplant centres (50%) across 15 European countries.

Association of GLP1R locus with mental ill-health endophenotypes and cardiometabolic traits: A trans-ancestry study in UK Biobank.

Aims: Glucagon-like peptide 1 receptor agonists (GLP1RA), used to treat type 2 diabetes and obesity, have been associated with off-target behavioural effects. We systematically assessed genetic variation in the GLP1R locus for impact on mental ill-health (MIH) and cardiometabolic phenotypes across diverse populations within UK Biobank.

Materials And Methods: All genetic variants with minor allele frequency >1% in the GLP1R locus were investigated for associations with MIH phenotypes and cardiometabolic phenotypes.

Cardiovascular health in breast cancer patients: insight on BRCA1/2 mutations impact.

Background: Breast cancer (BC) and cardiovascular disease (CVD) are prevalent comorbidities in aging populations. Advances in BC treatment have improved survival rates but increased the risk of CVD, particularly among younger patients with BRCA1/2 mutations. BRCA1/2 gene mutations, prevalent in younger BC patients, impair cardioprotective effects, elevating CVD risk alongside cancer treatments.

Measuring social integration, treatment, and mortality after substance use treatment: methodological elaborations in a 20-year follow-up study.

Objective: Alcohol and Other Drug (AOD) disorders cause substantial harm. Effective Substance Use Treatment (SUT) exists, but long-term outcomes remain inconclusive. This study used a 20-year prospective follow-up of 1248 service users entering SUT in Stockholm, Sweden, in 2000-2002 to elaborate on how different dimensions of long-term outcomes may be measured by register-based indicators.

Association of childhood maltreatment and adverse lifetime experiences with post-injury psychopathology: evidence from the China Severe Trauma Cohort.

Background: Adverse life experiences have been associated with increased susceptibilities to psychopathology in later life. However, their impact on psychological responses following physical trauma remains largely unexplored.

Methods: Based on the China Severe Trauma Cohort, we conducted a cohort study of 2937 patients who were admitted to the Trauma Medical Center of West China Hospital between June 2020 and August 2023.

Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer.

Introduction: Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear.

Specialized pro-resolving lipid mediators: a key player in resolving inflammation in autoimmune diseases.

Uncontrolled hyperactivation of the immune system is the central mechanism underlying the pathogenesis of autoimmune diseases. Timely control of the inflammatory response is essential to prevent inflammation progression and organ damage. Specialized pro-resolving lipid mediators (SPMs) are autacoid molecules derived from essential polyunsaturated fatty acids during acute inflammatory responses.

Three-dimensional aortic arch geometry and blood flow in neonates after surgical repair for aortic coarctation.

Background: Recurrent coarctation of the aorta (re-CoA) is a well-known although not fully understood complication after surgical repair, typically occurring in 10%-20% of cases within months after discharge.

Objectives: To (1) characterize geometry of the aortic arch and blood flow from pre-discharge magnetic resonance imaging (MRI) in neonates after CoA repair; and (2) compare these measures between patients that developed re-CoA within 12 months after repair and patients who did not.

Methods: Neonates needing CoA repair, without associated major congenital heart defects, were included.