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The PNPLA3-I148M Variant Confers an Antiatherogenic Lipid Profile in Insulin-resistant Patients

CONTEXT: The I148M (rs738409-G) variant in PNPLA3 increases liver fat content but may be protective against cardiovascular disease. Insulin resistance (IR) amplifies the effect of PNPLA3-I148M on liver fat. OBJECTIVE: To study whether PNPLA3-I148M confers an antihyperlipidemic effect in insulin-resistant patients. DESIGN: Cross-sectional study comparing the impact of PNPLA3-I148M on plasma lipids

Tonsillar cancer with high cd8+ t‐cell infiltration features increased levels of dendritic cells and transcriptional regulation associated with an inflamed tumor microenvironment

Human papillomavirus (HPV) is the main causal agent of tonsillar cancer (TC) and HPV+ TC has a favorable prognosis compared to HPV– disease. In this study, we examined aspects of the tumor microenvironment of TC, focusing on T‐cells, dendritic cells (DC), and macrophages. Fresh biopsies of TC and the contralateral healthy tonsil (HT) were obtained from 20 patients, analyzed by multiparameter flow

Simultaneous determination of folate and methotrexate metabolites in serum by LC-MS/MS during high-dose methotrexate therapy

High-dose methotrexate (HDMTX) is a central component in the treatment of acute lymphoblastic leukemia, osteosarcoma, and some lymphomas and brain tumors. MTX is given at lethal doses and then is followed by rescue treatment with folinic acid (FA). Despite FA rescue, many patients suffer severe toxicity. The pharmacokinetics of FA rescue have not been sufficiently studied. However, optimization of

Multimodal Mass Spectrometry Identifies a Conserved Protective Epitope in S. pyogenes Streptolysin O

An important element of antibody-guided vaccine design is the use of neutralizing or opsonic monoclonal antibodies to define protective epitopes in their native three-dimensional conformation. Here, we demonstrate a multimodal mass spectrometry-based strategy for in-depth characterization of antigen–antibody complexes to enable the identification of protective epitopes using the cytolytic exotoxin

Mediators, Metabolites and Atypical Immune Cells in Cardiovascular Disease

Cardiovascular disease (CVD) remains, despite intense research, the most common cause of death world-wide. The main underlying cause of CVD is atherosclerosis, which is characterised by chronic inflammation. CVD and atherosclerosis have a complex aetiology, which necessitates research into multiple areas in order to gain insight into the pathogenesis and find novel markers that could aid in identi

Long-term Follow-up of 84 Patients With Giant Prolactinomas-A Swedish Nationwide Study

PURPOSE: To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas. METHODS: Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 µg/L, tumor diameter ≥40 mm] identified in the Swedish Pituitary Register 1991-2018. RESULTS: Eighty-four patients [mean age 47 (SD ±16) years, 89% men] were included in th

Protocol for the T-REX-trial : Tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - An open, multicentre, randomised non-inferiority phase 3 trial

Introduction Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer.

Cellular and molecular cartography of muscle-invasive bladder cancer: Who benefits from neoadjuvant chemotherapy?

Muscle-invasive bladder cancer (MIBC) is characterised by significant molecular heterogeneity, with the tumour composition being further sculptured by local microenvironmental influences. This inherent complexity contributes to the divergent disease trajectories and the variable therapeutic susceptibility observed among patients. Consequently, there is an evident need for prognostic and predictive

Porous pavement for reduced tyre/road noise and improved air quality : Initial results from a case study

One possible solution to reduce noise resulting from tyre-pavement interaction is to use a porous pavement surface. A porous surface will reduce noise by decreasing air pressure gradients in the tyre-pavement contact as well as by decreasing the acoustical impedance of the road surface and reducing the horn effect. While reducing noise, other functional aspects of a pavement such as abrasion wear

The Influence of Pubertal Development on Autoantibody Appearance and Progression to Type 1 Diabetes in the TEDDY Study

CONTEXT: The 2 peaks of type 1 diabetes incidence occur during early childhood and puberty.OBJECTIVE: We sought to better understand the relationship between puberty, islet autoimmunity, and type 1 diabetes.METHODS: The relationships between puberty, islet autoimmunity, and progression to type 1 diabetes were investigated prospectively in children followed in The Environmental Determinants of Diab

Postnatal pesticide exposure and behavioural outcomes in children and adolescents : findings from South Africa

Introduction: Postnatal pesticide exposure and its association with child and adolescent behavioural outcomes remain underexplored in rural agricultural settings, particularly in Africa. This study examined behavioural outcomes in relation to urinary pesticide biomarkers and contextual exposure proxies in participants from the Child health Agricultural Pesticide (CapSA) cohort, South Africa. Metho

Does tattoo exposure increase the risk of skin cancer? A population-based case-control study

BACKGROUND AND AIM[|]The incidence of skin cancer has risen sharply over the past 30 years - coinciding with the rapidly increasing tattoo trend. In Sweden, 20% of the population is tattooed. The link between tattoos and skin cancer needs to be investigated, due to the presence of carcinogenic chemicals in tattoo ink, and the lack of epidemiological studies of the association. We aimed to investig

Differences in sexual violence against younger and older adults in complex humanitarian settings : a retrospective analysis from Médecins Sans Frontières in 2019-24

BACKGROUND: Sexual violence against older adults in humanitarian settings is poorly documented, leading to gaps in prevention and delivery of support services. This study aimed to document differences in assault characteristics between younger and older adults, by sex and displacement and disability status and region. METHODS: This retrospective, descriptive observational, multi-country study incl

Nuclear cell-free DNA on the loose: an early warning signal of ischemia–reperfusion injury in kidney transplantation

Introduction: Cell-free DNA is an emerging marker of allograft injury, yet its role in the immediate phase of ischemia–reperfusion injury remains incompletely understood.Methods: In this prospective cohort of 127 kidney transplant recipients (86 deceased donors, 41 living donors), intraoperative plasma samples were collected systemically pre-implantation and from the allograft vein postreperfusion

The Role of RB1 and Secondary Genomic Changes in the Development of Spindle Cell and Pleomorphic Lipomas

Spindle cell lipomas (SCL) and pleomorphic lipomas (PL) are today considered a single tumor entity (SCLPL). Atypical SCLPL, in contrast, represents a recently recognized related but distinct entity. Here we explored the correlation between genomic features and morphological aspects of SCLPL and atypical SCLPL and the role of the RB1 gene in tumor development. Seventy-one samples from 68 patients w

Fetal Aortic Isthmus and Descending Aorta

Doppler evaluation of the aortic isthmus, located between the left subclavian artery and the ductus arteriosus, can provide important information on fetal hemodynamic adaptation/deterioration related to intrauterine hypoxia. The aortic isthmus acts as a shunt deviating part of the blood flow from ductus arteriosus to the cranial circulation to maintain a normal oxygen delivery to the fetal brain.

Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study

Context: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable.Objective: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD.Design, patients, and methods: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2

Occupational noise exposure and acute effects on pulse rate and blood pressure

Environmental exposure to noise and particle matter (PM) are risk factors for cardiovascular disease (CVD). Although there are often higher levels in occupational settings, little is known about noise and particle exposures at work and CVD risks. We investigated occupational noise and particle exposures and acute effects on pulse rate and blood pressure. 46 active, non-smoking, male construction w

Sex-Specific Risk Factors for Deep Venous Thrombosis and Pulmonary Embolism in a Population-Based Historical Cohort Study of Middle-Aged and Older Individuals

BACKGROUND: Whether sex-specific differences exist for risk factors for pulmonary embolism (PE) and deep venous thrombosis (DVT), with the exception of pregnancy and estrogen therapy, has been sparsely studied. We aimed to study whether sex-specific differences of risk factors exist for noncancer-related DVT and PE in middle-aged and older individuals without cardiovascular history or previous dia

Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE) : a multicentre, open-label, randomised controlled trial

Background: The combination of infliximab and immunosuppressant therapy is a standard management strategy for patients with Crohn's disease. Concerns regarding the implications of long-term combination therapy provided the rationale for a formal clinical trial of treatment de-escalation. Our aim was to compare the relapse rate and the time spent in remission over 2 years between patients continuin