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Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery

Chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease, interstitial lung disease, and lung cancer, are among the leading causes of morbidity globally and impose major health and financial burdens on patients and society. Effective treatments are scarce, and relevant human model systems to effectively study CLD pathomechanisms and thus discover and validate potential new targe

No particle mass enhancement from induced atmospheric ageing at a rural site in northern Europe

A large portion of atmospheric aerosol particles consists of secondary material produced by oxidation reactions. The relative importance of secondary organic aerosol (SOA) can increase with improved emission regulations. A relatively simple way to study potential particle formation in the atmosphere is by using oxidation flow reactors (OFRs) which simulate atmospheric ageing. Here we report on the

Polygenic Risk Score for Coronary Heart Disease Modifies the Elevated Risk by Cigarette Smoking for Disease Incidence

BACKGROUND: Coronary heart disease (CHD) is a multifactorial disease with both genetic and environmental components. Smoking is the most important modifiable risk factor for CHD. Our aim was to test whether the increased CHD incidence by smoking is modified by genetic predisposition to CHD. METHODS AND RESULTS: Our study included 24 443 individuals from the MDCS (Malmö Diet and Cancer Study). A we

Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The hum

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men

Background: Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. Objective: To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Design, setting, participants: Study base

Claudin-4 Expression is Associated with Survival in Ovarian Cancer but Not with Chemotherapy Response

The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression mo

Smoking and Alcohol Intake but Not Muscle Strength in Young Men Increase Fracture Risk at Middle Age : A Cohort Study Linked to the Swedish National Patient Registry

We aimed to determine the relationship between handgrip strength, smoking, and alcohol consumption in young men and fracture risk at middle age. Thus, we carried out a cohort study including young men undergoing conscription examination in Sweden from September 1969 to May 1970 at a typical age of 18 years. Data on muscle strength, height, weight, and lifestyle factors were linked to the National

On the self-assembly of αB-crystallin

The molecular chaperone αB-crystallin is a small heat shock protein that inhibits the aggregation of, among others, Aβ42 and α-synuclein. These proteins are major hallmarks of Alzheimer's and Parkinson's disease, respectively. In order to understand the mechanism with which αB-crystallin performs its chaperone function it is essential to characterize its self-assembly in terms of aggregate size di

Reduced protein solubility - cause or consequence in amyloid disease?

In this perspective, we ask the question whether the apparently lower solubility of specific proteins in amyloid disease is a cause or consequence of the protein deposition seen in such diseases. We focus on Alzheimer's disease and start by reviewing the experimental evidence of disease-associated reduction in the measured concentration of amyloid β peptide, Aβ42, in cerebrospinal fluid. We propos

Combined Multicolor Immunofluorescence Staining and Spatial In Situ messenger RNA Expression Analysis Identifies Potential Fibrosis Drivers in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer. Bone marrow (BM) fibrosis in ALL has been associated with adverse outcomes; however, little is known about the mechanisms that cause fibrosis in ALL. Therefore, we established a novel and advanced analysis method by combining multicolor immunofluorescence (IF) staining with in situ RNA expression analysis (RNAscope) to inve

Kinetics of seeded protein aggregation : Theory and application

“Seeding” is the addition of preformed fibrils to a solution of monomeric protein to accelerate its aggregation into new fibrils. It is a versatile and widely used tool for scientists studying protein aggregation kinetics, as it enables the isolation and separate study of discrete reaction steps contributing to protein aggregation, specifically elongation and secondary nucleation. However, the see

Altered co-expression patterns of synovial fluid proteins related to the immune system and extracellular matrix organization in late stage OA, compared to non-OA controls

Objective: Synovial fluid contains proteins that may have been released from surrounding tissues, our aim was to gain new insights into the proteomic profiles of human synovial fluid in knees with and without osteoarthritis (OA). Methods: We used synovial fluid from 11 patients with end-stage medial compartment knee OA, aspirated during total knee replacement, and from 13 deceased donors who had n

High-efficiency microwave photodetection by cavity-coupled double quantum dots with single-cavity-photon sensitivity

We present a superconducting cavity-coupled double quantum dot (DQD) photodiode that achieves a maximum photon-to-electron conversion efficiency of 25% in the microwave domain. With a higher-quality-factor cavity and improved device design to prevent photon leakages through unwanted pathways, our device measures microwave signals down to the 100-aW power level and achieves sensitivity to probe mic

Fiber length and shape-dependent differences in hepatic nanomaterial localization in mice following pulmonary exposure

Background: Inhaled nanomaterials can translocate from the lungs into systemic circulation and reach the liver, which is the main secondary organ for nanomaterial uptake, potentially causing adverse effects. Understanding how inhaled nanomaterials localize within liver tissue is important for understanding their clearance mechanisms and potential toxicity. Previous in vivo studies have primarily f

Flame soot characterization using combined multi-wavelength thermo-optical analysis and Raman spectroscopy

Multi-wavelength thermo-optical analysis (MW-TOA) and Raman spectroscopy are commonly used methods to study soot sampled on filters, in terms of carbon content, nanostructure, and absorption properties. In this work, these techniques were combined to study how these characteristic properties of soot change in premixed flames, 1) at various flame heights during soot maturation and 2) as a result of

Ultrasonic cavitation shock wave exfoliation dynamics of 2D materials revealed in situ by MHz XFEL imaging and multiphysics modeling

Using megahertz x-ray free electron laser imaging with x-ray pulses of ~25 femtoseconds and a machine-learning strategy, we have conducted comprehensive in situ imaging studies on the dynamics of cavitation bubble clouds in ultrasound fields at the SPB/SFX beamline of the European XFEL. The research unambiguously revealed the quasi-simultaneous implosion of multiple bubbles and simultaneous collap

Association of change in physical activity with use of outpatient specialist care and hospitalisations among breast cancer survivors with type 2 diabetes in Sweden

Background: Studies in breast cancer patients have consistently shown that physical activity improves survival. We examined if change in physical activity from before to after a breast cancer diagnosis is associated with outpatient specialist care use and hospitalisations in women with type 2 diabetes mellitus (T2DM). Methods: This register-based cohort study included 2145 women with T2DM who self

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

Experimental insights on CIRLEM : Enhancing energy efficiency and flexibility in buildings

The growing complexity of urban energy systems, climate uncertainties, and geopolitical disruptions highlight the need for energy flexibility and smart management. Recent developments in smart buildings enable real-time adaptability and collective energy behavior through the deployment of Reinforcement Learning (RL), which optimizes energy use, integrates distributed resources, and enhances demand