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Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk : A Prospective Study in the EPIC Cohort

BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident

Association of Established Blood Pressure Loci With 10-Year Change in Blood Pressure and Their Ability to Predict Incident Hypertension

Background Genome-wide association studies have identified >1000 genetic variants cross-sectionally associated with blood pressure variation and prevalent hypertension. These discoveries might aid the early identification of subpopulations at risk of developing hypertension or provide targets for drug development, amongst other applications. The aim of the present study was to analyze the associat

Direct measurement of lipid membrane disruption connects kinetics and toxicity of Aβ42 aggregation

The formation of amyloid deposits in human tissues is a defining feature of more than 50 medical disorders, including Alzheimer’s disease. Strong genetic and histological evidence links these conditions to the process of protein aggregation, yet it has remained challenging to identify a definitive connection between aggregation and pathogenicity. Using time-resolved fluorescence microscopy of indi

Distribution of pressure on the breast in mammography using flexible and rigid compression plates : implications on patient handling

Background: Breast compression in mammography is important but is a source of discomfort and has been linked to screening non-attendance. Reducing compression has little effect on breast thickness, and likely little effect on image quality, due to force being absorbed in the stiff juxta thoracic area instead of in the central breast. Purpose: To investigate whether a flexible compression plate can

RHAPSODY, Biomarkers and Novel Clinical Trial design in type 2 diabetes (T2D) and prediabetes

Developing a novel therapeutic product for the treatment of type 2 diabetes (T2D) is a long, resource-intensive process. Novel biomarkers could potentially aid clinical trial design by shortening clinical trials or enabling better prediction of at-risk populations and/or disease progression. Novel clinical trial designs could lead to reduced costs of development and less burden to patients, due to

On the Mechanism of Self-Assembly by a Hydrogel-Forming Peptide

Self-assembling peptide-based hydrogels are a class of tunable soft materials that have been shown to be highly useful for a number of biomedical applications. The dynamic formation of the supramolecular fibrils that compose these materials has heretofore remained poorly characterized. A better understanding of this process would provide important insights into the behavior of these systems and co

Clinical profiles of post-load glucose subgroups and their association with glycaemic traits over time : An IMI-DIRECT study

Aim: To examine the hypothesis that, based on their glucose curves during a seven-point oral glucose tolerance test, people at elevated type 2 diabetes risk can be divided into subgroups with different clinical profiles at baseline and different degrees of subsequent glycaemic deterioration. Methods: We included 2126 participants at elevated type 2 diabetes risk from the Diabetes Research on Patie

Kinetic diversity of amyloid oligomers

The spontaneous assembly of proteins into amyloid fibrils is a phenomenon central to many increasingly common and currently incurable human disorders, including Alzheimer's and Parkinson's diseases. Oligomeric species form transiently during this process and not only act as essential intermediates in the assembly of new filaments but also represent major pathogenic agents in these diseases. While

Cardiovascular efficacy and safety of bococizumab in high-risk patients

Background: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. Methods: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly

Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes : An IMI-DIRECT study

AIM: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D. METHODS: The study included 787 indi

Downregulation of growth hormone in postural orthostatic tachycardia syndrome: insights from the SYSTEMA cohort

Background Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder occurring predominantly in young women. POTS is characterized by an excessive heart rate increase when assuming upright posture accompanied by symptoms of orthostatic intolerance. The pathophysiology of POTS has not been fully established and is believed to be multifactorial. Purpose We a

A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein-2 and zoledronic acid

Bone morphogenic proteins (BMPs) are the only true osteoinductive molecules. Despite being tremendously potent, their clinical use has been limited for reasons including supraphysiological doses, suboptimal delivery systems, and the pro-osteoclast effect of BMPs. Efforts to achieve spatially controlled bone formation using BMPs are being made. We demonstrate that a carrier consisting of a powder o

The interaction effect of sex and apolipoprotein E genotype in Alzheimer’s disease—rates of progression and prognosis.

Objectives: To investigate the interaction effect of sex and apolipoprotein E (APOE) genotype on long-term cognitive and functional outcomes and survival in Alzheimer’s disease (AD). Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicentre study in clinical practice involving 999 participants diagnosed with mild-to-moderate AD at the start of cholinesteras

Drug use disorder and risk of incident and fatal breast cancer : a nationwide epidemiological study

Purpose: Breast cancer is one of the most common cancer forms in women and it is often detected by screening. However, women with drug use disorders (DUD) are less likely to be reached by screening programs. In this study, we aimed to investigate breast cancer incidence, mortality and stage at time of diagnosis among women with DUD compared to the general female population in Sweden. Methods: We p

Genome-wide association study of self-reported walking pace suggests beneficial effects of brisk walking on health and survival

Walking is a simple form of exercise, widely promoted for its health benefits. Self-reported walking pace has been associated with a range of cardiorespiratory and cancer outcomes, and is a strong predictor of mortality. Here we perform a genome-wide association study of self-reported walking pace in 450,967 European ancestry UK Biobank participants. We identify 70 independent associated loci (P <

A reference map of potential determinants for the human serum metabolome

The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. Howev

How novel is Transformative Innovation Policy?

The focus and instruments of innovation policy have changed fundamentally over the last decades. Recently transformative innovative policy has caught the attention of scholars and policy makers, arguing that this is a new shift in the policy discourse. Even though grand challenges such as global warming and migration flows, as well as technological change such as artificial intelligence and indust

Resilience in the periphery: What an agency perspective can bring to the table

In this chapter, we study the relationship between regional economic resilience and agency. Especially since the 2008 recession, regional resilience has raised a lot of interest in economic geography. However, the resilience research has focused mostly on the structural perspective and the role of agency has gained less attention. Intentional and purposeful human actions can have an effect on regi

Alzheimer's pathology targets distinct memory networks in the ageing brain

Alzheimer's disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer's disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology