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Stellate cells and mesenchymal stem cells in benign mammary stroma are associated with risk factors for breast cancer - an observational study

Background: It is not known whether stromal cells in benign breast tissue can mediate risk of breast cancer. We recently described aldehyde dehydrogenase 1 A1 (ALDH1) positive (+) cells in morphologically normal breast stroma of premenopausal women, and the data indicated that their distribution is associated with clinical risk factors for breast cancer. The aim of the present study was to define

Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes

BackgroundWhile genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS).ResultsGWAS data on 7319 MM cases and 234,3

Patients' and physicians' disagreement on patients' understanding of clinical cancer trial information : A pairwise pilot study of mirroring subjective assessments compared with objective measurements

Background: Informed consent is a prerequisite for patients included in clinical trials. Trial design, inclusion criteria and legal requirements are increasingly complex. This complexity challenges design and delivery of written and oral trial information to ensure understandable information. To evaluate the level of concordance between patients' and informing physicians' assessments regarding pat

Determinants for non-sentinel node metastases in primary invasive breast cancer : A population-based cohort study of 602 consecutive patients with sentinel node metastases

Background: Sentinel node biopsy (SNB) is the standard procedure for axillary staging in patients with clinically lymph node negative invasive breast cancer. Completion axillary lymph node dissection (c-ALND) may not be necessary for all patients as a significant number of patients have no further metastases in non-sentinel nodes (non-SN) and c-ALND may not improve survival. The first aim of our s

Accumulated neighbourhood deprivation and coronary heart disease : A nationwide cohort study from Sweden

Objective Neighbourhood deprivation is a recognised predictor of coronary heart disease (CHD). The overall aim was to investigate if accumulated exposure to neighbourhood deprivation resulted in higher odds of CHD. Design This is a longitudinal cohort study. Models based on repeated assessments of neighbourhood deprivation as well as single-point-in-time assessments were compared. Setting Sweden.

An inflamed subtype of difficult-to-treat depression

BACKGROUND: Chronic low-grade inflammation may play a role in the pathophysiology of depression, at least in a subset of patients. High-sensitivity C-reactive protein (hs-CRP) has been used to define an inflamed subgroup of depression with specific clinical characteristics and symptoms. In this study we investigated biochemical and clinical characteristics in patients with difficult-to-treat depre

The contribution of population age-sex structure to the excess mortality estimates of 2020–2021 in Denmark, Finland, Iceland, Norway, and Sweden

The Nordic countries offer an ideal case study of the COVID-19 pandemic due to their comparability, high data quality, and variable mitigations. We investigated the age- and sex-specific mortality patterns during 2020–2021 for the five Nordic countries and analysed the total age- and sex-adjusted excess deaths, ratios of actual to expected death rates, and age-standardized excess death estimates.

Baseline Prostate-specific Antigen Level in Midlife and Aggressive Prostate Cancer in Black Men

Background: Prostate-specific antigen (PSA) measurement in midlife predicts long-term prostate cancer (PCa) mortality among white men. Objective: To determine whether baseline PSA level during midlife predicts risk of aggressive PCa in black men. Design, setting, and participants: Nested case-control study among black men in the Southern Community Cohort Study recruited between 2002 and 2009. A pr

An observational study on the molecular profiling of primary melanomas reveals a progression dependence on mitochondrial activation

Melanoma in advanced stages is one of the most aggressive tumors and the deadliest of skin cancers. To date, the histopathological staging focuses on tumor thickness, and clinical staging is a major estimate of the clinical behavior of primary melanoma. Here we report on an observational study with in‐depth molecular profiling at the protein level including post-translational modifications (PTMs)

Rapid multinodal acoustic trapping of extracellular vesicles for downstream mass spectrometry analysis

We report the use of multinodal acoustic trapping for high throughput and high capacity capturing of EV's (extracellular vesicles) for quantitative mass spectrometry analysis. The multinode trapping unit was shown to isolate sufficient amount of EV's from dilute biological samples (urine and cell culture supernatant) at flow rates of 500 ul/min within minutes, enabling EV proteome profiling. This

Mapping the melanoma plasma proteome (MPP) using single-shot proteomics interfaced with the WiMT database

Plasma analysis by mass spectrometry-based proteomics remains a challenge due to its large dynamic range of 10 orders in magnitude. We created a methodology for protein identification known as Wise MS Transfer (WiMT). Melanoma plasma samples from biobank archives were directly analyzed using simple sample preparation. WiMT is based on MS1 features between several MS runs together with custom prote

Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations

The risk of pancreatic cancer (PC) is increased in melanoma-prone families but the causal relationship between germline CDKN2A mutations and PC risk is uncertain, suggesting the existence of non-CDKN2A factors. One genetic possibility involves patients having mutations in multiple high-risk PC-related genes; however, no systematic examination has yet been conducted. We used next-generation sequenc

Genetic susceptibility to dyslipidemia and incidence of cardiovascular disease depending on a diet quality index in the Malmö diet and cancer cohort

Background: By taking diet quality into account, we may clarify the relationship between genetically elevated triglycerides (TG) and low-density lipoprotein-cholesterol (LDL-C), and better understand the inconsistent results regarding genetically elevated high-density lipoprotein-cholesterol (HDL-C), and cardiovascular disease (CVD) risk. Methods: We included 24,799 participants (62 % women, age 4

Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing

Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19

Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations

Strengthening the Reporting of Observational Studies in Epidemiology – nutritional epidemiology (STROBE-nut) : An extension of the STROBE statement

Concerns have been raised about the quality of reporting in nutritional epidemiology. Research reporting guidelines such as the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement can improve quality of reporting in observational studies. Herein, we propose recommendations for reporting nutritional epidemiology and dietary assessment research by extending the ST

Preclinical Characterization of 3β-(N-Acetyl l -cysteine methyl ester)-2aβ,3-dihydrogaliellalactone (GPA512), a Prodrug of a Direct STAT3 Inhibitor for the Treatment of Prostate Cancer

The transcription factor STAT3 is a potential target for the treatment of castration-resistant prostate cancer. Galiellalactone (1), a direct inhibitor of STAT3, prevents the transcription of STAT3 regulated genes. In this study we characterized 6 (GPA512, Johansson, M.; Sterner, O. Patent WO 2015/132396 A1, 2015), a prodrug of 1. In vitro studies showed that 6 is rapidly converted to 1 in plasma