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Molecular profiling reveals low- and high-grade forms of primary melanoma

PURPOSE: For primary melanomas, tumor thickness, mitotic rate and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma that predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early st

Swedish CDKN2A mutation carriers do not present the atypical mole syndrome phenotype.

Phenotypic characteristics were examined in melanoma-prone southern Swedish CDKN2A (p16-113insArg/p14ARF-128insSer) mutation families, in relation to the CDKN2A genotype, nevi, clinically atypical nevi (CAN) and melanoma. Individuals from eight melanoma-prone families, with index patients carrying the CDKN2A mutation, were offered skin examinations and genotyping (CDKN2A and MC1R). Ninety-three in

Worse glycaemic control in LADA patients than in those with type 2 diabetes, despite a longer time on insulin therapy.

AIMS/HYPOTHESIS: Our aim was to study whether glycaemic control differs between individuals with latent autoimmune diabetes in adults (LADA) and patients with type 2 diabetes, and whether it is influenced by time on insulin therapy. METHODS: We performed a retrospective study of 372 patients with LADA (205 men and 167 women; median age 54 years, range 35-80 years) from Swedish cohorts from Skåne (

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

X-ray forward diffraction wave-front propagation in Si and C single crystals : Simulations and experiments

The emergence of new high brilliance and high coherence facilities such as X-ray Free Electron Lasers (XFELs) and 4th generation synchrotrons open a new era in X-ray optics. Dynamical diffraction effects before disregarded are starting to play a role in the beam control of large scale facilities. In the case of XFEL facilities the temporal characteristics of the dynamical diffraction by thin perfe

Fast food outlets, physical activity facilities, and obesity among adults : a nationwide longitudinal study from Sweden

Background: While neighborhood deprivation is a well-known predictor of obesity, the mechanisms behind this association are unclear and these are important to clarify before designing interventions focusing on modifiable neighborhood environmental factors in order to reduce obesity risk. Objectives: This study examined the longitudinal association between availability of fast-food outlets and phys

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

Growing Inwards : Densification and Ecosystem Services in Comprehensive Plans from Three Municipalities in Southern Sweden

This article analyses how urban densification, primarily in relation to ecosystem services, is addressed in comprehensive plans from three cities in southernmost Sweden: Malmö, Lund and Helsingborg. The aim was to investigate and problematise how the comprehensive plans articulate and negotiate how to build dense cities while preserving and enhancing ecosystem services. A qualitative content analy

Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing

Hematopoiesis is regulated by the bone marrow (BM) stroma. However, cellular identities and functions of the different BM stromal elements in humans remain poorly defined. Based on single-cell RNA sequencing (scRNAseq), we systematically characterized the human non-hematopoietic BM stromal compartment and we investigated stromal cell regulation principles based on the RNA velocity analysis using s

Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids with Aortic Stenosis

Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets. Objective: To identify novel genetic loci and pathways associated with AS. Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44703 participants (3469 cases of AS) of self-reported European ance

Prospective isolation of radiation induced erythroid stress progenitors reveals unique transcriptomic and epigenetic signatures enabling increased erythroid output

Massive expansion of erythroid progenitor cells is essential for surviving anemic stress. Research towards understanding this critical process, referred to as stress-erythropoiesis, has been hampered due to the lack of specific marker-combinations enabling analysis of the distinct stress-progenitor cells capable of providing radioprotection and enhanced red blood cell production. Here we present a

Deep proteomic analysis on biobanked paraffine-archived melanoma with prognostic/predictive biomarker read-out

The discovery of novel protein biomarkers in melanoma is crucial. Our introduction of formalin-fixed paraffin-embedded (FFPE) tumor protocol provides new opportunities to understand the progression of melanoma and open the possibility to screen thousands of FFPE samples deposited in tumor biobanks and available at hospital pathology departments. In our retrospective biobank pilot study, 90 FFPE sa

Proteomic analysis enables distinction of early- versus advanced-stage lung adenocarcinomas

BACKGROUND: A gel-free proteomic approach was utilized to perform in-depth tissue protein profiling of lung adenocarcinoma (ADC) and normal lung tissues from early and advanced stages of the disease. The long-term goal of this study is to generate a large-scale, label-free proteomics dataset from histologically well-classified lung ADC that can be used to increase further our understanding of dise

High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression.

BACKGROUND: High expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer. FINDINGS: Immunohistochemical RBM3 expression was examined in a tissue microarray

Cancer among patients with diabetes, obesity and abnormal blood lipids: a population-based register study in Sweden.

OBJECTIVE: To study how the incidence of cancer is related to diabetes, obesity or abnormal blood lipids. METHODS: Diagnosis of diabetes, obesity or abnormal blood lipids was studied 0-10 years prior to the diagnosis of cancer in 19,756 cases of cancer and in 147,324 controls matched regarding age, sex and domicile. RESULTS: Diabetes was significantly more common prior to diagnosis in patients w

Prevalence of germline TP53 mutations and history of Li-Fraumeni syndrome in families with childhood adrenocortical tumors, choroid plexus tumors, and rhabdomyosarcoma: A population-based survey.

PURPOSE: Whether childhood adrenocortical tumors (ACTs), choroid plexus tumors (CPTs), and rhabdomyosarcoma (RMS) are early manifestation of Li-Fraumeni syndrome (LFS) is uncertain. In this study, we evaluated the frequency of germline TP53 mutations and family history in a population-based series of patients. PATIENTS AND METHODS: We identified children (≤18 years) diagnosed between 1958 and

Using Cluster Theory to Calculate the Experimental Structure Factors of Antibody Solutions

Monoclonal antibody solutions are set to become a major therapeutic tool in the years to come, capable of targeting various diseases by clever design of their antigen binding site. However, the formulation of stable solutions suitable for patient self-administration typically presents challenges, as a result of the increase in viscosity that often occurs at high concentrations. Here, we establish