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Gene expression identifies heterogeneity of metastatic propensity in high-grade soft tissue sarcomas

BACKGROUND: Metastatic propensity of soft tissue sarcoma (STS) is heterogeneous and may be determined by gene expression patterns that do not correlate well with morphology. The authors have reported gene expression patterns that distinguish 2 broad classes of clear cell renal carcinoma (ccRCC-gene set), and other patterns that can distinguish heterogeneity of serous ovarian carcinoma (OVCA-gene s

Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch syndrome founder mutation

Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation familie

Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium.

Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individua

Two new routes to make blood: Hematopoietic specification from pluripotent cell lines vs. reprogramming of somatic cells.

Transplantation of hematopoietic stem cells (HSCs) to treat hematological disorders is routinely used in the clinic. However, HSC therapy is hindered by the requirement of finding HLA-matched donors, as well as attaining sufficient numbers of long-term HSCs in the graft. Therefore, ex vivo expansion of transplantable HSC remains one of the "holy grails" of hematology. Without the ability to mainta

A Memory-Efficient Finite Volume Method for Advection-Diffusion-Reaction Systems with Non-Smooth Sources

We present a parallel matrix-free implicit nite volume scheme for the solution of unsteady three-dimensional advection-diusion-reaction equations with smooth and Dirac-Delta source terms. The scheme is formally second order in space and a Newton-Krylov method is employed for the appearing nonlinear systems in the implicit time integration. The matrix-vector product required is hardcoded without an

Interobserver variability in the evaluation of mismatch repair protein immunostaining

Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced

Ezrin expression in rectal cancer predicts time to development of local recurrence

Improved outcome after rectal cancer surgery requires identification of novel risk factors of tumour recurrence in order to personalise therapy, that is, enhanced selection of high-risk patients to additional radiochemotherapy or intensified follow-up. In several tumour types, including colorectal cancer, high expression of the membrane-cytoskeleton linker ezrin has been suggested to impair progno

Diabetes and Onset of Natural Menopause: Results From the European Prospective Investigation Into Cancer and Nutrition EDITORIAL COMMENT

The age at natural menopause (ANM) in the Western world ranges from 40 to 60 years, with an average onset of 51 years. The exact mechanisms underlying the timing of ANM are not completely understood. Both genetic and environmental factors are involved. The best-established environmental factor affecting ANM is smoking; menopause occurs 1 to 2 years earlier in smokers. In addition to genetic and en

Country of birth modifies the association of fatty liver index with insulin action in Middle Eastern immigrants to Sweden.

Non-alcohol fatty liver disease (NAFLD) is a strong risk factor for insulin resistance and type 2 diabetes. The prevalence of NAFLD varies across populations of different ethnic backgrounds but the prevalence in Middle Eastern populations, which are at high risk of type 2 diabetes, is largely unknown. Using fatty liver index (FLI) as a proxy for NAFLD the aim was to calculate the odds of NAFLD (FL

Justice ‘Under’ Law: The Bodily Incarnation of Legal Conceptions Over Time

The article uses embodiment and the experiential basis of conceptual metaphor to argue for the metaphorical essence of abstract legal thought. Abstract concepts like ‘law’ and ‘justice’ need to borrow from a spatial, bodily, or physical prototype in order to be conceptualised, seen, for example, in the fact that justice preferably is found ‘under’ law. Three conceptual categories of how law is con

IGF1 htSNPs in relation to IGF-1 levels in young women from high-risk breast cancer families: implications for early-onset breast cancer

High levels of insulin-like growth factor-1 (IGF-1) have been associated with increased risk of developing several types of cancer including breast cancer. A set of nine haplotype tagging SNPs (htSNPs) in the IGF1 gene were associated with IGF-1 levels and prostate cancer in a Swedish population. We aimed to study the nine htSNPs in three haplotype blocks (block1: rs855211, rs35765, rs2162679; blo

Increased serum type I interferon activity in early systemic sclerosis patients is associated with antibodies against Sjögren's syndrome antigens and nuclear ribonucleoprotein antigens.

Objective: To study serum type I interferon (IFN) activity in patients with early systemic sclerosis (SSc). Method: Serum type I IFN activity was measured in 33 consecutive patients with SSc and a disease duration of < 2 years and in 13 healthy individuals by calculating a type I IFN score according to the induction of six IFN-α regulated genes in a reporter cell line. Results: Twenty-seven per ce

Human induced pluripotent stem cell-derived cortical neurons integrate in stroke-injured cortex and improve functional recovery.

Stem cell-based approaches to restore function after stroke through replacement of dead neurons require the generation of specific neuronal subtypes. Loss of neurons in the cerebral cortex is a major cause of stroke-induced neurological deficits in adult humans. Reprogramming of adult human somatic cells to induced pluripotent stem cells is a novel approach to produce patient-specific cells for au

Common Inherited Variation in Mitochondrial Genes Is Not Enriched for Associations with Type 2 Diabetes or Related Glycemic Traits

Mitochondrial dysfunction has been observed in skeletal muscle of people with diabetes and insulin-resistant individuals. Furthermore, inherited mutations in mitochondrial DNA can cause a rare form of diabetes. However, it is unclear whether mitochondrial dysfunction is a primary cause of the common form of diabetes. To date, common genetic variants robustly associated with type 2 diabetes (T2D) a

Balancing Life with an Increased Risk of Cancer: Lived Experiences in Healthy Individuals with Lynch Syndrome

Possibilities to undergo predictive genetic testing for cancer have expanded, which implies that an increasing number of healthy individuals will learn about cancer predisposition. Knowledge about how an increased risk of disease influences life in a long-term perspective is largely unknown, which led us to explore lived experiences in healthy mutation carriers with Lynch syndrome. Individual inte

Single cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity.

In order to investigate molecular events involved in the regulation of lymphoid lineage commitment, we crossed lambda5 reporter transgenic mice to Rag1-GFP knock in mice. This allowed us to sub-fractionate common lymphoid progenitors (CLPs) and pre-pro-B (Fraction A) cells into lambda5(-)Rag1(low), lambda5(-)Rag1(high) and lambda5(+)Rag1(high) cells. Clonal in vitro differentiation analysis demons

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study o