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Multiregion whole-exome sequencing uncovers the genetic evolution and mutational heterogeneity of early-stage metastatic melanoma

Cancer genome sequencing has shed light on the underlying genetic aberrations that drive tumorigenesis. However, current sequencing-based strategies, which focus on a single tumor biopsy, fail to take into account intratumoral heterogeneity. To address this challenge and elucidate the evolutionary history of melanoma, we performed whole-exome and transcriptome sequencing of 41 multiple melanoma bi

A brain potential signalling linguistic pre-activation? : an analysis of the pre-activation negativity (PrAN)

Introduction: It has previously been found that strongly predicted words can be pre-activated in constraining contexts (e.g. DeLong, Urbach & Kutas, 2005). Furthermore, it has been suggested that an anticipated continuation from one syllable to another can be pre-activated before it is present in the input (Roll, Söderström, Mannfolk, Shtyrov, Johansson, van Westen & Horne, 2015). We descr

KAP1 controls endogenous retroviruses in embryonic stem cells

More than forty per cent of the mammalian genome is derived from retroelements, of which about one-quarter are endogenous retroviruses (ERVs). Some are still active, notably in mice the highly polymorphic early transposon (ETn)/MusD and intracisternal A-type particles (IAP). ERVs are transcriptionally silenced during early embryogenesis by histone and DNA methylation (and reviewed in ref. 7), alth

Occupational sedentariness and breast cancer risk

Background: Epidemiological studies have indicated that physical activity reduces the risk of developing breast cancer. More recently, sedentary behavior has been suggested as a risk factor independent of physical activity level. The purpose of the present study was to investigate occupational sedentariness and breast cancer risk in pre- and postmenopausal women. Materials and methods: In a popula

What socioeconomic factors are associated with different levels of antenatal care visits in Bangladesh? A behavioral model

We identify the socioeconomic determinants of three levels of antenatal care (ANC) visits (no, intermediate [1–3], and recommended [≥4]) in Bangladesh using a behavior model framework for health care utilization. Using multinomial logistic regression, we found that different levels of visits had different determinants; for example, media exposure increased the likelihood of intermediate compared w

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

The absence of aldehyde dehydrogenase 1 A1-positive cells in benign mammary stroma is associated with risk factors for breast cancer

In this study, aldehyde dehydrogenase 1 (ALDH1)-expressing cells in stroma of histologically normal breast tissue from premenopausal women were investigated in situ regarding cellular morphology, cell distribution, and relation to the additional stem cell markers, CD44 (+) and CD24 (-). These results were correlated with hormonal and genetic risk factors for breast cancer. Triple immunofluorescenc

Validation of novel biomarkers for prostate cancer progression by the combination of bioinformatics, clinical and functional studies

The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clin

MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes.

Monoamine and acetylcholine neurotransmitters from the autonomic nervous system (ANS) regulate insulin secretion in pancreatic islets. The molecular mechanisms controlling neurotransmitter signaling in islet β cells and their impact on diabetes development are only partially understood. Using a glucose-intolerant, MafA-deficient mouse model, we demonstrate that MAFA controls ANS-mediated insulin s

Weak associations between human leucocyte antigen genotype and acute myocardial infarction.

Objectives. Human leucocyte antigens (HLAs) are polymorphic molecules involved in antigen presentation. Associations between HLA type and autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis, are well established but the potential association of genetic variation affecting antigen presentation with cardiovascular disease has not been systematically investigated in large cohorts. T

Cell number and timing of transplantation determine survival of human neural stem cell grafts in stroke-damaged rat brain.

Neural stem cells (NSCs) derived from human fetal striatum and transplanted as neurospheres survive in stroke-damaged striatum, migrate from the implantation site, and differentiate into mature neurons. Here, we investigated how various steps of neurogenesis are affected by intrastriatal transplantation of human NSCs at different time points after stroke and with different numbers of cells in each

Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients.

ABSTRACT: BACKGROUND: There is an insufficient number of reliable prognostic and response predictive biomarkers in colorectal cancer (CRC) management. In a previous study, we found that high tumour tissue expression of tumour-associated trypsin inhibitor (TATI) correlated with liver metastasis and an impaired prognosis in CRC. The aim of this study was to investigate the prognostic validity of ser

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

Changing clinical presentation of angiosarcomas after breast cancer: from late tumors in edematous arms to earlier tumors on the thoracic wall.

Angiosarcoma is a rare complication of breast cancer treatment. In order to define predictors, clinical presentation, and outcome, we characterized a population-based 50-year cohort of angiosarcomas after breast cancer. Clinical data were collected from all females with previous breast cancer who developed angiosarcomas/lymphangiosarcomas on the thoracic wall/upper extremity between 1958 and 2008

Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide.

Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide.

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

Association between fat intake, physical activity and mortality depending on genetic variation in FTO.

Objective:We wanted to explore if FTO genotype interacts with fat intake, or leisure-time physical activity, on fat mass, lean mass and mortality.Subjects and methods:Among 22 799 individuals (44-74 years) in the population-based Malmö diet and cancer cohort that were genotyped for rs9939609 in FTO and had information on dietary intake (from a modified diet history method) and no history of diabet

Conditions for Reconciliation: Narratives of Survivors from the War in Bosnia and Herzegovina

Abstract in Uncoded languages Namen prispevka:Namen prispevka je analizirati ponovno podane izkušnje 27-ih preživelih vojne v Bosni in Hercegovini v 90-ih letih prejšnjega stoletja. V pripovedih smo pregledali verbalne znake sprave in pomiritve ter analizirali opisane izraze za spravo. Metode: Gradivo za raziskavo je bilo zbrano s kvalitativnimi intervjuji 27-ih posameznikov, ki so preživeli vojnoPurpose: The aim of this article was to analyze the retold experiences of 27 survivors from the 1990s war in Bosnia and Herzegovina. I have examined verbal markers of reconciliation and implacability and analyzed the described terms for reconciliation that are being actualized in the narratives. Design: The material for the study was gathered through qualitative interviews with 27 individuals who

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