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Global expression of AMACR transcripts predicts risk for prostate cancer - a systematic comparison of AMACR protein and mRNA expression in cancerous and noncancerous prostate.

The high false negative rates for initial prostate biopsies refer a large number of the men for repeat biopsies each year. Therefore, biomarkers associated with high risk of the presence of malignancy in histologically benign biopsies could provide a tool to discriminate the patients who need repeat biopsy or intensive follow-up from those who do not. Here we examined the diagnostic applicability

Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer

Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRC

Neural grafting in Parkinson's disease: problems and possibilities

Neural transplantation has emerged as a possible therapy for Parkinson's disease (PD). Clinical studies performed during the 1990s, where dopaminergic neurons derived from the human embryonic brain were transplanted into striatum of patients with PD, provided proof-of-principle that long-lasting therapeutic benefits can be achieved. Subsequent studies, in particular two that followed a double-blin

Genetic loci influencing kidney function and chronic kidney disease

Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into me

Dating Components of Human Atherosclerotic Plaques

Rationale: Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied. Objective: In the present study, we determined the biological age of different

Genetic Variants of Coagulation Factor XI Show Association with Ischemic Stroke Up to 70 Years of Age

Background and Purpose: Coagulation factor XI (FXI) has an important role in the propagation and stabilization of a thrombus upon vessel injury. High FXI levels have been implicated in thrombotic diseases including ischemic stroke. The aim of our study was to investigate whether FXI gene (F11) variants are associated with ischemic stroke. Methods: The discovery sample, the Sahlgrenska Academy Stud

Embedded 3D Printing in Self-Healing Annealable Composites for Precise Patterning of Functionally Mature Human Neural Constructs

Human in vitro models of neural tissue with tunable microenvironment and defined spatial arrangement are needed to facilitate studies of brain development and disease. Towards this end, embedded printing inside granular gels holds great promise as it allows precise patterning of extremely soft tissue constructs. However, granular printing support formulations are restricted to only a handful of ma

Labour market consequences of an early-onset disability : the case of cerebral palsy

The labour market consequences of early-onset or congenital disabilities have received little attention in the literature. In this paper, we study the consequences of cerebral palsy (CP), a lifelong early onset disability, and pathways through which it affects labour outcomes. We use data from multiple linked Swedish National Population Registers between 1990 and 2015 and apply both regression and

Quantum networks using rare-earth ions

We review concepts and recent work related to creating light-matter interfaces for future quantum networks based on rare-earth ion-doped crystals. More precisely, we explore their unique suitability for creating photon sources, optical quantum memories for light, and qubits that allow quantum information processing. In addition, we review the state-of-the-art of elementary quantum repeater links,

Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli

Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical ne

Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson's disease therapy

Parkinson's disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathway

Direct conversion of human fibroblasts to functional excitatory cortical neurons integrating into human neural networks

Background: Human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated. Methods: Here we screened for transcription factor combinations that could potentially convert human fibroblasts to functional excitatory cortical neurons. The induced cortical (iCtx) cells were analyzed for cortical neuronal identity using immunocytochem

Secular trends in sickness absence among Swedish patients with ankylosing spondylitis and psoriatic arthritis

The aim was to investigate whether secular trends in sickness absence (SA) were present in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) receiving their diagnosis between 2002 and 2011. A repeated cross-sectional study design was used. Patients were identified in the Skåne Healthcare Register (SHR). A washout period of 18 months was applied. The general population seeking

Genetic anticipation in Swedish Lynch syndrome families

Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS) caused by mutations in DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have an earlier onset compared to the general population. However, age at first primary cancer varies wit

Association analysis identifies 65 new breast cancer risk loci

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of

Obesity, metabolic factors and risk of different histological types of lung cancer : A Mendelian randomization study

BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and eval

Markers of basement membrane remodeling are associated with higher mortality in patients with known atherosclerosis

Background-Patients with atherosclerosis have a high risk of cardiovascular events and death. Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix proteins in the intima. We hypothesized that dysregulated remodeling of the basement membrane proteins may be associated with clinical outcomes in patients with atherosclerosis. Methods and Results-Neoepitope fragme

Biogenic aerosol particles in the earth system model EC-earth

Treatments of emissions of primary biological aerosol particles (PBAP) were implemented in the global Earth System model EC-Earth. These emission schemes were improved to account for the strong peaks of PBAP concentrations in connection to precipitation events, which has been measured recently. The model is now able to treat the emission of bacteria, spores and pollen in dependency of precipitatio

Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children

Background: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from se