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Challenges in the Identification of MSH6-Associated Colorectal Cancer: Rectal Location, Less Typical Histology, and a Subset With Retained Mismatch Repair Function.

Identification of Lynch syndrome tumors is challenging. This relates particularly to MSH6-associated cases, which show reduced penetrance of colorectal cancer and a higher age at diagnosis. We recorded the clinical and morphologic features of 52 MSH6-associated colorectal cancers in comparison with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confi

Risk predictions for individual patients from logistic regression were visualized with bar-line charts.

OBJECTIVE: The interface of a computerized decision support system is crucial for its acceptance among end users. We demonstrate how combined bar-line charts can be used to visualize predictions for individual patients from logistic regression models. STUDY DESIGN AND SETTING: Data from a previous diagnostic study aiming at predicting the immediate risk of acute coronary syndrome (ACS) among 634 p

Self-reported limitations in physical function are common 6 months after out-of-hospital cardiac arrest.

BackgroundOut-of-hospital cardiac arrest (OHCA) survivors generally report good health-related quality of life, but physical aspects of health seem more affected than other domains. Limitations in physical function after surviving OHCA have received little attention.AimsTo describe physical function 6 months after OHCA and compare it with a group of ST elevation myocardial infarction (STEMI) contr

Identification of polymorphisms in Apolipoprotein M gene and their relationship with risk of recurrent venous thromboembolism

Apolipoprotein M (ApoM) plasma levels have been reported to be associated with risk of venous thromboembolism (VTE) recurrence. However, the role of genetic alterations in the ApoM gene in VTE recurrence remains unknown. The aim of this study was to identify genetic aberrations in ApoM gene in VTE recurrence and their role in prediction of VTE recurrence in a prospective follow-up study of 1465 VT

Epidemiology of Familial Aggregation of Venous Thromboembolism

Familial aggregation (clustering) of venous thromboembolism (VTE) is the clustering of VTE within a family. Though several genes, such as antithrombin, protein C, protein S, factor V, and prothrombin are associated with the familial clustering of VTE, these loci only partially explain the familial aggregation of VTE. The epidemiology of the familial aggregation of VTE exhibits typical characterist

Preparedness for side effects and bother in symptomatic men after radical prostatectomy in a prospective, non-randomized trial, LAPPRO

Background: Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery. There are no published studies evaluating this belief. Therefore, we aimed to study the level of preparedness before radical prostatectomy and the level of bother experienced from uri

Statistical power considerations in genotype-based recall randomized controlled trials

Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for gene-metformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and

Expression of the TPa and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer : Clinical significance and diagnostic potential

The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPa and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown. This stud

Psychological Well-being and Private and Professional Psychosocial Support After Prostate Cancer Surgery : A Follow-up at 3, 12, and 24 Months After Surgery

Background Cross-sectional studies indicate that a cancer patient's partner is important in regard to the patient's psychological well-being. This has yet to be investigated in a large prospective setting. Objective To investigate types of psychosocial support and whether men improved their well-being at 12 and 24 mo after radical prostatectomy. Design, setting, and participants In a group of 1446

PBX3 is a putative biomarker of aggressive prostate cancer

There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3

Control Design Based on FMI: A Diesel Engine Control Case Study

Modelica allows systems to be described with reuseable components and with a high precision. To be able to use such complex models efficiently, high demands are set on tools that allow the user to extract the information needed from the models in a straight-forward manner. For this purpose, design-of-experiments techniques can be used to systematically analyze the complex models.In this paper, it

Novel microRNA regulators of atrial natriuretic peptide production

Atrial natriuretic peptide (ANP) has a central role in regulating blood pressure in humans. Recently, microRNA 425 (miR-425) was found to regulate ANP production by binding to the mRNA of NPPA, the gene encoding ANP. mRNAs typically contain multiple predicted microRNA (miRNA)-binding sites, and binding of different miRNAs may independently or coordinately regulate the expression of any given mRNA.

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10-8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negati

Properties of the 4-Kallikrein Panel Outside the Diagnostic Gray Zone : Meta-Analysis of Patients with Positive Digital Rectal Examination or Prostate Specific Antigen 10 ng/ml and Above

Purpose: The 4-kallikrein panel, commercially available as the 4Kscore™, is a reflex test for prostate cancer early detection that has been extensively validated in multiple international cohorts. It has been suggested that use of such reflex tests be limited to those with prostate specific antigen less than 10 ng/ml and negative digital rectal examination. We aimed to determine the value of the p

Efficiency Optimal, Maximum Pressure Control in Compression Ignition Engines

Ever since the invention of the internal combustion engine, there has been an interest in optimizing the in-cylinder pressure to achieve reliable and efficient work output. With the use of in-cylinder pressure sensors, piezoelectric injector actuation, the possibility of multiple injection events and the increased availability of computation power, cycle-to-cycle, in-cylinder pressure optimization

Human and murine hematopoietic stem cell aging is associated with functional impairments and intrinsic megakaryocytic/erythroid bias

Aging within the human hematopoietic system associates with various deficiencies and disease states, including anemia, myeloid neoplasms and reduced adaptive immune responses. Similar phenotypes are observed in mice and have been linked to alterations arising at the hematopoietic stem cell (HSC) level. Such an association is, however, less established in human hematopoiesis and prompted us here to

On the interactions between RNA and titrateable lipid layers : implications for RNA delivery with lipid nanoparticles

Characterising the interaction between cationic ionisable lipids (CIL) and nucleic acids (NAs) is key to understanding the process of RNA lipid nanoparticle (LNP) formation and release of NAs from LNPs. Here, we have used different surface techniques to reveal the effect of pH and NA type on the interaction with a model system of DOPC and the CIL DLin-MC3-DMA (MC3). At only 5% MC3, differences in

Superconductivity and magnetism in the surface states of ABC-stacked multilayer graphene

ABC-stacked multilayer graphene (ABC-MLG) exhibits topological surface flat bands with a divergent density of states, leading to many-body instabilities at charge neutrality. Here, we explore electronic ordering within a mean-field approach with full generic treatment of all spin-isotropic, two-site charge density and spin interactions up to next-nearest-neighbor (NNN) sites. We find that surface

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