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The BRCA1-Δ11q alternative splice isoform bypasses germline mutations and promotes therapeutic resistance to PARP inhibition and cisplatin

Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a B

Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort

Objective: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer. Material and methods: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostat

Making Predictive Biomarkers Readily Available

Detection of the androgen receptor splice variant 7 in circulating tumor cells and in prostate cancer tissue harbors prognostic and predictive information. The true value of measuring androgen receptor splice variant 7 to predict response to different treatments is still unproven but is currently under evaluation in clinical trials.

Requirements engineering in open innovation

During the last two decades a slow but steady change of external factors has set-up new conditions affecting the way in how software producing firms create and leverage innovations. Firms now need to look outside of their boundaries and start interacting with the open environment that encompasses them in order to stay innovative and keep a competitive advantage. To facilitate this shift Requiremen

Variable Elimination for Scalable Receding Horizon Temporal Logic Planning

Correct-by-construction synthesis of high-level reactive control relies on the use of formal methods to generate controllers with provable guarantees on their behavior. While this approach has been successfully applied to a wide range of systems and environments, it scales poorly. A receding horizon framework mitigates this computational blowup, by decomposing the global control problem into sever

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

Roux-en-Y gastric bypass versus calorie restriction: support for surgery as the direct contributor to aloncltered responses of insulin and incretins to a mixed meal

AbstractObjectiveTo study the immediate effects of Roux-en-Y gastric bypass (RYGB) on glucose homeostasis, insulin, and incretin responses to mixed-meal tests compared with the effects of calorie restriction (CR).SettingUniversity-affiliated bariatric surgery clinic.BackgroundRYGB induces remission of type 2 diabetes (T2 D) long before significant weight loss occurs. The time course and underlying

Macrophage colony-stimulating factor receptor marks and regulates a fetal myeloid-primed B-cell progenitor in mice

Although it is well established that unique B-cell lineages develop through distinct regulatory mechanisms during embryonic development, much less is understood about the differences between embryonic and adult B-cell progenitor cells, likely to underpin the genetics and biology of infant and childhood PreB acute lymphoblastic leukemia (PreB-ALL), initiated by distinct leukemia-initiating transloc

Effects of a culturally adapted lifestyle intervention on cardio-metabolic outcomes : a randomized controlled trial in Iraqi immigrants to Sweden at high risk for Type 2 diabetes

Background andAims Middle-Eastern immigrants constitute a growing proportion of the Swedish population and are at high risk for Type 2 diabetes. This calls for a more proactive preventive approach for dealing with diabetes risk in this target group. The aim was to test the effect of a culturally adapted lifestyle intervention programme on changes in lifestyle habits and cardio-metabolic outcomes c

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