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Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer

Analysis of the genomic landscape of prostate cancer has identified different molecular subgroups with relevance for novel or existing targeted therapies. The recent approvals of the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and rucaparib in the metastatic castration-resistant prostate cancer (mCRPC) setting signal the need to embed molecular diagnostics in the clinical pathway of pat

Metabolic factors and the risk of small intestine cancers : Pooled study of 800 000 individuals in the metabolic syndrome and cancer project

To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Among 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex-specific hazard ratios (HRs) of small intestine cancer by levels of BMI, mean arteri

Prevention of posttraumatic osteoarthritis at the time of injury : Where are we now, and where are we going?

This overview of progress made in preventing post-traumatic osteoarthritis (PTOA) was delivered in a workshop at the Orthopaedics Research Society Annual Conference in 2019. As joint trauma is a major risk factor for OA, defining the molecular changes within the joint at the time of injury may enable the targeting of biological processes to prevent later disease. Animal models have been used to te

Low thyroid hormone receptor alpha-2 (THRα-2) tumor expression is associated with unfavorable tumor characteristics and high breast cancer mortality

BackgroundThe active thyroid hormone triiodothyronine (T3) has been found to have an estrogen-like effect on breast cancer cells. Thyroid hormone receptor alpha-2 (THRα-2) acts as an antagonist for triiodothyronine (T3) signaling, and a low expression has been associated with unfavorable tumor characteristics and a higher mortality in breast cancer. However, the evidence are not conclusive. The pr

New developments in virtual reality-assisted treatment of aggression in forensic settings: The case of VRAPT

Aggression is a known problem in individuals being cared for in forensic settings, yet the evidence base for its treatment is scarce. Virtual Reality (VR) has been proposed as a promising addition to interventions in forensic settings, as it may increase the motivation among participants, bridge the gap between real life, therapeutic and laboratory experiences, and increase the ecological validity

Attenuated early pregnancy weight gain by prenatal lifestyle interventions does not prevent gestational diabetes in the LIFE-Moms consortium

Aims: To examine the effect of lifestyle (diet and physical activity) interventions on the prevalence of GDM, considering the method of GDM ascertainment and its association with early pregnancy characteristics and maternal and neonatal outcomes in the LIFE-Moms consortium. Methods: LIFE-Moms evaluated the effects of lifestyle interventions to optimize gestational weight gain in 1148 pregnant wome

Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals

Background: Saturated fat (SFA) has consistently been shown to increase liver fat, but the response appears variable at the individual level. Phenotypic and genotypic characteristics have been demonstrated to modify the hypercholesterolemic effect of SFA but it is unclear which characteristics that predict liver fat accumulation in response to a hypercaloric diet high in SFA. Objective: To identif

Can the validity of a cohort be improved by reweighting based on register data? Evidence from the Swedish MDC study

Background: In any study with voluntary participation, self-selection risks leading to invalid conclusions. If the determinants of selection are observed, it is however possible to restore the parameters of interest by reweighting the sample to match the population, but this approach has seldom been applied in epidemiological research. Methods: We reweighted the Malmö Diet and Cancer (MDC) study b

Synthesis and Characterization of a Biocomposite Bone Bandage for Controlled Delivery of Bone-Active Drugs in Fracture Nonunions

Fracture nonunions are common in orthopedics and their treatment often involves multiple surgical interventions. The aim of this study was to fabricate and characterize a gelatin-nano-hydroxyapatite membrane (GM)-based bone bandage for controlled delivery of bio-active molecules; recombinant human bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) to promote osteoinduction and prevent c

Standard mortality rates and years of life lost for serologically defined adult-onset type 1 and type 2 diabetes – A fifteen year follow-up

Aims: The Diabetes Incidence in Kronoberg (DIK) study of adult-onset diabetes used serological classification. Standard Mortality Rates (SMR) and Years of Life Lost (YLL) 15 years after adult-onset (18–100 years) of diabetes were compared to the population of Kronoberg. Methods: Of 1609/1660 (97%) patients, 112 (7%) had type 1 (T1D) (GADA+ and/or ICA+, and/or C-peptide < 0.25 nmol/l), and 1497 (93

Cervical cancer among Swedish women with drug use disorders : A nationwide epidemiological study

Background/Aim: Cervical cancer incidence and mortality has decreased after introduction of national screening in Sweden, but women with drug use disorders (DUD) are less likely to participate in screening programs. We aimed to investigate cervical cancer incidence and mortality among women with DUD compared to the general female population in Sweden. Methods: We conducted a cohort study based on

Development and validation of a lifestyle-based model for colorectal cancer risk prediction : the LiFeCRC score

Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to sc

Realization of Ultrahigh Quality InGaN Platelets to be Used as Relaxed Templates for Red Micro-LEDs

In this work, arrays of predominantly relaxed InGaN platelets with indium contents of up to 18%, free from dislocations and offering a smooth top c-plane, are presented. The InGaN platelets are grown by metal-organic vapor phase epitaxy on a dome-like InGaN surface formed by chemical mechanical polishing of InGaN pyramids defined by 6 equivalent {101&macr; 1} planes. The dome-like surface is f

Compressed Sensing for Reconstructing Coherent Multidimensional Spectra

We apply two sparse reconstruction techniques, the least absolute shrinkage and selection operator (LASSO) and the sparse exponential mode analysis (SEMA), to two-dimensional (2D) spectroscopy. The algorithms are first tested on model data, showing that both are able to reconstruct the spectra using only a fraction of the data required by the traditional Fourier-based estimator. Through the analys

Towards classification criteria for early-stage knee osteoarthritis : A population-based study to enrich for progressors

Objective: To facilitate a greater likelihood of favorable response to new disease-modifying therapies, recruitment of patients at an earlier stage of their disease into clinical trials may be an attractive strategy. Hence, there is a need to develop widely accepted classification criteria for early-stage knee osteoarthritis (OA). We have proposed a set of classification criteria for early-stage k

Assessment of lifestyle factors helps to identify liver fibrosis due to non-alcoholic fatty liver disease in obesity

Only some individuals with obesity develop liver fibrosis due to non-alcoholic fatty liver disease (NAFLD-fibrosis). We determined whether detailed assessment of lifestyle factors in addition to physical, biochemical and genetic factors helps in identification of these patients. A total of 100 patients with obesity (mean BMI 40.0 ± 0.6 kg/m2 ) referred for bariatric surgery at the Helsinki Univers

The PNPLA3-I148M Variant Confers an Antiatherogenic Lipid Profile in Insulin-resistant Patients

CONTEXT: The I148M (rs738409-G) variant in PNPLA3 increases liver fat content but may be protective against cardiovascular disease. Insulin resistance (IR) amplifies the effect of PNPLA3-I148M on liver fat. OBJECTIVE: To study whether PNPLA3-I148M confers an antihyperlipidemic effect in insulin-resistant patients. DESIGN: Cross-sectional study comparing the impact of PNPLA3-I148M on plasma lipids

Benefits and constrains of covalency : the role of loop length in protein stability and ligand binding

Protein folding is governed by non-covalent interactions under the benefits and constraints of the covalent linkage of the backbone chain. In the current work we investigate the influence of loop length variation on the free energies of folding and ligand binding in a small globular single-domain protein containing two EF-hand subdomains—calbindin D9k. We introduce a linker extension between the s