Whole genome sequencing of breast cancer.

Breast cancer was the first to take advantage of targeted therapy using endocrine therapy, and for up to 20% of all breast cancer patients a further significant improvement has been obtained by HER2-targeted therapy. Greater insight in precision medicine is to some extent driven by technical and computational progress, with the first wave of a true technical advancement being the application of transcriptomic analysis. Molecular subtyping further improved our understanding of breast cancer biology and has through a new tumor classification enabled allocation of personalized treatment regimens.

Shared heritability and functional enrichment across six solid cancers.

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r = 0.

Completeness of testing in patients with medullary thyroid carcinoma in Denmark 1997-2013: a nationwide study.

Background: The completeness of arranged during ransfection () testing in patients with medullary thyroid carcinoma (MTC) was recently reported as 60%. However, the completeness on a population level is unknown. Similarly, it is unknown if the first Danish guidelines from 2002, recommending testing in all MTC patients, improved completeness in Denmark.

Evaluating the use of responsive art therapy in an inpatient child and adolescent mental health services unit.

Objectives: We describe the use of responsive art therapy in an inpatient child and adolescent mental health services unit, including its acceptability rated through a satisfaction questionnaire.

Methods: A patient satisfaction questionnaire was developed to collect feedback from 46 adolescents. Images from therapy were photographed and collated looking for patterns across diagnoses and stages of treatment.

Sequential fractionation of the lignocellulosic components in hardwood based on steam explosion and hydrotropic extraction.

Background: The forest biorefinery plays an important part in the evolving circular bioeconomy due to its capacity to produce a portfolio of bio-based and sustainable fuels, chemicals, and materials. To tap into its true potential, more efficient and environmentally benign methods are needed to fractionate woody biomass into its main components (cellulose, hemicellulose, and lignin) without reducing their potential for valorization. This work presents a sequential fractionation method for hardwood based on steam pretreatment (STEX) and hydrotropic extraction (HEX) with sodium xylene sulfonate.

Survival and Long-Term Biochemical Cure in Medullary Thyroid Carcinoma in Denmark 1997-2014: A Nationwide Study.

Background: Survival of medullary thyroid carcinoma (MTC) subgroups in relation to the general population is poorly described. Data on the factors predicting long-term biochemical cure in MTC patients are nonexistent at a population level. A nationwide retrospective cohort study of MTC in Denmark from 1997 to 2014 was conducted, aiming to detect subgroups with survival similar to that of the general population and to identify prognostic factors for disease-specific survival and long-term biochemical cure.

Replication of newly proposed TNM staging system for medullary thyroid carcinoma: a nationwide study.

A recent study proposed new TNM groupings for better survival discrimination among stage groups for medullary thyroid carcinoma (MTC) and validated these groupings in a population-based cohort in the United States. However, it is unknown how well the groupings perform in populations outside the United States. Consequently, we conducted the first population-based study aiming to evaluate if the recently proposed TNM groupings provide better survival discrimination than the current American Joint Committee on Cancer (AJCC) TNM staging system (seventh and eighth edition) in a nationwide MTC cohort outside the United States.

Deep targeted sequencing of in chronic lymphocytic leukemia: clinical impact at diagnosis and at time of treatment.

In chronic lymphocytic leukemia, mutations and deletion of chromosome 17p are well-characterized biomarkers associated with poor progression-free and overall survival following chemoimmunotherapy. Patients harboring low burden mutations with variant allele frequencies of 0.3-15% have been shown to have similar dismal outcome as those with high burden mutations.

The Problematic Use of Dietary Reference Intakes to Assess Magnesium Status and Clinical Importance.

Determination of the public health concern about magnesium (Mg) in health and disease has been confounded by the lack of a practical measure of status. This has resulted in a lack of consistency in associating Mg deficiency with specific pathological conditions. Some attempts at associating Mg with a chronic disease have used the Dietary Reference Intakes (DRIs) as a status assessment measure.

Incidence and prevalence of multiple endocrine neoplasia 2A in Denmark 1901-2014: a nationwide study.

Background: The incidence and prevalence of multiple endocrine neoplasia 2A (MEN2A) have only been reported once in a nationwide setting. However, it is unclear whether the figures are representative of other populations, as the major component of the syndrome, hereditary medullary thyroid carcinoma (MTC), has been reported as rare in the same country. We conducted a nationwide retrospective cohort study of MEN2A in Denmark from 1901 to 2014, aiming to describe the incidence and prevalence.

Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study.

Background: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear.

Methods: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer.

Using microarray-based subtyping methods for breast cancer in the era of high-throughput RNA sequencing.

Breast cancer is a highly heterogeneous disease that can be classified into multiple subtypes based on the tumor transcriptome. Most of the subtyping schemes used in clinics today are derived from analyses of microarray data from thousands of different tumors together with clinical data for the patients from which the tumors were isolated. However, RNA sequencing (RNA-Seq) is gradually replacing microarrays as the preferred transcriptomics platform, and although transcript abundances measured by the two different technologies are largely compatible, subtyping methods developed for probe-based microarray data are incompatible with RNA-Seq as input data.

Copenhagen Prospective Personalized Oncology (CoPPO)-Clinical Utility of Using Molecular Profiling to Select Patients to Phase I Trials.

Purpose: We evaluated the clinical benefit of tumor molecular profiling to select treatment in the phase I setting.

Experimental Design: Patients with advanced solid cancers and exhausted treatment options referred to a phase I unit were included in a prospective, single-center, single-arm open-label study (NCT02290522). Tumor biopsies were obtained for comprehensive genomic analysis including whole-exome sequencing and RNA sequencing.

Hair cortisol in newly diagnosed bipolar disorder and unaffected first-degree relatives.

Objective: Hair cortisol is a promising new biomarker of retrospective systemic cortisol concentration. In this study, we compared hair cortisol concentrations in patients with newly diagnosed bipolar disorder (BD), their unaffected first-degree relatives and healthy individuals and identified potential predictors of hair cortisol concentrations in patients with BD.

Method: In a cross-sectional design, we compared hair cortisol concentrations in 181 patients with newly diagnosed/first episode BD, 42 of their unaffected first-degree relatives and 101 healthy age- and sex-matched individuals with no personal or first-degree family history of affective disorder.

Circulating tumor DNA as a marker of treatment response in BRAF V600E mutated non-melanoma solid tumors.

Purpose: We evaluated longitudinal tracking of BRAF V600E in circulating cell-free DNA (cfDNA) as a marker of treatment response to BRAF inhibitor (BRAFi) combination therapies in non-melanoma solid tumors included in the Copenhagen Prospective Personalized Oncology (CoPPO) program.

Experimental Design: Patients with BRAF V600E-mutated tumors were treated with combination therapies including BRAFi. Quantification of mutant cfDNA from plasma was determined and correlated to clinical outcomes.

Reproductive Function in a Population of Young Faroese Men with Elevated Exposure to Polychlorinated Biphenyls (PCBs) and Perfluorinated Alkylate Substances (PFAS).

Semen quality may be adversely affected by exposure to environmental chemicals such as polychlorinated biphenyls (PCBs) and perfluorinated alkylate substances (PFASs) that are persistent and may act as endocrine disrupting compounds. The aim of this study was to explore whether PCBs or PFASs exposure were associated with abnormalities in semen quality or reproductive hormones in Faroese men. This population based cross-sectional study includes 263 Faroese men (24⁻26 years) who delivered a semen sample for assessment of sperm concentration, total sperm count, semen volume, morphology and motility.

Effects of Nutritional Deficiency of Boron on the Bones of the Appendicular Skeleton of Mice.

Scientific evidence has shown the nutritional importance of boron (B) in the remodeling and repair of cancellous bone tissue. However, the effects of the nutritional deficiency of B on the cortical bone tissue of the appendicular skeleton have not yet been described. Thus, a study was performed to histomorphometrically evaluate the density of osteocyte lacunae of cortical bone of mouse femora under conditions of nutritional deficiency of B and to analyze the effects of the deficiency on the biomechanical properties of mouse tibiae.

Cross sectional study of multiresistant bacteria in Danish emergency departments: prevalence, patterns and risk factors for colonization (AB-RED project).

Background: Multiresistant bacteria (MRB) is an increasing problem. Early identification of patients with MRB is mandatory to avoid transmission and to target the antibiotic treatment. The emergency department (ED) is a key player in the early identification of patients who are colonized with MRB.

MicroRNA-based classifiers for diagnosis of oral cavity squamous cell carcinoma in tissue and plasma.

Background: MicroRNAs (miRNAs) hold promise as diagnostic cancer biomarkers. Here we aimed to define the miRNome in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM), and to identify and validate new diagnostic miRNAs and miRNA combinations in formalin-fixed paraffin-embedded (FFPE) tissue samples and plasma samples.

Methods: We performed next-generation miRNA sequencing in FFPE tissue samples of OSCC (n = 80) and NOM (n = 8).

A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.

Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci.

Genomic alterations accompanying tumour evolution in colorectal cancer: tracking the differences between primary tumours and synchronous liver metastases by whole-exome sequencing.

Background: Colorectal cancer (CRC) patients with metastatic disease can become cured if neoadjuvant treatment can enable a resection. The search for predictive biomarkers is often performed on primary tumours tissue. In order to assess the effectiveness of tailored treatment in regard to the primary tumour the differences in the genomic profile needs to be clarified.

High treatment adherence, satisfaction, motivation, and health-related quality of life with fingolimod in patients with relapsing-remitting multiple sclerosis - results from a 24-month, multicenter, open-label Danish study.

Purpose: Treatment adherence is a prerequisite for treatment success and therefore an important consideration to assure that therapeutic goals are achieved both from a patient point of view and for optimal health care resource utilization. Published data on treatment adherence with fingolimod (Gilenya) are limited. Therefore, this study investigated treatment adherence in patients with relapsing-remitting multiple sclerosis (RRMS) treated with fingolimod in Denmark.

Deep sequencing of human papillomavirus positive loco-regionally advanced oropharyngeal squamous cell carcinomas reveals novel mutational signature.

Background: The genetic profile for human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) remains largely unknown. The purpose of this study was to sequence tissue material from a large cohort of locoregionally-advanced HPV+ OPSCCs.

Methods: We performed targeted deep sequencing of 395 cancer-associated genes in 114 matched tumor/normal loco-regionally advanced HPV+ OPSCCs.