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Exploring the effect of menstrual loss and dietary habits on iron deficiency in teenagers : A cross-sectional study

Adolescent girls are particularly susceptible to iron deficiency due to increased iron requirements during the pubertal growth spurt, combined with iron loss following menarche. This study aimed to investigate the prevalence of heavy menstrual bleeding in an adolescent population using the SAMANTA questionnaire and to explore its relationship with dietary habits and iron deficiency. This cross-sec

Evaluating cell-specific gene expression using single-cell and single-nuclei RNA-sequencing data from human pancreatic islets of the same donors

Single-cell and single-nuclei RNA-sequencing (scRNA-seq and snRNA-seq) analyze cell-specific transcriptomes. However, only snRNA-seq applies to frozen biobanked samples. For human pancreatic islets, marker genes and reference-based cell type annotation methods are mainly from scRNA-seq datasets and may not be suitable for snRNA-seq. We compared human islet scRNA-seq and snRNA-seq data from the sam

Anpassning för personer med funktionsnedsättning i arbetslivet - Arbetsgivarens ansvar för att motverka bristande tillgänglighet

År 2015 infördes bristande tillgänglighet som en självständig diskrimineringsform i den svenska diskrimineringslagen, i syfte att stärka delaktigheten i arbetslivet för personer med funktionsnedsättning. Trots reformen visar statistik att skillnader i sysselsättning, arbetsförmåga och upplevd diskriminering fortsatt är betydande i jämförelse med övriga befolkningen. Detta aktualiserar centrala rätIn 2015, lack of accessibility was introduced as a separate form of discrimination in the Swedish Discrimination Act. The reform aimed to improve access to employment for people with disabilities. Despite this change, statistics show that large differences in employment, work capacity and experiences of discrimination remain compared to the rest of the population. This raises important legal quest

Stochastic unfolding of nanoconfined DNA : Experiments, model and Bayesian analysis

Nanochannels provide a means for detailed experiments on the effect of confinement on biomacromolecules, such as DNA. Here we introduce a model for the complete unfolding of DNA from the circular to linear configuration. Two main ingredients are the entropic unfolding force and the friction coefficient for the unfolding process, and we describe the associated dynamics by a non-linear Langevin equa

Cardiovascular disease in systemic lupus erythematosus is associated with increased levels of biomarkers reflecting receptor-activated apoptosis

Background and aims: There is convincing evidence that adaptive immune responses affect the development of atherosclerosis and thrombosis and several autoimmune diseases are associated with increased cardiovascular risk. However, our understanding of the underlying mechanisms remains limited. We investigated how biomarkers reflecting four aspects of autoimmunity: apoptosis, inflammation, tissue de

Worse breast cancer prognosis in insulin treated diabetic patients - A population based registry study in Sweden

Background. Diabetes may be linked to incidence of different tumor diseases and prognosis through various mechanisms such as the disease itself, hyperglycemia, obesity and anti-diabetes therapy. Material and methods. The study includes all women with BC diagnosed in Sweden between 2000 through 2008 (n=54406). The women had no previous cancer diagnosis during the period of 1958-1999. Dates of birth

Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing

Cyclin-dependent kinase 8 (CDK8) is a mediator complex-associated transcriptional regulator that acts depending on context and cell type. While primarily under investigation as potential cancer therapeutics, some inhibitors of CDK8—and its paralog CDK19—have been reported to affect the osteoblast lineage and bone formation. This study investigated the effects of two selective CDK8/19 inhibitors on

The Molecular Evolution of Castration-resistant Prostate Cancer

CONTEXT: Androgen deprivation therapy (ADT) is the backbone of treatment for advanced prostate cancer. However, castration-resistant prostate cancer (CRPC) nearly invariably develops through a range of different molecular mechanisms accompanied by progression to a more aggressive phenotype.OBJECTIVE: To understand the key molecular mechanisms leading to CRPC and the functional implications of this

Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma

Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFβ Smad signalling, which i

Longitudinal and postural changes of blood pressure predict dementia : the Malmö Preventive Project

The role of blood pressure (BP) changes in dementia is debatable. We aimed to analyse how resting and postural BP changes relate to incident dementia over a long-term follow-up. In the prospective population-based Malmö Preventive Project, 18,240 study participants (mean age: 45 ± 7 years, 63% male) were examined between 1974 and 1992 with resting and standing BP measurement, and re-examined betwe

Endometrial cancer risk prediction including serum-based biomarkers : results from the EPIC cohort

Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we

The prognostic impact of NK/NKT cell density in periampullary adenocarcinoma differs by morphological type and adjuvant treatment

Background: Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described. Methods: Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours fro

Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes

Background: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D. Methods: Renin was analyzed by the Proximity Extension Assay in subject

Serum vitamin D (25OHD3) levels and the risk of different subtypes of breast cancer : A nested case-control study

Background: Previous studies regarding the association between serum 25-hydroxyvitamin D (25OHD3) and breast cancer risk have not been conclusive. The aim of this study was to investigate the potential association between pre-diagnostic serum 25OHD3 levels and the risk of different subtypes of breast cancer. Materials and methods: The study was based on The Malmö Diet and Cancer Study recruiting 1

Engineered allele substitution at PPARGC1A rs8192678 alters human white adipocyte differentiation, lipogenesis, and PGC-1α content and turnover

Aims/hypothesisPPARGC1A encodes peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), a central regulator of energy metabolism and mitochondrial function. A common polymorphism in PPARGC1A (rs8192678, C/T, Gly482Ser) has been associated with obesity and related metabolic disorders, but no published functional studies have investigated direct allele-specific effects in adipocyte bi

Precision medicine in complex diseases - : Molecular subgrouping for improved prediction and treatment stratification

Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop

Acoustophoresis for label-free separation and concentration of cancer cells

Here, an acoustophoresis chip is presented that is capable of separating cancer cells from white blood cells (WBCs) and subsequently concentrating the recovered cells in the same chip. The chip utilizes ultrasound standing waves in two dimensions to pre-align, separate and concentrate the cells. 92% of the cancer cells could be recovered while keeping the contamination level of WBCs to only 0.6%.

A phenome-wide comparative analysis of genetic discordance between obesity and type 2 diabetes

Obesity and type 2 diabetes are causally related, yet there is considerable heterogeneity in the consequences of both conditions and the mechanisms of action are poorly defined. Here we show a genetic-driven approach defining two obesity profiles that convey highly concordant and discordant diabetogenic effects. We annotate and then compare association signals for these profiles across clinical an

Circulating cotinine concentrations and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

Background: Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine-a nicotine metabolite and biomarker of recent tobacco exposure-provides additional information on lung cancer risk. Methods: The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnos