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Background: To identify amino acids that can predict risk of 90-day mortality in patients with acute dyspnea. Method: Plasma levels of nine amino acids were analyzed 663 adult patients admitted to the Emergency Department (ED) with acute dyspnea. Cox proportional hazards models were used to examine the relation between amino acid levels and the risk of 90-day mortality. Result: Eighty patients (12
Multiple Myeloma (MM) is the second most common hematological malignancy. It is defined by an uncontrolled growth of plasma cells, usually in the bone marrow. Clinically it is complicated by hypercalcemia, renal failure, anaemia, and bone pain. Although recent advances in the treatment have extended survival and quality-of-life considerably, MM remains a fatal disease.Since the 1920’s MM has been
Soaking small molecules into the solvent channels of protein crystals is the most common method of obtaining crystalline complexes with ligands such as substrates or inhibitors. The solvent channels of some protein crystals are large enough to allow the incorporation of macromolecules, but soaking of protein guests into protein crystals has not been reported. Such protein host crystals (here given
Splicing and translation are two of the key steps of post-transcriptional regulation of gene expression. Their tight regulation is essential for development, whereas their deregulation is involved in cancer pathogenesis. Nevertheless, many of the molecular mechanisms controlling these processes are still unknown. Hence, the main aim of this thesis is to elucidate novel regulatory mechanisms that a
Background: Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other than MMR proteins. Methods: We compared the expression patterns of cytokeratins (CK7 and CK20), mucins
microRNAs (miRNA) are small, noncoding RNAs that bind to messenger RNAs (mRNAs) and regulate their activity. They are, therefore, important posttranscriptional regulators. In recent years it has become clear that miRNAs regulate large genetic networks, rather than single genes, and that one gene can be targeted by several miRNAs. To understand the role of miRNAs in cells or tissues, it is therefor
Hematopoietic stem and progenitor cells (HSPCs) in the fetus and adult possess distinct molecular landscapes that regulate cell fate and change their susceptibility to initiation and progression of hematopoietic malignancies. Here, we applied in-depth quantitative proteomics to comprehensively describe and compare the proteome of fetal and adult HSPCs. Our data uncover a striking difference in com
Purpose: High plasma copeptin, a marker of vasopressin, predicts diabetes mellitus. We tested if copeptin could be suppressed by increased water intake in healthy individuals, and if a water-induced change in copeptin was accompanied by altered concentrations of glucose, insulin or glucagon. Methods: Thirty-nine healthy individuals underwent, in random order, 1 week of high water intake (3 L/day o
Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel
Background: Diet is a determinant of gut microbiota. Both diet and gut microbiota have been linked to metabolic diseases. Objective: We aimed to examine data-driven food patterns in relation to the prevalence of prediabetes and gut microbiota composition and food pattern-associated bacteria in relation to prediabetes. Methods: Food patterns were extracted using principal component analysis in 1726
In a future climate change perspective, the interactions among different life-forms of primary producers will likely be altered, leading to changes in the relative dominance among macrophytes, filamentous, and planktonic algae. In order to improve the possibilities to forecast future ecosystem services and function, we therefore conducted a long-term mesocosm study where primary producers were exp
Background: Musculoskeletal pain is common in the general population and constitutes a major public health problem. A large proportion of these conditions may be work related. The aim of this study was to explore the relative importance of physical, psychosocial and personal factors, in number of pain sites and in five specific pain sites, among women in common professions with a broad variety of
B lymphocyte-induced maturation protein-1 (Blimp-1), the transcription factor encoded by the gene Prdm1, plays a number of crucial roles in the adaptive immune system, which result in the maintenance of key effector functions of B- and T-cells. Emerging clinical data, as well as mechanistic evidence from mouse studies, have additionally identified critical functions of Blimp-1 in the maintenance o
Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 partic
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 lo
Purpose: Carriers of CDKN2A mutations have high risks of melanoma and certain other cancers. In this study we examined the occurrence of tumors among CDKN2A wild type (wt) members of melanoma-prone families with CDKN2A mutations. Methods: Swedish and US melanoma-prone families with CDKN2A mutations were included. Data was collected on tumors diagnosed among family members. Among the CDKN2A mutated
Our aim was to identify serum microRNAs (miRNAs) in healthy humans which associate with future onset of both diabetes mellitus and cardiovascular disease. We performed global profiling of 753 mature human miRNAs in serum of 12 pilot subjects followed by measurement of 47 consistently expressed miRNAs in fasting serum of 553 healthy subjects from the baseline exam (1991–1994) of the population base
National virtual multidisciplinary team meetings have been established in Swedish cancer care in response to centralized treatment of rare cancers. Though national meetings grant access to a large multidisciplinary network, we hypothesized that video-based meetings may challenge participants’ contributions to the case discussions. We investigated participants’ views and used observational tools to
Background: Case review and discussion at multidisciplinary team meetings (MDTMs) have evolved into standard practice in cancer care with the aim to provide evidence-based treatment recommendations. As a basis for work to optimize the MDTMs, we investigated participants' views on the meeting function, including perceived benefits and barriers. Methods: In a cross-sectional study design, 244 health
