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With the advent of multimodality therapy, the overall five-year survival rate from childhood cancer has improved considerably now exceeding 80% in developed European countries. This growing cohort of survivors, with many years of life ahead of them, has raised the necessity for knowledge concerning the risks of adverse long-term sequelae of the life-saving treatments in order to provide optimal sc
Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are
Hypoglycaemia (low plasma glucose) is a serious and potentially fatal complication of insulin-treated diabetes. In healthy individuals, hypoglycaemia triggers glucagon secretion, which restores normal plasma glucose levels by stimulation of hepatic glucose production. This counterregulatory mechanism is impaired in diabetes. Here we show in mice that therapeutic concentrations of insulin inhibit g
We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic β cells (Fh1βKO mice) appear normal for 6–8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1α or Nrf2. Progressive hyperglycem
Soil organic matter (SOM) supports the Earth's ability to sustain terrestrial ecosystems, provide food and fiber, and retains the largest pool of actively cycling carbon. Over 75% of the soil organic carbon (SOC) in the top meter of soil is directly affected by human land use. Large land areas have lost SOC as a result of land use practices, yet there are compensatory opportunities to enhance prod
We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin-like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer c
Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this stud
Ferritin heavy chain (FTH1) is a 21-kDa subunit of the ferritin complex, known for its role in iron metabolism, and which has recently been identified as a favorable prognostic protein for triple negative breast cancer (TNBC) patients. Currently, it is not well understood how FTH1 contributes to an anti-tumor response. Here, we explored whether expression and cellular compartmentalization of FTH1
Three metabolite patterns have previously shown prospective inverse associations with the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins (Pattern
Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. Here, we conducted a genome-wide association study (GWAS) involving 1,554 cases/1,973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from the EPITHYR consortium. Our results confirmed the association with the know
To assess whether anthropometric measures (body mass index [BMI], waist-hip ratio [WHR], and estimated fat mass [EFM]) are independently associated with major adverse cardiovascular events (MACE), and to assess their added prognostic value compared with serum total-cholesterol. The study population comprised 109,509 individuals (53% men) from the MORGAM-Project, aged 19–97 years, without establish
Background. Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. Methods. We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD du
AIMS: Cellular communication network factor 2 (CCN2) is a matricellular protein implicated in fibrotic diseases, with ongoing clinical trials evaluating anti-CCN2-based therapies. By uncovering CCN2 as abundantly expressed in non-diseased artery tissue, this study aimed to investigate the hypothesis that CCN2 plays a pivotal role in maintaining smooth muscle cell (SMC) phenotype and protection aga
We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele was associated with modest but statistically significant increased risk of T2D (odds ratio (OR) = 1.11
BACKGROUND: Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated.METHODS: Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific difference
Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene varian
Brevmall Postadress Box 117, 221 00 Lund, Besöksadress Paradisgatan 5 Telefon 046-222 30 31 eller 046-222 00 00 E-post asa.bergenudd@bygg.lu.se Webbadress www.lu.se Rektor Föreskrift avseende intern upplåtelse av lokal inom Lunds universitet Beslutad av rektor 2021-09-23. Med stöd av 2 kap 5§ högskolelagen (1992:1434) föreskriver universitetet följande; 1. INLEDNING 1.1 Syfte Föreskriften reglerar
Popular Abstract in Swedish Händerna utsätts dagligen för olika typer av faror. Handskador av varierande omfattning är därför inte ovanliga. Dessa kan drabba både barn och vuxna, såväl under fritiden som i arbetslivet. Panoramat av handskador har förändrats. För omkring 40 år sedan var handskador vanligt förekommande på arbetsplatsen, men har sedan dess minskat så att de för 20 år sedan utgjorde uHand injuries have a profound impact not only on the patient’s activity of daily living and during leisure time but also on working capability. Such injuries may therefore also generate substantial costs for society in terms of sick-leave and treatment. In the present thesis, the panorama, costs (within the health-care system, due to lost production and total costs), outcome and health status of p
Popular Abstract in Swedish Nästan 35% av den totala avrinningen i Gula floden härstammar från dess källområde och vattenförsörjningen nedströms är därför beroende av de rådande förhållandena i detta område. Minskad vattenföring i floden på grund av klimatförändringar förväntas leda till negativa konsekvenser för de 110 miljoner invånarna i avrinningsområdet och problem uppstår för såväl jordbrukeThe source region of the Yellow River contributes about 35% of the total water yield in the Yellow River basin playing an important role for meeting the downstream water resources requirements. The declining water availability caused by climate change in the source region of the Yellow River is expected to have severe repercussions for the 110 million basin inhabitants in terms of water resources
