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The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glyc
Many studies use sedimentary biogenic silica (bSiO2) stable isotopes (e.g., δ30Si) as paleoproxies but neglect signals from other sedimentary reactive SiO2 phases. We quantified δ30Si for multiple reactive Si pools in coastal river-plume sediments, revealing up to −5‰ difference between acid-leachable and alkaline-digestible amorphous SiO2. Thus, previous studies have missed valuable information o
Rapporten utgör den första av tre delrapporter och redovisar resultatet av forskning på uppdrag av Försvarsmakten.The report is the first of three sub-reports and presents the results of a research commissioned by the Swedish Armed Forces.
The discovery of the CRISPR-Cas9 system has revolutionized several areas of biological research by making genome engineering easy, affordable, fast, accessible and scalable. One field that has not yet benefited from this technological advance is that of mitochondrial DNA research. Study I addresses the challenges associated with adapting CRISPR-Cas9 to the mitochondrial environment, and identifies
OBJECTIVE: To evaluate circumferential resection margin (CRM) as a risk factor for distant metastasis (DM) in rectal cancer.SUMMARY BACKGROUND DATA: The treatment of rectal cancer has evolved over the last decades. Surgical radicality is considered the most important factor in preventing recurrences including local and distant. CRM ≤1.0 mm is considered to increase recurrence risk. This study expl
Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant t
BACKGROUND: A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC.METHODS: This multicentr
AIM: We aim to compare machine learning with neural network performance in predicting R0 resection (R0), length of stay > 14 days (LOS), major complication rates at 30 days postoperatively (COMP) and survival greater than 1 year (SURV) for patients having pelvic exenteration for locally advanced and recurrent rectal cancer.METHOD: A deep learning computer was built and the programming environment
AIM: At presentation, 15-20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection.METHOD: Data from 20 international institutions that performed simultaneous pelvic exenteration and li
OBJECTIVE: To determine factors associated with outcomes following pelvic exenteration for advanced nonrectal pelvic malignancy.BACKGROUND: The PelvEx Collaborative provides large volume data from specialist centers to ascertain factors associated with improved outcomes.METHODS: Consecutive patients who underwent pelvic exenteration for nonrectal pelvic malignancy between 2006 and 2017 were identi
Background: Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is technically challenging but increasingly performed in specialist centres. The aim of this study was to compare outcomes of exenteration over time.Methods: This was a multicentre retrospective study of patients who underwent exenteration for LARC and LRRC between 2004 and 2015. Su
OBJECTIVE: Palliative pelvic exenteration (PPE) is a technically complex operation with high morbidity and mortality rates, considered in patients with limited life expectancy. There is little evidence to guide practice. We performed a systematic review to evaluate the impact of PPE on symptom relief and quality of life (QoL).METHODS: A systematic review was conducted according to the PRISMA guide
Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for
Vitamin D regulates parathyroid cell proliferation and secretion of PTH. Increased prevalence of the polymorphic vitamin D receptor (VDR) alleles b, a, and T has been reported in sporadic primary hyperparathyroidism (PHPT), suggesting that these genetic variants may predispose to the disease. Recently, another polymorphism in the VDR gene was related to bone mineral density, and this VDR-FokI poly
OBJECTIVES: The cell cycle regulator cyclin D1 plays an important role in parathyroid tumourigenesis. The NciI polymorphism in exon 4 has recently been associated with early onset of hereditary nonpolyposis colorectal cancer and is a prognostic indicator of nonsmall cell lung cancer and squamous cell carcinomas. Furthermore, a limited study of 28 primary hyperparathyroidism (pHPT) patients display
OBJECTIVE: Hyperparathyroidism (HPT) refers to states of excessive production of parathyroid hormone (PTH). The eukaryotic cell cycle is driven forward by cyclins and their cyclin-dependent kinase (CDK) partners. Cyclin-dependent kinase inhibitors (CKIs), which generally inhibit cell cycle progression, modulate the activity of cyclin-CDK complexes.DESIGN: In order to quantify the expression of the
Vitamin D receptor (VDR) and 25-hydroxyvitamin D3 1-alpha-hydroxylase expression have recently been shown to be upregulated in several tumors and thought to represent an important endogenous response to tumor progression. Little is known about the expression of these proteins in thyroid carcinoma, although previous reports have documented evidence of the biological effect of vitamin D in thyroid c
