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INTRODUCTION: A granular understanding of the mechanisms linking tau pathology to cognitive decline in Alzheimer's disease is crucial. We investigate mediating effects of medial temporal lobe (MTL) and neocortical neurodegeneration on tau-induced domain-specific cognitive impairment in amyloid-beta (Aβ) positive cognitively normal and impaired adults.METHODS: We assessed magnetic resonance imaging
Amyloid-β (Aβ) is hypothesized to facilitate the spread of tau pathology beyond the medial temporal lobe. However, there is evidence that, independently of Aβ, age-related tau pathology might be present outside of the medial temporal lobe. We therefore aimed to study age-related Aβ-independent tau deposition outside the medial temporal lobe in two large cohorts and to investigate potential downstr
Despite the glimmer of hope provided by the discovery and commercialization of bone morphogenetic protein-2 (BMP-2) as a bone graft substitute, side effects related to the use of supraphysiological doses have hindered its clinical usage. In this study, we compared the osteoinductive potential of BMP-2 homodimer with a heterodimer of BMP-2/7, both delivered via a collagen-hydroxyapatite (CHA) scaff
Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other AP
Spina bifida (SB) is a debilitating birth defect caused by multiple gene and environment interactions. Though SB shows non-Mendelian inheritance, genetic factors contribute to an estimated 70% of cases. Nevertheless, identifying human mutations conferring SB risk is challenging due to its relative rarity, genetic heterogeneity, incomplete penetrance, and environmental influences that hamper genome
BACKGROUND: In the Netherlands, surgery for peritoneal metastases of colorectal cancer (PMCRC) is centralised, whereas PMCRC is diagnosed in all hospitals. This study assessed whether hospital of diagnosis affects treatment selection and overall survival (OS).METHODS: Between 2005 and 2015, all patients with synchronous PMCRC without systemic metastases were selected from the Netherlands Cancer Re
INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is currently considered the standard of care for pseudomyxoma peritonei, mesothelioma and peritoneal metastases (PM) from colorectal cancer. CRS + HIPEC has also been suggested as a potential treatment option in PM of the much rarer small bowel cancer. Therefore, the current study was undertaken to inve
BACKGROUND: The purpose of the present study was to evaluate the value of discussing rectal cancer patients in a multidisciplinary team (MDT).METHODS: All treated rectal cancer patients (>T1M0) diagnosed in 2006-2008 were included. According to the national guidelines, neoadjuvant (chemo)radiotherapy should be given to all rectal cancer patients. Patients were scored as "discussed" (MDT+) only if
BACKGROUND: Obesity, assessed by body mass index (BMI), is an established risk factor for 13 cancers. We aimed to identify further potential obesity-related cancers and to quantify their association with BMI relative to that of established obesity-related cancers.METHODS: Using Cox regression models on 4,142,349 individuals in Sweden (mean age 27.1 years at weight measurement), we calculated hazar
IMPORTANCE: Randomized controlled trials (RCTs) in children and adolescents provide evidence for patients, families, researchers, clinicians, regulators, funders, policymakers, and other interest holders to inform decisions about health care interventions and improve outcomes for young patients and their families. To critically evaluate, interpret, and apply trial results, readers require access t
Cerebral perivascular spaces (PVS) are small physiological structures around blood vessels in the brain. MRI visible PVS are associated with ageing and cerebral small vessel disease (SVD). 7 Tesla (7T) MRI improves PVS detection. We investigated the association of age, vascular risk factors, and imaging markers of SVD with PVS counts on 7 T MRI, in 50 persons aged ≥ 40. The average PVS count ± SD
Lung diseases continue to present a large burden to public health, especially in industrialized countries. For abetter understanding of the underlying patho-mechanisms in lung related diseases as well as for testing theefficacy of novel therapies, preclinical studies in animal models are indispensable. The significance of preclinical X-ray based micro-computed tomography (µCT) research lies in its
Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility for prostate cancer (PCa) screening. Using genome-wide summary statistics from 95,768 PCa-free men, we conducted a transcriptome-wide association study (TWAS) to examine impacts of genetically predicted gene expression on PSA. Analyses identified 41 statistically significant (p < 0.05/12,192 = 4.10×10
Retrotransposons are mobile DNA sequences duplicated via transcription and reverse transcription of an RNA intermediate. Cis-regulatory elements encoded by retrotransposons can also promote the transcription of adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mammalian neurons. It is, however, unclear whether L1 sequences are mobile in only some neuronal lineage
The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is a hallmark of cancer, and L1 mutagenesis has been described in numerous human malignancies. We previously employed retrotransposon capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) samples from patients infected with he
Hexavalent chromium Cr(VI) is a human carcinogen, but the current exposure to Cr(VI) at Swedish workplaces is unknown.Recruitment of 113 workers with potential Cr(VI) exposure and 72 controls was combined with measurements of inhalable Cr(VI) (only exposed workers) and total Cr in urine and red blood cells (RBC), Bayesian analysis of occupational exposure limit (OEL) compliance was used, as well a
Objective: Analyze the outcomes of endovascular complex abdominal and thoracoabdominal aortic aneurysm repair using the Cook fenestrated device with the modified preloaded delivery system (MPDS) with a biport handle and preloaded catheters. Methods: A multicenter retrospective single arm cohort study was performed, including all consecutive patients with complex abdominal aortic aneurysm repair an
PURPOSE: A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.METHODS: Women with invasive breast cancer were included, 98,397 of European ancestry and 12,920
INTRODUCTION: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an upda
