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RIC3 variants are not associated with Parkinson's disease in large European, Latin American, or East Asian cohorts

Parkinson's disease (PD) is a complex neurodegenerative disorder in which both rare and common genetic variants contribute to disease risk. Multiple genes have been reported to be linked to monogenic PD but these only explain a fraction of the observed familial aggregation. Rare variants in RIC3 have been suggested to be associated with PD in the Indian population. However, replication studies yie

Accessible data curation and analytics for international-scale citizen science datasets

The Covid Symptom Study, a smartphone-based surveillance study on COVID-19 symptoms in the population, is an exemplar of big data citizen science. As of May 23rd, 2021, over 5 million participants have collectively logged over 360 million self-assessment reports since its introduction in March 2020. The success of the Covid Symptom Study creates significant technical challenges around effective da

Relationship Between Magnetic Resonance Imaging Features and Knee Pain Over Six Years in Knees Without Radiographic Osteoarthritis at Baseline

Objective: To explore whether magnetic resonance imaging (MRI) features suggestive of knee osteoarthritis (OA) are associated with presence of knee pain in possible early-stage OA development. Methods: We included 294 participants from the Osteoarthritis Initiative (mean ± SD age 50 ± 3 years; 50% women) with baseline Kellgren/Lawrence grade of 0 in both knees, all of whom had received knee MRIs a

Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary br

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotat

Decompression of the greater occipital nerve improves outcome in patients with chronic headache and neck pain — a retrospective cohort study

Background: Compression of the greater occipital nerve (GON) may contribute to chronic headache, neck pain, and migraine in a subset of patients. We aimed to evaluate whether GON decompression could reduce pain and improve quality of life in patients with occipital neuralgia and chronic headache and neck pain. Methods: In this retrospective cohort study, selected patients with neck pain and headac

Synthesis and characterization of Au@Zn core@shell aerosol nanoparticles generated by spark ablation and on-line PVD

An interesting subset of nanoparticles is core-shell nanoparticles: encapsulating a core particle of one material with a shell of another material can be utilized to combine and even extend the properties of the respective material. Strategies to synthesize core-shell nanoparticles in the aerosol phase remain relatively unexplored, despite the benefit of the continuous, ambient pressure nature of

Dynamic Processes in Metal-Semiconductor Nanoparticle Heterostructures

Over the last years, there have been huge research efforts in the synthesis of advanced nanoparticle heterostructures to promote their performance in photocatalysis.[1] Especially, the combination of metals with semiconductors has been identified as a potential approach to enhance the photocatalytic activity via efficient charge carrier separation enabled by plasmon- exciton coupling.[2] The physi

Self-report versus clinician-ratings in the assessment of aggression in violent offenders

Background: The construct of aggression is central to work with violent offenders, but it is a broad construct that can be assessed by many different methods and instruments. Its measurement may, however, have profound implications for treatment planning. We need more knowledge about how different methods for assessing aggression relate to each other. Aims: Our aims were to investigate, first, the

Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer

Analysis of the genomic landscape of prostate cancer has identified different molecular subgroups with relevance for novel or existing targeted therapies. The recent approvals of the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and rucaparib in the metastatic castration-resistant prostate cancer (mCRPC) setting signal the need to embed molecular diagnostics in the clinical pathway of pat

Prevention of posttraumatic osteoarthritis at the time of injury : Where are we now, and where are we going?

This overview of progress made in preventing post-traumatic osteoarthritis (PTOA) was delivered in a workshop at the Orthopaedics Research Society Annual Conference in 2019. As joint trauma is a major risk factor for OA, defining the molecular changes within the joint at the time of injury may enable the targeting of biological processes to prevent later disease. Animal models have been used to te

Surface-Catalyzed Secondary Nucleation Dominates the Generation of Toxic IAPP Aggregates

The aggregation of the human islet amyloid polypeptide (IAPP) is associated with diabetes type II. A quantitative understanding of this connection at the molecular level requires that the aggregation mechanism of IAPP is resolved in terms of the underlying microscopic steps. Here we have systematically studied recombinant IAPP, with amidated C-terminus in oxidised form with a disulphide bond betwe

Low thyroid hormone receptor alpha-2 (THRα-2) tumor expression is associated with unfavorable tumor characteristics and high breast cancer mortality

BackgroundThe active thyroid hormone triiodothyronine (T3) has been found to have an estrogen-like effect on breast cancer cells. Thyroid hormone receptor alpha-2 (THRα-2) acts as an antagonist for triiodothyronine (T3) signaling, and a low expression has been associated with unfavorable tumor characteristics and a higher mortality in breast cancer. However, the evidence are not conclusive. The pr

HAMLET a human milk protein-lipid complex induces a pro-inflammatory phenotype of myeloid cells

HAMLET is a protein-lipid complex with a specific and broad bactericidal and tumoricidal activity, that lacks cytotoxic activity against healthy cells. In this study, we show that HAMLET also has general immune-stimulatory effects on primary human monocyte-derived dendritic cells and macrophages (Mo-DC and Mo-M) and murine RAW264.7 macrophages. HAMLET, but not its components alpha-lactalbumin or o

Screening of small molecules using the inhibition of oligomer formation in α-synuclein aggregation as a selection parameter

The aggregation of α-synuclein is a central event in Parkinsons’s disease and related synucleinopathies. Since pharmacologically targeting this process, however, has not yet resulted in approved disease-modifying treatments, there is an unmet need of developing novel methods of drug discovery. In this context, the use of chemical kinetics has recently enabled accurate quantifications of the micros

Synthesis and Characterization of a Biocomposite Bone Bandage for Controlled Delivery of Bone-Active Drugs in Fracture Nonunions

Fracture nonunions are common in orthopedics and their treatment often involves multiple surgical interventions. The aim of this study was to fabricate and characterize a gelatin-nano-hydroxyapatite membrane (GM)-based bone bandage for controlled delivery of bio-active molecules; recombinant human bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) to promote osteoinduction and prevent c

Cervical cancer among Swedish women with drug use disorders : A nationwide epidemiological study

Background/Aim: Cervical cancer incidence and mortality has decreased after introduction of national screening in Sweden, but women with drug use disorders (DUD) are less likely to participate in screening programs. We aimed to investigate cervical cancer incidence and mortality among women with DUD compared to the general female population in Sweden. Methods: We conducted a cohort study based on

A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers

Aberrant soluble oligomers formed by the amyloid-β peptide (Aβ) are major pathogenic agents in the onset and progression of Alzheimer’s disease. A variety of biomolecules can influence the formation of these oligomers in the brain, although their mechanisms of action are still largely unknown. Here, we studied the effects on Aβ aggregation of DOPAL, a reactive catecholaldehyde intermediate of dopa