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Cell Sep 2021The hidden world of amyloid biology has suddenly snapped into atomic-level focus, revealing over 80 amyloid protein fibrils, both pathogenic and functional. Unlike... (Review)
Review
The hidden world of amyloid biology has suddenly snapped into atomic-level focus, revealing over 80 amyloid protein fibrils, both pathogenic and functional. Unlike globular proteins, amyloid proteins flatten and stack into unbranched fibrils. Stranger still, a single protein sequence can adopt wildly different two-dimensional conformations, yielding distinct fibril polymorphs. Thus, an amyloid protein may define distinct diseases depending on its conformation. At the heart of this conformational variability lies structural frustrations. In functional amyloids, evolution tunes frustration levels to achieve either stability or sensitivity according to the fibril's biological function, accounting for the vast versatility of the amyloid fibril scaffold.
Topics: Amyloidogenic Proteins; Animals; Disease; Evolution, Molecular; Humans; Polymorphism, Genetic; Protein Folding; Protein Stability
PubMed: 34534463
DOI: 10.1016/j.cell.2021.08.013 -
Current Protocols in Human Genetics Dec 2019Genome-wide variation data with millions of genetic markers have become commonplace. However, the potential for interpretation and application of these data for clinical... (Review)
Review
Genome-wide variation data with millions of genetic markers have become commonplace. However, the potential for interpretation and application of these data for clinical assessment of outcomes of interest, and prediction of disease risk, is currently not fully realized. Many common complex diseases now have numerous, well-established risk loci and likely harbor many genetic determinants with effects too small to be detected at genome-wide levels of statistical significance. A simple and intuitive approach for converting genetic data to a predictive measure of disease susceptibility is to aggregate the effects of these loci into a single measure, the genetic risk score. Here, we describe some common methods and software packages for calculating genetic risk scores and polygenic risk scores, with focus on studies of common complex diseases. We review the basic information needed, as well as important considerations for constructing genetic risk scores, including specific requirements for phenotypic and genetic data, and limitations in their application. © 2019 by John Wiley & Sons, Inc.
Topics: Disease; Genetic Markers; Genetic Predisposition to Disease; Genotype; Humans; Multifactorial Inheritance; Phenotype; Risk Factors; Software
PubMed: 31765077
DOI: 10.1002/cphg.95 -
British Journal of Sports Medicine Apr 2020Injury and illness surveillance, and epidemiological studies, are fundamental elements of concerted efforts to protect the health of the athlete. To encourage...
International Olympic Committee consensus statement: methods for recording and reporting of epidemiological data on injury and illness in sport 2020 (including STROBE Extension for Sport Injury and Illness Surveillance (STROBE-SIIS)).
Injury and illness surveillance, and epidemiological studies, are fundamental elements of concerted efforts to protect the health of the athlete. To encourage consistency in the definitions and methodology used, and to enable data across studies to be compared, research groups have published 11 sport-specific or setting-specific consensus statements on sports injury (and, eventually, illness) epidemiology to date. Our objective was to further strengthen consistency in data collection, injury definitions and research reporting through an updated set of recommendations for sports injury and illness studies, including a new Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist extension. The IOC invited a working group of international experts to review relevant literature and provide recommendations. The procedure included an open online survey, several stages of text drafting and consultation by working groups and a 3-day consensus meeting in October 2019. This statement includes recommendations for data collection and research reporting covering key components: defining and classifying health problems; severity of health problems; capturing and reporting athlete exposure; expressing risk; burden of health problems; study population characteristics and data collection methods. Based on these, we also developed a new reporting guideline as a STROBE Extension-the STROBE Sports Injury and Illness Surveillance (STROBE-SIIS). The IOC encourages ongoing in- and out-of-competition surveillance programmes and studies to describe injury and illness trends and patterns, understand their causes and develop measures to protect the health of the athlete. Implementation of the methods outlined in this statement will advance consistency in data collection and research reporting.
Topics: Athletic Injuries; Checklist; Disease; Epidemiologic Research Design; Humans; Sports Medicine
PubMed: 32071062
DOI: 10.1136/bjsports-2019-101969 -
Clinical and Experimental Rheumatology Feb 2022Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance.
METHODS
We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate.
RESULTS
We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly.
CONCLUSIONS
The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.
Topics: Autoantibodies; Humans; Ligases; Syndrome
PubMed: 35225224
DOI: 10.55563/clinexprheumatol/8xj0b9 -
Biomedica : Revista Del Instituto... Dec 2019
Topics: Disease; Health; Humans; Microbiota; Prebiotics; Probiotics; Symbiosis
PubMed: 31860173
DOI: No ID Found -
BMC Public Health Oct 2023Sedentary behaviour has become the new reference of living, which has paralleled the increase in the prevalence of multiple chronic diseases. Here, we highlight the...
Sedentary behaviour has become the new reference of living, which has paralleled the increase in the prevalence of multiple chronic diseases. Here, we highlight the evidence to date and propose specific topics of interest for the Collection at BMC Public Health, titled "Sedentary behaviour and disease risk".
Topics: Humans; Sedentary Behavior; Disease; Risk Factors
PubMed: 37858149
DOI: 10.1186/s12889-023-16867-2 -
Cells Sep 2021Almost 25 years have passed since a mutation of a formin gene, , was identified as being responsible for a human inherited disorder: a form of sensorineural hearing... (Review)
Review
Almost 25 years have passed since a mutation of a formin gene, , was identified as being responsible for a human inherited disorder: a form of sensorineural hearing loss. Since then, our knowledge of the links between formins and disease has deepened considerably. Mutations of and six other formin genes (, , , , and ) have been identified as the genetic cause of a variety of inherited human disorders, including intellectual disability, renal disease, peripheral neuropathy, thrombocytopenia, primary ovarian insufficiency, hearing loss and cardiomyopathy. In addition, alterations in formin genes have been associated with a variety of pathological conditions, including developmental defects affecting the heart, nervous system and kidney, aging-related diseases, and cancer. This review summarizes the most recent discoveries about the involvement of formin alterations in monogenic disorders and other human pathological conditions, especially cancer, with which they have been associated. In vitro results and experiments in modified animal models are discussed. Finally, we outline the directions for future research in this field.
Topics: Disease; Female; Formins; Humans; Male
PubMed: 34685534
DOI: 10.3390/cells10102554 -
Biological Chemistry Oct 2021
Topics: Disease; Health; Humans
PubMed: 34700365
DOI: 10.1515/hsz-2021-0390 -
Annals of the Rheumatic Diseases Oct 2023Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic...
OBJECTIVE
Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease.
METHODS
Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort.
RESULTS
Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers).
CONCLUSION
The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.
Topics: Humans; United States; Chondrocalcinosis; Rheumatology; Calcium Pyrophosphate; Calcinosis; Syndrome
PubMed: 37495237
DOI: 10.1136/ard-2023-224575 -
Nature Communications Apr 2021Genome-wide association studies (GWAS) are not fully comprehensive, as current strategies typically test only the additive model, exclude the X chromosome, and use only...
Genome-wide association studies (GWAS) are not fully comprehensive, as current strategies typically test only the additive model, exclude the X chromosome, and use only one reference panel for genotype imputation. We implement an extensive GWAS strategy, GUIDANCE, which improves genotype imputation by using multiple reference panels and includes the analysis of the X chromosome and non-additive models to test for association. We apply this methodology to 62,281 subjects across 22 age-related diseases and identify 94 genome-wide associated loci, including 26 previously unreported. Moreover, we observe that 27.7% of the 94 loci are missed if we use standard imputation strategies with a single reference panel, such as HRC, and only test the additive model. Among the new findings, we identify three novel low-frequency recessive variants with odds ratios larger than 4, which need at least a three-fold larger sample size to be detected under the additive model. This study highlights the benefits of applying innovative strategies to better uncover the genetic architecture of complex diseases.
Topics: Age Factors; Aging; Disease; Gene Frequency; Genetic Predisposition to Disease; Genome, Human; Genome-Wide Association Study; Genotype; Haplotypes; Humans; Phenotype; Polymorphism, Single Nucleotide
PubMed: 33893285
DOI: 10.1038/s41467-021-21952-4