Novel Blood-Based RNA Profiles can Predict Human Degenerative Cervical Myelopathy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE223227 | GEO | 2024/10/05
REPOSITORIES: GEO
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Project description:Degenerative myelopathy (DM) is a canine disease very similar to amyotrophic lateral sclerosis (ALS) in humans. We previously showed that DM is a promising model for ALS, as genome-wide association identified a mutation in SOD1, a known ALS gene. In this study, we identify a modifier gene, SP110, which strongly affects overall disease risk and age-of-onset in Pembroke Welsh corgis at risk of DM. Dissecting the complex genetics of this disease in a model organism may lead to new insights about risk and progression in both canine and human patients. 15 DM-affected and 31 unaffected PWC homozygous for SOD1 mutation genotyped using the Illumina CanineHD array (~170,000 SNPs genomewide)
2016-06-01 | E-GEOD-80735 | biostudies-arrayexpress
Project description:Degenerative myelopathy (DM) is a canine disease very similar to amyotrophic lateral sclerosis (ALS) in humans. We previously showed that DM is a promising model for ALS, as genome-wide association identified a mutation in SOD1, a known ALS gene. In this study, we identify a modifier gene, SP110, which strongly affects overall disease risk and age-of-onset in Pembroke Welsh corgis at risk of DM. Dissecting the complex genetics of this disease in a model organism may lead to new insights about risk and progression in both canine and human patients. 15 DM-affected and 10 unaffected Boxers homozygous for SOD1 mutation genotyped using the Illumina CanineHD array (~170,000 SNPs genomewide)
2016-06-01 | E-GEOD-80315 | biostudies-arrayexpress
Project description:Degenerative myelopathy (DM) is a canine disease very similar to amyotrophic lateral sclerosis (ALS) in humans. We previously showed that DM is a promising model for ALS, as genome-wide association identified a mutation in SOD1, a known ALS gene. In this study, we identify a modifier gene, SP110, which strongly affects overall disease risk and age-of-onset in Pembroke Welsh corgis at risk of DM. Dissecting the complex genetics of this disease in a model organism may lead to new insights about risk and progression in both canine and human patients.
2016-06-01 | GSE80735 | GEO
Project description:Degenerative myelopathy (DM) is a canine disease very similar to amyotrophic lateral sclerosis (ALS) in humans. We previously showed that DM is a promising model for ALS, as genome-wide association identified a mutation in SOD1, a known ALS gene. In this study, we identify a modifier gene, SP110, which strongly affects overall disease risk and age-of-onset in Pembroke Welsh corgis at risk of DM. Dissecting the complex genetics of this disease in a model organism may lead to new insights about risk and progression in both canine and human patients.
2016-06-01 | GSE80315 | GEO
Project description:The degeneration of cartilage endplate in cervical disc is considered as a basis of cervical spondylosis. Owing to the important role of post-transcriptional gene regulation in phenotypes and functions of cells, non-coding ribonucleic acid (ncRNA) molecules contributed to the regulation.Degenerated cervical vertebral endplate cartilage specimens were collected from patients with cervical intervertebral disc degeneration (CIDD) that suffered from cervical spondylosis myelopathy, who had received anterior cervical discectomy and fusion (ACDF). CE specimens of healthy subjects were obtained from patients with a cervical fracture who received ACDF at The Second Affiliated Hospital of Nanchang University (Nanchang, China) and adopted SBC human ceRNA array V1.0（4×180K）. The results revealed that expressions of369 lncRNAs, 246 mRNAs, 578 circRNAs were different between degenerated cartilage endplate and healthy cartilage endplate. The functions of differentially expressed lncRNAs and co-expressed potential targeting genes were predicted by analyzing Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis. Furthermore, we analyzed and find the co-expression and interaction patterns of different RNAs and possible ceRNA mechanism. The present study provided a systematic perspective on the potential function of non-coding RNAs (ncRNAs) in the degeneration of cartilage endplate in CIDD.
2020-07-04 | GSE153761 | GEO
Project description:(1) Background: Cervical vertigo (CV) represents a controversial entity, with a prevalence ranging from reported high frequency to negation of CV existence. (2) Objectives: To assess the prevalence and cause of vertigo in patients with a manifest form of severe cervical spondylosis-degenerative cervical myelopathy (DCM) with special focus on CV. (3) Methods: The study included 38 DCM patients. The presence and character of vertigo were explored with a dedicated questionnaire. The cervical torsion test was used to verify the role of neck proprioceptors, and ultrasound examinations of vertebral arteries to assess the role of arteriosclerotic stenotic changes as hypothetical mechanisms of CV. All patients with vertigo underwent a detailed diagnostic work-up to investigate the cause of vertigo. (4) Results: Symptoms of vertigo were described by 18 patients (47%). Causes of vertigo included: orthostatic dizziness in eight (22%), hypertension in five (14%), benign paroxysmal positional vertigo in four (11%) and psychogenic dizziness in one patient (3%). No patient responded positively to the cervical torsion test or showed significant stenosis of vertebral arteries. (5) Conclusions: Despite the high prevalence of vertigo in patients with DCM, the aetiology in all cases could be attributed to causes outside cervical spine and related nerve structures, thus confirming the assumption that CV is over-diagnosed.
| S-EPMC8201049 | biostudies-literature
Project description:Degenerative cervical myelopathy (DCM) is a spinal cord condition that results in progressive non-traumatic compression of the cervical spinal cord. Spine surgeons must consider a large quantity of information relating to disease presentation, imaging features, and patient characteristics to determine if a patient will benefit from surgery for DCM. We applied a supervised machine learning approach to develop a classification model to predict individual patient outcome after surgery for DCM. Patients undergoing surgery for DCM as a part of the AOSpine CSM-NA or CSM-I prospective, multi-centre studies were included in the analysis. Out of 757 patients 605, 583, and 539 patients had complete follow-up information at 6, 12, and 24 months respectively and were included in the analysis. The primary outcome was improvement in the SF-6D quality of life indicator score by the minimum clinically important difference (MCID). The secondary outcome was improvement in the modified Japanese Orthopedic Association (mJOA) score by the MCID. Predictor variables reflected information about pre-operative disease severity, disease presentation, patient demographics, and comorbidities. A machine learning approach of feature engineering, data pre-processing, and model optimization was used to create the most accurate predictive model of outcome after surgery for DCM. Following data pre-processing 48, 108, and 101 features were chosen for model training at 6, 12, and 24 months respectively. The best performing predictive model used a random forest structure and had an average area under the curve (AUC) of 0.70, classification accuracy of 77%, and sensitivity of 78% when evaluated on a testing cohort that was not used for model training. Worse pre-operative disease severity, longer duration of DCM symptoms, older age, higher body weight, and current smoking status were associated with worse surgical outcomes. We developed a model that predicted positive surgical outcome for DCM with good accuracy at the individual patient level on an independent testing cohort. Our analysis demonstrates the applicability of machine-learning to predictive modeling in spine surgery.
| S-EPMC6448910 | biostudies-literature
Project description:BackgroundDegenerative cervical myelopathy (DCM) is widely accepted as the most common cause of adult myelopathy worldwide. Despite this, there is no specific term or diagnostic criteria in the International Classification of Diseases 11th Revision and no Medical Subject Headings (MeSH) or an equivalent in common literature databases. This makes searching the literature and thus conducting systematic reviews or meta-analyses imprecise and inefficient. Efficient research synthesis is integral to delivering evidence-based medicine and improving research efficiency.ObjectiveThis study aimed to illustrate the difficulties encountered when attempting to carry out a comprehensive and accurate evidence search in the field of DCM by identifying the key sources of imprecision and quantifying their impact.MethodsTo identify the key sources of imprecision and quantify their impact, an illustrative search strategy was developed using a validated DCM hedge combined with contemporary strategies used by authors in previous systematic reviews and meta-analyses. This strategy was applied to Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE) databases looking for relevant DCM systematic reviews and meta-analyses published within the last 5 years.ResultsThe MEDLINE via PubMed search strategy returned 24,166 results, refined to 534 papers after the application of inclusion and exclusion criteria. Of these, 32.96% (176/534) results were about DCM, and 18.16% (97/534) of these were DCM systematic reviews or meta-analyses. Non-DCM results were organized into imprecision categories (spinal: 268/534, 50.2%; nonspinal: 84/534, 15.5%; and nonhuman: 8/534, 1.5%). The largest categories were spinal cord injury (75/534, 13.67%), spinal neoplasms (44/534, 8.24%), infectious diseases of the spine and central nervous system (18/534, 3.37%), and other spinal levels (ie, thoracic, lumbar, and sacral; 18/534, 3.37%). Counterintuitively, the use of human and adult PubMed filters was found to exclude a large number of relevant articles. Searching a second database (EMBASE) added an extra 12 DCM systematic reviews or meta-analyses.ConclusionsDCM search strategies face significant imprecision, principally because of overlapping and heterogenous search terms, and inaccurate article indexing. Notably, commonly employed MEDLINE filters, human and adult, reduced search sensitivity, whereas the related articles function and the use of a second database (EMBASE) improved it. Development of a MeSH labeling and a standardized DCM definition would allow comprehensive and specific indexing of DCM literature. This is required to support a more efficient research synthesis.
| S-EPMC7317636 | biostudies-literature
Project description:Degenerative cervical myelopathy (DCM) is a common progressive disease of the spinal cord which can cause tetraplegia. Despite its prevalence, few studies have investigated the pathophysiology of DCM. Macroautophagy is a cellular process which degrades intracellular contents and its disruption is thought to contribute to many neurodegenerative diseases. The present study tests the hypothesis that macroautophagy is impaired in DCM. To address this, we utilised a collection of post-mortem cervical spinal cord samples and investigated seven DCM cases and five human controls. Immunohistochemical staining was used to visualise proteins involved in autophagy. This demonstrated significantly reduced numbers of LC3 puncta in cases versus controls (p = 0.0424). Consistent with reduced autophagy, we identified large aggregates of p62 in four of seven cases and no controls. Tau was increased in two of five cases compared to controls. BCL-2 was significantly increased in cases versus controls (p = 0.0133) and may explain this reduction in autophagy. Increased BCL-2 (p = 0.0369) and p62 bodies (p = 0.055) were seen in more severe cases of DCM. This is the first evidence that autophagy is impaired in DCM; the impairment appears greater in more severe cases. Further research is necessary to investigate whether macroautophagy has potential as a therapeutic target in DCM.
| S-EPMC9279443 | biostudies-literature
Project description:ObjectiveDegenerative cervical myelopathy [DCM] is a disabling and increasingly prevalent group of diseases. Heterogeneous reporting of trial outcomes limits effective inter-study comparison and optimisation of treatment. This is recognised in many fields of healthcare research. The present study aims to assess the heterogeneity of outcome reporting in DCM as the premise for the development of a standardised reporting set.MethodsA systematic review of MEDLINE and EMBASE databases, registered with PROSPERO (CRD42015025497) was conducted in accordance with PRISMA guidelines. Full text articles in English, with >50 patients (prospective) or >200 patients (retrospective), reporting outcomes of DCM were eligible.Results108 studies, assessing 23,876 patients, conducted world-wide, were identified. Reported outcome themes included function (reported by 97, 90% of studies), complications (reported by 56, 52% of studies), quality of life (reported by 31, 29% of studies), pain (reported by 29, 27% of studies) and imaging (reported by 59, 55% of studies). Only 7 (6%) studies considered all of domains in a single publication. All domains showed variability in reporting.ConclusionsSignificant heterogeneity exists in the reporting of outcomes in DCM. The development of a consensus minimum dataset will facilitate future research synthesis.
| S-EPMC4970758 | biostudies-literature