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| 4. |
- Pecquet, C, et al.
(författare)
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Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants
- 2019
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 133:25, s. 2669-2681
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Tidskriftsartikel (refereegranskat)abstract
- Calreticulin (CALR) +1 frameshift mutations in exon 9 are prevalent in myeloproliferative neoplasms. Mutant CALRs possess a new C-terminal sequence rich in positively charged amino acids, leading to activation of the thrombopoietin receptor (TpoR/MPL). We show that the new sequence endows the mutant CALR with rogue chaperone activity, stabilizing a dimeric state and transporting TpoR and mutants thereof to the cell surface in states that would not pass quality control; this function is absolutely required for oncogenic transformation. Mutant CALRs determine traffic via the secretory pathway of partially immature TpoR, as they protect N117-linked glycans from further processing in the Golgi apparatus. A number of engineered or disease-associated TpoRs such as TpoR/MPL R102P, which causes congenital thrombocytopenia, are rescued for traffic and function by mutant CALRs, which can also overcome endoplasmic reticulum retention signals on TpoR. In addition to requiring N-glycosylation of TpoR, mutant CALRs require a hydrophobic patch located in the extracellular domain of TpoR to induce TpoR thermal stability and initial intracellular activation, whereas full activation requires cell surface localization of TpoR. Thus, mutant CALRs are rogue chaperones for TpoR and traffic-defective TpoR mutants, a function required for the oncogenic effects.
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| 5. |
- Abat, F, et al.
(författare)
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Current trends in tendinopathy : consensus of the ESSKA basic science committee. Part II
- 2018
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Ingår i: Journal of experimental orthopaedics. - : Springer. - 2197-1153. ; 5:38
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Tidskriftsartikel (refereegranskat)abstract
- The treatment of painful chronic tendinopathy is challenging. Multiple non-invasive and tendon-invasive methods are used. When traditional non-invasive treatments fail, the injections of platelet-rich plasma autologous blood or cortisone have become increasingly favored. However, there is little scientific evidence from human studies supporting injection treatment. As the last resort, intra- or peritendinous open or endoscopic surgery are employed even though these also show varying results. This ESSKA basic science committee current concepts review follows the first part on the biology, biomechanics and anatomy of tendinopathies, to provide a comprehensive overview of the latest treatment options for tendinopathy as reported in the literature.
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| 6. |
- Abat, F., et al.
(författare)
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Current trends in tendinopathy : consensus of the ESSKA basic science committee. Part I: biology, biomechanics, anatomy and anexercise-based approach
- 2017
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Ingår i: Journal of Experimental Orthopaedics. - : Springer. - 2197-1153. ; 4:1
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Forskningsöversikt (refereegranskat)abstract
- Chronic tendinopathies represent a major problem in the clinical practice of sports orthopaedic surgeons, sports doctors and other health professionals involved in the treatment of athletes and patients that perform repetitive actions. The lack of consensus relative to the diagnostic tools and treatment modalities represents a management dilemma for these professionals. With this review, the purpose of the ESSKA Basic Science Committee is to establish guidelines for understanding, diagnosing and treating this complex pathology.
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- Mouton-Liger, F., et al.
(författare)
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CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer's disease
- 2020
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein kinase erbB4 (ErbB4) and was linked to schizophrenia. The NRG1/ErbB4 complex is neuroprotective, can trigger synaptogenesis and plasticity, increases the expression of NMDA and GABA receptors, and can induce neuroinflammation. This complex can reduce memory formation. In Alzheimer's disease (AD) brains, NRG1 accumulates in neuritic plaques. It is difficult to determine if NRG1 has beneficial and/or detrimental effects in AD. BACE1 levels are increased in AD brains and cerebrospinal fluid (CSF) and may lead to enhanced NRG1 secretion, but no study has assessed CSF NRG1 levels in AD and mild cognitive impairment (MCI) patients. Methods: This retrospective study included 162 patients suffering from AD dementia (54), MCI with progression to AD dementia (MCI-AD) (27), non-AD MCI (30), non-AD dementias (30), and neurological controls (27). All patients had neurological examinations, brain MRI, and neuropsychological evaluations. After written informed consent and using enzyme-linked immunosorbent assays (ELISAs), CSF samples were evaluated for A beta 1-42, A beta 1-40, total tau (T-tau), phosphorylated tau on threonine 181 (P-tau), BACE1, growth-associated protein 43 (GAP 43), neurogranin (Ng), and NRG1. Results: Levels of NRG1 were significantly increased in the CSF of AD (+ 36%) and MCI-AD (+ 28%) patients compared to neurological controls and also non-AD MCI and non-AD dementias. In addition, in AD and MCI-AD patients, NRG1 levels positively correlated with A beta 1-42 but not with T-tau, P-tau, and BACE1 levels and negatively correlated with MMSE scores. A longitudinal follow-up study of AD patients revealed a trend (p = 0.08) between CSF NRG1 levels and cognitive decline. In the overall population, NRG1 correlated with MMSE and the synaptic biomarkers GAP 43 and neurogranin. Conclusions: Our results showed that CSF NRG1 levels are increased in AD and MCI-AD as compared to controls and other dementias. CSF NRG1 levels are associated with cognitive evolution, and a major outcome of our findings is that synaptic NRG1 could be involved in the pathophysiology of AD. Modulating brain NRG1 activity may represent a new therapeutic target in AD.
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| 9. |
- Spennacchio, P., et al.
(författare)
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Evaluation modalities for the anatomical repair of chronic ankle instability
- 2020
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 28, s. 163-176
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Several evaluation modalities are reported in the literature dealing with the operative treatment of chronic ankle instability (CAI) both to establish the CAI diagnosis leading to the surgical indication and to assess the effectiveness of ankle stabilisation procedure. The purpose of this study is to present an overview of the pre- and postoperative evaluation modalities reported in the literature dealing with CAI operative treatment. The comprehensive analysis of the different modalities chosen by researchers is expected to suggest critical points in current evaluation ability of CAI surgical treatment. Methods Systematic review of the literature on surgical treatment of CAI through anatomic procedures. Pubmed, Embase and Cochrane electronic databases were analysed, from 2004 to 2018. Results One-hundred-and-four studies met inclusion in this systematic review. 88 out of 104 studies analysed preoperative mechanical laxity of the ankle to depict the ligamentous insufficiency related to the subjective feeling of functional instability. Stress radiographs and manual stress examination of the ankle were the two most common modalities to evaluate joint laxity, reported in 67 and 53 studies, respectively. Clinical Outcome Measurement Scales (COMs) is the most common evaluation modality (102 out of 104 studies) to assess CAI surgical outcome. The American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale (AOFAS) and the Karlsson score are the most frequent COMs, reported in the 66% and 33%, respectively of the included literature. The radiographic analysis of ankle laxity after stabilisation procedures is the second most frequent postoperative evaluation modality, reported in 55 out 104 studies. Conclusions There is a lack of standardization among researchers related to both the criteria to establish the CAI diagnosis leading to the surgical indication and the modality chosen to evaluate the effectiveness of surgical treatment. Future standardization of evaluation modalities in the CAI population is desirable to increase consistency of reported data.
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| 10. |
- Vrillon, A., et al.
(författare)
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Plasma neuregulin 1 as a synaptic biomarker in Alzheimer's disease: a discovery cohort study
- 2022
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Synaptic dysfunction is an early core feature of Alzheimer's disease (AD), closely associated with cognitive symptoms. Neuregulin 1 (NRG1) is a growth and differentiation factor with a key role in the development and maintenance of synaptic transmission. Previous reports have shown that changes in cerebrospinal fluid (CSF) NRG1 concentration are associated with cognitive status and biomarker evidence of AD pathology. Plasma biomarkers reflecting synaptic impairment would be of great clinical interest. Objective To measure plasma NRG1 concentration in AD patients in comparison with other neurodegenerative disorders and neurological controls (NC) and to study its association with cerebrospinal fluid (CSF) core AD and synaptic biomarkers. Methods This retrospective study enrolled 127 participants including patients with AD at mild cognitive impairment stage (AD-MCI, n = 27) and at dementia stage (n = 35), non-AD dementia (n = 26, A beta-negative), non-AD MCI (n = 19), and neurological controls (n=20). Plasma and CSF NRG1, as well as CSF core AD biomarkers (A beta 42/A beta 40 ratio, phospho-tau, and total tau), were measured using ELISA. CSF synaptic markers were measured using ELISA for GAP-43 and neurogranin and through immunoprecipitation mass spectrometry for SNAP-25. Results Plasma NRG1 concentration was higher in AD-MCI and AD dementia patients compared with neurological controls (respectively P = 0.005 and P < 0.001). Plasma NRG1 differentiated AD MCI patients from neurological controls with an area under the curve of 88.3%, and AD dementia patients from NC with an area under the curve of 87.3%. Plasma NRG1 correlated with CSF NRG1 (beta = 0.372, P = 0.0056, adjusted on age and sex). Plasma NRG1 was associated with AD CSF core biomarkers in the whole cohort and in A beta-positive patients (beta = -0.197-0.423). Plasma NRG1 correlated with CSF GAP-43, neurogranin, and SNAP-25 (beta = 0.278-0.355). Plasma NRG1 concentration correlated inversely with MMSE in the whole cohort and in A beta-positive patients (all, beta = -0.188, P = 0.038; A beta+: beta = -0.255, P = 0.038). Conclusion Plasma NRG1 concentration is increased in AD patients and correlates with CSF core AD and synaptic biomarkers and cognitive status. Thus, plasma NRG1 is a promising non-invasive biomarker to monitor synaptic impairment in AD.
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| 11. |
- Cristiani, R, et al.
(författare)
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Meniscal ramp lesions: a lot is known, but a lot is also unknown…
- 2023
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Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 31:7, s. 2535-2539
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Grudniewicz, A, et al.
(författare)
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Predatory journals: no definition, no defence
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 576:7786, s. 210-212
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Królikowska, A., et al.
(författare)
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Improving the reliability of measurements in orthopaedics and sports medicine
- 2023
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - 0942-2056. ; 31, s. 5277-5285
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Tidskriftsartikel (refereegranskat)abstract
- A large space still exists for improving the measurements used in orthopaedics and sports medicine, especially as we face rapid technological progress in devices used for diagnostic or patient monitoring purposes. For a specific measure to be valuable and applicable in clinical practice, its reliability must be established. Reliability refers to the extent to which measurements can be replicated, and three types of reliability can be distinguished: inter-rater, intra-rater, and test-retest. The present article aims to provide insights into reliability as one of the most important and relevant properties of measurement tools. It covers essential knowledge about the methods used in orthopaedics and sports medicine for reliability studies. From design to interpretation, this article guides readers through the reliability study process. It addresses crucial issues such as the number of raters needed, sample size calculation, and breaks between particular trials. Different statistical methods and tests are presented for determining reliability depending on the type of gathered data, with particular attention to the commonly used intraclass correlation coefficient.
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| 15. |
- Mabrouk, A., et al.
(författare)
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MCID and PASS in Knee Surgeries. Theoretical Aspects and Clinical Relevance References
- 2023
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 31, s. 2060-2067
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Forskningsöversikt (refereegranskat)abstract
- The application and interpretation of patient-reported outcome measures (PROM), following knee injuries, pathologies, and interventions, can be challenging. In recent years, the literature has been enriched with metrics to facilitate our understanding and interpretation of these outcome measures. Two commonly utilized tools include the minimal clinically important difference (MCID) and the patient acceptable symptoms state (PASS). These measures have demonstrated clinical value, however, they have often been under- or mis-reported. It is paramount to use them to understand the clinical significance of any statistically significant results. Still, it remains important to know their caveats and limitations. In this focused report on MCID and PASS, their definitions, methods of calculations, clinical relevance, interpretations, and limitations are reviewed and presented in a simple approach.
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| 16. |
- Prentice, H. A., et al.
(författare)
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Patient demographic and surgical characteristics in anterior cruciate ligament reconstruction: a description of registries from six countries
- 2018
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 52:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective Findings from individual anterior cruciate ligament reconstruction (ACLR) registry studies are impactful, but how various registries from different countries compare with different patient populations and surgical techniques has not been described. We sought to describe six ACLR registry cohorts to understand variation across countries. Methods Five European registries and one US registry participated. For each registry, all primary ACLR registered between registry establishment through 31December 2014 were identified. Descriptive statistics included frequencies, proportions, medians and IQRs. Revision incidence rates following primary ACLR were computed. Results 101 125 ACLR were included: 21820 in Denmark, 300 in Luxembourg, 17556 in Norway, 30422 in Sweden, 2972 in the UK and 28055 in the US. In all six cohorts, males (range: 56.8%-72.4%) and soccer injuries (range: 14.1%-42.3%) were most common. European countries mostly used autografts (range: 93.7%-99.7%); allograft was most common in the US (39.9%). Interference screw was the most frequent femoral fixation in Luxembourg and the US (84.8% and 42.9%), and suspensory fixation was more frequent in the other countries (range: 43.9%-75.5%). Interference was the most frequent tibial fixation type in all six cohorts (range: 64.8%-98.2%). Three-year cumulative revision probabilities ranged from 2.8% to 3.7%. Conclusions Similarities in patient demographics and injury activity were observed between all cohorts of ACLR. However, graft and fixation choices differed. Revision rates were low. This work, including >100 000 ACLR, is the most comprehensive international description of contemporary practice to date.
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