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Contactins are a group of cell adhesion molecules that are mainly expressed in the brain and play pivotal roles in the organization of axonal domains, axonal guidance, neuritogenesis, neuronal development, synapse formation and plasticity, axo-glia interactions and neural regeneration. Contactins comprise a family of six members. Their absence leads to malformed axons and impaired nerve conduction. Contactin mediated protein complex formation is critical for the organization of the axon in early central nervous system development. Mutations and differential expression of contactins have been identified in neuro-developmental or neurological disorders. Taken together, contactins are extensively studied in the context of nervous system development. This review summarizes the physiological roles of all six members of the Contactin family in neurodevelopment as well as their involvement in neurological/neurodevelopmental disorders. 相似文献
104.
Melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC) are the most common skin cancer types in fair-skinned individuals. Risk of developing cancer is partly due to genetic factors, meaning that individuals who inherit certain DNA variations have an increased susceptibility to cancer. Disease-associated variations are often identified using genome-wide association studies (GWAS), in which millions of variants are assessed for impact on disease risk. Although individual variants generally do not predict risk, combining the effects of many variants into a polygenic risk score (PRS) may be informative in identifying individuals with increased skin cancer risk. Researchers based at Massachusetts General Hospital and The Ohio State University in the USA reviewed published genetic studies of skin cancer risk, by searching two databases of scientific publications. Twenty-one GWAS and 11 PRS studies for skin cancer were identified which showed that genes involved in skin colour affected all three cancer types, and some of the risk variants overlapped between types. Different PRS were associated with approximately 2-to-3-fold increases in risk of developing melanoma, cSCC, and BCC. Addition of non-genetic risk factors to the PRS for melanoma led to improved risk prediction ability of 2-7%. For cSCC and BCC, small improvements in predictive ability of about 2% were observed when PRS were used with other non-genetic factors. The authors concluded that while existing data indicate that PRS may modestly improve the ability to accurately predict risk of developing melanoma, cSCC, or BCC, additional research is needed to clarify their clinical usefulness in assessing skin cancer risk. 相似文献
105.
Milan Milojevic Patrick W. Serruys Joseph F. Sabik David E. Kandzari Erick Schampaert Ad J. van Boven Ferenc Horkay Imre Ungi Samer Mansour Adrian P. Banning David P. Taggart Manel Sabaté Anthony H. Gershlick Andrzej Bochenek Jose Pomar Nicholas J. Lembo Nicolas Noiseux John D. Puskas Arie Pieter Kappetein 《Journal of the American College of Cardiology》2019,73(13):1616-1628
Background
The randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial reported a similar rate of the 3-year composite primary endpoint of death, myocardial infarction (MI), or stroke in patients with left main coronary artery disease (LMCAD) and site-assessed low or intermediate SYNTAX scores treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Whether these results are consistent in high-risk patients with diabetes, who have fared relatively better with CABG in most prior trials, is unknown.Objectives
In this pre-specified subgroup analysis from the EXCEL trial, the authors sought to examine the effect of diabetes in patients with LMCAD treated with PCI versus CABG.Methods
Patients (N = 1,905) with LMCAD and site-assessed low or intermediate CAD complexity (SYNTAX scores ≤32) were randomized 1:1 to PCI with everolimus-eluting stents versus CABG, stratified by the presence of diabetes. The primary endpoint was the rate of a composite of all-cause death, stroke, or MI at 3 years. Outcomes were examined in patients with (n = 554) and without (n = 1,350) diabetes.Results
The 3-year composite primary endpoint was significantly higher in diabetic compared with nondiabetic patients (20.0% vs. 12.9%; p < 0.001). The rate of the 3-year primary endpoint was similar after treatment with PCI and CABG in diabetic patients (20.7% vs. 19.3%, respectively; hazard ratio: 1.03; 95% confidence interval: 0.71 to 1.50; p = 0.87) and nondiabetic patients (12.9% vs. 12.9%, respectively; hazard ratio: 0.98; 95% confidence interval: 0.73 to 1.32; p = 0.89). All-cause death at 3 years occurred in 13.6% of PCI and 9.0% of CABG patients (p = 0.046), although no significant interaction was present between diabetes status and treatment for all-cause death (p = 0.22) or other endpoints, including the 3-year primary endpoint (p = 0.82) or the major secondary endpoints of death, MI, or stroke at 30 days (p = 0.61) or death, MI, stroke, or ischemia-driven revascularization at 3 years (p = 0.65).Conclusions
In the EXCEL trial, the relative 30-day and 3-year outcomes of PCI with everolimus-eluting stents versus CABG were consistent in diabetic and nondiabetic patients with LMCAD and site-assessed low or intermediate SYNTAX scores.(Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776) 相似文献106.
107.
N. Shor R. Deschamps A. Cobo Calvo E. Maillart H. Zephir J. Ciron C. Papeix F. Durand-Dubief A. Ruet X. Ayrignac M. Cohen K. Deiva D. Laplaud B. Bourre B. Audoin N. Collongues S. Vukusic F. Cotton R. Marignier 《Revue neurologique》2021,177(1-2):39-50
Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS. 相似文献
108.
109.
In this paper, we use optimal parameter selection technique to develop two models involving single‐vendor–multiple‐buyer supply chain, which are called the dynamic independent optimization (DIO) model and the dynamic synchronized cycles (DSC) model, respectively. These models are, respectively, similar to the traditional static independent policy model and the traditional static synchronized cycle model, except that the deterministic demands of the buyers in the above two static models are now being replaced by the stochastic demands satisfying a Wiener process, which have more real‐life applications. Similar to the above static synchronized cycles model, the synchronization of the supply chain in our DSC model is also achieved by scheduling the delivery days of the buyers and coordinating them with the vendor's production cycle. Finding the optimal expected system costs of the DIO model and the DSC model involves solving optimal parameter selection problems governed by ordinary differential equations, whose final times are continuous decision variables and discrete decision variables, respectively. Computational methods have been developed for solving these problems. Numerical results show that the coordinated policy is better than the independent optimization policy, in terms of minimizing the expected system cost of the entire supply chain. Sensitivity analysis is performed to test the effect of changing the cost coefficients and the value on the performances of these models, where is the ratio of the total mean demand rate of all the buyers over the vendor's production rate. 相似文献
110.
M.F. Werner A. López-Rueda F.X. Zarco J. Blasco L. San Román S. Amaro E. Carrero R. Valero L. Oleaga J.M. Macho N. Bargalló 《Radiologia》2019,61(2):143-152