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981.
Kornelia Neveling Ilse Feenstra Christian Gilissen Lies H. Hoefsloot Erik‐Jan Kamsteeg Arjen R. Mensenkamp Richard J. T. Rodenburg Helger G. Yntema Liesbeth Spruijt Sascha Vermeer Tuula Rinne Koen L. van Gassen Danielle Bodmer Dorien Lugtenberg Rick de Reuver Wendy Buijsman Ronny C. Derks Nienke Wieskamp Bert van den Heuvel Marjolijn J.L. Ligtenberg Hannie Kremer David A. Koolen Bart P.C. van de Warrenburg Frans P.M. Cremers Carlo L.M. Marcelis Jan A.M. Smeitink Saskia B. Wortmann Wendy A.G. van Zelst‐Stams Joris A. Veltman Han G. Brunner Hans Scheffer Marcel R. Nelen 《Human mutation》2013,34(12):1721-1726
The advent of massive parallel sequencing is rapidly changing the strategies employed for the genetic diagnosis and research of rare diseases that involve a large number of genes. So far it is not clear whether these approaches perform significantly better than conventional single gene testing as requested by clinicians. The current yield of this traditional diagnostic approach depends on a complex of factors that include gene‐specific phenotype traits, and the relative frequency of the involvement of specific genes. To gauge the impact of the paradigm shift that is occurring in molecular diagnostics, we assessed traditional Sanger‐based sequencing (in 2011) and exome sequencing followed by targeted bioinformatics analysis (in 2012) for five different conditions that are highly heterogeneous, and for which our center provides molecular diagnosis. We find that exome sequencing has a much higher diagnostic yield than Sanger sequencing for deafness, blindness, mitochondrial disease, and movement disorders. For microsatellite‐stable colorectal cancer, this was low under both strategies. Even if all genes that could have been ordered by physicians had been tested, the larger number of genes captured by the exome would still have led to a clearly superior diagnostic yield at a fraction of the cost. 相似文献
982.
Introduction
Inflammation is a very important part of innate immunity and is regulated in many steps. One such regulating step is the cytokine network, where tumor necrosis factor α (TNF-α) plays one of the most important roles.Methods
A PubMed and Web of Science databases search was performed for studies providing evidences on the role of TNF-α in inflammation, apoptosis, and cancer.Results and Conclusion
This review concisely summarizes the role of this pro-inflammatory cytokine during inflammation. It is focused mainly on TNF-α intracellular signaling and its influence on the typical inflammatory features in the organism. Being one of the most important pro-inflammatory cytokines, TNF-α participates in vasodilatation and edema formation, and leukocyte adhesion to epithelium through expression of adhesion molecules; it regulates blood coagulation, contributes to oxidative stress in sites of inflammation, and indirectly induces fever. The connection between TNF-α and cancer is mentioned as well. 相似文献983.
Bissinger Ricarda Müller Daniel David Reymus Marcel Khazaei Yegane Hickel Reinhard Bücher Katharina Kühnisch Jan 《Clinical oral investigations》2021,25(1):133-143
Clinical Oral Investigations - The objectives of this retrospective clinical study were to describe characteristics of crown fractures in permanent teeth and to investigate the survival of pulp... 相似文献
984.
Rues Stefan Schmitter Marc Kappel Stefanie Sonntag Robert Kretzer Jan Philippe Nadorf Jan 《Clinical oral investigations》2021,25(3):1265-1272
Clinical Oral Investigations - Conventional dental implants inserted in the molar region of the maxilla will reach into the sinus maxillaris when alveolar ridge height is limited. When surgery is... 相似文献
985.
Radhakrishnan Sabarinathan Hakim Tafer Stefan E. Seemann Ivo L. Hofacker Peter F. Stadler Jan Gorodkin 《Human mutation》2013,34(4):546-556
Structural characteristics are essential for the functioning of many noncoding RNAs and cis‐regulatory elements of mRNAs. SNPs may disrupt these structures, interfere with their molecular function, and hence cause a phenotypic effect. RNA folding algorithms can provide detailed insights into structural effects of SNPs. The global measures employed so far suffer from limited accuracy of folding programs on large RNAs and are computationally too demanding for genome‐wide applications. Here, we present a strategy that focuses on the local regions of maximal structural change between mutant and wild‐type. These local regions are approximated in a “screening mode” that is intended for genome‐wide applications. Furthermore, localized regions are identified as those with maximal discrepancy. The mutation effects are quantified in terms of empirical P values. To this end, the RNAsnp software uses extensive precomputed tables of the distribution of SNP effects as function of length and GC content. RNAsnp thus achieves both a noise reduction and speed‐up of several orders of magnitude over shuffling‐based approaches. On a data set comprising 501 SNPs associated with human‐inherited diseases, we predict 54 to have significant local structural effect in the untranslated region of mRNAs. RNAsnp is available at http://rth.dk/resources/rnasnp . 相似文献
986.
Validation of a finite element model of a unilateral external fixator in a rabbit tibia defect model
Kavin Karunratanakul Greet Kerckhofs Johan Lammens Johan Vanlauwe Jan Schrooten Hans Van Oosterwyck 《Medical engineering & physics》2013,35(7):1037-1043
In case of large segmental defects in load-bearing bones, an external fixator is used to provide mechanical stability to the defect site. The overall stiffness of the bone–fixator system is determined not only by the fixator design but also by the way the fixator is mounted to the bone. This stiffness is an important factor as it will influence the biomechanical environment to which tissue engineering scaffolds and regenerating tissues are exposed. A finite element (FE) model can be used to predict the system stiffness. The goal of this study is to develop and validate a 3D anatomical FE model of a bone–fixator system which includes a previously developed unilateral external fixator for a large segmental defect model in the rabbit tibia. It was hypothesized that the contact interfaces between bone and fixator screws play a major role for the prediction of the stiffness. In vitro mechanical testing was performed in order to measure the axial stiffness of cortical bone from mid-shaft rabbit tibiae and of the tibia–fixator system, as well as the bending stiffness of individual fixator screws, inserted in bone. μCT-based case-specific FE models of cortical bone and SCREW–BONE specimens were created to simulate the corresponding mechanical test set-ups. The Young's modulus of rabbit cortical bone as well as appropriate screw–bone contact settings were derived from those FE models. We then used the derived settings in an FE model of the tibia–fixator system. The difference between the FE predicted and measured axial stiffness of the tibia–fixator system was reduced from 117.93% to 7.85% by applying appropriate screw–bone contact settings. In conclusion, this study shows the importance of screw–bone contact settings for an accurate fixator stiffness prediction. The validated FE model can further be used as a tool for virtual mechanical testing in the design phase of new tissue engineering scaffolds and/or novel patient-specific external fixation devices. 相似文献
987.
Jørn Heggelund Marius S. Fimland Jan Helgerud Jan Hoff 《European journal of applied physiology》2013,113(6):1565-1573
This study compared maximal strength training (MST) with equal training volume (kg × sets × repetitions) of conventional strength training (CON) primarily with regard to work economy, and second one repetition maximum (1RM) and rate of force development (RFD) of single leg knee extension. In an intra-individual design, one leg was randomized to knee-extension MST (4 or 5RM) and the other leg to CON (3 × 10RM) three times per week for 8 weeks. MST was performed with maximal concentric mobilization of force while CON was performed with moderate velocity. Eight untrained or moderately trained men (26 ± 1 years) completed the study. The improvement in gross work economy was ?0.10 ± 0.08 L min?1 larger after MST (P = 0.011, between groups). From pre- to post-test the MST and CON improved net work economy with 31 % (P < 0.001) and 18 % (P = 0.01), respectively. Compared with CON, the improvement in 1RM and dynamic RFD was 13.7 ± 8.4 kg (P = 0.002) and 587 ± 679 N s?1 (P = 0.044) larger after MST, whereas isometric RFD was of borderline significance 3,028 ± 3,674 N s?1 (P = 0.053). From pre- to post-test, MST improved 1RM and isometric RFD with 50 % (P < 0.001) and 155 % (P < 0.001), respectively whereas CON improved 1RM and isometric RFD with 35 % (P < 0.001) and 83 % (P = 0.028), respectively. Anthropometric measures of quadriceps femoris muscle mass and peak oxygen uptake did not change. In conclusion, 8 weeks of MST was more effective than CON for improving work economy, 1RM and RFD in untrained and moderately trained men. The advantageous effect of MST to improve work economy could be due to larger improvements in 1RM and RFD. 相似文献
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