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991.
992.
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
993.
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994.
Jasper Vonk Jaron Grard de Wit Floris Jan Voskuil Max Johannes Hendrikus Witjes 《Oral diseases》2021,27(1):21-26
Early diagnosis and radical surgical excision of oral squamous cell carcinomas are essential for achieving optimal treatment outcomes. To date, diagnostic tools that rely on anatomical anomalies provide limited information and resolution in clinical practice. As a result, oral cancer is often detected in an advanced stage. Also, no reliable real‐time intraoperative tools are readily available for the evaluation of surgical resection margins. Fluorescence imaging visualises biological processes that occur in early carcinogenesis and could, therefore, enable detection of small tumours in early stages. Furthermore, due to the high sensitivity and spatial resolution, fluorescence imaging could assist in resection margin assessment during surgery. In this review, we discuss several techniques that employ fluorescence for early diagnosis and surgical guidance in oral squamous cell carcinoma and present future perspectives on the potential of fluorescence imaging in oral cancer in the near future. 相似文献
995.
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
996.
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
997.
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
998.
Malgorzata I. Srebniak Lisanne Mout Diane Van Opstal Robert‐Jan H. Galjaard 《Human mutation》2013,34(9):1298-1303
Using whole‐genome array testing instead of karyotyping in prenatal diagnosis for all indications may be desirable because of the higher diagnostic yield and shorter reporting time. The goal of this research was finding the optimal array resolution that could replace routine prenatal karyotyping in cases without ultrasound abnormalities, for example, referred for advanced maternal age or abnormal first trimester screening. As variants of unknown clinical significance (VOUS), if reported, might complicate decision‐making about continuation of pregnancy, such an optimal array resolution should have a high abnormality detection rate and reveal a minimal amount of VOUS. The array data of 465 fetuses were retrospectively evaluated with several resolution levels, and the Decipher microdeletion/microduplication syndrome list was reviewed to assess what could be theoretically missed with a lower resolution. A 0.5‐Mb resolution showed a high diagnostic yield potential and significantly minimized the number of VOUS. Based on our experience, we recommend genomic SNP array as a first‐tier test in prenatal diagnosis. The resolution should be chosen based on the indication. In cases of fetal ultrasound abnormalities or intrauterine fetal death (IUFD), high‐resolution analysis should be done. In other cases, we advise replacing karyotyping by SNP array analysis with 0.5 Mb resolution. 相似文献
999.
Lubna Khatoon Muhammad Ishtiaq Jan Inam Ullah Khan Farhat Ullah Salman A. Malik 《Acta parasitologica / Witold Stefański Institute of Parasitology, Warszawa, Poland》2013,58(4):564-569
Malaria is wide spread in poor world and its burden has been assessed by the enumeration of malarial parasites in blood of patients. This study was designed to find a relationship between social structure, and spread of malaria in Khyber agency. The average parasite density was 2050 parasite/μl in Khyber Agency. Due to economic and social setup most of the people have habit of sleeping in open air thus playing role in high malaria prevalence and Plasmodium vivax remains the prevalent species. Genetic study performed on 110 Blood samples showed less genetic diversity for both Plasmodium vivax and Plasmodium falciparum. Eight alleles were distinguished both for Pvmsp 3α and Pvmsp 3β in total of 20 and 39 amplified samples of P. vivax respectively. Out of 17 samples amplified for P. falciparum 11 showed genotype K1 and 10 for MAD at Pfmsp-1 while 14 alleles were identified for 3D7/1C and two for FC27 of corresponding families of Pfmsp-2 gene. This shows that Plasmodium parasites are not genetically diverse in Khyber agency. 相似文献
1000.
Jan Wieding Robert Souffrant Wolfram Mittelmeier Rainer Bader 《Medical engineering & physics》2013,35(4):422-432
Repairing large segmental defects in long bones caused by fracture, tumour or infection is still a challenging problem in orthopaedic surgery. Artificial materials, i.e. titanium and its alloys performed well in clinical applications, are plenary available, and can be manufactured in a wide range of scaffold designs. Although the mechanical properties are determined, studies about the biomechanical behaviour under physiological loading conditions are rare. The goal of our numerical study was to determine the suitability of open-porous titanium scaffolds to act as bone scaffolds. Hence, the mechanical stability of fourteen different scaffold designs was characterized under both axial compression and biomechanical loading within a large segmental distal femoral defect of 30 mm. This defect was stabilized with an osteosynthesis plate and physiological hip reaction forces as well as additional muscle forces were implemented to the femoral bone. Material properties of titanium scaffolds were evaluated from experimental testing. Scaffold porosity was varied between 64 and 80%. Furthermore, the amount of material was reduced up to 50%. Uniaxial compression testing revealed a structural modulus for the scaffolds between 3.5 GPa and 19.1 GPa depending on porosity and material consumption. The biomechanical testing showed defect gap alterations between 0.03 mm and 0.22 mm for the applied scaffolds and 0.09 mm for the intact bone. Our results revealed that minimizing the amount of material of the inner core has a smaller influence than increasing the porosity when the scaffolds are loaded under biomechanical loading. Furthermore, an advanced scaffold design was found acting similar as the intact bone. 相似文献