140 research outputs found
Target prediction and a statistical sampling algorithm for RNA-RNA interaction
It has been proven that the accessibility of the target sites has a critical
influence for miRNA and siRNA. In this paper, we present a program, rip2.0, not
only the energetically most favorable targets site based on the
hybrid-probability, but also a statistical sampling structure to illustrate the
statistical characterization and representation of the Boltzmann ensemble of
RNA-RNA interaction structures. The outputs are retrieved via backtracing an
improved dynamic programming solution for the partition function based on the
approach of Huang et al. (Bioinformatics). The time and space
algorithm is implemented in C (available from
\url{http://www.combinatorics.cn/cbpc/rip2.html})Comment: 7 pages, 10 figure
Development and Integration of DOPS as Formative Tests in Head and Neck Ultrasound Education : Proof of Concept Study for Exploration of Perceptions
In Germany, progress assessments in head and neck ultrasonography training have been
carried out mainly theoretically and lack standardisation. Thus, quality assurance and comparisons
between certified courses from various course providers are difficult. This study aimed to develop
and integrate a direct observation of procedural skills (DOPS) in head and neck ultrasound education
and explore the perceptions of both participants and examiners. Five DOPS tests oriented towards
assessing basic skills were developed for certified head and neck ultrasound courses on national
standards. DOPS tests were completed by 76 participants from basic and advanced ultrasound
courses (n = 168 documented DOPS tests) and evaluated using a 7-point Likert scale. Ten examiners
performed and evaluated the DOPS after detailed training. The variables of âgeneral aspectsâ (6.0
Scale Points (SP) vs. 5.9 SP; p = 0.71), âtest atmosphereâ (6.3 SP vs. 6.4 SP; p = 0.92), and âtest task
settingâ (6.2 SP vs. 5.9 SP; p = 0.12) were positively evaluated by all participants and examiners. There
were no significant differences between a basic and advanced course in relation to the overall results
of DOPS tests (p = 0.81). Regardless of the courses, there were significant differences in the total
number of points achieved between individual DOPS tests. DOPS tests are accepted by participants
and examiners as an assessment tool in head and neck ultrasound education. In view of the trend
toward âcompetence-basedâ teaching, this type of test format should be applied and validated in
the future
Comments and illustrations of the WFUMB CEUS liver guidelines: Rare benign focal liver lesion, part I.
Improved detection and characterization of common focal liver lesions (FLL) are the main topics of the World Federation for Ultrasound in Medicine and Biology (WFUMB) guidelines on the use of contrast-enhanced ultrasound (CEUS). On stateof-the-art CEUS imaging, to create a library of rare FLL, especially concerning their atypical imaging characteristics, might be helpful for improving clinical diagnostic efficiency. In this review, we aim to summarize the ultrasound and CEUS features of rare benign FLL. Currently there are limited reports and images published
Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma
© Impact Journals, LLC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group 3 medulloblastoma cells. Genomic profiling of Group 3 medulloblastoma cells treated with alsterpaullone confirmed inhibition of cell cycle-related genes, and down-regulation of MYC. Our results demonstrate the preclinical efficacy of using a targeted therapy approach for Group 3 medulloblastomas. Specifically, we provide rationale for advancing alsterpaullone as a targeted therapy in Group 3 medulloblastoma.This study was supported by the Canadian Cancer Society (Grant #2011-70051), the Pediatric Brain Tumor Foundation of the United States, the Brain Tumour Foundation of Canada, Meaganâs Walk, b.r.a.i.n.child and the Wiley Fund at the Hospital for Sick Children.info:eu-repo/semantics/publishedVersio
Comments and illustrations of the WFUMB CEUS liver guidelines: Rare benign focal liver lesion, part II.
It is important to be familiar with the typical imaging features of the uncommon or even extremely rare focal liver lesions (FLL). Current guidelines of the World Federation for Ultrasound in Medicine and Biology (WFUMB) is aimed at assessing the usefulness of contrast enhanced ultrasound (CEUS) in the management of various FLL. In this review, we aim to summarize the ultrasound and CEUS characteristics with literature review of some extremely rare benign FLL, which might be helpful for improving diagnostic efficiency clinically
The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants
Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups. Discussion at the meeting generated a series of consensus statements and recommendations from the attendees, which comment on the prognostic evaluation and treatment decisions of patients with intracranial ependymoma (WHO Grade II/III) based on the knowledge of its molecular subgroups. The major consensus among attendees was reached that treatment decisions for ependymoma (outside of clinical trials) should not be based on grading (II vs III). Supratentorial and posterior fossa ependymomas are distinct diseases, although the impact on therapy is still evolving. Molecular subgrouping should be part of all clinical trials henceforth
The German National Registry of Primary Immunodeficiencies (2012-2017)
Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software StataÂź and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1â25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0â88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%âsubcutaneous; 29%âintravenous; 1%âunknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment
TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma
Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit
Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas
Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective single-institution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was >20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was >20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume â„20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3-6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to > 12 months. Hearing was stable under treatment. The safety of everolimus was manageable. Although the primary endpoint was not reached, further studies are required to confirm the potential for stabilization of everolimus
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