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McLaughlin H.M.,Laboratory for Molecular Medicine | McLaughlin H.M.,Lansdowne Partners | Kelly M.A.,Lansdowne Partners | Hawley P.P.,Boston Childrens Hospital Boston | And 7 more authors.
BMC Medical Genetics | Year: 2013

Background: Variants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. To date, only ~50 disease-associated variants have been described, and the majority of these lead to dominant-negative effects. However, the complete genotypic spectrum of desminopathy is not well established.Case presentation: Next-generation sequencing was performed on 51 cardiac disease genes in a proband with profound skeletal myopathy, dilated cardiomyopathy, and respiratory dysfunction. Our analyses revealed compound heterozygous DES variants, both of which are predicted to lead to a loss-of-function. Consistent with recessive inheritance, each variant was identified in an unaffected parent.Conclusions: This case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies. © 2013 McLaughlin et al.; licensee BioMed Central Ltd. Source


Lin C.,Boston Childrens Hospital Boston | Dligach D.,Boston Childrens Hospital Boston | Dligach D.,Harvard University | Miller T.A.,Boston Childrens Hospital Boston | And 4 more authors.
Journal of the American Medical Informatics Association | Year: 2016

Objective: To develop an open-source temporal relation discovery system for the clinical domain. The system is capable of automatically inferring temporal relations between events and time expressions using a multilayered modeling strategy. It can operate at different levels of granularity- from rough temporality expressed as event relations to the document creation time (DCT) to temporal containment to fine-grained classic Allenstyle relations. Materials and Methods: We evaluated our systems on 2 clinical corpora. One is a subset of the Temporal Histories of Your Medical Events (THYME) corpus, which was used in SemEval 2015 Task 6: Clinical TempEval. The other is the 2012 Informatics for Integrating Biology and the Bedside (i2b2) challenge corpus. We designed multiple supervised machine learning models to compute the DCT relation and within-sentence temporal relations. For the i2b2 data, we also developed models and rule-based methods to recognize cross-sentence temporal relations. We used the official evaluation scripts of both challenges to make our results comparable with results of other participating systems. In addition, we conducted a feature ablation study to find out the contribution of various features to the system's performance. Results: Our system achieved state-of-the-art performance on the Clinical TempEval corpus and was on par with the best systems on the i2b2 2012 corpus. Particularly, on the Clinical TempEval corpus, our system established a new F1 score benchmark, statistically significant as compared to the baseline and the best participating system. Conclusion: Presented here is the first open-source clinical temporal relation discovery system. It was built using a multilayered temporal modeling strategy and achieved top performance in 2 major shared tasks. © The Author 2015. Source


Huckfeldt R.M.,Boston Childrens Hospital Boston | Shah A.S.,Boston Childrens Hospital Boston
Journal of AAPOS | Year: 2014

Infarction of the orbital wall is an uncommon manifestation of sickle cell disease (SCD) that may mimic an infectious process. We report a patient with two separate orbital infarctions with different presenting symptoms involving different bones. Radiologic-guided sampling of a periosteal fluid collection in the first episode showed likely sterile inflammatory exudates. This case highlights the range of findings in orbital wall infarction in SCD as well as helpful clinical and imaging entities that may differentiate infarction from infection, allowing early diagnosis and appropriate management. Copyright © 2014 by the American Association for Pediatric Ophthalmology and Strabismus. Source

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