Germline pathogenic variants in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms.

High-grade gastroenteropancreatic (HG-GEP) NEN are highly aggressive cancers. The molecular etiology of these tumors remains unclear and the prevalence of pathogenic germline variants in patients with HG-GEP-NEN is unknown. We assessed sequencing data of 360 cancer genes in normal tissue, from 240 patients with HG GEP-NEN; 198 patients with NEC and 42 with NET G3. Applying strict criteria, we identified pathogenic germline variants and compared the frequency with previously reported data from 33 different cancer types. We found a recurrent MYOC variant in 3 patients and a recurrent MUTYH variant in 2 patients, indicating that these genes may be important underlying risk factors for HG-GEP-NEN, when mutated. Further, germline variants were found in canonical tumor suppressor genes, such as TP53, RB1, BRIP1 and BAP1. Overall, we found that 4.5% of patients with NEC and 9.5% of patients with NET G3 carry germline pathogenic or highly likely pathogenic variants. Applying identical criteria for variant classification in-silico to mined data from 33 other cancer types, the median percentage of patients carrying pathogenic or highly likely pathogenic variants was 3.4% (range: 0-17%). The patients with NEC and pathogenic germline variants had a median overall survival of 9 months, similar to what is generally expected for metastatic GEP-NEC. A patient with NET G3 and pathogenic MUTYH variant had much shorter overall survival than expected. The fraction of HG GEP-NEN with germline pathogenic variants is relatively high, but still <10%, meaning that that germline mutations cannot be the major underlying cause of HG GEP-NEN

Edaravone Guards Dopamine Neurons in a Rotenone Model for Parkinson's Disease

3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), an effective free radical scavenger, provides neuroprotection in stroke models and patients. In this study, we investigated its neuroprotective effects in a chronic rotenone rat model for Parkinson's disease. Here we showed that a five-week treatment with edaravone abolished rotenone's activity to induce catalepsy, damage mitochondria and degenerate dopamine neurons in the midbrain of rotenone-treated rats. This abolishment was attributable at least partly to edaravone's inhibition of rotenone-induced reactive oxygen species production or apoptotic promoter Bax expression and its up-regulation of the vesicular monoamine transporter 2 (VMAT2) expression. Collectively, edaravone may provide novel clinical therapeutics for PD

Impact on balance while walking in occupational footwear

Analysis of human balance in a occupational and ergonomic populatio

Surgical and Medical Perioperative Management of Sickle Cell Retinopathy: A Literature Review

The most common ophthalmic manifestation of sickle cell disease (SCD) is sickle cell retinopathy (SCR), which can lead to loss of vision due to complications of proliferative sickle retinopathy (PSR). Eventually, vitreoretinal surgery may be indicated in these patients to help preserve or improve vision. Unfortunately, SCD can cause systemic and ophthalmic vaso-occlusive and ischemic complications, which necessitates adequate perioperative planning in these patients undergoing surgery. The purpose of this review was to appraise studies of patients with PSR undergoing vitreoretinal surgery to identify the common medical and surgical perioperative measures employed in these cases. The full-texts of 11 original studies published between 1973 and 2018 were reviewed. Over the last 16 years, 7 studies of 108 eyes undergoing posterior segment surgery for vitreoretinal complications of PSR did not report any ischemic complications related to SCD. It is likely that modern surgical techniques dramatically reduced the risk of these complications. Perioperatively, most studies avoided retrobulbar anesthesia and the use of epinephrine, and the use of exchange transfusions is seemingly not required prophylactically in these patients undergoing vitreoretinal surgery. Customized perioperative planning may be required in complex cases, and these patients should be identified and treated through collaboration between ophthalmic surgeons and hematology specialists

Key-Frame Based Motion Representations for Pose Sequences

Modelling human motion is critical for computer vision tasks that aim to perceive human behaviour. Extending current learning-based approaches to successfully model long-term motions remains a challenge. Recent works rely on autoregressive methods, in which motions are modelled sequentially. These methods tend to accumulate errors, and when applied to typical motion modelling tasks, are limited up to only four seconds. We present a non-autoregressive framework to represent motion sequences as a set of learned key-frames without explicit supervision. We explore continuous and discrete generative frameworks for this task and design a key-framing transformer architecture to distill a motion sequence into key-frames and their relative placements in time. We validate our learned key-frame placement approach with a naive uniform placement strategy and further compare key-frame distillation using our transformer architecture with an alternative common sequence modelling approach. We demonstrate the effectiveness of our method by reconstructing motions up to 12 seconds

Three dimensional visualisation and quanitiative characterisation of combusition flames

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