Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Phosphatase of regenerating liver-3 (PRL-3) has deserved attention as a crucial molecule in the multiple steps of metastasis. In the present study, we examined the mechanisms regulating PRL-3 expression, and assessed the clinical potential of PRL-3-targeted therapy in gastric cancer.</p> <p>Methods</p> <p>PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) treatment was evaluated against cancer cells with different genetic and expression status.</p> <p>Results</p> <p>PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40) among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20), but in none (0/37) among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (<it>P </it>= 0.021). PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression.</p> <p>Conclusions</p> <p>We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression.</p

Cerebellar Transcranial Magnetic Stimulation Improves Ataxia in Minamata Disease

Minamata disease (MD) is a form of intoxication involving the central nervous system and is caused by ingesting seafood from methylmercury-contaminated areas in Japan. In MD, cerebellar ataxia is a cardinal feature observed in approximately 80% of MD patients. Although cerebellar transcranial magnetic stimulation (TMS) has recently been used for treating cerebellar ataxia, the optimal stimulation conditions remain unclear. Here, we report the first case of cerebellar ataxia in an MD patient that was significantly improved after high-frequency cerebellar TMS. To determine the optimal stimulation conditions, we examined the excitability of the primary motor cortex (M1) using resting-state functional magnetic resonance imaging (rs-fMRI). rs-fMRI revealed M1 hyperconnectivity, which was indicative of activation of the dentato-thalamo-cortical (DTC) pathway. Thus, high-frequency cerebellar TMS was applied to inhibit the DTC pathway. Improvement of cerebellar ataxia was only observed after real TMS, not sham stimulation. As this effect was consistent with inhibition of hyperconnectivity of M1, the effectiveness of high-frequency cerebellar TMS for cerebellar ataxia was thought to be caused by inhibition of the DTC pathway. Therefore, we suggest that the evaluation of M1 excitability using rs-fMRI can be effective for determining the optimal TMS stimulation conditions for cerebellar ataxia

臥床患者の水平移動法の違いによる看護学生の主観的な容易性の検討

本研究の目的は、看護学生に複数の方法で臥床患者の水平移動を実施してもらい、移動方法と実施時に感じた主観的な容易性との関連を明らかにすることである。同意を得た看護学生16 名を対象に、上方水平移動と左右水平移動の模擬患者への実施を求めた。その際に看護者が感じた主観的な容易性を4件法で評価した。自由記載は、Microsoft excel を用いてキーワード分析を行った。結果、上方水平移動の主観的な容易性は順に、シート法、古武術法、キネステティク法であった。左右水平移動の主観的な容易性は高い順に、グローブ法、キネステティク法、古武術法であった。上方水平移動の頻出記載語は多い順に、「動」、「力」、「できた」であった。左右水平移動の頻出記載語は多い順に、「動」、「腰」、「身体」であった。以上より、シート法とグローブ法は看護学生にとっても主観的な容易性の高い、臨床の場や看護教育の中で広く活用されるべき体位変換方法と推察された

An Early Biomarker Algorithm Predicts Lethal Graft-Vs-Host Disease and Survival after Allogeneic Hematopoietic Cell Transplantation

n/

オンデマンド看護過程展開とハイブリッド基礎看護学実習のための看護教育方法の提案

A看護系大学では、COVID-19の影響により2020年度前期のすべての科目と実習がオンデマンドとなった。看護過程展開論もオンデマンド授業となり、学内ネットワークシステム（kyonet）の授業およびディスカッションボード機能（プロジェクト学習）を用いた課題提出とグループワークを実施した。基礎看護学実習Ⅱは、臨地での実習が困難となったため、ハイブリッド実習にて実施した。ハイブリッド実習では教員が難易度を考慮した事例を設定し、看護過程展開論の授業方法と同様の方法で実施したため、学生は混乱なく実習を進めることができた。模擬事例を用いて既習の方法と同様に情報取集を行い、援助実施においても慣れ親しんだ学内の環境で実施できた。また、プロジェクト学習の利用により、学生は他の学生の成果物や指導内容を閲覧でき、学習内容を共有できたことと、教員が解答例を提示したことにより、学生は自身の修正点に気づきやすくなったと考えられた

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

臥床患者の上方水平移動法の比較分析

患者を移動する際には、ボディメカニクスを習得すると腰痛を予防できることは周知されているが、習得は難しく腰痛予防教育が困難な現状は否定できない。本研究は、看護師の動作に着眼し、患者および看護師に負担が少ないとされているキネステティク法、古武術法およびスライディングシート法による上方水平移動方法の比較検討を目的とした。看護師1名が23名の対象に実施した結果、3 つの知見が得られた。①看護師の動作には高い再現性が認められた、②看護師の体幹と股関節の角度は、大きい順にスライディングシート法、キネステティク法、古武術法であった、③上方水平移動の所要時間は、短い順にスライディングシート法、古武術法、キネステティク法であった

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV