Construction of a system for determining the difficulty of medical terms in patient documents

患者から「医師や薬剤師が使う言葉が難しい」「説明文を読んでも理解できない」といった訴えを聞くことがある。そこで、難易度評価試験を実施し、データを分析することで、患者向け文書で使われる「医療用語を含む文章」を、医療知識のない人でも理解できる「わかりやすい文章」に変更するシステムを作成することを目的にした。165単語中無作為に20単語を抽出して医療者, 薬学生, 一般に行ったテストデータを解析し、特異的パターンを示す14単語を抽出した。この14単語についてフォーカスグループによるインタビュー調査を実施したところ、単語単独の意味ではなく、複合語に関しての理解しづらさを感じていることが明らかとなった。We sometimes hear complaints from patients that the language used by doctors and pharmacists is difficult or that they cannot understand the explanatory text. Therefore, we conducted a difficulty evaluation test and analyzed the data to create a system to change "sentences containing medical terms" used in documents for patients into "easy-to-understand sentences" that can be understood even by users without medical knowledge. Quiz response data from medical professionals, pharmacy students, and the general public were analyzed to identify 14 words that exhibit specific patterns. Focus group interviews were conducted with these 14 words, which revealed that respondents had more difficulty understanding compound words than the meaning of each word alone.研究分野：医療統計学，データサイエン

Fingolimod (FTY720) Stimulates Ca²⁺/Calcineurin Signaling in Fission Yeast

<div><p>Fingolimod hydrochloride (FTY720) is the first in class of sphingosine 1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis via down-regulation of G protein-coupled S1P receptor 1 by its phosphorylated form (FTY720-P). Many studies have revealed that FTY720 exerts various biological effects, including antitumor activities, angiogenesis inhibition, Ca²⁺ mobilization and apoptosis, independently of S1P receptors. However, the exact mechanisms underlying their effects or signaling pathways mediated by FTY720 have not been completely established. To gain further insights into molecular mechanisms of FTY720 action, the effect of FTY720 on Ca²⁺ signaling in fission yeast was analyzed. The addition of Ca²⁺ enhanced the sensitivity induced by FTY720, and mutants lacking genes required for calcium homeostasis, including calcineurin and its downstream transcription factor, <u>P</u>pb1-<u>r</u>esponsive zinc finger protein (Prz1), were hypersensitive to FTY720 and CaCl₂. The effect of FTY720 on calcineurin signaling was monitored by utilizing a luciferase reporter construct fused to three tandem repeats of the calcineurin-dependent response element (CDRE), which gives an accurate measure of calcineurin activity. The addition of FTY720 increased calcineurin activity as well as Ca²⁺ influx in a concentration-dependent manner. Notably, the FTY720-mediated Ca²⁺ influx and calcineurin activation were reduced markedly by the deletion of <i>yam8</i>⁺ or <i>cch1</i>⁺ encoding putative subunits of a Ca²⁺ channel. Consistently, the deletion of Pmk1 mitogen-activated protein kinase (MAPK), which plays an important role in the activation of the Yam8/Cch1 channel, markedly decreased the intracellular Ca²⁺ levels upon FTY720 treatment. These results suggest that the FTY720-stimulated Ca²⁺/calcineurin signaling activation partly involves the Yam8/Cch1 channel in fission yeast.</p> </div

FTY720 stimulates Ca²⁺/calcineurin signaling via the Yam8/Cch1 channel.

<p>(A) The wild-type (wt), Δ<i>yam8</i>, Δ<i>cch1</i>, or Δ<i>yam8</i>Δ<i>cch1</i> cells harboring pKB6892 (<i>adh1</i>-GFP-19-AEQ) were treated with 10 μM FTY720 or vehicle (basal), and the experiments were performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>. The histogram was calculated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>. Bars, SD. (B) Effects of GdCl₃ on the FTY720-induced increase in the cytoplasmic Ca²⁺ level. The experiments were performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>, except that 1 mM or 10 mM of GdCl₃ were also added to the EMM medium. The histogram was calculated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4A</a>. (C) Deletion of Yam8 or Cch1 reduced markedly calcineurin activation induced by FTY720. The wild-type (wt), Δ<i>yam8</i>, Δ<i>cch1</i>, or Δ<i>yam8</i>Δ<i>cch1</i> cells harboring the reporter plasmid (wt 3×CDRE::luc(R2.2)) were monitored as described in the legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g003" target="_blank">Figure 3(B)</a>.　(D) Deletion of Yam8 or Cch1 enhanced the sensitivity to FTY720. A serial dilution assay of the wild-type (wt), Δ<i>yam8</i>, Δ<i>cch1</i>, and Δ<i>yam8</i>Δ<i>cch1</i> mutant cells grown in rich YPD medium containing the indicated concentrations of FTY720. </p

Intracellular Ca²⁺ levels on FTY720 treatment.

<p>(A) Left: Monitoring of intracellular Ca²⁺ levels in wild-type (wt) cells harboring <i>adh1</i>-GFP-19-AEQ (pKB6892) treated with various concentrations of FTY720 at a time point of 5 min and the luminescence was followed for 1 h. An aequorin assay was performed as described in the Materials and Methods. The data shown are the representative of multiple experiments. Right: Graph shows the average of peak heights from three independent experiments shown in the left column of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>. Bars, SD. (B) Effects of EGTA and CaCl₂ on the FTY720-induced increase in the cytoplasmic Ca²⁺ level. The experiments were performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>, except that prior to the addition of FTY720, 20 mM EGTA (left) or 100 mM CaCl₂ (middle) were added to the EMM medium. Right: The histogram was calculated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4A</a>. (C) (D) Effects of EGTA and CaCl₂ on the FTY720-induced increase in the calcineurin activity. The experiments were performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g003" target="_blank">Figure 3 (B)</a> with wt 3×CDRE, except that prior to the addition of 10 μM FTY720, 10 mM or 20 mM EGTA or 200 mM CaCl₂ were added to the EMM medium. The histogram was calculated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g003" target="_blank">Figure 3 (B)</a>.</p