Aberrant Expression of TFF1, TFF2, and PDX1 and Their Diagnostic Value in Lobular Endocervical Glandular Hyperplasia

Lobular endocervical glandular hyperplasia (LEGH) is a distinct benign glandular lesion expressing gastric gland mucous cell-type mucin (N-acetylglucosaminal -> 4galactose -> R [GlcNAc alpha 1 -> 4Gal -> R]). To investigate histogenesis and diagnostic markers of LEGH, we examined the immunohistochemical expression profile of gastric surface mucous cell (MUC5AC and TFF1), gastric gland mucous cell (MUC6, TFF2, and GlcNAc alpha 1 -> 4Gal -> R), gastric pyloric epithelial cell (PDX1), and endocervical cell (keratan sulfate) markers in normal endocervix samples and benign glandular lesions (nabothian cysts, tunnel clusters, and LEGHs). MUC5AC and MUC6 were expressed in normal endocervical mucosa and benign glandular lesions. TFF1, TFF2, GlcNAc alpha 1 -> 4Gal -> R, and PDX1 were expressed only in LEGH. Keratan sulfate was expressed in normal endocervical mucosa and benign glandular lesions. In LEGH, gastric surface mucous cell and gastric gland mucous cell differentiation were demonstrated, and transdifferentiation from endocervical mucosa into gastric pyloric mucosa was suggested. In addition to GlcNAc alpha 1 -> 4Gal -> R, TFF1, TFF2, and PDX1 are additional useful markers for LEGH.ArticleAMERICAN JOURNAL OF CLINICAL PATHOLOGY. 135(2):253-261 (2011)journal articl

英語教育における流暢さと即興力の育成 ── 中学生の話すことにおける意識の一考察 ──

The major goals of this study are to examine junior high school students’ awareness of fluency and impromptu skill in terms of speaking in English as a Foreign Language (hereafter, EFL) and to consider what to do, by way of future research and creation of daily lessons, in order to raise awareness and to develop their practical speaking abilities.　Recent Japanese EFL education (see MEXT 2017a-e) emphasizes that developing learners’ fluency and impromptu skill is particularly important.　This is because traditional Japanese EFL education has focused on acquisition of grammar, drawing learners’ attention to individual forms rather than to meaning.　Problematic outcomes of such an approach are tendencies for learners to comprehend texts/utterances in a heavy bottom-up manner and to refrain from speaking/writing without confirming that what they are about to say/write is grammatically correct.　In this study, 419 junior high school students in 1st to 3rd grades responded to a short paper-and-pencil questionnaire that examined their awareness of fluency and impromptu skill in EFL speaking.　Results of analyses showed a significant difference in awareness of impromptu skill between 1st and 2nd grades and between 1st and 3rd grades, whereas no significant differences were found in awareness of fluency between these three grades.　Moreover, results of analyses showed no correlation between 1st graders’ mid-term/ final exam scores and their awareness of fluency/impromptu skill, but showed a correlation between 2nd graders’ final exam scores and their awareness of fluency and between 2nd graders’ final exam scores and their awareness of impromptu skill.　Based on this and other information obtained in the study, we consider issues for future research and creation of classroom activities that develop fluency and impromptu skill in Japanese EFL education

A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part

This multicenter, double-blind, phase 2a part of a phase 2/3 study assessed the efficacy and safety of ensitrelvir, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor, in Japanese patients with mild-to-moderate coronavirus disease 2019 (COVID-19) or asymptomatic ARSCoV- 2 infection. Sixty-nine patients were randomized (1:1:1) to orally receive 5-day ensitrelvir fumaric acid (375 mg on day 1 followed by 125 mg daily, or 750 mg on day 1 followed by 250 mg daily) or placebo and followed up until day 28. The primary outcome was the change from baseline in the SARS-CoV-2 viral titer. A total of 16, 14, and 17 patients in the ensitrelvir 125 mg, ensitrelvir 250 mg, and placebo groups, respectively, were included in the intention-to-treat population (mean age: 38.0 to 40.4 years). On day 4, the change from baseline in SARS-CoV-2 viral titer (log10 50% tissue culture infectious dose/mL) in patients with positive viral titer and viral RNA at baseline was greater with ensitrelvir 125 mg (mean [standard deviation], –2.42 [1.42]; P = 0.0712) and 250 mg (–2.81 [1.21]; P = 0.0083) versus placebo (–1.54 [0.74]); ensitrelvir treatment reduced SARS-CoV-2 RNA by –1.4 to –1.5 log10 copies/ mL versus placebo. The viral titer and viral RNA were similar across groups on and after day 6. The median time to infectious viral clearance decreased by approximately 50 h with ensitrelvir treatment. All adverse events were mild to moderate. Ensitrelvir treatment demonstrated rapid SARS-CoV-2 clearance and was well tolerated (Japan Registry of Clinical Trials identifier: jRCT2031210350)

AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells