Exoskeleton for the Mind: Exploring Strategies Against Misinformation with a Metacognitive Agent

Misinformation is a global problem in modern social media platforms with few solutions known to be effective. Social media platforms have offered tools to raise awareness of information, but these are closed systems that have not been empirically evaluated. Others have developed novel tools and strategies, but most have been studied out of context using static stimuli, researcher prompts, or low fidelity prototypes. We offer a new anti-misinformation agent grounded in theories of metacognition that was evaluated within Twitter. We report on a pilot study (n=17) and multi-part experimental study (n=57, n=49) where participants experienced three versions of the agent, each deploying a different strategy. We found that no single strategy was superior over the control. We also confirmed the necessity of transparency and clarity about the agent's underlying logic, as well as concerns about repeated exposure to misinformation and lack of user engagement.Comment: Pages 209-22

レゾルシル酸ラクトンLL-Z1640-2の成人T細胞白血病/リンパ腫に対する治療効果

Adult T-cell leukaemia/lymphoma (ATL) remains incurable. The NF-κB and interferon regulatory factor 4 (IRF4) signalling pathways are among the critical survival pathways for the progression of ATL. TGF-β-activated kinase 1 (TAK1), an IκB kinase-activating kinase, triggers the activation of NF-κB. The resorcylic acid lactone LL-Z1640-2 is a potent irreversible inhibitor of TAK1/extracellular signal-regulated kinase 2 (ERK2). We herein examined the therapeutic efficacy of LL-Z1640-2 against ATL. LL-Z1640-2 effectively suppressed the in vivo growth of ATL cells. It induced in vitro apoptosis and inhibited the nuclear translocation of p65/RelA in ATL cells. The knockdown of IRF4 strongly induced ATL cell death while downregulating MYC. LL-Z1640-2 as well as the NF-κB inhibitor BAY11-7082 decreased the expression of IRF4 and MYC at the protein and mRNA levels, indicating the suppression of the NF-κB-IRF4-MYC axis. The treatment with LL-Z1640-2 also mitigated the phosphorylation of p38 MAPK along with the expression of CC chemokine receptor 4. Furthermore, the inhibition of STAT3/5 potentiated the cytotoxic activity of LL-Z1640-2 against IL-2-responsive ATL cells in the presence of IL-2. Therefore, LL-Z1640-2 appears to be an effective treatment for ATL. Further studies are needed to develop more potent compounds that retain the active motifs of LL-Z1640-2

キサンチンオキシダーゼ阻害薬febuxostatはNrf2を活性化し脂肪細胞分化を抑制する

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical inducer of antioxidants, which is bound and repressed by a kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. The Keap1-Nrf2 axis appears to be a major mechanism for robust inducible antioxidant defenses. Here, we demonstrate that febuxostat, a xanthine oxidase inhibitor, alleviates the increase in adipose tissue mass in obese mouse models with a high-fat diet or ovariectomy. Febuxostat disrupts in vitro adipocytic differentiation in adipogenic media. Adipocytes appeared at day 7 in absence or presence of febuxostat were 160.8 ± 21.2 vs. 52.5 ± 12.7 (p < 0.01) in 3T3–L1 cells, and 126.0 ± 18.7 vs. 55.3 ± 13.4 (p < 0.01) in 10T1/2 cells, respectively. Adipocyte differentiation was further enhanced by the addition of hydrogen peroxide, which was also suppressed by febuxostat. Interestingly, febuxostat, but not allopurinol (another xanthine oxidase inhibitor), rapidly induced the nuclear translocation of Nrf2 and facilitated the degradation of Keap1, similar to the electrophilic Nrf2 activator omaveloxolone. These results suggest that febuxostat alleviates adipogenesis under oxidative conditions, at least in part by suppressing ROS production and Nrf2 activation. Regulation of adipocytic differentiation by febuxostat is expected to inhibit obesity due to menopause or overeating

粘液性嚢胞腺腫の悪性化との鑑別に苦慮した膵未分化癌の1例

症例は70歳代の女性．7年前に膵尾部単純性嚢胞と診断され，経過観察中であった．4ヶ月持続する発熱と心窩部痛の精査を目的として入院した．入院時のCTでは多発肝腫瘍を認め，嚢胞内には結節病変を，嚢胞周囲には出血・感染を示唆する所見を認めた．以上より，嚢胞性病変が癌化して転移・浸潤をきたし，嚢胞周囲に膿瘍を形成したものと考えて対症的に治療したが，第15病日に死亡した．剖検所見から嚢胞の癌化は否定され，嚢胞に近接して発生した膵未分化癌と，肝転移，肺転移等の多臓器転移，腹膜播種と診断された

リュウキ ケイセイ オ テイ シタ ミブンカ ガタ イ ネンマク ナイ ガン ニ タイ シ ナイシキョウ チリョウ オ シコウ シタ 1 レイ

症例は67才男性.上部消化管内視鏡検査で胃前庭部前壁に0-I+IIc型隆起性病変を指摘され,生検結果は低分化型腺癌の診断であった.適応拡大病変と診断して内視鏡的胃粘膜下層剥離術(ESD)施行し適応拡大治癒切除であった.フォローの内視鏡で初回病変の近傍に0-I+IIc型の隆起を主体とした病変を認め,生検結果は印環細胞癌であり,再度ESDを施行した.初回病変のような,隆起を主体とした未分化型粘膜内癌の症例は稀である.二回目の病変の成因は,局所再発・腫瘍移植(implantation)・異時性癌のいずれか確定は困難であったが,貴重な症例と思われたので報告したA 67-year-old man was diagnosed with a small elevated undifferentiated gastric adenocarcinoma in situ and subsequently underwent endoscopic submucosal dissection (ESD). Curative resection was achieved. Fifteen months later, a new lesion was found near the ESD scar of the first lesion. This lesion was similarly elevated, and histopathological examination of the biopsy specimen revealed signet ring cell carcinoma. We performed ESD again for this lesion. Elevated early gastric cancer in which histological examination shows undifferentiated adenocarcinoma and depth M is very rare. We searched for elevated early undifferentiated gastric cancers in the PubMed and Ichushi databases and find only nine cases. The cause of the second lesion was suspected to be either local recurrence, or implantation or metachronous cancer, but it seemed to be very difficult to diagnose exactly. It should be careful observation, even if obtained curative resection of undifferentiated intramucosal gastric cancer by ESD

Scaffolding Student Learning in the Discipline-Specific Knowledge through Contemporary Science Practices: Developing High-School Students’ Epidemiologic Reasoning through Data Analysis

Thesis (Ph.D.)--University of Washington, 2015Science is a disciplined practice about knowing puzzling observations and unknown phenomena. Scientific knowledge of the product is applied to develop technological artifacts and solve complex problems in society. Scientific practices are undeniably relevant to our economy, civic activity, and personal lives, and thus public education should help children acquire scientific knowledge and recognize the values in relation to their own lives and civil society. Likewise, developing scientific thinking skills is valuable not only for becoming a scientist, but also for becoming a citizen who is able to critically evaluate everyday information, select and apply only the trustworthy, and make wise judgments in their personal and cultural goals as well as for obtaining jobs that require complex problem solving and creative working in the current knowledge-based economy and rapid-changing world. To develop students’ scientific thinking, science instruction should focus not only on scientific knowledge and inquiry processes, but also on its epistemological aspects including the forms of causal explanations and methodological choices along with epistemic aims and values under the social circumstances in focal practices. In this perspective, disciplinary knowledge involves heterogeneous elements including material, cognitive, social, and cultural ones and the formation differs across practices. Without developing such discipline-specific knowledge, students cannot enough deeply engage in scientific “practices” and understand the true values of scientific enterprises. In this interest, this dissertation explores instructional approaches to make student engagement in scientific investigations more authentic or disciplinary. The present dissertation work is comprised of three research questions as stand-alone studies written for separate publication. All of the studies discuss different theoretical aspects related to disciplinary engagement in epidemiologic inquiry and student development in epidemiologic reasoning. The first chapter reviews literature on epistemological instruction and explores theoretical frameworks for epistemically-guided instruction. The second chapter explores methodological strategies to elicit students’ disciplinary understanding and demonstrates an approach with a case study in which students engaged in a curriculum unit for an epidemiologic investigation. The last chapter directs the focus into scientific reasoning and demonstrates how the curriculum unit and its scaffolds helped students develop epidemiologic reasoning with a focus on population-based reasoning