Signaling by Blurring *

Abstract A blurred instruction can have a signaling purpose. A sender wants to persuade a receiver to take an informed action. The sender can control the noise in the signal of an action recommendation. A precise signal makes the receiver worry about the high cost of actions, whereas an imprecise signal confuses the receiver about what action to take. We show that the sender uses the noise as a credible signal of the low cost of actions in order to persuade the receiver to take action. The less precise the signal, the less costly actions appear and the more likely the receiver takes action. The signal becomes noisier as the agents' interests become more congruent: imprecision signals congruence. JEL classification: C72, D82, D8

Examining Minimal Important Change of the Self-Assessment Scale of Clinical Reasoning in Occupational Therapy

The purpose of the study was to establish and quantify the minimal important change (MIC) value necessary to determine gains or losses in clinical reasoning during student fieldwork assignments as measured by the Self-Assessment of Clinical Reasoning in Occupational Therapy (SA-CROT). This multicenter prospective longitudinal study was conducted with students on their occupational therapy fieldwork in Japan. Two anchor-based methods were used to estimate the MIC values: a receiver operating characteristic-based method and a predictive modeling-based method. The MIC was adjusted based on the percentage of participants who exhibited improvement. Administered were the SA-CROT and the Global Rating of Change (GRC) scale as an anchor. A total of 111 students from 11 occupational therapy educational programs in Japan responded (response rate 29%). Overall, there was a significant difference (p \u3c .001, effect size was r = .80) in SA-CROT before and after fieldwork, and 81% of students showed improvement in the GRC scale. The adjusted MIC value was 3.69, with 95% confidence interval of 2.29–4.97. This anchor-based, adjusted MIC value is the most reliable value to interpret the changes in SA-CROT before and after fieldwork. The SA-CROT\u27s MIC value can be used as a cut-off point from a learner-centered perspective when considering educational methods and environments in fieldwork

Ultrastructure of influenza virus ribonucleoprotein complexes during viral RNA synthesis

The single-stranded, negative-sense, viral genomic RNA (vRNA) of influenza A virus is encapsidated by viral nucleoproteins (NPs) and an RNA polymerase to form a ribonucleoprotein complex (vRNP) with a helical, rod-shaped structure. The vRNP is responsible for transcription and replication of the vRNA. However, the vRNP conformation during RNA synthesis is not well understood. Here, using high-speed atomic force microscopy and cryo-electron microscopy, we investigated the native structure of influenza A vRNPs during RNA synthesis in vitro. Two distinct types of vRNPs were observed in association with newly synthesized RNAs: an intact, helical rod-shaped vRNP connected with a folded RNA and a deformed vRNP associated with a looped RNA. Interestingly, the looped RNA was a double-stranded RNA, which likely comprises a nascent RNA and the template RNA detached from NPs of the vRNP. These results suggest that while some vRNPs keep their helical structures during RNA synthesis, for the repeated cycle of RNA synthesis, others accidentally become structurally deformed, which likely results in failure to commence or continue RNA synthesis. Thus, our findings provide the ultrastructural feature of vRNPs during RNA synthesis

Prognosis factors in the treatment of bisphosphonate-related osteonecrosis of the jaw - Prognostic factors in the treatment of BRONJ -

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a relatively rare but serious side effect of bisphosphonate (BP)-based treatments. This retrospective study aimed to investigate the risk factors and predictive markers in cases where patients were refractory to a recommended conservative treatment offered in our hospital. Patients and Methods: This single-center study collated the medical records of all patients treated for BRONJ between 2004 and 2011. A complete medical history, including detailed questionnaires, was collected for all patients, focusing on identifying underlying risk factors, clinical features, location and bone marker levels of BRONJ. Results: The mean BRONJ remission rate was 57.6%, and the median duration of remission was seven months. Eighteen patients (34.6%) had persistent or progressive disease with a recommended conservative treatment for BRONJ. Notably, urinary cross-linked N-terminal telopeptide of type 1 collagen (NTX) levels in those resistant to conservative treatment tended to be lower than in patients that healed well. Conclusions: We confirm that a significant proportion of BRONJ sufferers are refractory to a recommended conservative treatment and find that anticancer drugs, periodontal disease, the level of bone exposure and the dosage of intravenous BPs (e.g. zoledronate) represent specific risk factors in BRONJ that may determine the success of a recommended conservative treatment. Additionally, the NTX levels might be able to be a prognostic factor for the conservative treatment of BRONJ; additional research is necessary

Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming

Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging

PGL-III, a Rare Intermediate of <i>Mycobacterium leprae</i> Phenolic Glycolipid Biosynthesis, Is a Potent Mincle Ligand

Although leprosy (Hansen's disease) is one of the oldest known diseases, the pathogenicity of Mycobacterium leprae (M. leprae) remains enigmatic. Indeed, the cell wall components responsible for the immune response against M. leprae are as yet largely unidentified. We reveal here phenolic glycolipid-III (PGL-III) as an M. leprae-specific ligand for the immune receptor Mincle. PGL-III is a scarcely present trisaccharide intermediate in the biosynthetic pathway to PGL-I, an abundant and characteristic M. leprae glycolipid. Using activity-based purification, we identified PGL-III as a Mincle ligand that is more potent than the well-known M. tuberculosis trehalose dimycolate. The cocrystal structure of Mincle and a synthetic PGL-III analogue revealed a unique recognition mode, implying that it can engage multiple Mincle molecules. In Mincle-deficient mice infected with M. leprae, increased bacterial burden with gross pathologies were observed. These results show that PGL-III is a noncanonical ligand recognized by Mincle, triggering protective immunity. </p

National seroepidemiological study of COVID-19 after the initial rollout of vaccines: Before and at the peak of the Omicron-dominant period in Japan

BACKGROUND: Based on routine surveillance data, Japan has been affected much less by COVID-19 compared with other countries. To validate this, we aimed to estimate SARS-CoV-2 seroprevalence and examine sociodemographic factors associated with cumulative infection in Japan. METHODS: A population-based serial cross-sectional seroepidemiological investigation was conducted in five prefectures in December 2021 (pre-Omicron) and February-March 2022 (Omicron [BA.1/BA.2]-peak). Anti-nucleocapsid and anti-spike antibodies were measured to detect infection-induced and vaccine/infection-induced antibodies, respectively. Logistic regression was used to identify associations between various factors and past infection. RESULTS: Among 16 296 participants (median age: 53 [43-64] years), overall prevalence of infection-induced antibodies was 2.2% (95% CI: 1.9-2.5%) in December 2021 and 3.5% (95% CI: 3.1-3.9%) in February-March 2022. Factors associated with past infection included those residing in urban prefectures (Tokyo: aOR 3.37 [95% CI: 2.31-4.91], Osaka: aOR 3.23 [95% CI: 2.17-4.80]), older age groups (60s: aOR 0.47 [95% CI 0.29-0.74], 70s: aOR 0.41 [95% CI 0.24-0.70]), being vaccinated (twice: aOR 0.41 [95% CI: 0.28-0.61], three times: aOR 0.21 [95% CI: 0.12-0.36]), individuals engaged in occupations such as long-term care workers (aOR: 3.13 [95% CI: 1.47-6.66]), childcare workers (aOR: 3.63 [95% CI: 1.60-8.24]), food service workers (aOR: 3.09 [95% CI: 1.50-6.35]), and history of household contact (aOR: 26.4 [95% CI: 20.0-34.8]) or non-household contact (aOR: 5.21 [95% CI:3.80-7.14]) in February-March 2022. Almost all vaccinated individuals (15 670/15 681) acquired binding antibodies with higher titers among booster dose recipients. CONCLUSIONS: Before Omicron, the cumulative burden was >10 times lower in Japan (2.2%) compared with the US (33%), the UK (25%), or global estimates (45%), but most developed antibodies owing to vaccination