ROLE OF GUT MICROBIOME HOMEOSTASIS, INTEGRITY OF THE INTESTINAL EPITHELIAL CELLS, AND THE (ENDOGENOUS) BUTYRATE IN ENDURING A HEALTHY LONG LIFE.

The influence of gut microbiomes on health has been gaining significance lately. More emphasis is their role in neurological illnesses as several of the metabolites and factors produced by the gut affect the brain via the gut-brain axis. Among all the gut microbiome produced metabolites, butyrate has been considered the most significant. Externally supplemented butyrate though has health benefits, when evaluated thoroughly, it is understood that there have been different pathways involved in the production of butyrate by the gut microbiome with the produced butyrate even being detrimental, though majority are beneficial. Importantly maternal butyrate supplementation has resulted in detrimental effects in the offspring. In this background, a black yeast Aureobasidium pullulans produced biological response modifier beta glucans (BRMGs) has shown beneficial outcome (anti-inflammatory: decrease in IL-6, Ferritin, C-reactive protein in COVID-19, D-Dimer; anti-fibrotic in fatty liver disease; improvement of behaviour and sleep with increase in α-synuclein, melatonin in autism) along with its effect on increasing the butyrate producing bacteria in the gut. Since only advantageous outcome has been reported with this BRMG produced butyrate, it is worth being considered as a yardstick for evaluation of exogenously supplemented and endogenous produced butyrate for their differential effects on host and its offspring.

The response of local governments and public health centers to COVID-19: looking for infectious disease control due to the change of trend and mutations of the virus

Public Health Centers of Japan. of which there are 468 across the country as of April 2022. are at the core of health crisis management. responding to natural disasters and infectious diseases according to the Community Health Act (1994). Under the Infectious Diseases Control La these centers have made repeated efforts to respond to COV1D-19 from the first to the seventh waves while epidemic dynamics changed. variants emerged. and pathogenicity fluctuated. All centers essentially play a common role in infectious disease control (answering questions and consultations. testing, registering cases, coordinating healthcare. transporting confirmed patients, following up with patients and close contacts. carrying out epidemiological investigations. issuing notifications for recommendations on hospital stays and work restrictions. etc.). 'forever, due to the varying number of cases and healthcare resources depending on the region, the actual work was not identical, and local governments. which operate the centers. took different appreoclws. Looking back on the epidemic, the first, second, and third waves saw travel restrictions implemented across the country, and were characterized by a demand for testing that exceeded capacity. At that time. COVID-19 was a threat to the respiratory system, no effective treatment or vaccination was available. and the number of healthcare institutions diagnosing and treating cases was inadequate. The fourth wave saw the Alpha variant ripping through nursing homes putting a significant burden on healthcare. while the fifth wave saw the Delta variant spreading mainly from Tokyo after the Olympics. The sixth and seventh waves came with the highly. Contagious Omicron variant. leading to skyrocketing patient numbers and the public health capacity quickly being overwhelmed. Local governments considered ways to reduce the burden on Public Health Centers, including outsourcing. Over this 2.5 year period, numerous advisories were issued by the Ministry of Health, Labor, and Welfare (MHLW), and the Japanese Association of Public Health Center Directors has advocated actively on behalf of the centers. Given that Japan is a disaster-prone country, Public Health Centers in Japan are expected to play a pivotal role in crisis preparedness, responses to, and recovery from natural disasters and infectious diseases. As a coordination hub to protect lives and maintain health, here we strongly suggest that public health centers implement the lessons learned from COVID-19 to collaborate with healthcare institutions and long-term care facilities, and evolve into a sustainable social framework to advance pandemic preparedness in their respective communities.

Phase II study of neoadjuvant concurrent chemo-immuno-radiation therapy followed by surgery and adjuvant immunotherapy for resectable stage IIIA-B N2 non-small cell lung cancer: SQUAT trial (WJOG 12119L)

Background: Neoadjuvant chemo-immunotherapy (CheckMate 816 regimen) has become a standard of care in treatment of resectable non-small cell lung cancer (NSCLC) patients in some countries. Addition of radiation therapy (RT) may further improve local control in locally advanced NSCLC patients. Here, we report the primary endpoint, major pathologic response (MPR), of the SQUAT trial (WJOG 12119L, JapicCTI- 195069)-a multicenter, prospective, single-arm, phase II trial of neoadjuvant concurrent chemo-immuno-radiation therapy followed by surgical resection and adjuvant immunotherapy for resectable stage IIIA-B N2 NSCLC. Method(s): Patients with resectable stage IIIA-B N2 NSCLC received concurrent chemoradiotherapy [weekly paclitaxel (40 mg/m2)/carboplatin (AUC 2) for 5 weeks plus involved-field RT 50 Gy] and immunotherapy [durvalumab (1500 mg) Q4W for 2 cycles] followed by surgical resection and adjuvant immunotherapy (durvalumab for up to 1 year). The primary endpoint was MPR rate according to an independent central review (ICR). We assumed the threshold of the MPR rate to be 40% and the expected rate to be 65% with a significance level alpha=0.05 (one-sided) and power 0.8. The sample size was 31 patients, including the 10% ineligible patients. Result(s): Between Jan 2020 and Feb 2022, 31 patients were enrolled from 10 institutions in Japan. Thirty-one patients were evaluated for safety, and 30 patients for efficacy. Of 30 patients (median age, 64 years), 70% and 63% had clinical stage IIIA and non-squamous histology, respectively. The MPR and pathological complete response (pCR) rates by ICR were 63% (90% CI, 47-78, 95% CI, 44-80) and 20% (95% CI, 8-39), respectively. Complete resection was not performed due to adverse events (2 pts) and disease progression (3 pts). Among 25 patients who received complete resection, the MPR and pCR rates were 76% (95% CI, 55-91) and 24% (95% CI, 9-45), respectively. No 30-day postoperative mortality was reported. Conclusion(s): The primary endpoint of MPR rate was met in SQUAT trial. This result suggests that this treatment strategy is promising for resectable stage IIIA-B N2 NSCLC. Clinical trial identification: JapicCTI-195069. Legal entity responsible for the study: WJOG (West Japan Oncology Group). Funding(s): AstraZeneca. Disclosure: T. Miyoshi: Financial Interests, Institutional, Research Grant: AstraZeneca. A. Hamada: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Ono Pharmaceuticals;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Institutional, Research Grant: AstraZeneca. J. Soh: Financial Interests, Personal, Invited Speaker: Ethicon, Covidien, Intutive;Financial Interests, Institutional, Research Grant: AstraZeneca. A. Hata: Financial Interests, Institutional, Research Grant: MSD, Eli Lilly, Boehringer Ingelheim, AstraZeneca;Financial Interests, Personal, Invited Speaker: Eli Lilly, Chugai, Pfizer, AstraZeneca, Boehringer Ingelheim. Y. Yatabe: Financial Interests, Personal, Invited Speaker: MSD, Chugai-pharma, AstraZeneca, Pfizer, Thermo Fisher Science, ArcherDx, Novartis, Elli-Lily, Daiichi Sankyo, Jansen-Pharma, Amgen;Financial Interests, Institutional, Research Grant: Thermo Fisher Science, ArcherDx, AstraZeneca. J. Suzuki: Financial Interests, Institutional, Research Grant: AstraZeneca. M. Tsuboi: Financial Interests, Personal, Invited Speaker, Lecture: Johnson & Johnson Japan;Financial Interests, Personal, Advisory Board, Lectures, Advisory boards: AstraZeneca KK, Chugai Pharmaceutical Co.,Ltd, MSD;Financial Interests, Personal, Invited Speaker, Lectures: Eli Lilly Japan, Bristol Myers Squibb KK, Teijin Pharma, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical Co.,Ltd;Financial Interests, Personal, Advisory Board, Advisory boards: Novartis;Financial Interests, Personal, Invited Speaker: Daiichi Sankyo company limited, MSD, AstraZeneca, Novartis;Financial Interests, Institutional, Research Grant: Beohringer-Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical Co.,Ltd, Bristol Myers Squibb KK, Novartis;Financial Interests, Institutional, Invited Speaker: Eli Lilly Japan. H. Horinouchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Novartis, Pfizer, Boehringer Ingelheim, Kyowa-Kirin, Nihon Kayaku, AbbVie, Roche/Chugai;Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Amgen, Nihon Kayaku;Financial Interests, Institutional, Research Grant: Roche/Chugai, Merck Sharp & Dohme, Daiichi Sankyo, ONO pharmaceutical, AstraZeneca;Financial Interests, Institutional, Invited Speaker: AbbVie. I. Yoshino: Financial Interests, Institutional, Research Grant: AstraZeneca. T. Masayuki: Financial Interests, Institutional, Research Grant: AstraZeneca. S. Toyooka: Financial Interests, Personal, Invited Speaker: Chugai, Taiho, Ono Pharmaceuticals, Kyorin, Daiichi Sankyo, Medtronic, Johnson and Johnson;Financial Interests, Personal, Advisory Role: Kyorin;Financial Interests, Institutional, Research Grant: Illumina, Eurofins, Taiho, Chugai, Eli Lilly, AstraZeneca. M. Okada: Financial Interests, Institutional, Research Grant: AstraZeneca. T. Go: Financial Interests, Institutional, Research Grant: AstraZeneca. M. Yamashita: Financial Interests, Institutional, Research Grant: AstraZeneca. N. Yamamoto: Financial Interests, Personal, Invited Speaker: MSD K.K, AstraZeneca, Ono Pharmaceutical Co., Ltd., Thermo Fisher Scientific, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, Pfizer Inc., Bristol Myers Squibb, Nippon Kayaku, GlaxoSmithKline K.K., Sanofi K.K., Hisamitsu Pharmaceutical Co.,Inc., Merk biopharma;Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, Bristol Myers Squibb, Nippon Kayaku, Life Technologies Japan Ltd., Amgen Inc., Guardant Health Japan, Janssen Pharmaceutical K.K.;Financial Interests, Institutional, Research Grant: MSD K.K;Financial Interests, Institutional, Invited Speaker: AstraZeneca, Ono Pharm ceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., Amgen Inc., Janssen Pharmaceutical K.K.;Financial Interests, Institutional, Funding: Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Toppan printing, Terumo. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Nippon Kayaku Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co.,Ltd., Bayer Yakuhin, Ltd., CMIC ShiftZero K.K., Life Technologies Japan Ltd., Neo Communication, Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., 3H Clinical Trial Inc., Care Net, Inc., Medical Review Co., Ltd., Medical Mobile Communications co., Ltd, Yodosha Co., Ltd., Nikkei Business Publications, Inc., Japan Clinical Research Operations, CMIC Co., Ltd., Novartis Pharma K.K., Taiyo Pharma Co., Ltd.;Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co.,Ltd., Eli Lilly Japan K.K.;Financial Interests, Institutional, Other, patents sales fee: Daiichi Sankyo Co., Ltd.;Financial Interests, Institutional, Research Grant: Parexel International Corp., Pra Healthsciences, Eps Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co.,Ltd,., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co.,Ltd., MSD K.K., Ono Pharmaceutical Co.,Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services Japan K.K., Syneos Health Clinical K.K., Nippon Kayaku Co.,Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan linical Research Operations, Takeda Pharmaceutical Co.,Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Sysmex Corporation, Medical Reserch Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Novartis Pharma K.K., Srl, Inc. T. Mitsudomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Novartis, MSD, Bristol Myers Squibb, Ono, Pfizer, Eli Lilly, Merck Biopharma;Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Chugai, Novartis, MSD, Bristol Myers Squibb, Ono, Pfizer, Amgen, Janssen, Takeda, Eli-Lilly;Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, AstraZeneca, Chugai, MSD, Taiho, Daiichi Sankyo, Ono;Non-Financial Interests, Personal, Leadership Role: Interanational Association for Study of Lung Cancer. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology

The Current Status of Thrombosis and Anticoagulation Therapy in patients with COVID-19 in Japan: From the CLOT-COVID Study

Background: Data on thrombosis and current real-world management strategies for anticoagulation therapy are important for an optimal management of patients with coronavirus disease 2019 (COVID-19) Methods: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. Also subanalysis is performed for D-dimer at the admission and influence of sex with adjustment confounders with multivariable logistic regression model. Result(s): Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. During the hospitalization, 38 patients (1.3%)and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrastenhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism(71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4%withmoderate COVID-19, and 9.5%with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. The higher D-dimer levels in the 3rd tertile (>=1.1 mug/mL) in 2,771 patients who had D-dimer levels measured at admission. were independently associated with a higher risk of VTE during hospitalization (adjusted odds ratio 4.83 [95% confidence interval 1.93-12.11;P<0.001];reference=1st tertile).Men had more severe status of the COVID-19 at admission compared with women (Mild: 57% versus 66%, Moderate: 34% versus 29%, and Severe: 9.1% versus 5.7%, P < 0.001). During the hospitalization, men more often developed thrombosis than women (2.5% [95%CI, 1.9-3.3%] versus 0.8% [95%CI, 0.4- 1.6%], P = 0.001). Men had numerically higher incidences of thrombosis than women in all subgroups of the worst severity of COVID-19during the hospitalization (Mild: 0.3% versus 0.0%, Moderate: 1.6% versus 1.0%, and Severe: 11.1% versus 4.3%) Conclusion(s): In the large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients was common especially in patients with severe COVID-19. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19 in Japan. In contrast to previous studies outside Japan, the risk of thrombosis in Japanese patients with COVID-19 may be relatively low, and racial differences may have to be considered. In subanalysis higher D-dimer levels at admission were associated with a higher risk of VTE events during hospitalization. Men had more severe status of the COVID-19 than women, and the risk of development of thrombosis was higher in men compared with women.

The COVID-19 pandemic and risks in East Asia: Media, social reactions, and theories

Using "risk" as a conceptual lens, this book analyzes how communities across East Asia responded to the disruption unleashed by the COVID-19 pandemic. The contributors to this book look at how governments, societies, and individuals have perceived, experienced, dealt with and interpreted the pandemic and the transformations it has brought across countries like Japan, South Korea, Taiwan, Vietnam, and the Philippines. They examine pressing concerns such as infodemic, digital health literacy, media cynicism, telework, and digital inequalities in conjunction with issues such as public trust, identity formation, nationalism, and social fragmentation. They look at a wide range of questions relating to communication, mediation, and reactions to the challenges of the pandemic. An insightful resource for scholars of risk studies and of East Asian societies, the book is also a valuable reference for students and researchers of media and communication studies and sociology. © 2023 selection and editorial matter, Nobuto Yamamoto;individual chapters, the contributors.

Global impact of the COVID-19 pandemic on stroke care and intravenous thrombolysis

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods. Background: The COVID-19 pandemic led to widespread repercussions on the delivery of health care worldwide. Design/Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by ICD-10 codes and/or classifications in stroke center databases. Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI,-11.7 to-11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI,-13.8 to-12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI,-13.7 to-10.3, p=0.001). There were greater declines in primary compared to comprehensive stroke centers (CSC) for stroke hospitalizations (-17.3% vs-10.3%, p<0.0001) and IVT (-15.5% vs-12.6%, p=0.0001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) months of the pandemic, with greater recovery in hospitals with lower COVID-19 hospitalization volume, high volume stroke center, and CSC. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722/52,026) of all stroke admissions. Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months, with greater recovery in hospitals with lower COVID-19 hospitalizations, high volume stroke centers, and CSCs.

An Integrated Online Learning Approach Using a Smartphone-Based Active Learning System and a Web Video On-Demand System

In general, at the universities the lecturers use the grades to evaluate the students’ performance. However, the grades do not show the accumulated knowledge. Thus, the students can’t understand whether they have studied enough to understand all the topics of the lecture. In our previous work, we implemented a smartphone-based Active Learning System (ALS), which uses 360-degrees cameras for searching the students’ location. By using the ALS, we can judge the students’ learning style. However, in the case of remote or online lectures, we need to improve our system. Recently, because of COVID-19, most of the universities are using online learning systems. However, the used online learning systems are not yet stable and we cannot get students’ learning status as in the case of ALS. Therefore, in this paper, we present an integrated approach using ALS and a Web video on-demand system for online remote lectures. © 2021, Springer Nature Switzerland AG.