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A Research-co-Creation of Care: Feminist Speculation, Collaboration, and Curation in the Decameron 2.0 Virtual Gallery

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UNIVERSITY OF TORONTO QUARTERLY 2024年第4期93卷 612-652页

作者： Tschofen, Monique O'flynn, Siobhan Armstrong, Jolene Fan, Lai-Tze Fisher, Caitlin Pruska-Oldenhof, Izabella Joosse, Angela Maaren, Kari Egan, Kelly Toronto Metropolitan Univ Dept English Toronto ON Canada Univ Toronto Univ Coll Canadian Studies Program Teaching Stream Toronto ON Canada Athabasca Univ Ctr Humanities Athabasca AB Canada Univ Waterloo Canada Res Chair Technol & Social Change Dept Sociol & Legal Studies Waterloo ON Canada Augmented Real Lab Toronto ON Canada Immers Storytelling Lab Toronto ON Canada York Univ Sch Arts Media Performance & Design Toronto ON Canada Elect Literature Org Toronto ON Canada Toronto Metropolitan Univ Creat Sch Toronto ON Canada Canadian Res Knowledge Network Ottawa ON Canada Toronto Metropolitan Univ Dept English Toronto ON Canada Toronto Metropolitan Univ Chang Sch Continuing Educ Toronto ON Canada Trent Univ Cultural Studies Peterborough ON Canada

This paper presents the evolving work of the Decameron Collective, a group of women Canadian scholars and artists who, during the early COVID-19 pandemic (2020-2022), built a body of creative works as an interactive, virtual gallery of visual, audio, and textual media inspired by Giovanni Boccaccio's Decameron (1353). More than a gloss on Boccaccio's text, Decameron 2.0 is a feminist project of collaborative and curational worldbuilding. We describe our practice of co-creating and curating, making a case for interdisciplinary praxis-led approaches of research-creation that embody both a mode of inquiry and a practice of feminist ethics and care. We describe the world of Decameron 2.0 - its courtyards, caves, and rooms of spells, and the affordances of the webGL spatial navigation that contributes to the intermediality within and between the works. The intertextual spatialization of works in Decameron 2.0 and the non-linear exploratory affordances of the virtual environment extend into our academic thinking/theorizing through centripetal and centrifugal frames. In homage to the polyphony of mediaeval manuscript culture, and as an intervention against the flattening of so much academic discourse, we use illustrations, hyperlinks, margins, page layout, and metacommentary. This paratextuality illustrates what we call thinking-together and honours the differences among our individual voices and perspectives. This paper contributes to current critical and cultural understandings of making, care, communication, and feminist practice and models how multi-institutional collaboration can be reshaped in the era of and after COVID-19.

关键词： pandemics feminist collaboration care research creation Decameron

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Target Human Detection Based on Matching of Walking Motion Signals Between Smartphone and Robot for Human Following

Target Human Detection Based on Matching of Walking Motion S...

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IEEE/SICE International Symposium on System Integration

作者： Naomichi Otake Kazuyuki Morioka Graduate School of Advanced Mathematical Sciences Network Design Program Meiji University Japan

ISBN: (数字)9781728166674

ISBN: (纸本)9781728166681

This paper introduces a target human following mobile robot system. Especially, the robot follows a smartphone user as the target. The proposed system includes global following based on Wi-Fi-based waypoint maps and local following based on walking state matching. This paper focuses on target human detection for local following based on cross-correlation coefficients of walking motion signals including vertical acceleration data measured by target user's smartphone and horizontal velocities of legs measured by an LRF installed in the robot. Also, this paper provides results of detection experiments. The results show that higher cross-correlation coefficients can be obtained for the target human than the other pedestrians. Next, a method for calculating the cross-correlation coefficients online is introduced, and the results of the experiment are shown. These results show that the following target can be identified in online calculation of cross-correlation coefficients. That contributes for development of actual human following system.

关键词： Legged locomotion Acceleration Robot sensing systems Wireless fidelity Robot kinematics

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Factors associated with not smoking among Aboriginal and Torres Strait Islander adolescents and young people: Analysis of data from the 2014 to 15 National Aboriginal and Torres Strait Islander Social Survey

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HEALTH PROMOTION JOURNAL OF AUSTRALIA 2025年第1期36卷 e942页

作者： Cameron, Emilie Freund, Megan Eades, Sandra Turner, Nicole Davis, Robert Heris, Christina Rumbel, Jennifer Clapham, Matthew Bryant, Jamie Univ Newcastle Fac Hlth & Med Sch Med & Publ Hlth Hlth Behav Res Collaborat Callaghan NSW Australia Hunter Med Res Inst Equ Hlth & Wellbeing Program New Lambton Hts NSW Australia Univ Melbourne Ctr Epidemiol & Biostat Sch Populat & Global Hlth Carlton Vic Australia NSW Rural Doctors Network St Leonards NSW Australia Australian Natl Univ Natl Ctr Aboriginal & Torres Strait Islander Wellb Natl Ctr Epidemiol & Populat Hlth Coll Hlth & Med Canberra ACT Australia Hunter Med Res Inst Sch Psychol Sci Syst Neurosci Grp New Lambton Hts NSW Australia Univ Newcastle Wollotuka Inst Callaghan NSW Australia Hunter Med Res Inst Clin Res Design Informat Technol & Stat Support New Lambton Hts NSW Australia

Issue AddressedSmoking rates have been steadily declining among Aboriginal and Torres Strait Islander people. Examining the factors associated with not smoking in young people is crucial for understanding the motivations and influences that lead individuals to adopt healthy *** analysis was undertaken of data collected as part of the National Aboriginal and Torres Strait Islander Social Survey (NATSISS) 2014-15 (n = 1456). Factors associated with not smoking were explored with three multivariate regressions: (1) socio-demographic characteristics;(2) health, social and emotional factors;and (3) cultural identity ***, 66% of Aboriginal and Torres Strait Islander young people aged 15-24 years did not smoke. Factors associated with not smoking included being younger, female, and engaged in study or employment. Those who lived with no smoking in the house, had lower illicit drug and alcohol use, and participated in Aboriginal or Torres Strait Islander sports carnivals were also more likely to be *** findings reinforce the influence of social determinants on smoking behaviour. Efforts to reduce smoking among Aboriginal and Torres Strait Islander young people should focus on removing barriers to education and employment, promoting positive peer and family influences within households, taking a multi-drug approach to cessation, and considering cultural identity and its role in promoting healthy *** What?Understanding the protective factors associated with not smoking in young Aboriginal and Torres Strait Islander people will help with developing effective policies and initiatives to improve health outcomes.

关键词： adolescent behaviour Australian Aboriginal and Torres Strait Islander peoples Indigenous peoples smoking prevention tobacco smoking

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Complementary strengths of water footprint and life cycle assessments in analyzing global freshwater appropriation and its local impacts - Recommendations from an Interdisciplinary discussion series

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ECOLOGICAL INDICATORS 2025年 174卷

作者： Berger, Markus Gerbens-Leenes, Winnie Karandish, Fatemeh Aldaya, Maite M. Boulay, Anne-Marie Hogeboom, Rick J. Link, Andreas Manzardo, Alessandro Mialyk, Oleksandr Motoshita, Masaharu Nunez, Montserrat Pfister, Stephan Rosenbaum, Ralph K. Scherer, Laura Su, Han Wohler, Lara Univ Twente Chair Multidisciplinary Water Management Enschede Netherlands Univ Groningen Energy & Sustainabil Res Inst Groningen ESRIG Groningen Netherlands Wageningen Univ & Res Earth Syst & Global Change Grp Wageningen Netherlands Publ Univ Navarre UPNA Sci Dept Pamplona Spain Publ Univ Navarra UPNA Inst Sustainabil & Food Chain Innovat IS FOOD Pamplona Spain Polytech Montreal CIRAIG Montreal PQ Canada Water Footprint Network Enschede Netherlands Tech Univ Berlin Chair Sustainable Engn Berlin Germany Univ Padua Dept Civil Construct & Environm Engn ICEA Padua Italy Natl Inst Adv Ind Sci & Technol Res Inst Sci Safety & Sustainabil Tsukuba Japan Inst Agrifood Res & Technol IRTA Sustainabil Biosyst Res Program Caldes De Montbui Barcelona Spain Swiss Fed Inst Technol Inst Environm Engn Ecol Syst Design Dept Civil Environm & Geomat Engn Zurich Switzerland Leiden Univ Inst Environm Sci CML Leiden Netherlands

Considering globally increasing water challenges, the analysis of water use along supply chains is of great relevance and can be tackled by mainly two methodological approaches: Water Footprint Assessment (WFA) and Life Cycle Assessment (LCA). While sharing the same goal of promoting sustainable water use, both methods developed in different contexts and scientific communities. This has led to heated debates on methodological presuppositions that at times has become unconstructive. To build mutual understanding and enable a fruitful cooperation, researchers from both communities have exchanged over the course of two years. This paper summarizes the outcomes of this discussion series by providing i) a description of the development of both approaches and their ways of assessing freshwater consumption and pollution, ii) an application in a case study, and iii) an analysis of strengths and weaknesses in relation to questions decision-makers may have. Our analysis revealed that WFA's strength lies in its ability to measure freshwater appropriation, water-use efficiency, water scarcity and total pollution levels. This makes WFA particularly useful for crop selection as well as agricultural and river basin water management. With its focus on assessing impacts, LCA is strong in quantifying potential consequences of water use for humans and ecosystems. This makes it particularly useful for assessing complex supply chains and for analysing water-related impacts in combination with other environmental aspects. Rather than being in competition with each other, we emphasize the individual and complementary strengths of both approaches and their joint efforts in addressing the world's pressing water challenges.

关键词： Water footprint Water use Water management Supply chain management Environmental impacts

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Comparative Analysis of Real-Time Multi-Person Pose Detection in Electrical Industrial Safety Scenarios Using YOLOv8-Pose and OpenPose

Comparative Analysis of Real-Time Multi-Person Pose Detectio...

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Electronic Communications, Internet of Things and Big Data (ICEIB), International Conference on

作者： Shang-Te Tsai Zong-Rong Wu Pin-Hsuan Lin Chin-Hsiung Chen Wei Chien Yu-Cheng Chang School of Art and Design Sanming University Fujian China Department of Technical and Vocational Program in Artificial Intelligence National Yunlin University of Science and Technology Yunlin Taiwan Department of Business Administration National Central University Taoyuan Taiwan Department of Electrical Engineering New Taipei Municipal Tamsui Commercial Industrial Vocational Senior High School New Taipei Taiwan Department of Computer Information and Network Engineering Lunghwa University of Science and Technology Taoyuan Taiwan Department of Computer Science and Information Engineering National Taipei University of Technology Taipei Taiwan

ISBN: (数字)9798350360721

ISBN: (纸本)9798350360738

We reviewed the application of modern technology for rapid and accurate multi-person real-time pose detection in the hazardous field of electrical engineering. We focused on two leading pose detection technologies: YOLOv8 and OpenPose. To optimize performance, we integrated these two techniques into the LSTM model for training and investigated frame rates and accuracy.

关键词： Training Accuracy Microcontrollers Neural networks Real-time systems Safety Internet of Things

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Evaluation of Avocados as a Possible Source of Listeria monocytogenes Infections, United States, 2016 to 2019

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JOURNAL OF FOOD PROTECTION 2021年第7期84卷 1122-1126页

作者： Pomeroy, Mary Conrad, Amanda Pettengill, James B. McClure, Monica Wellman, Allison A. Marus, Jessie Huffman, Jasmine Wise, Matthew Ctr Dis Control & Prevent Epidem Intelligence Serv Program Div Sci Educ & Profess Dev Atlanta GA 30333 USA Ctr Dis Control & Prevent Div Foodborne Waterborne & Environm Dis Atlanta GA 30333 USA US FDA Off Analyt & Outreach College Pk MD 20740 USA US FDA Coordinated Outbreak Response & Evaluat Network Ctr Food Safety & Appl Nutr College Pk MD 20740 USA Weems Design Studio Inc 300 Satellite BlvdSuite 205 Suwanee GA 30024 USA

Outbreaks of Listeria monocytogenes infections have historically been associated with contaminated deli meats, but recent outbreaks have been linked to produce. To date, avocados have not been identified as the source of any outbreaks of L. monocytogenes infections in the United States, but avocado samples have yielded strains that were closely related genetically to clinical L. monocytogenes isolates. To determine whether avocados have been a source of listeriosis, we conducted a retrospective review of epidemiological data for clinical isolates that were genetically related to isolates from avocados. Using a national database, we identified clusters containing clinical and at least one avocado isolate. We then selected clusters based upon isolation dates, cluster and composition size, and available food history data. For each cluster, we assessed (i) whether avocado consumption was higher among case patients in the cluster than among those with sporadic illnesses and (ii) whether the only food isolates within the cluster were from avocados. If both conditions were met, the link was considered "likely," if one condition was met the link was considered "possible," and if neither condition was met evidence was "limited." Five of 15 clusters met the criteria for assessment. Of these, two were classified as having "limited" evidence for a link to avocados, two as "possible," and one as "likely." For the cluster considered "likely," avocado consumption was significantly higher among case patients in the cluster compared with sporadic illnesses (odds ratio, 8.5;95% confidence interval, 1.5 to 86.5). We identified three clusters that were likely or possibly linked to avocados, which suggests that avocados could be a source of listeriosis in the United States. Messaging on safe handling might be warranted for groups at higher risk, but further research is first needed to better characterize the ecology of pathogens on avocados and the likelihood of internalization of L. mo

关键词： Avocados Food safety Listeriosis Whole genome sequencing

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Critical transitions in the Amazon forest system

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NATURE 2024年第7999期626卷 555-564页

作者： Flores, Bernardo M. Montoya, Encarni Sakschewski, Boris Nascimento, Nathalia Staal, Arie Betts, Richard A. Levis, Carolina Lapola, David M. Esquivel-Muelbert, Adriane Jakovac, Catarina Nobre, Carlos A. Oliveira, Rafael S. Borma, Laura S. Nian, Da Boers, Niklas Hecht, Susanna B. ter Steege, Hans Arieira, Julia Lucas, Isabella L. Berenguer, Erika Marengo, Jose A. Gatti, Luciana V. Mattos, Caio R. C. Hirota, Marina Univ Fed Santa Catarina Grad Program Ecol Florianopolis Brazil Spanish Natl Res Council Geosci Barcelona Barcelona Spain Leibniz Assoc Potsdam Inst Climate Impact Res Potsdam Germany Univ Sao Paulo Inst Adv Studies Sao Paulo Brazil Univ Utrecht Copernicus Inst Sustainable Dev Utrecht Netherlands Met Off Hadley Ctr Exeter England Univ Exeter Global Syst Inst Exeter England Univ Estadual Campinas Ctr Meteorol & Climat Res Appl Agr Campinas Brazil Univ Birmingham Sch Geog Earth & Environm Sci Birmingham England Univ Birmingham Birmingham Inst Forest Res Birmingham England Univ Fed Santa Catarina Dept Plant Sci Florianopolis Brazil Univ Estadual Campinas Dept Plant Biol Campinas Brazil Natl Inst Space Res Div Impacts Adaptat & Vulnerabil DIIAV Sao Jose Dos Campos Brazil Tech Univ Munich Sch Engn & Design Earth Syst Modelling Munich Germany Univ Calif Los Angeles Luskin Sch Publ Affairs Los Angeles CA USA Univ Calif Los Angeles Inst Environm Los Angeles CA USA Nat Biodivers Ctr Leiden Netherlands Univ Utrecht Quantitat Biodivers Dynam Utrecht Netherlands Sci Panel Amazon SPA Sao Jose Dos Campos Brazil Sustainable Dev Solut Network New York NY USA Univ Oxford Environm Change Inst Oxford England Ctr Nacl Monitoramento & Alertas Desastres Nat Sao Jose Dos Campos Brazil Unesp CEMADEN Grad Program Nat Disasters Sao Jose Dos Campos Brazil Korea Univ Grad Sch Int Studies Seoul South Korea Princeton Univ Program Atmospher & Ocean Sci Princeton NJ USA Univ Fed Santa Catarina Dept Phys Grp IpES Florianopolis Brazil

The possibility that the Amazon forest system could soon reach a tipping point, inducing large-scale collapse, has raised global concern1-3. For 65 million years, Amazonian forests remained relatively resilient to climatic variability. Now, the region is increasingly exposed to unprecedented stress from warming temperatures, extreme droughts, deforestation and fires, even in central and remote parts of the system1. Long existing feedbacks between the forest and environmental conditions are being replaced by novel feedbacks that modify ecosystem resilience, increasing the risk of critical transition. Here we analyse existing evidence for five major drivers of water stress on Amazonian forests, as well as potential critical thresholds of those drivers that, if crossed, could trigger local, regional or even biome-wide forest collapse. By combining spatial information on various disturbances, we estimate that by 2050, 10% to 47% of Amazonian forests will be exposed to compounding disturbances that may trigger unexpected ecosystem transitions and potentially exacerbate regional climate change. Using examples of disturbed forests across the Amazon, we identify the three most plausible ecosystem trajectories, involving different feedbacks and environmental conditions. We discuss how the inherent complexity of the Amazon adds uncertainty about future dynamics, but also reveals opportunities for action. Keeping the Amazon forest resilient in the Anthropocene will depend on a combination of local efforts to end deforestation and degradation and to expand restoration, with global efforts to stop greenhouse gas emissions. Analyses of drivers of water stress are used to predict likely trajectories of the Amazon forest system and suggests potential actions that could prevent system collapse.

关键词： Climate and Earth system modelling Ecosystem ecology Ecosystem services Sustainability

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Mailed fecal testing and patient navigation versus usual care to improve rates of colorectal cancer screening and follow-up colonoscopy in rural Medicaid enrollees: a cluster-randomized controlled trial

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IMPLEMENTATION SCIENCE COMMUNICATIONS 2022年第1期3卷 1页

作者： Coronado, Gloria D. Leo, Michael C. Ramsey, Katrina Coury, Jennifer Petrik, Amanda F. Patzel, Mary Kenzie, Erin S. Thompson, Jamie H. Brodt, Erik Mummadi, Raj Elder, Nancy Davis, Melinda M. Kaiser Permanente Ctr Hlth Res 3800 N Interstate Ave Portland OR 97227 USA Oregon Rural Practice Based Res Network 3181 SW Sam Jackson Pk RdMail Code L222 Portland OR 97239 USA OHSU Biostat & Design Program 3181 SW Sam Jackson Pk RdMail Code CB669 Portland OR 97239 USA OHSU Sch Med OHSU Family Med 3181 SW Sam Jackson Pk RdMail Code L222 Portland OR 97239 USA OHSU PSU Sch Publ Hlth 3181 SW Sam Jackson Pk RdMail Code L222 Portland OR 97239 USA

BackgroundScreening reduces incidence and mortality from colorectal cancer (CRC), yet US screening rates are low, particularly among Medicaid enrollees in rural communities. We describe a two-phase project, SMARTER CRC, designed to achieve the National Cancer Institute Cancer MoonshotSM objectives by reducing the burden of CRC on the US population. Specifically, SMARTER CRC aims to test the implementation, effectiveness, and maintenance of a mailed fecal test and patient navigation program to improve rates of CRC screening, follow-up colonoscopy, and referral to care in clinics serving rural Medicaid *** I activities in SMARTER CRC include a two-arm cluster-randomized controlled trial of a mailed fecal test and patient navigation program involving three Medicaid health plans and 30 rural primary care practices in Oregon and Idaho;the implementation of the program is supported by training and practice facilitation. Participating clinic units were randomized 1:1 into the intervention or usual care. The intervention combines (1) mailed fecal testing outreach supported by clinics, health plans, and vendors and (2) patient navigation for colonoscopy following an abnormal fecal test result. We will evaluate the effectiveness, implementation, and maintenance of the intervention and track adaptations to the intervention and to implementation strategies, using quantitative and qualitative methods. Our primary effectiveness outcome is receipt of any CRC screening within 6 months of enrollee identification. Our primary implementation outcome is health plan- and clinic-level rates of program delivery, by component (mailed FIT and patient navigation). Trial results will inform phase II activities to scale up the program through partnerships with health plans, primary care clinics, and regional and national organizations that serve rural primary care clinics;scale-up will include webinars, train-the-trainer workshops, and collaborative learning ***

关键词： Medicaid Colorectal cancer screening Mailed FIT outreach Fecal test Fecal immunochemical test (FIT) Follow-up colonoscopy Implementation science Rural Primary care

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Exploring the Landscape of Standards and Guidelines in AgeTech design and Development: Scoping Review and Thematic Analysis

JMIR AGING

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JMIR AGING 2024年 7卷 e58196页

作者： Abhari, Shahabeddin Mcmurray, Josephine Randhawa, Tanveer Bin Noon, Gaya Hanjahanja-Phiri, Thokozani Mcneil, Heather Manning, Fiona Debergue, Patricia Teague, Jennifer Morita, Plinio Pelegrini Univ Waterloo Sch Publ Hlth Sci 200 Univ Ave West Waterloo ON N2L 3G1 Canada Wilfrid Laurier Univ Lazaridis Sch Business & Econ Community Hlth Brantford ON Canada Natl Res Council Canada Aging Pl Challenge Program Ottawa ON Canada Canadian Stand Assoc Toronto ON Canada Univ Waterloo Dept Syst Design Engn Waterloo ON Canada Univ Waterloo Res Inst Aging Waterloo ON Canada Univ Hlth Network Techna Inst Ctr Digital Therapeut Toronto ON Canada Univ Toronto Inst Hlth Policy Management & Evaluat Dalla Lana Sch Publ Hlth Toronto ON Canada

Background: AgeTech (technology for older people) offers digital solutions for older adults supporting aging in place, including digital health, assistive technology, Internet of Things, medical devices, robotics, wearables, and sensors. This study underscores the critical role of standards and guidelines in ensuring the safety and effectiveness of these technologies for the health of older adults. As the aging demographic expands, the focus on robust standards becomes vital, reflecting a collective commitment to improving the overall quality of life for older individuals through thoughtful and secure technology integration. Objective: This scoping review aims to investigate the current state of standards and guidelines applied in AgeTech design and development as reported in academic literature. We explore the existing knowledge of these standards and guidelines and identify key gaps in the design and development of AgeTech guidelines and standards in scholarly publications. Methods: The literature review adhered to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Searches were carried out across multiple databases, including Scopus, IEEE, PubMed, Web of Science, EBSCO, CINAHL, Cochrane, and Google Scholar, using a search string incorporating concepts such as "older people," "technology," and "standards or guidelines." Alternative terms, Boolean operators, and truncation were used for comprehensive coverage in each database. The synthesis of results and data analysis involved both quantitative and qualitative methods. Results: Initially, 736 documents were identified across various databases. After applying specific inclusion and exclusion criteria and a screening process, 58 documents were selected for full-text review. The findings highlight that the most frequently addressed aspect of AgeTech standards or guidelines is related to "design and development," constituting 36% (21/58) of the

关键词： aging in place technology gerontechnology AgeTech assistive technology older adult aging ambient assisted living active assisted living

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In Silico and Ex Vivo Analyses of the Inhibitory Action of the Alzheimer Drug Posiphen and Primary Metabolites with Human Acetyl- and Butyrylcholinesterase Enzymes

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ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE 2022年第2期5卷 70-79页

作者： Batool, Sidra Furqan, Tiyyaba Mahmood, Muhammad Sibte Hasan Tweedie, David Kamal, Mohammad A. Greig, Nigel H. COMSATS Univ Dept Biosci Islamabad 45550 Pakistan Grand River Hosp Dept Med Kitchener ON N2G IG3 Canada NIA Drug Design & Dev Sect Translat Gerontol Branch Intramural Res ProgramNIH Baltimore MD 21224 USA Sichuan Univ West China Sch Nursing Inst Syst Genet Frontiers Sci Ctr Dis Related Mol NetworkWest Ch Chengdu 610041 Sichuan Peoples R China King Abdulaziz Univ King Fahd Med Res Ctr Jeddah 21589 Saudi Arabia Daffodil Int Univ Fac Allied Hlth Sci Dept Pharm Dhaka 1340 Bangladesh Novel Global Community Educ Fdn Enzymo Hebersham NSW 2770 Australia Australian Natl Univ Res Sch Chem Canberra ACT 2601 Australia

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Ongoing research to develop AD treatments has characterized multiple drug targets including the cholinergic system, amyloid-beta peptide, phosphory-lated tau, and neuroinflammation. These systems have the potential to interact to either drive or slow AD progression. Promising agents that simultaneously impact many of these drug targets are the AD experimental drug Posiphen and its enantiomer phenserine that, currently, are separately being evaluated in clinical trials. To define the cholinergic component of these agents, the anticholinesterase activities of a ligand dataset comprising Posiphen and primary metabolites ((+)-N1-norPosiphen, (+)-N8-norPosiphen, and (+)-N1,N8-bisnorPosiphen) were characterized and compared to those of the enantiomer phenserine. The "target" dataset involved the human cholinesterase enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Binding interactions between the ligands and targets were analyzed using Autodock 4.2. The computationally determined inhibitory action of these ligands was then compared to ex vivo laboratory-measured values versus human AChE and BChE. While Posiphen lacked AChE inhibitory action, its major and minor metabolites (+)-N1-norPosiphen and (+)-N1,N8-bisnorPosiphen, respectively, possessed modest AChE inhibitory activity, and Posiphen and all metabolites lacked BChE action. Phenserine, as a positive control, demonstrated AChE-selective inhibitory action. In light of AChE inhibitory action deriving from a major and minor Posiphen metabolite, current Posiphen clinical trials in AD and related disorders should additionally evaluate AChE inhibition;particularly if Posiphen should be combined with a known anticholinesterase, since this drug class is clinically approved and the standard of care for AD subjects, and excessive AChE inhibition may impact drug tolerability.

关键词： Posiphen acetylcholinesterase butyrylcholinesterase Alzheimer's disease cholinesterase inhibitors molecular docking (+)-N1-norPosiphen (+)-N8-norPosiphen (+)-N1 N8-bisnorPosiphen phenserine

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