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Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in nonalcoholic steatohepatitis patients

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Acta Pharmaceutica Sinica B 2023年第1期13卷 1-28页

作者： Solène Marie kayla L.Frost raymond k.hau Lucy Martinez-Guerrero Jailyn M.Izu Cassandra M.Myers Stephen H.Wright Nathan J.Cherrington College of Pharmacy Department of Pharmacology&ToxicologyUniversity of ArizonaTucsonAZ 85721USA College of Medicine Department of PhysiologyUniversity of ArizonaTucsonAZ 85724USA

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and transporters.Non-alcoholic steatohepatitis(NASH)causes disease-specific alterations to the absorption,distribution,metabolism,and excretion(ADME)processes,including a decrease in protein expression of basolateral uptake transporters,an increase in efflux transporters,and modifications to enzyme activity.This can result in increased drug exposure and adverse drug reactions(ADRs).Our goal was to predict drugs that pose increased risks for ADRs in NASH patients.Bibliographic research identified 71 drugs with reported ADRs in patients with liver disease,mainly non-alcoholic fatty liver disease(NAFLD),54 of which are known substrates of transporters and/or metabolizing enzymes.Since NASH is the progressive form of NAFLD but is most frequently undiagnosed,we identified other drugs at risk based on NASH-specific alterations to ADME processes.Here,we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH,based on their transport and/or metabolism processes.It encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients,especially when eliminated through multiple pathways altered by the disease.Therefore,these results may inform clinicians regarding the selection of drugs for use in NASH patients.

关键词： Non-alcoholic steatohepatitis Hepatic elimination Transporter Enzyme Pharmacokinetics Drug-drug interaction Liver Adverse drug reaction

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Prioritizing Strategies for Building the Resilience of Public Health Systems to Disasters Across Multiple Communities and Countries

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International Journal of Disaster Risk Science 2024年第1期15卷 1-17页

作者： Benjamin J.Ryan Mayumi kako Shelby Garner Rok Fink Ismail Tayfur Jonathan Abrahams Sanjaya Bhatia Adriana Campelo Matthew Fendt Alicia Fontenot Nahuel Arenas Garcia Tim Hatch Ryoma kayano LaShonda Malrey‑Horne Makiko MacDermot Md Moshiur Rahman Chaverle Noel Shuhei Nomura Jeremy P.Novak Maria Opazo kendell Oliver Luciana Peters Sohel Rahman PerihanŞimşek Andrew Stricklin raymond Swienton Bryan W.Brooks Frist College of Medicine Belmont UniversityNashvilleTN 37212USA Department of Environmental Science Environmental Health Science ProgramCollege of Arts and SciencesBaylor UniversityWacoTX 76798USA Division of Nursing Science School of Biomedical and Health SciencesHiroshima UniversityHiroshima 734-8553Japan Gordon E.Inman College of Health Sciences and Nursing Belmont UniversityNashvilleTN 37212USA Faculty of Health Sciences University of Ljubljana1000 LjubljanaSlovenia Department of Emergency Medicine University of Health Sciences34668 IstanbulTurkey Monash University Accident Research Center MelbourneVIC 3800Australia Global Education and Training Institute United Nations Ofce for Disaster Risk ReductionIncheon 22004Republic of Korea Regional Ofce for the Americas and Caribbean United Nations Ofce for Disaster Risk ReductionPanama City 0843-03441Panama Engineering and Computer Science Baylor UniversityWacoTX 76798USA Department of Public Health Robbins College of Health and Human SciencesBaylor UniversityWacoTX 76798USA Alabama Department of Public Health MontgomeryAL 36092USA World Health Organization Centre for Health Development(WHO kobe Centre) Kobe 651-0073Japan Waco-McLennan County Public Health District WacoTX 76707USA Department of Health Policy and Management School of MedicineKeio UniversityTokyo 160-8582Japan Department of Global Health Policy Graduate School of MedicineThe University of TokyoTokyo 113-0033Japan Tokyo Foundation for Policy Research Tokyo 106-6234Japan Global Development College BrisbaneQLD 4000Australia Municipality of Pudahuel 13124 PudahuelChile City Hall of Porto Alegre Porto Alegre 90010-170Brazil Ministry of Health and Family Welfare Government of the People’s Republic of BangladeshDhaka 1000Bangladesh Department of Emergency Aid and Disaster Management Trabzon University61335 TrabzonTurkey Department of Emergency Medicine UT SouthwesternDallasTX 75390USA

The COVID-19 pandemic highlighted the urgent need to strengthen public health systems.In response,the United Nations Disaster Risk Reduction(UNDRR) Public Health System Resilience Scorecard(Scorecard) was applied in workshops across multiple countries.The aim of our research was to explore the workshop findings to develop priority strategies for strengthening public health system resilience.We conducted a workshop from 14 to 16 March 2023,at the UNDRR Global Education and Training Institute in Incheon,Republic of korea.A sequential modified Delphi method was utilized to develop a set of prioritized resilience strategies.These were drawn from 70 strategies identified from 13 distinct workshops in eight countries.After two surveys,23 strategies were finalized.Ten received ratings of "High" or Very High" from89% of participants.These related to the inclusion of public health risks in emergency plans,integrating multidisciplinary teams into public health,enabling local transport mechanisms,and improving the ability to manage an influx of patients.The Scorecard provides an adaptable framework to identify and prioritize strategies for strengthening public health system resilience.By leveraging this methodology,our study demonstrated how resilience strategies could inform disaster risk reduction funding,policies,and actions.

关键词： Health system resilience Public policy Resilience scorecard Workshops

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Direct ink writing to fabricate porous acetabular cups from titanium alloy

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Bio-Design and Manufacturing 2023年第2期6卷 121-135页

作者： Naima Valentin Weijian Hua Ashish k.kasar Lily raymond Pradeep L.Menezes Yifei Jin Mechanical Engineering Department University of NevadaRenoRenoNV 89557USA

Acetabular cups,which are among themost important implants in total hip arthroplasty,are usually made from titanium alloys with high porosity and adequate mechanical properties.The current three-dimensional(3D)printing approaches to fabricate customized acetabular cups have some inherent disadvantages such as high cost and energy consumption,residual thermal stress,and relatively low efficiency.Thus,in this work,a direct ink writing method was developed to print a cup structure at room temperature,followed by multi-step heat treatment to form microscale porous structure within the acetabular cup.Our method is facilitated by the development of a self-supporting titanium-6 aluminum-4 vanadium(Ti64)ink that is composed of Ti64 particles,bentonite yield-stress additive,ultraviolet curable polymer,and photo-initiator.The effects of Ti64 and bentonite concentrations on the rheological properties and printability of inks were systematically investigated.Moreover,the printing conditions,geometrical limitations,and maximum curing depth were explored.Finally,some complex 3D structures,including lattices with different gap distances,honeycomb with a well-defined shape,and an acetabular cup with uniformly distributed micropores,were successfully printed/fabricated to validate the effectiveness of the proposed method.

关键词： Acetabular cup Direct ink writing Titanium alloy Bentonite Heat treatment

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High-performance warm white LED based on thermally stable all inorganic perovskite quantum dots

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Opto-Electronic Advances 2023年第3期6卷 84-87页

作者： Jr-hau He Department of Materials Science and Engineering City University of Hong KongHong Kong 999077China

All inorganic CsPbBr_(3) quantum dots(QDs)are regarded as excellent candidates for next-generation emitters due to their high photoluminescence quantum yield(PLQY)and defect tolerance.However,the poor stability and degraded luminescent performance may impede their further commercialization because of the separation of conventional ligands from the QDs surfaces.Recently,Zang replaced the regular oleic acid with 2-hexyl-decanoic acid(DA),which possesses higher binding energy on the QDs surfaces,to act as ligands of QDs,exhibiting PLQY of 96%and excellent stabilities against ethanol and water.WLEDs with DA-modified CsPbBr_(3) QDs achieved improved thermal stability,a color rendering index of 93,a power efficiency of 64.8 lm/W and a properly correlated color temperature value of 3018 k,implying their prominent applications in solid-state lighting and displays.

关键词： inorganic quantum performance

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Consortium for the Human Information and Neurocognitive Endophenotype (CHINE) in China's Mainland: An example from neurological soft signs for neuropsychiatric disorders

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Chinese Science Bulletin 2011年第32期56卷 3409-3415页

作者： CHAN raymond C k Neuropsychology and Applied Cognitive Neuroscience Laboratory Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences

Increasing efforts to identify alternate expressions of neuropsychiatric disorders that are broader than the DSM or ICD diagnostic criteria needed to diagnose them reflects a growing consensus that multidimensional expressions of neuropsychiatric disorders may advance the search for underlying etiological or modulatory factors. Endophenotypic research can be considered to be one of the most promising strategies to bridge the gap between genomic complexity and the phenotypic heterogeneity observed in neuropsychiatric disorders. However, the majority of endophenotype studies were limited to our western counterparts, very little has been done and initiated by scholars in China's Mainland. In this paper, we urge the need to establish a potential central consortium for endophenotypes to study neuropsychiatric disorders in China's Mainland. In particular, we illustrate a potential example of neurological soft signs in following the steps for building the consortium.

关键词：精神障碍中国大陆神经茅根信息人力多维表达式 ICD

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Geodynamic evolution of the Tethyan lithosphere as recorded in the Spontang Ophiolite,South Ladakh ophiolites(NW Himalaya,India)

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Geoscience Frontiers 2022年第1期13卷 326-349页

作者： Mallika k.Jonnalagadda Mathieu Benoit Shivani Harshe Romain Tilhac raymond A.Duraiswami Michel Grégoire Nitin R.karmalkar Interdisciplinary School of Science Savitribai Phule Pune UniversityPune 411007India Department of Geology Savitribai Phule Pune UniversityPune 411007India Géosciences Environnement Toulouse CNRS-CNES-IRD-UniversitéPaul SabatierObservatoire Midi Pyrénées31400 ToulouseFrance Instituto Andaluz de Ciencias de la Tierra(IACT) CSIC–Universidad de Granada18100 ArmillaGranadaSpain Vice-Chancellor’s Office Savitribai Phule Pune UniversityPune 411007India

The Spontang Ophiolite complex represents the most complete ophiolite sequence amongst the South Ladakh ophiolites and comprises mantle rocks(depleted harzburgites,dunites and minor lherzolites)as well as crustal rocks(basalt,isotropic gabbros,layered gabbros etc.).In the present study,detailed geochemistry(whole rock as well as mineral chemistry)and Sr-Nd isotopic analyses of thirty-six ultramaficmafic samples have been attempted to constraint the evolution and petrogenetic history of the Tethyan oceanic crust.Major,trace-element and REE patterns of the peridotites and their minerals indicate that the lherzolites experienced lower degrees of partial melting resembling abyssal peridotites(at higher temperatures,TREE=$1216℃)than the harzburgites(6%–8%versus 15%–17%).Elevated eNd(t)and variable^(87) Sr/^(86) Sr(t)ratios along with REE patterns suggest that the Spontang mafic rocks display N-MORB affinity with negligible participation of oceanic sediments in their genesis are originated from a depleted upper mantle with little contribution from subduction-related fluids.MORB-type Neotethyan oceanic crust is associated with the earliest phase of subduction(of older Jurassic age)through which a younger intra-oceanic island arc(Spong arc)subsequently developed.Harzburgites REE display typical U-shaped patterns,suggesting that these rocks have been metasomatized by LREE-enriched fluids.On the other side,mafic rocks are characterized by heterogeneous(Nb/La)PMand(Hf/Sm)PMand relatively homogeneous eNd(t),indicating interaction of subduction-related melts with the upper mantle during the initiation of subduction,in Early Cretaceous times.

关键词： Peridotites Mafic rocks Partial melting Metasomatism Ladakh

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BSkCN and BSAML: blind signatures from the module lattice and the asymmetric module lattice

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Frontiers of Computer Science 2023年第6期17卷 175-177页

作者： Xiaofan LIU Wei REN kim-kwang raymond CHOO School of Computer Science China University of GeosciencesWuhan 430074China Department of Information Systems and Cyber Security University of Texas at San AntonioSan AntonioTX 78249-0631USA

1 Introduction Blind signature allows a user to obtain the signature of a message from a signer without revealing the information of the message,as well as defending against forgery.In recent years,there have been increased efforts to design post-quantum blind signature schemes,since it is known that classical cryptography assumptions(e.g.,integer factoring problem and discrete logarithm problem)are not secure against attacks carried out using quantum computers[1].One popular approach is to design blind signature schemes using lattice.The first lattice-based blind signature scheme is proposed by Rückert[2],who also presented a general process of constructing lattice-based blind signature influenced by Lyubashevskys’s secure framework[3].Rückert’s approach achieves both blindness and one-more unforgeability in the random oracle model.Since then,many other blind signature schemes have extended Rückert signature scheme.For example,based on Crystals-Dilithium[4](one of the NIST post-quantum signature standardization),Le et al.[5]created a blind signature from module lattices.

关键词： signature blind constructing

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An open compute and data federation as an alternative to monolithic infrastructures for big Earth data analytics

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Big Earth Data 2023年第3期7卷 812-830页

作者： Björn Backeberg ZdeněkŠustr Enol Fernández Gennadii Donchyts Arjen Haag J.B.raymond Oonk Gerben Venekamp Benjamin Schumacher Stefan Reimond Charis Chatzikyriakou Deltares DelftThe Netherlands Nansen Environmental and Remote Sensing Center BergenNorway CESNET PragueCzech Republic EGI Foundation AmsterdamThe Netherlands SURF/SURFsara AmsterdamThe Netherlands Earth Observation Data Centre for Water Resources Monitoring GmbH ViennaAustria

An adequate compute and storage infrastructure supporting the full exploitation of Copernicus and Earth Observation datasets is currently not available in Europe.This paper presents the cross-disciplinary open-source technologies being leveraged in the C-SCALE project to develop an open federation of compute and data providers as an alternative to monolithic infrastructures for processing and analysing Copernicus and Earth Observation data.Three critical aspects of the federation and the chosen technologies are elaborated upon:(1)federated data discovery,(2)federated access and(3)software distribution.With these technologies the open federation aims to provide homogenous access to resources,thereby enabling its users to generate meaningful results quickly and easily.This will be achieved by abstracting the complexity of infrastructure resource access provisioning and orchestration,including discovery of data across distributed archives,away from the end-users.Which is needed because end-users wish to focus on analysing ready-to-use data products and models rather than spending their time on the setup and maintenance of complex and heterogeneous IT infrastructures.The open federation will support processing and analysing the vast amounts of Copernicus and Earth Observation data that are critical for the implementation of the Destination Earth resp.Digital Twins vision for a high precision digital model of the Earth to model,monitor and simulate natural phenomena and related human activities.

关键词： Open compute and data federation big Earth data analytics federated data discovery federated access software distribution

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Macrocyclic-ligand Induced Synthesis of Aryl Ethynides with Divergent Silver（I） Clusters

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Chinese Journal of Chemistry 2017年第12期35卷 1824-1828页

作者： Guangmian Ji Siqi Zhang Sam C. k. hau Liang Zhao The key Laboratory ofBioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education) Department of Chemistry Tsinghua University Beijing 100084 China Department of Chemistry Hong Kong Baptist University Kowloon Hong Kong SAR China

二在结构上描绘了超分子的体系结构说出的 metal-cluster-centered [Ag 8(1,2-(CC)2-C6 H 4)(Py[6])(CF3 公司 2)6]

关键词：银(I) 体系结构分叉芳基簇合成相互作用超分子

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Organotypic Models for Functional Drug Testing of Human Cancers

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Biomedical Engineering Frontiers 2023年第1期4卷 103-112页

作者： Yu Ling Huang Lindsay k.Dickerson Heidi kenerson Xiuyun Jiang Venu Pillarisetty Qiang Tian Leroy Hood Taranjit S.Gujral raymond S.Yeung Division of Human Biology Fred Hutchinson Cancer CenterSeattleWAUSA Department of Surgery University of WashingtonSeattleWAUSA National Research Center for Translational Medicine Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Institute for Systems Biology Phenome Health InstituteSeattleWAUSA

In the era of personalized oncology,there have been accelerated efforts to develop clinically relevant platforms to test drug sensitivities of individual cancers.An ideal assay will serve as a diagnostic companion to inform the oncologist of the various treatments that are sensitive and insensitive,thus improving outcome while minimizing unnecessary toxicities and costs.To date,no such platform exists for clinical use,but promising approaches are on the horizon that take advantage of improved techniques in creating human cancer models that encompass the entire tumor microenvironment,alongside technologies for assessing and analyzing tumor response.This review summarizes a number of current strategies that make use of intact human cancer tissues as organotypic cultures in drug sensitivity testing.

关键词： Cancer horizon Human

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