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Bile acid metabolism and signaling in health and disease:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2014-2064页

作者： joshua S.Fleishman Sunil Kumar Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNYUSA

Bile acids,once considered mere dietary surfactants,now emerge as critical modulators of macronutrient(lipid,carbohydrate,protein)metabolism and the systemic pro-inflammatory/anti-inflammatory *** acid metabolism and signaling pathways play a crucial role in protecting against,or if aberrant,inducing cardiometabolic,inflammatory,and neoplastic conditions,strongly influencing health and *** curative treatment exists for any bile acid influenced disease,while the most promising and well-developed bile acid therapeutic was recently rejected by the ***,we provide a bottom-up approach on bile acids,mechanistically explaining their biochemistry,physiology,and pharmacology at canonical and non-canonical *** this mechanistic model of bile acids,we explain how abnormal bile acid physiology drives disease pathogenesis,emphasizing how ceramide synthesis may serve as a unifying pathogenic feature for cardiometabolic *** provide an in-depth summary on pre-existing bile acid receptor modulators,explain their shortcomings,and propose solutions for how they may be ***,we rationalize novel targets for further translational drug discovery and provide future *** than dismissing bile acid therapeutics due to recent setbacks,we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.

关键词： metabolism rejected shortcomings

Phrenic nerve block: the key to managing acute biliary pain?

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World Journal of Emergency Medicine 2024年第1期15卷 62-63页

作者： Michael Shalaby joshua luftig Department of Emergency Medicine and Critical Care Herbert Wertheim College of Medicine at Florida International UniversityMiami 33199USA Advanced Emergency Ultrasound Mount Sinai Medical CenterMiami Beach 33140USA Department of Emergency Medicine Highland HospitalAlameda Health SystemOakland 94602USA

Over the past two decades,the USA has witnessed a steep rise in the incidence of acute cholecystitis(AC),[1]even among children,[2]with over 200,000 cases annually.[3]Patients with AC often present to the emergency department(ED)experiencing severe distress,with most describing their pain level as“intolerable.”[4]Furthermore,there is usually a considerable delay before surgery,with a median time from diagnosis of AC to surgery of 28.5 h,[5]and a substantial percentage of patients wait as long as 10 d.[6]Prolonged delays before surgery lead to increased opioid use,which is associated with extended hospital stays and higher rates of readmission after cholecystectomy.[7]Furthermore,opioids can lead to vomiting,respiratory depression,delirium,and ultimately addiction.[8]We propose a novel regional anesthesia technique for managing AC:right phrenic nerve *** method could offer improved pain control and a more favorable risk profile in selected patients when compared to current ED practices.

关键词： pain anesthesia diagnosis

Resilience conferred by APOE-R136S:a defense bestowed by nature to combat Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 831-832页

作者： Bin Xiao joshua Kuruvilla Eng-King Tan Department of Neurology National Neuroscience InstituteSingaporeSingapore Neuroscience Academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore Neuroscience and Behavioural Disorders Program Duke-NUS Medical SchoolSingaporeSingapore

In two recent articles published in Nature Neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune *** et *** Chen et *** provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.

关键词： protective al. Alzheimer

Biocompatible Biphasic Iontronics Enable Neuron-like Ionic Signal Transmission

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Research 2024年第3期2024卷 795-796页

作者： Xiaoyi Wang Aleksandar P.Ivanov joshua B.Edel Department of Chemistry Imperial College LondonMolecular Sciences Research HubLondon W12 OBZUK

Biocompatible connections between external artificial devices and living organisms show promise for future neuroprosthetics and *** study in Science by Zhao and colleagues introduces a cascade-heterogated biphasic gel(HBG)iontronic device,which facilitates electronic-to-multi-ionic signal transduction for abiotic–biotic *** by neuron signaling,the HBG device demonstrated its biocompatibility by regulating neural activity in biological tissue,paving the way for wearable and implantable devices,including brain–computer interfaces.

关键词： asi Signal Neuron

Obstructive sleep apnea:Overlooked comorbidity in patients with diabetes

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World Journal of Diabetes 2024年第7期15卷 1448-1460页

作者： Eric D Tenda joshua Henrina Jin H Cha Muhammad R Triono Ersananda A Putri Dahliana J Aristy Dicky l Tahapary Division of Respirology and Critical Care Department of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia Head of Research Group Artificial Intelligence and Digital Health Indonesian Medical Education and Research InstituteFaculty of Medicine University of IndonesiaDKI JakartaJakarta Pusat 10430Indonesia Division of Endocrinology Metabolism and DiabetesDepartment of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia

In this review article,we explore the interplay between obstructive sleep apnea(OSA)and type 2 diabetes mellitus(T2DM),highlighting a significant yet often overlooked *** delve into the pathophysiological links between OSA and diabetes,specifically how OSA exacerbates insulin resistance and disrupts glucose *** research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related *** the importance of comprehensive management,including weight control and positive airway pressure therapy,the study advocates integrated approaches to improve outcomes for patients with T2DM and *** review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.

关键词： Obstructive sleep apnea Type 2 diabetes mellitus Macrovascular Microvascular Weight loss Positive airway pressure

3D laparoscopy and fluorescence imaging can improve surgical precision for hepatectomy

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 544-547页

作者： joshua Sheng Hao lim Vishal G.Shelat Department of General Surgery Tan Tock Seng HospitalSingaporeSingapore

laparoscopic hepatectomy for the treatment of hepatocellular carcinoma(HCC)has been shown to have superior short-term and comparable long-term outcomes compared with open hepatectomy in experienced centres(1).Short-term advantages include small incisions,reduced post-operative pain,faster recovery,reduced blood loss and lower risk of complications(2).However,the loss of tactile sensation makes it challenging to accurately locate lesions and define tumour margins.

关键词： 3D laparoscopy hepatocellular carcinoma(HCC) indocyanine green dye(ICG dye) liver resection

Mechanically driven assembly of biomimetic 2D-material microtextures with bioinspired multifunctionality

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Nano Research 2024年第2期17卷 663-678页

作者： Yang li lin Jing joshua M.little Haochen Yang Tsai-Chun Chung Po-Yen Chen Department of Chemical and Biomolecular Engineering University of MarylandCollege ParkMD 20740USA Maryland Robotics Center University of MarylandCollege ParkMD 20742USA School of Materials Science and Engineering Nanyang Technological University50 Nanyang AvenueSingapore 639798Singapore

Nature provides a wealth of bio-inspiration for advanced material *** various nanomaterials into biomimetic microtextures with bioinspired functionalities has spurred increasing research interests and facilitated technological advances in various *** recent years,two-dimensional materials(2DMs)have emerged as important building block units in the biomimicry field due to their distinct chemical,physical,electrical,electrochemical,and catalytic *** this review article,various mechanically driven assembly approaches are summarized to fabricate various genealogies of biomimetic 2DM microtextures with bio-inspired ***,sequential deformation strategies are discussed to programmably construct higher dimensional 2DM microtextures,ranging from wrinkles/crumples(one-time deformation)to multiscale hierarchies(multiple deformations).Next,the current progress using higher dimensional 2DM microtextures to imitate different biological structures and/or induce bio-inspired multifunctionality is systematically *** showcases of bio-inspiration and biomimicry using different 2DM nanosheets are highlighted:(1)wrinkle patterns of an earthworm that spur the design of strain sensors with programmable working ranges and sensitivities,(2)wrinkle appearance of a Shar-Pei dog that motivates the fabrication of stretchable energy storage devices,(3)hierarchical scale textures of a desert lizard that inspire cation-induced gelation platforms for 2DM aerogels,and(4)wrinkle skin of an elephant that influences the development of 2DM protective skin for soft ***,challenges and future opportunities of adopting 2DM nanosheets to assemble biomimetic microstructures with synergistic functionalities are discussed.

关键词： two-dimensional(2D)materials mechanically driven assembly biomimetic microtextures functional nanocomposite bio-inspired multifunctionality

Progression of e-ticketing implementation for state transportation agencies for asphalt materials

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Journal of Road Engineering 2024年第1期4卷 80-92页

作者： joshua Withrow Gabriel B.Dadi Hala Nassereddine Department of Civil Engineering University of KentuckyLexingtonKY 40506USA Kentucky Transportation Cabinet FrankfortKY 40622USA

E-ticketing,which has been promoted by the Federal Highway Administration(FHWA)“every day counts”(EDC)initiative,utilizes software applications to digitally track and store information regarding highway construction materials paid by state transportation agencies(STAs)by weight in unit bid contract *** often face implementation barriers such as institutional inertia,or the resistance by stakeholders to adopt changes from the status quo,including new *** purpose of this paper is to determine the progression of STA e-ticketing policy adoption,specifically with a focus on asphalt paving operations,due to the COVID-19 *** accomplish this research effort,previous FHWA data,National Cooperative Highway Research Program(NCHRP)data,and other literatures are reviewed to determine an implementation *** data is collected from the American Association of State Highway and Transportation Officials Committee on Con-struction to gain current feedback from STAs and their highway contractor partners after the COVID-19 ***,a case study featuring the Kentucky Transportation Cabinet(KYTC),the Kentucky Association of Highway Contractors(KAHC),and the Plantmix Asphalt Industry of Kentucky(PAIKY)is performed to provide more in-depth *** major finding includes a statistically significant result indicating increased imple-mentation of e-ticketing for asphalt operations within the last two years,along with noting benefits including employee safety,task loading,and project documentation along with concerns regarding cellular connectivity and procurement *** findings indicate the importance of STAs investing in partnership with con-tractors to improve stakeholder buy-in before proceeding towards e-ticketing adoption.

关键词： Asphalt paving Construction inspection E-ticketing COVID-19

O'Hare Airport roadway traffic prediction via data fusion and Gaussian process regression

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Journal of Traffic and Transportation Engineering(English Edition) 2024年第4期11卷 721-732页

作者： Damola M.Akinlana Arindam Fadikar Stefan M.Wild Natalia Zuniga-Garcia joshua Auld Department of Mathematics and Statistics University of South FloridaTampaFL 33620USA Decision and Infrastructure Sciences Division Argonne National LaboratoryLemontIL 60439USA Applied Mathematics and Computational Research Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Department of Industrial Engineering and Management Sciences Northwestern UniversityEvanstonIL 60208USA Argonne National laboratory Energy SystemsLemontIL 60439USA

This study proposes an approach of leveraging information gathered from multiple traffic data sources at different resolutions to obtain approximate inference on the traffic distribution of Chicago's O'Hare Airport ***,it proposes the ingestion of traffic datasets at different resolutions to build spatiotemporal models for predicting the distribution of traffic volume on the road *** to its good adaptability and flexibility for spatiotemporal data,the Gaussian process(GP)regression was employed to provide short-term forecasts using data collected by loop detectors(sensors)and supplemented by telematics *** GP regression is used to make predictions of the distribution of the proportion of sensor data traffic volume represented by the telematics data for each location of the ***,the fitted GP model can be used to determine the approximate traffic distribution for a testing location outside of the training *** in the transportation sector can find the results of this work helpful for making informed decisions relating to current and future transportation conditions in the area.

关键词： Spatio-temporal Data fusion Gaussian process Multimodal data Airport traffic O'Hare Airport