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High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis

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Infectious Diseases of Poverty 2015年第1期4卷 300-315页

作者： Ting li Peter D.Ziniel Pan-qing He Valerie P.Kommer Gregory J.Crowther Min He Qing liu Wesley C.Van Voorhis david l.williams Ming-Wei Wang The National Center for Drug Screening Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Immunology and Microbiology Rush University Medical CenterChicagoIL 60612USA Division of Allergy and Infectious Diseases University of WashingtonSeattleWA 98195USA

Background:Schistosomiasis,a parasitic disease also known as bilharzia and snail fever,is caused by different species of flatworms,such as Schistosoma mansoni(***).Thioredoxin glutathione reductase(TGR)from ***(SmTGR)is a well-characterized drug target for schistosomiasis,yet no anti-SmTGR compounds have reached clinical trials,suggesting that therapeutic development against schistosomiasis might benefit from additional scaffolds targeting this ***:A high-throughput screening(HTS)assay in vitro against SmTGR was developed and applied to a diverse compound *** activity was quantified with ThioGlo®,a reagent that fluoresces upon binding to the free sulfhydryl groups of the reaction product GSH(reduced glutathione).Results:We implemented an HTS effort against 59,360 synthetic *** the primary screening,initial hits(928 or 1.56%)showing greater than 90%inhibition on SmTGR activity at a final concentration of 10μM for each compound were *** tests were carried out to confirm the effects of these hits and to explore the concentration-dependent response *** a result,74 of them(0.12%)representing 17 chemical scaffolds were confirmed and showed a great concentration-dependent inhibitory trend against SmTGR,including structures previously shown to be lethal to schistosomal *** these,two scaffolds displayed a limited structure-activity *** tested in cultured larvae,39 compounds had cidal activity in 48 h,and five of them killed larvae completely at 3.125μ*** these,three compounds also killed adult worms ex vivo at concentrations between 5μM and 10μ***:These confirmed hits may serve as starting points for the development of novel therapeutics to combat schistosomiasis.

关键词： High-throughput screening Schistosomiasis Inhibitor Thioredoxin glutathione reductase

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Multiple sclerosis is at a checkpoint: advancing the program

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Neural Regeneration Research 2025年第3期20卷 811-812页

作者： Brandon C.Smith Jessica l.williams Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Biological Geologicaland Environmental SciencesCleveland State UniversityClevelandOHUSA

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b... 详细信息

关键词： Hauser sclerosis damage

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Artificial intelligence analysis of videos to augment clinical assessment:an overview

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Neural Regeneration Research 2024年第4期19卷 717-718页

作者： david C.Wong Stefan williams University of leeds leeds Teaching Hospitals Trust LeedsUK

Observation is a fundamental part of the practice of clinical *** of movement is particularly important for the *** such as Parkinson’s disease,multiple sclerosis,stroke,epilepsy,and many others affect a person’s movement in characteristic *** some conditions,changes in the patient’s voice can be included in this-changes in sound caused by changes in the movements of *** clinician’s detection of a characteristic abnormality,and their judgment of its severity,plays a central role in both diagnosis and the assessment of prognosis or response to ***,that practice depends upon a limited resource of experienced *** addition,these experts are limited by human visual judgment,which cannot reliably or precisely detect and measure small or subtle changes in movement(williams et al.,2023).

关键词： clinical epilepsy diagnosis

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A multi-sensor appiproach to calving detection

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Information Processing in Agriculture 2024年第1期11卷 45-64页

作者： Anita Z.Chang david l.Swain Mark G.Trotter Institute for Future Farming Systems School of HealthMedicaland Applied SciencesCentral Queensland UniversityRockhamptonQueensland 4700Australia

The advent of remote livestock monitoring systems provides numerous possibilities for improving on-farm productivity,efficiency,and *** potential application for these systems is for the detection of calving *** study describes the integration of data from multiple sensor sources,including accelerometers,global navigation satellite systems(GNsS),an accelerometer-derived rumination algorithm,a walk-over-weigh unit,and a weather station for parturition detection using a support vector machine *** best performing model utilised data from GNsS,the ruminating algorithm,and weather stations to achieve 98.6%accuracy,with 88.5%sensitivity and 100%*** topranking features of this model were primarily GNSS *** study provides an overview as to how various sensor systems could be integrated on-farm to maximise calving detection for improved production and welfare outcomes.

关键词： Accelerometer GNSS GPS Rumination Sensor WOW

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Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout:Insights and therapeutic strategies

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World Journal of Gastroenterology 2024年第40期30卷 4404-4410页

作者： Abhay Kumar Singh Siva Sundara Kumar Durairajan Ashok Iyaswamy leonard l.williams Department of Microbiology School of Life SciencesCentral University of Tamil NaduTiruvarurTN 610005India School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China School of Chinese Medicine Hong Kong Baptist UniversityHong Kong 999077China Department of Biochemistry Karpagam Academy of Higher EducationCoimbatore 641021India Center for Excellence in Post-Harvest Technologies North Carolina Agricultural and Technical State UniversityGreensboroNC 27411United States

Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney *** gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy *** article focused on the complex interconnection between alterations in the gut microbiota and the development of this *** studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout ***,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory *** examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways ***,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and *** also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.

关键词： Gut microbiota Dysbiosis Gout Hyperuricemia Inflammation Intestinal barrier Probiotics Prebiotics Fecal microbiota transplantation

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Modeling analytics in COVID-19: prediction, prevention, control, and evaluation

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Journal of Management Analytics 2021年第3期8卷 424-442页

作者： Yang lu Therese l.williams Department of Information Systems and Operations Management University of Central OklahomaEdmondOKUSA

The outbreak of COVID-19 has attracted attention from all around the *** and institutions have adopted ways to fight COVID-19, but itsprevalence is still strong. The SIR model has important reference value for thenovel coronavirus epidemic, offering both preventive measures and the ability topredict future trends. Based on an analysis of the classical epidemiological SIRmodel along with key parameters, this paper aims to analyze the patterns ofCOVID-19, to discuss potential anti-COVID-19 measures, and to explain whywe need to conduct appropriate measures against COVID-19. The use of theSIR model can play an important role in public health emergencies. Among theparameters of the SIR model, the contact ratio and the reproduction ratio arethe factors that have the potential to mitigate the consequences of ***-COVID-19 measures include wearing a mask, washing one’s hands,keeping social distance, and staying at home if possible.

关键词： COVID-19 epidemiological compartment model SIR model the contact ratio the reproduction ratio social distancing

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Three-stage pyrolysis–steam reforming–water gas shift processing of household,commercial and industrial waste plastics for hydrogen production

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Waste Disposal and Sustainable Energy 2024年第1期6卷 25-37页

作者： Rayed Alshareef Robert Sait-Stewart Mohamad A.Nahil Paul T.williams School of Chemical and Process Engineering University of LeedsLeedsLS29JTUK

Five common single plastics and nine different household,commercial and industrial waste plastics were processed using a three-stage(i)pyrolysis,(ii)catalytic steam reforming and(iii)water gas shift reaction system to produce *** of plastics produces a range of different hydrocarbon species which are subsequently catalytically steam reformed to produce H_(2)and CO and then undergo water gas shift reaction to produce further H_(2).The process mimics the commercial process for hydrogen production from natural *** of the single polyalkene plastics(high-density polyethylene(HDPE),low-density polyethylene(lDPE),and polypropylene(PP))produced similar H_(2)yields between 115 mmol and 120 mmol per gram *** though PS produced an aromatic product slate from the pyrolysis stage,further stages of reforming and water gas shift reaction produced a gas yield and composition similar to that of the polyalkene plastics(115 mmol H_(2)per gram plastic).PET gave significantly lower H_(2)yield(41 mmol per gram plastic)due to the formation of mainly CO,CO_(2)and organic acids from the pyrolysis stage which were not conducive to further reforming and water gas shift reaction.A mixture of the single plastics typical of that found in municipal solid waste produced a H_(2)yield of 102 mmol per gram *** the gas yields and composition from the single plastics enabled an estimation of the yields from a simulated waste plastic mixture and a‘real-world’waste plastic mixture to be *** different household,commercial and industrial waste plastic mixtures produced H_(2)yields between 70 mmol and 107 mmol per gram *** H_(2)yield and gas composition from the single waste plastics gave an indication of the type of plastics in the mixed waste plastic samples.

关键词： Waste plastic Hydrogen Catalyst Pyrolysis reforming Water gas shift

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Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma

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World Journal of Gastroenterology 2024年第29期30卷 3479-3487页

作者： Miriam lópez-Gómez Maria Morales Rebeca Fuerte Marta Muñoz Pedro-david Delgado-lópez Jorge Francisco Gómez-Cerezo Enrique Casado Department of Medical Oncology Precision Oncology LaboratoryInfanta Sofía University HospitalSan Sebastián de los Reyes 28231MadridSpain Department of Medical Oncology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain Department of Internal Medicine Infanta Sofía University HospitalSan Sebastián de los Reyes 28703MadridSpain Department of Pathology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain Department of Neurosurgery Burgos University HospitalBurgos 09006Spain Department of Internal Medicine Infanta Sofía University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain Department of Medical Oncology Infanta Sofia University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain

BACKGROUND Helicobacter pylori(***)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between *** infection and esophageal *** mechanisms underlying this supposedly protective effect remain *** To determine the prevalence of *** infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our *** We retrospectively reviewed the prevalence of *** infection in a cohort of patients diagnosed with esophageal *** or previous proton pump inhibitor(PPI)usage was also *** A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were *** was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal ***,54 patients(60.7%)presented at stages III and *** *** infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous *** infection had stage *** one patient had received prior *** eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI *** In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous *** *** also reviewed the medical history of the patients,concluding that the majority had received or were on PPI *** minimal prevalence of *** infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

关键词： Helicobacter pylori Eradication Esophageal tumor Dysbiosis Proton pump inhibitors Carcinogenesis Microbiota Incidence

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Outcome of meniscal repairs in paediatric population:A tertiary centre experience

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World Journal of Orthopedics 2024年第6期15卷 547-553页

作者： Ayman Gabr Samson williams Sophie Dodd Nick Barton-Hanson Department of Trauma&Orthopaedics West Suffolk HospitalSuffolk IP332QZUnited Kingdom Department of Trauma and Orthopaedics Alder Hey Children's HospitalLiverpool L145ABUnited Kingdom

BACKGROUND Meniscal sparing surgery is a widely utilised treatment option for unstable meniscal tears with the aim of minimising the risk of progression towards ***,there is limited data in the literature on meniscal repair outcomes in skeletally immature *** To evaluate the re-operation rate and functional outcomes of meniscal repairs in children and *** We performed a retrospective review of all patients who underwent arthroscopic meniscal repair surgery between January 2007 and January *** patients were under the age of 18 at the time of *** were all performed by a single *** was gathered from our hospital Electronic Patient Records *** primary outcome measure was re-operation rate(need for further surgery on the same meniscus).Secondary outcome measures were surgical complications and patient reported outcome measures that were International Knee Documentation Committee(IKDC),Tegner and lysholm *** We identified 59 patients who underwent 66 All-inside meniscal repairs(32 medial meniscus and 34 lateral meniscus).Meniscal repairs were performed utilizing FasT-Fix(Smith and Nephew)*** were 37 males and 22 females with an average age of 14 years(range 6-16).The average follow-up time was 53 months(range 26-140).Six patients had concomitant anterior cruciate ligament reconstruction surgery along with the meniscal *** were no requiring further meniscal repairs and 9 patients underwent partial *** mean postoperative IKDC score was 88(44-100),Tegner score was 7(2-10)and lysholm score was 94(57-100).CONClUSION Our results showed that arthroscopic repair of meniscal tears in the paediatric population is an effective treatment option that has a low failure rate and good postoperative clinical with the advantage of preserving meniscal tissues.

关键词： Meniscus Meniscal repair Outcome Meniscal preservation

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Electrifying Ba_(0.5)Sr_(0.5)Co_(0.8)Fe_(0.2)O_(3-δ) for focalized heating in oxygen transport membranes

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Journal of Energy Chemistry 2024年第4期91卷 99-110页

作者： Marwan laqdiem Julio García-Fayos laura Almar Alfonso J.Carrillo Álvaro Represa JoséM.lópez Nieto Sonia Escolástico david Catalán-Martinez Jose M.Serra Instituto de Tecnología Química(Universitat Politècnica de València–Consejo Superior de Investigaciones Científicas) Av.Los Naranjos s/nE-46022 ValenciaSpain

Industry decarbonization requires the development of highly efficient and flexible technologies relying on renewable energy resources,especially biomass and solar/wind *** the case of pure oxygen production,oxygen transport membranes(OTMs)appear as an alternative technology for the cryogenic distillation of air,the industrially-established process of producing ***,OTMs could provide oxygen from different sources(air,water,CO_(2),etc.),and they are more flexible in adapting to current processes,producing oxygen at 700^(-1)000℃.Furthermore,OTMs can be integrated into catalytic membrane reactors,providing new pathways for different *** first part of this study was focused on electrification on a traditional OTM material(Ba_(0.5)Sr_(0.5)Co_(0.8)Fe_(0.2)O_(3-δ)),imposing different electric currents/voltages along a capillary *** to the emerging Joule effect,the membrane-surface temperature and the associated O_(2) permeation flux could be ***,the OTM is electrically and locally heated and reaches 900℃on the surface,whereas the surrounding of the membrane was maintained at 650℃.The O_(2)permeation flux reached for the electrified membranes was~3.7 Nml min^(-1)cm^(-2),corresponding to the flux obtained with an OTM non-electrified at 900℃.The influence of depositing a porous Ce_(0.8)Tb_(0.2)O_(2-δ) catalytic/protective layer on the outer membrane surface revealed that lower surface temperatures(830℃)were detected at the same imposed electric ***,the electrification concept was demonstrated in a catalytic membrane reactor(CMR)where the oxidative dehydrogenation of ethane(ODHE)was carried *** reaction is very sensitive to temperature,and here,we demonstrate an improvement of the ethylene yield by reaching moderate temperatures in the reaction chamber while the O_(2) injection into the reaction can be easily fine-tuned.

关键词： Oxygen permeation Oxidative dehydrogenation of ethane Oxygen transport membranes Joule effect Mixed ionic-electronic conductors Catalytic membrane reactors

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