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Novel,non-colonizing,single-strain live biotherapeutic product ADS024 protects against Clostridioides difficile infection challenge in vivo

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世界胃肠病理生理学杂志:英文版(电子版) 2023年第4期14卷 71-85页

作者： christopher k murphy Michelle M O’Donnell James W Hegarty Sarah Schulz Colin Hill R Paul Ross Mary C Rea Ronald Farquhar Laurent Chesnel Research and Development Adiso Therapeutics Inc.ConcordMA 01742United States APC Microbiome Ireland University College CorkCork T12 K8AFIreland Teagasc Food Research Centre Moorepark FermoyCork P61 C996Ireland Executive Leadership Team Adiso Therapeutics Inc.ConcordMA 01742United States

BACkGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(***)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly *** recently reported the isolation of ADS024,a Bacillus velezensis(***)strain,which demonstrated direct in vitro bactericidal activity against ***,with minimal collateral impact on other members of the gut *** this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse *** To investigate the in vivo efficacy of *** ADS024 in protecting against CDI challenge in mouse *** To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with *** the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown *** single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of *** ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar *** the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on *** studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical mani

关键词： Gut Single-strain live biotherapeutic product ADS024 Clostridioides difficile Clostridioides difficile challenge model Microbiota

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Comparative utility of vestibular function tests in patients with peripheral and central vestibular dysfunction

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Journal of Otology 2024年第1期19卷 5-9页

作者： Cameron B.Fattahi christopher Zaro Janice J.Chung Richard F.Lewis Divya A.Chari Department of Otolaryngology-Head and Neck Surgery UMASS Memorial Medical CenterUniversity of Massachusetts Chan Medical SchoolWorcesterMAUSA Jenks Vestibular Physiology Laboratory Massachusetts Eye and EarBostonMAUSA Department of Otolaryngology-Head and Neck Surgery Massachusetts Eye and EarHarvard Medical SchoolBostonMAUSA Department of Neurology Harvard Medical SchoolBostonMAUSA

Background: Bithermal caloric irrigation, video head impulse test(vHIT), and rotational testing are commonly used to assess peripheral vestibular function, but the relative clinical utility of each test in differentiating patients with peripheral vestibulopathy is ***: To determine whether(1) the combination of two or more vestibular tests enhances diagnostic utility over a single test;(2) abnormal test results on vestibular tests correlate with one ***: Retrospective analysis of data collected from multidisciplinary vestibular clinics at two academic medical centers from 2016 to ***: 150 patients(54.10 ± 15.09 years, 88 females) were included. No individual test was significantly better at predicting the presence of peripheral vestibular damage(p > 0.05). vHIT test results improved significantly when combined with either the caloric test(p = 0.007) or rotary chair test(p = 0.039). Caloric and rotational testing had high sensitivity(74.65% and 76.06%, respectively) and specificity(83.54% and 78.48%, respectively). vHIT demonstrated excellent specificity(89.87%) but poor sensitivity(47.89%). Caloric, vHIT, and rotary chair tests results did not correlate with one another(p > 0.05).Conclusions: Vestibular function tests have comparable diagnostic utility, yet each offers unique advantages. Caloric and rotational testing may be best suited for screening peripheral damage and vHIT may function ideally as a confirmatory test.

关键词： vestibular patients specificity

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Surgeon preferences in the treatment of thumb carpometacarpal osteoarthritis

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World Journal of Orthopedics 2024年第5期15卷 435-443页

作者： Edward J Wu Bradley W Fossum Wyatt Vander Voort christopher O Bayne Robert M Szabo Department of Orthopedic Surgery University of Minnesota Medical SchoolMinneapolisMN 55455United States Department of Orthopaedic Surgery UC Davis School of MedicineSacramentoCA 95817United States

BACkGROUND Primary thumb carpometacarpal(CMC)osteoarthritis is one of the most common conditions encountered by hand *** the vast number of operations that have been proposed,none have demonstrated results significantly superior to trapeziectomy *** The purpose of our study was to determine why surgeons opt for their technique in treating CMC *** A cross-sectional survey of active members of the American Society for Surgery of the Hand was conducted to evaluate the reasons behind their preferred technique in the treatment of isolated thumb CMC *** were contacted by email once and provided with a link to a de-identified survey consisting of 5 treatment questions and 5 demographic *** Of 950 responses were received.40.5%of surgeons preferred trapeziectomy+ligament reconstruction tendon interposition(LRTI),followed by trapeziectomy+suspensionplasty(28.2%),suture button suspension(5.9%),trapeziectomy alone(4.6%),prosthetic arthroplasty(3.2%),arthrodesis(1.1%),and other(6.6%).Proponents of trapeziectomy+LRTI cited familiarity(73.2%),exposure during fellowship(48.8%)and less proximal migration(60%)to be the main reasons affecting their *** who preferred trapeziectomy+suspensionplasty most reported simplicity(74.9%),fewer complications(45.3%),less proximal migration(43.8%),and avoidance of autogenous tissue harvest(42.7%).Advocates of suture button suspension cited avoidance of autogenous tissue harvest(80.4%),shorter immobilization(76.8%),and quicker recovery(73.2%)with their *** of trapeziectomy alone cited simplicity(97.7%),fewer complications(86.4%),and avoidance of autogenous tissue harvest(59.1%).In their comments,45%of surgeons choosing trapeziectomy alone cited evidence as an additional *** of prosthetic arthroplasty cited improved pinch strength(83.3%)and improved range of motion(63.3%),while those preferring arthrodesis cited better pinch strength(90%)and freque

关键词： Thumb carpometacarpal Osteoarthritis Trapeziectomy Ligament reconstruction tendon interposition Suspensionplasty Preferences Trends

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Uterine receptivity and the plasma membrane transformation

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Cell Research 2004年第4期14卷 259-267页

作者： christopher R murphy Department of Anatomy and Histology The University of Sydney NSW 2006. Australia

This review begins with a brief commentary on the diversity of placentation mechanisms, and then goes on to examine the extensive alterations which occur in the plasma membrane of uterine epithelial cells during early pregnancy across species. Ultrastructural, biochemical and more general morphological data reveal that strikingly common phenomena occur in this plasma membrane during early pregnancy despite the diversity of placental types-from epitheliochorial to hemochorial, which ultimately form in different species. To encapsulate the concept that common morphological and molecular alterations occur across species, that they are found basolaterally as well as apically, and that moreover they are an ongoing process during much of early pregnancy, not just an event at the time attachment, the term ’plasma membrane transformation’ is suggested which also emphasises that alterations in this plasma membrane during early pregnancy are key to uterine receptivity.

关键词： uterine epeithelial cells membrane tranformation.

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High-entropy oxide,(FeCoNiMnV)_(x)O,boost the oxygen evolution

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ChemPhysMater 2024年第1期3卷 111-117页

作者： Chendong kou Meiling Qin Wei Song Weijun Zhu Jieshu Zhou christopher Dorma Momo Jr Hongyan Liang School of Materials Science and Engineering Tianjin UniversityTianjin 300350China CETC Deqing Huaying Electronics Co. Ltd.China

The sluggish kinetics of the oxygen evolution reaction(OER),an essential half-reaction of water splitting,lead to high OER overpotential and low energy-conversion efficiency,hampering its industrial ***,considerable attention has been paid to the development of efficient catalysts to accelerate the *** this study,we synthesized the high-entropy oxides[(FeCoNiMnV)_(x)O]and used them as efficient OER catalysts.A simple oil-phase method was used to synthesize(FeCoNiMnV)_(x)*** catalytic performances of the(FeCoNiMnV)_(x)O catalysts were modified by tuning the reaction *** optimized(FeCoNiMnV)_(x)O catalyst exhibited multiple elemental interactions and abundant exposed active sites,leading to an overpotential of approximately 264 mV to reach a current density of 10 mA cm^(-2) in 1 M kOH and stability of 50 h at 1000 mA cm^(-2).Thus,a highly active OER catalyst was *** study provides an efficient approach for the synthesis of high-entropy oxides.

关键词： High-entropy oxides Solvothermal method Oxygen evolution reaction Water splitting

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Assessing the Efficacy of Wheat-Soybean Based Intercropping System at Different Plant Densities in Bambili, Cameroon

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American Journal of Plant Sciences 2024年第4期15卷 235-251页

作者： Lendzemo E. Tatah Jeazet k. Teitiogo Oben Tom Tabi Tange D. Achiri Njualem D. khumbah Chi christopher Tamu Department of Crop Production Technology College of Technology University of Bamenda Bambili Cameroon Department of Agronomic and Applied Molecular Sciences Faculty of Agriculture and Veterinary Medicine University of Buea Buea Cameroon School of Tropical Agriculture and Natural Resource Catholic University of Cameroon Bamenda Cameroon Department of Agricultural and Environmental Engineering College of Technology University of Bamenda Bambili Cameroon

Wheat is one of the most important cereals in the world, serving as a staple for millions globally. In the wake of the geopolitical crisis between Russia and Ukraine, it has become incumbent for many countries to invest in wheat production. Improving cropping systems for wheat production is paramount. Intercropping cereals with legumes has tremendous advantages. Therefore, this study was designed to optimize wheat production by intercropping it with soybean at different densities. Between March and August 2023, a randomized complete block design trial was conducted in Bambili, North West of Cameroon with treatments T1 (wheat monocrop at 200,000 plants ha−1), T2 (soybean monocrop at 250,000 plants ha−1), T3 (200,000 wheat and 125,000 soybean ha−1), T4 (100,000 wheat and 250,000 soybean ha−1), T5 (200,000 wheat and 250,000 soybean ha−1) and T6 (100,000 wheat and 125,000 soybean ha−1). Results revealed that growth parameters of wheat were not significantly influenced by monocrop or intercrop. The yield of wheat was significantly higher in the monocrop than the intercrop treatments, with slight variation amongst the intercrop treatments. Soybean yield was higher in the monocrop than in the intercrop, with no variations amongst the intercrop treatments. Only the land equivalence ratio (LER) for T5 was greater than 1.0. The competitive ratio for T5 was 0.54 for wheat and 1.90 for soybean, comparatively lower than the other monocrop treatments. Intercropping wheat and soybean at 200,000:250,000 ratio is recommended.

关键词： Competitive Ration Land Equivalence Ration Intercrop Soybean Wheat

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Amorphous Iridium Oxide-Integrated Anode Electrodes with Ultrahigh Material Utilization for Hydrogen Production at Industrial Current Densities

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Nano-Micro Letters 2024年第10期16卷 225-239页

作者： Lei Ding kui Li Weitian Wang Zhiqiang Xie Shule Yu Haoran Yu David ACullen Alex keane kathy Ayers christopher BCapuano Fangyuan Liu Pu-Xian Gao Feng-Yuan Zhang Department of Mechanical Aerospace and Biomedical EngineeringUniversity of TennesseeKnoxvilleTN 37996USA Oak Ridge National Lab Center for Nanophase Materials SciencesOak RidgeTN 37831USA Nel Hydrogen WallingfordCT 06492USA Institute of Materials Science University of ConnecticutStorrsCT 06269USA Department of Materials Science and Engineering University of ConnecticutStorrsCT 06269USA

Herein,ionomer-free amorphous iridium oxide(IrO_(x))thin electrodes are first developed as highly active anodes for proton exchange membrane electrolyzer cells(PEMECs)via low-cost,environmentally friendly,and easily scalable electrodeposition at room *** with a Nafion 117 membrane,the IrO_(x)-integrated electrode with an ultralow loading of 0.075 mg cm^(-2)delivers a high cell efficiency of about 90%,achieving more than 96%catalyst savings and 42-fold higher catalyst utilization compared to commercial catalyst-coated membrane(2 mg cm^(-2)).Additionally,the IrO_(x)electrode demonstrates superior performance,higher catalyst utilization and significantly simplified fabrication with easy scalability compared with the most previously reported ***,the remarkable performance could be mainly due to the amorphous phase property,sufficient Ir^(3+)content,and rich surface hydroxide groups in ***,due to the high activity,high cell efficiency,an economical,greatly simplified and easily scalable fabrication process,and ultrahigh material utilization,the IrO_(x)electrode shows great potential to be applied in industry and accelerates the commercialization of PEMECs and renewable energy evolution.

关键词： Ionomer-free Amorphous IrOx electrodes Ultrahigh material utilization Scalable electrodeposition Hydrogen production

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A Hybrid Approach for Predicting Probability of Default in Peer-to-Peer (P2P) Lending Platforms Using Mixture-of-Experts Neural Network

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Journal of Data Analysis and Information Processing 2024年第2期12卷 151-162页

作者： christopher Watitwa Makokha Ananda kube Oscar Ngesa Department of Mathematics Pan African University Institute of Basic Sciences Technology and Innovation Nairobi Kenya Department of Mathematics and Actuarial Sciences Kenyatta University Nairobi Kenya Department of Mathematics Statistics and Physical Sciences Taita Taveta University Voi Kenya

Peer-to-peer (P2P) lending offers an alternative way to access credit. Unlike established lending institutions with proven credit risk management practices, P2P platforms rely on numerous independent variables to evaluate loan applicants’ creditworthiness. This study aims to estimate default probabilities using a mixture-of-experts neural network in P2P lending. The approach involves coupling unsupervised clustering to capture essential data properties with a classification algorithm based on the mixture-of-experts structure. This classic design enhances model capacity without significant computational overhead. The model was tested using P2P data from Lending Club, comparing it to other methods like Logistic Regression, AdaBoost, Gradient Boosting, Decision Tree, Support Vector Machine, and Random Forest. The hybrid model demonstrated superior performance, with a Mean Squared Error reduction of at least 25%.

关键词： Credit-Scoring Clustering Classification Neural Networks

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Pressure-responsive pH-triggered layer-by-layer coating of paclitaxel-eluting balloon catheters for instant high-dose drug delivery for percutaneous coronary artery intervention

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Nano Research 2024年第10期17卷 9141-9151页

作者： Jeong Yu Lee Shonit Nair Sharma Sung-Yu Hong Young-Guk ko Yangsoo Jang Minjae Do Michael christopher Stark Qiwen Peng Benjamin Allen Mossburg Bo Chan Seo Yuhan Lee Department of Materials Science and Engineering Korea Advanced Institute of Science and TechnologyDaejeon 305-701Republic of Korea Department of Anesthesiology Perioperativeand Pain MedicineCenter for Accelerated Medical Innovation&Center for NanomedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA Department of Biological Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA Cardiovascular Product Evaluation Center Yonsei University College of MedicineSeoul 120-752Republic of Korea Division of Cardiology Department of Internal MedicineSeverance Cardiovascular HospitalYonsei University College of MedicineSeoul 120-752Republic of Korea

Cardiovascular diseases remain the leading cause of mortality worldwide,with percutaneous coronary interventions(PCI)using drug-eluting stents(DES)as the standard treatment for coronary artery *** advancements in DES technology,challenges such as restenosis and stent thrombosis still necessitate further interventions and carry considerable risks,highlighting an urgent need for a novel therapeutic approach with lower restenosis rates and reduced reintervention *** balloons(DEBs)coated with anti-proliferative agents offer a novel method of local drug delivery for reducing restenosis by directly administering drugs to the lesion ***,efficient delivery of drugs within the brief procedural window while minimizing drug loss during maneuvering to the target site remains a ***,we developed a pressure-responsive and pH-triggered,paclitaxel(PTX)coated DEB catheter for rapid and high-dose delivery of paclitaxel to the lesion sites,overcoming the limitations of drug dispersion and inefficiencies associated with conventional *** the charge reversion of albumin around its isoelectric point,paclitaxel-loaded human serum albumin nanoparticles(PTX-HSA-NPs)and heparin were coated using a layer-by-layer deposition method at pH *** exposure to physiological pH(i.e.,7.4),the coating is rapidly released from the balloon *** with a protective shellac coating,the DEB achieved controlled release of high-dose paclitaxel to the arterial tissue in vivo(up to 400μg per gram tissue),exceeding current DEBs in the *** results suggest the pH-responsive,multi-layer coated DEB’s potential for superior procedural outcomes,addressing a critical unmet need in PCI.

关键词： drug-eluting balloon layer-by-layer coating coronary artery disease paclitaxel

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Inpatient management of iron deficiency anemia in pediatric patients with inflammatory bowel disease: A single center experience

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World Journal of Clinical Pediatrics 2024年第1期13卷 107-117页

作者： krishanth Manokaran Jonathan Spaan Giulio Cataldo christopher Lyons Paul D Mitchell Tatyana Sare LoriA Zimmerman Paul A Rufo Center for Inflammatory Bowel Disease Boston Children's HospitalBostonMA 02115United States Institutional Centers for Clinical and Translational Research Boston Children's HospitalBostonMA 02115United States

BACkGROUND Screening for iron deficiency anemia(IDA)is important in managing pediatric patients with inflammatory bowel disease(IBD).Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous(IV)iron to treat IDA in this *** To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our *** A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019.92 patients met study criteria for IDA,of which 57 received IV iron,17 received oral iron,and 18 were discharged prior to receiving iron *** Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9(±0.2)g/dL in mean(±SE)hemoglobin(Hb)concentration by the first ambulatory follow-up,compared to patients who received oral iron 0.8(±0.3)g/dL or no iron 0.8(±0.3)g/dL(P=0.03).One out of 57(1.8%)patients that received IV iron therapy experienced an adverse *** Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.

关键词： Iron deficiency anemia Pediatric inflammatory bowel disease Intravenous iron therapy Inflammatory bowel disease

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