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Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars

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Protein & Cell 2010年第1期1卷 82-95页

作者： Isaac M.Westwood Sanjib Bhakta Angela J.Russell elizabeth fullam Matthew C.Anderton Akane Kawamura Andrew W.Mulvaney Richard J.Vickers Veemal Bhowruth Gurdyal S.Besra Ajit Lalvani Stephen G.Davies Edith Sim Department of Pharmacology University of OxfordOxford OX13QTUnited Kingdom Chemistry Research Laboratory Department of Organic ChemistryUniversity of OxfordOxford OX13QLUnited Kingdom School of Biosciences University of BirminghamEdgbastonBirmingham B152TTUnited Kingdom Tuberculosis Immunology Group Department of Respiratory MedicineNational Heart and Lung InstituteWright Fleming Institute of Infection and ImmunityImperial College LondonNorfolk PlaceLondon W21PGUnited Kingdom Structure-Based Drug Design Team Sections of Structural Biology and Cancer TherapeuticsInstitute of Cancer ResearchChester Beatty LaboratoriesLondon SW36JBUnited Kingdom Institute of Structural and Molecular Biology Department of Biological ScienceBirkbeckUniversity of LondonLondon WC1E 7HXUnited Kingdom

New anti-tubercular drugs and drug targets are urgently needed to reduce the time for treatment and also to identify agents that will be effective against Mycobacterium tuberculosis persisting *** have a unique cell *** of the gene for arylamine N-acetyltransferase(NAT)decreases mycobacterial cell wall lipids,particularly the distinctive mycolates,and also increases antibiotic susceptibility and killing within macrophage of Mycobacterium bovis *** nat gene and its associated gene cluster are almost identical in sequence in *** BCG and *** gene cluster is essential for intracellular survival of *** have therefore used pure NAT protein for high-throughput screening to identify several classes of small molecules that inhibit NAT ***,we characterize one class of such molecules—triazoles—in relation to its effects on the target enzyme and on both *** BCG and *** most potent triazole mimics the effects of deletion of the nat gene on growth,lipid disruption and intracellular *** also present the structure-activity relationship between NAT inhibition and effects on mycobacterial growth,and use ligand-protein analysis to give further insight into the structure-activity *** conclude that screening a chemical library with NAT protein yields compounds that have high potential as anti-tubercular agents and that the inhibitors will allow further exploration of the biochemical pathway in which NAT is involved.

关键词： N-acetyltransferase Mycobacterium tuberculosis triazoles screening

Childhood sleep:assessments,risk factors,and potential mechanisms

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World Journal of Pediatrics 2024年第2期20卷 105-121页

作者： Jianghong Liu Xiaopeng Ji elizabeth Rovit Susannah Pitt Terri Lipman School of Nursing University of Pennsylvania418 Curie Blvd.Room 426Claire M.Fagin HallPhiladelphiaPA 19104USA School of Nursing College of Health SciencesUniversity of DelawareNewarkDE 19716USA Geisinger Commonwealth School of Medicine ScrantonPA 18510USA

Background Sleep problem is a highly prevalent health issue among pediatric populations across the *** this review,we aimed to identify risk factors contributing to sleep deficiency and poor sleep hygiene in *** biological,psychosocial,and environmental mechanisms as well as research gaps in the literature are also *** sources A comprehensive search for relevant English language full-text,peer-reviewed publications was performed focusing on pediatric sleep studies from prenatal to childhood and adolescence in a variety of indexes in PubMed,SCOPUS,and Psych *** relevant data based and systematic reviews are *** This paper summarizes many risk factors for childhood sleep problems,including biological(e.g.,genetics,gender,age and puberty,prenatal factors,postnatal factors);nutritional(e.g.,macronutrients,micronutrients,omega-3 fatty acids,obesity);environmental(e.g.,heavy metals,noise,light,air pollution);interpersonal(e.g.,family,exposure to violence,screen media use,physical injury);and community/socioeconomic variables(e.g.,racial/ethnicity and cultural factors,neighborhood conditions and socioeconomic status,school factors,public health disasters/emergencies),to better understand the development of sleep problems in *** Poor childhood sleep is a multifactorial issue affected by a wide range of prenatal and early-life biological,environmental,and psychosocial risk factors and contributors.A better understanding of these risk factors and their mechanisms is an important first step to develop future research and prevention programs focusing on pediatric sleep problems.

关键词： Child sleep Pediatrics Risk factor Mechanisms

IMAGE-BUILDING AND FRAMING PROCESSES OF AN ANTI-MOTHER/-WOMAN IN CICERO’S PRO CLUENTIO

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Journal of Ancient Civilizations 2024年第1期39卷 51-72,124页

作者： Hongxia Zhang elizabeth Webster IHAC NENUChangchun

In this case study we explore Cicero’s processes of framing and image-building regarding the concept of an anti-mother/-*** this we examine Cicero’s portrayal of Sassia,a woman who features as one of the main antagonists of his speech Pro *** analyse Cicero’s depiction of Sassia’s evilness towards her son,Cluentius,through the lens of frame and framing *** doing so,this case study aims to present a deeper understanding of Cicero’s stratagems(e.g.,priming,calling for action;nudging,pushing someone towards action;and affordance,offering a frame to act outside of or within)which were employed in order to devise a negative characterisation of *** application of this methodological approach to Cicero’s framing of Sassia provides a new scope for analysing not only the classical text itself but also for the analysis of ancient human society to which it belonged.

关键词： affordance Cicero frames&framing image-building nudging&priming Roman Republic stereotypes

Ecosystem Services of Grazed Grasslands in the Flooding Pampa

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Phyton-International Journal of Experimental Botany 2024年第6期93卷 1179-1202页

作者： elizabeth J.Jacobo Adriana M.Rodríguez Facultad de Agronomía Área de AgroecologíaUniversidad de Buenos AiresBuenos Aires1417Argentina Facultad de Agronomía Departamento de Producción AnimalUniversidad de Buenos AiresBuenos Aires1417Argentina

The Flooding Pampa grasslands are the last remnant of the Rio de la Plata grasslands in ***-genic interventions have led to severe degradation and,as a result,the ecosystem services provided by the grass-lands are declining,in terms of provisioning,regulating,and supporting *** synthesized the existing literature on the ecosystem goods and services provided by these grasslands under grazing in different conditions and conservation *** found that plant and animal diversity and primary production are the most studied ecosystem services,while climate regulation,water supply,nutrient cycling,meat production and erosion control,in that order,are less *** services are *** grazing and glyphosate spraying are the main drivers of grassland *** grazing and conservative stocking rates have been shown to reverse degradation and demonstrate that livestock production is compatible with ecosystem conserva-tion by maintaining regulating and provisioning *** these management strategies are poorly integrated,improving their implementation will require important changes in farmers’decisions and the development of policies that create the economic conditions for this to *** is needed to understand the conditions that prevent the knowledge generated from being transferred to producers and translated into practices that would improve the provision of ecosystem services.

关键词： Salado basin sustainability biodiversity rangelands meat production adaptative multi paddock grazing process technologies agroecology

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 129-138页

作者： Sudha Kodali Ashton A Connor Souhail Thabet elizabeth W Brombosz R Mark Ghobrial Sherrie and Alan Conover Center for Liver Disease and Transplantation Houston Methodist HospitalHoustonTX 77030USA JC Walter Jr Transplant Center Houston Methodist HospitalHoustonTX 77030USA Department of Medicine Weill Cornell Medical CollegeNew YorkNYUSA Department of Surgery Houston Methodist HospitalHoustonTX 77030USA Department of Surgery Weill Cornell Medical CollegeNew YorkNYUSA School of Medicine New Giza UniversityGizaEgypt

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality *** resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative ***,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor *** transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable ***,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT *** studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced *** selection criterion is the tumor response to neoadjuvant *** with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant *** index that helps predict the treatment outcome is the *** survival outcomes have also opened the door for living donor LT for *** undergoing LT for iCCA now have statistically similar survival rates as patients undergoing *** combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

关键词： Liver transplantation Cholangiocarcinoma Hepatectomy Transplant oncology Liver neoplasm

Childhood sleep:physical,cognitive,and behavioral consequences and implications

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World Journal of Pediatrics 2024年第2期20卷 122-132页

作者： Jianghong Liu Xiaopeng Ji Susannah Pitt Guanghai Wang elizabeth Rovit Terri Lipman Fan Jiang School of Nursing University of Pennsylvania418 Curie Blvd.Room 424Claire M.Fagin HallPhiladelphiaPA 19104USA College of Health Sciences University of DelawareNewarkDE 19716USA Geisinger Commonwealth School of Medicine ScrantonPA 18510USA Pediatric Translational Medicine Institute Department of Developmental and Behavioral PediatricsSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background Sleep problems in children have been increasingly recognized as a major public health *** research has extensively studied and presented many risk factors and potential mechanisms for children’s sleep *** this paper,we aimed to identify and summarize the consequences and implications of child sleep *** sources A comprehensive search for relevant English language full-text,peer-reviewed publications was performed focusing on pediatric sleep studies from prenatal to childhood and adolescence in a variety of indexes in PubMed,SCOPUS,and Psych Info published in the past two *** relevant data-based articles and systematic reviews are *** Many adverse consequences are associated with child sleep deficiency and other sleep problems,including physical outcomes(e.g.,obesity),neurocognitive outcomes(e.g.,memory and attention,intelligence,academic performance),and emotional and behavioral outcomes(e.g.,internalizing/externalizing behaviors,behavioral disorders).Current prevention and intervention approaches to address childhood sleep problems include nutrition,exercise,cognitive–behavioral therapy for insomnia,aromatherapy,acupressure,and *** interventions may be particularly important in the context of coronavirus disease *** research and policy strategies can target the risk factors of child sleep as well as the efficacy and accessibility of *** Given the increasing prevalence of child sleep problems,which have been shown to affect children’s physical and neurobehavioral wellbeing,understanding the multi-aspect consequences and intervention programs for childhood sleep is important to inform future research direction as well as a public health practice for sleep screening and intervention,thus improving sleep-related child development and health.

关键词： Behavior Child sleep Consequences Implications Neurocognitive Physical Prevention/intervention

Evaluation of New Graduate Nursing Orientation Program

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Open Journal of Nursing 2024年第8期14卷 433-446页

作者： elizabeth Arroyo Department of Education Capella University Minneapolis USA

The study site is a holistic patient-centered organization that has developed a 16-week long orientation program for new graduate nurses entering the hospital setting. The purpose of the program is for new graduate nurses to gain the confidence, competence, and critical thinking skills for providing safe patient care. The issue occurring within the organization is that there is an increasing rise in the number of turnover rates of new graduates leaving the hospital, thus making evaluating the program a necessity to problem-solving. There has been no evaluation of the program in the past five years to reveal why the increase in the recent turnover rates. The data collected during the interview process was coded and categorized into three main sections: organizational, substantive, and theoretical. The evaluator used an organizational category to investigate for board areas or issues within the problem attempting to be solved. The evaluator concluded from the results and findings that the issue, a poor preceptor-preceptee relationship was seen by all stakeholders involved. The literature presented concludes that continuous evaluation of orientation programs is crucial for the professional and personal growth of new graduate nurses in the hospital.

关键词： New Graduate Nurses Preceptors Turnover Orientation

Removing Splitting/Modeling Error in Projection/Penalty Methods for Navier-Stokes Simulations with Continuous Data Assimilation

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Communications in Mathematical Research 2024年第1期40卷 1-29页

作者： elizabeth Hawkins Leo G.Rebholz Duygu Vargun Department of Mathematical Sciences Clemson UniversityClemsonSC 29634USA

We study continuous data assimilation(CDA)applied to projection and penalty methods for the Navier-Stokes(NS)*** and projection methods are more efficient than consistent Ns discretizations,however are less accurate due to modeling error(penalty)and splitting error(projection).We show analytically and numerically that with measurement data and properly chosen parameters,CDA can effectively remove these splitting and modeling errors and provide long time optimally accurate solutions.

关键词： Navier-Stokes equations projection method penalty method continuous data assimilation

Role of buccal mucosa graft ureteroplasty in the surgical management of pyeloplasty failure

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Asian Journal of Urology 2024年第3期11卷 373-376页

作者： Matthew Lee elizabeth Nagoda David Strauss Matthew Loecher Michael Stifelman Lee Zhao Department of Urology Lewis Katz School of MedicineTemple UniversityPhiladelphiaPAUSA Department of Urology Hackensack Meridian School of MedicineHackensack University Medical CenterHackensackNJUSA Department of Urology New York University Grossman School of MedicineNew York University Langone Health SystemNew YorkNYUSA

Objective:Secondary pyeloplasty for recurrent ureteropelvic junction obstructions may be a safe and feasible surgical option for *** study aimed to demonstrate outcomes of utilizing a non-transecting buccal mucosa graft ureteroplasty for management of recurrent ureteropelvic junction obstruction after prior failed ***:We performed a retrospective review of our Collaborative of Reconstructive Robotic Ureteral Surgery database for all consecutive patients who underwent buccal mucosa graft ureteroplasty between April 2012 and June 2022 for management of recurrent ureteropelvic junction obstructions after prior failed *** primary outcome included surgical success which was defined as the absence of flank pain and no obstruction on ***:Overall,ten patients were included in our *** median stricture length was 2.5(interquartile range[IQR]1.8-4.0)*** median operative time was 230.5(IQR 199.5-287.0)min and median estimated blood loss was 50.0(IQR 28.8-102.5)*** a median follow-up of 10.3(IQR 6.2-14.8)months,80%of patients were surgically successful and there were no major(ClavieneDindo Grade>2)***:Buccal mucosa graft ureteroplasty is a valuable non-transecting surgical option for patients with recurrent ureteropelvic junction obstructions who failed prior pyeloplasty and has comparable outcomes to the literature regarding standard transecting techniques.

关键词： Ureteral obstruction Buccal mucosagraft Pyeloplasty Robotic Stricture