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Cellular interplay to 3D in vitro microphysiological disease model:cell patterning microbiota-gut-brain axis

Bio-Design and Manufacturing 2024年第3期7卷 320-357页

作者： Kamare Alam lakshmi nair Souvik Mukherjee Kulwinder Kaur Manjari Singh Santanu Kaity Velayutham Ravichandiran Sugato Banerjee Subhadeep Roy Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Pharmaceutical Sciences Assam UniversitySilchar 788011India Department of Pharmaceutical Sciences Guru Ghasidas UniversityKoniBilaspur 495009C.G.India School of Pharmacy and Biomolecular Sciences RCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Tissue Engineering Research Group Department of Anatomy and Regenerative MedicineRCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Department of Pharmaceutics National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Natural Products National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India

The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the gut.Homeostasis between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological conditions.The most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune cells.However,each pathway is intertwined with a complex one.With the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative diseases.This paper briefly retraces the possible communication pathways between the gut microbiome and the brain.It further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the elderly.These diseases also decrease patients’quality of life.Hence,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the diseases.Remodeling of MGBA in the laboratory uses many molecular technologies and biomaterial advances.Spheroids and organoids provide a more realistic picture of the cell and tissue structure than monolayers.Combining them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between them.Cutting-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

关键词： Microbiota-gut-brain axis Neurodegeneration 3D disease model Organoid Transwell system

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The Quest toward limb regeneration:a regenerative engineering approach

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Regenerative Biomaterials 2016年第2期3卷 123-125页

作者： Cato T.Laurencin lakshmi S.nair Department of Orthopaedic Surgery Institute for Regenerative EngineeringRaymond and Beverly Sackler Center for BiomedicalBiologicalPhysical and Engineering SciencesUniversity of Connecticut HealthFarmingtonCT 06030USA Department of Biomedical Engineering University of ConnecticutStorrsCT 06269USA Department of Materials Science and Engineering University of ConnecticutStorrsCT 06269USA Department of Chemical and Biomolecular Engineering University of ConnecticutStorrsCT 06269USA Department of Craniofacial Sciences School of Dental MedicineUniversity of Connecticut HealthFarmingtonCT 06030USA.

The Holy Grail to address the clinical grand challenge of human limb loss is to develop innovative strategies to regrow the amputated limb.The remarkable advances in the scientific understanding of regeneration,stem cell science,material science and engineering,physics and novel surgical approaches in the past few decades have provided a regenerative tool box to face this grand challenge and address the limitations of human wound healing.Here we discuss the convergence approach put forward by the field of Regenerative Engineering to use the regenerative tool box to design and develop novel translational strategies to limb regeneration.

关键词： regenerative engineering limb regeneration stem cells advanced biomaterial science clinical translation

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Enhancing the Surface Properties of a Bioengineered Anterior Cruciate Ligament Matrix for Use with Point-of-Care Stem Cell Therapy

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Engineering 2021年第2期7卷 153-161页

作者： Xiaohua Yu Paulos Y.Mengsteab Ganesh Narayanan lakshmi S.nair Cato T.Laurencin Connecticut Convergence Institute for Translation in Regenerative Engineering University of Connecticut HealthFarmingtonCT 06030USA Raymond and Beverly Sackler Center for Biological Physical and Engineering SciencesUniversity of Connecticut HealthFarmingtonCT 06030USA Department of Orthopedic Surgery University of Connecticut HealthFarmingtonCT 06030USA Department of Biomedical Engineering University of ConnecticutStorrsCT 06269USA Department of Materials Science and Engineering University of ConnecticutStorrsCT 06269USA Department of Chemical and Biomolecular Engineering University of ConnecticutStorrsCT 06269USA Department of Reconstructive Sciences University of Connecticut HealthFarmingtonCT 06030USA

We have previously developed a poly(L-lactic)acid(PLLA)bioengineered anterior cruciate ligament(ACL)matrix that has demonstrated enhanced healing when seeded with primary ACL cells prior to implantation in a rabbit model,as compared with the matrix alone.This suggests that improving cell adhesion on the matrix may beneficially affect the healing response and long-term performance of the bioengineered ACL matrix.One regenerative engineering approach involves enhancing the surface properties of the matrix to support cell adhesion and growth in combination with point-of-care stem cell therapy.Herein,we studied the cell adhesion properties of PLLA braided microfiber matrices enhanced through the physical adsorption of fibronectin and air plasma treatment.We evaluated the kinetics and binding efficiency of fibronectin onto matrices at three time points and three fibronectin concentrations.Incubating the matrix for 120 min in a solution of 25 lgmL1 fibronectin achieved the greatest binding efficiency to the matrix and cellular adhesion.Exposing the matrices to air plasma treatment for 5 min before fibronectin adsorption significantly enhanced the cell adhesion of rabbit bone marrow-derived mesenchymal stem cells(R-BMMSCs)24 h post cell seeding.Finally,cellular proliferation was monitored for up to 21 d,the matrices were exposed to air plasma treatment,and fibronectin adsorption was found to result in enhanced cell number.These findings suggest that exposure to air plasma treatment and fibronectin adsorption enhances the cellular adhesion of PLLA braided microfiber matrices and may improve the clinical efficacy of the matrix in combination with point-of-care stem cell therapies.

关键词： Anterior cruciate ligament Ligament Poly(L-lactic)acid plasma treatment Fibronectin Stem cells Adhesion

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Regenerative Engineering for Knee Osteoarthritis Treatment： Biomaterials and Cell-Based Technologies

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Engineering 2017年第1期3卷 16-27页

作者： Jorge L. Escobar Ivirico Maumita Bhattacharjee Emmanuel Kuyinu lakshmi S. nair Cato T. Laurencin Institute for Regenerative Engineering University of Connecticut Health Center Farrnington CT 06030 USA Raymond and Beverly Sackler Center for Biomedical Biological Physical and Engineering Sciences University of Connecticut Health Center Farmington CT 06030 USA Department of Orthopaedic Surgery University of Connecticut Health Center Farmington CT 06030 USA Department of Biomedical Engineering School of Engineering University of Connecticut Storrs CT 06269 USA Department of Materials Science and Engineering School of Engineering University of Connecticut Storrs CT 06269 USA Institute of Materials Science University of Connecticut Storrs CT 06269 USA Department of Craniofacial Sciences School of Dental Medicine University of Connecticut Health Center Farmington CF 06030 USA Department of Chemical and Biomolecular Engineering School of Engineering University of Connecticut Storrs CT 06269 USA

膝关节骨性关节炎(OA)是世界上最常见的关节炎,其发病率逐年上升。不断上涨的治疗费用给患者带来了经济负担。膝关节OA治疗的两个早期干预目标是减轻膝关节的疼痛和关节软骨的损害。目前用于治疗膝关节OA的方法虽取得了一定疗效,但仍没... 详细信息

膝关节骨性关节炎(OA)是世界上最常见的关节炎,其发病率逐年上升。不断上涨的治疗费用给患者带来了经济负担。膝关节OA治疗的两个早期干预目标是减轻膝关节的疼痛和关节软骨的损害。目前用于治疗膝关节OA的方法虽取得了一定疗效,但仍没有一种方法可达到全膝关节置换术(TKA)的治疗效果。TKA主要应用于治疗末期膝关节OA,其缺点是有手术侵入性和手术费用昂贵。因而,应该重视创新性的再生技术,以推迟甚至消除患者对TKA的需求。一些基于生物材料和细胞的疗法目前正处于发展阶段,并已在临床前和临床研究方面取得了初步进展。单独或联合应用先进的生物材料和干细胞治疗膝关节OA可减轻疼痛,使损害的关节软骨再生。在此综述中,我们讨论了膝关节OA疼痛和软骨损害的发病机制,并探讨了该病的最新治疗策略及其局限性。

关键词：膝关节骨性关节炎骨关节炎疼痛间充质干细胞生物材料再生工程

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Diverting agents in the oil and gas industry:A comprehensive analysis of their origins,types,and applications

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Petroleum Research 2024年第1期9卷 72-84页

作者： Namrata Bist Abhishek nair Kriti Yadav Anirbid Sircar Pandit Deendayal Energy University GandhinagarGujarat382007India Department of Geology Patna UniversityAshok RajpathPatna800005India

During the life of a well,treatments are carried out to boost productivity by stimulating initially unproduced zones.These treatments include hydraulic fracturing,matrix acidization,and acid fracturing,among others.Hydraulic fracturing treatment is generally applied to deeper reservoirs of oil or natural gas for enhanced recovery.By infusing proppant,water,and chemicals under extreme pressure during the fracturing procedure,fissures in and beneath the reservoir layer can be accessed and expanded.Another stimulating procedure,matrix acidization,involves injecting acid down the drilling hole to permeate the rock fissures at stresses lower than the fracture stress.In addition,carbonate reservoir acid fracturing stimulation is commonly used as an acid treatment technique whereby a pressure greater than the formation disintegration pressure or spontaneous fracture closure pressure is used to compress acid into the reservoir.These treatments allow existing wells to sustain hydrocarbon production without new wells being drilled.Diverters,when employed efficiently,can prevent the need to use a rig to provide momentary physical barriers,thus lowering the cost of the workover.Recent improvements in diversion technology make use of a variety of degradable particles that act as momentary bridges,either at the perforation entries or inside the existing fractures.The aim of this study is to introduce different types of mechanical and chemical diverters used to enhance the productivity of wells.This study explains the concepts of different types of diverters and their applications in several formations,it will also help readers to understand the selection procedures based on the suitability and requirements of diverter use by case studies from around the world.

关键词： Refracturing Well treatment Chemical diverter Mechanical diverter Acid fracturing

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Tubularized incised plateurethroplasty and grafted tubularized incised plate urethroplasty: systematic review, metaanalysis and trial sequential analysis

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World Journal of Pediatric Surgery 2024年第1期7卷 10-19页

作者： Nitinkumar Borkar Charu Tiwari Abhijit nair Debajyoti Mohanty C K Sinha Jai Kumar Mahajan Paediatric Surgery All India Institute of Medical Sciences-RaipurRaipurChhattisgardhIndia Department of Anaesthesiology Ibra HospitalbraOman General Surgery All India Institute of Medical Sciences-RaipurRaipurChhattisgardhIndia Paediatric Surgery St George's University Hospitals NHS Foundation TrustLondonUK Pediatric Surgery PGIMERChandigarhIndia

Background Hypospadias is one of the most common genital birth defects.There are around 300 various techniques available for the repair of hypospadias.This study aims to compare the reported outcomes of Tubularized incised plate urethroplasty(TIP)and Grafted TIP(GTIP)repair in children undergoing primary hypospadiasrepair.Methods This meta-analysisadhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,and we framed our research question using the population,intervention,control and outcomes format.We conducted comprehensive electronic searches across various databases,employing a Boolean search strategy with predefined search terms.Only randomized controlled trials(RCTs)were included for quantitative analysis.Results Totally,10 RCTs met our inclusion criteria for quantitative analysis.The results indicated that urethrocutaneous fistula,glans dehiscence,and stricture rates were comparable between the two groups.The incidence of meatal stenosis was found to be significantly lower in the GTIP group with a relative risk(RR)of 0.32(95%confidence interval(Cl)0.15 to 0.67).Conclusion The coucomes UCF,glans dehiscence,and stricture rates were comparable between the two groups.Notably,the incidence of meatal stenosis was found to be significantly lower in the grafted TIP group.In terms of operative time,our quantitative synthesis demonstrated that the TIP group had a shorter operative time than the GTIP group with significant heterogeneity.

关键词： plate grafted analysis

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Multiplexed fluorescence and scatter detection with single cell resolution using on-chip fiber optics for droplet microfluidic applications

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Microsystems & Nanoengineering 2024年第2期10卷 207-218页

作者： Preksha Gupta Ambili Mohan Apurv Mishra Atindra nair Neeladri Chowdhury Dhanush Balekai Kavyashree Rai Anil Prabhakar Taslimarif Saiyed Discovery Innovation Accelerator Centre for Cellular and Molecular PlatformsBellary RoadBengaluru560065KarnatakaIndia Department of Electrical Engineering Indian Institute of Technology MadrasChennai600036Tamil NaduIndia

Droplet microfluidics has emerged as a critical component of several high-throughput single-cell analysis techniques in biomedical research and diagnostics.Despite significant progress in the development of individual assays,multiparametric optical sensing of droplets and their encapsulated contents has been challenging.The current approaches,most commonly involving microscopy-based high-speed imaging of droplets,are technically complex and require expensive instrumentation,limiting their widespread adoption.To address these limitations,we developed the OptiDrop platform;this platform is a novel optofluidic setup that leverages the principles of flow cytometry.Our platform enables on-chip detection of the scatter and multiple fluorescence signals from the microfluidic droplets and their contents using optical fibers.The highly customizable on-chip optical fiber-based signal detection system enables simplified,miniaturized,low-cost,multiparametric sensing of optical signals with high sensitivity and single-cell resolution within each droplet.To demonstrate the ability of the OptiDrop platform,we conducted a differential expression analysis of the major histocompatibility complex(MHC)protein in response to IFNγstimulation.Our results showed the platform’s ability to sensitively detect cell surface biomarkers using fluorescently labeled antibodies.Thus,the OptiDrop platform combines the versatility of flow cytometry with the power of droplet microfluidics to provide wide-ranging,scalable optical sensing solutions for research and diagnostics.

关键词： scatter enable resolution

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Health Systems Strengthening to Tackle the Global Burden of Pediatric and Congenital Heart Disease: A Diagonal Approach

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Congenital Heart Disease 2024年第2期19卷 131-138页

作者： Dominique Vervoort Amy Verstappen Sreehari Madhavankutty nair Chong Chin Eu Bistra Zheleva Institute of Health Policy Management and EvaluationUniversity of TorontoTorontoCanada Division of Cardiac Surgery University of TorontoTorontoCanada Global Alliance for Rheumatic and Congenital Hearts PhiladelphiaUSA Department of Health Services Government of KeralaKeralaIndia Ministry of Health PutrajayaMalaysia Children’s HeartLink MinneapolisUSA

1 Background Congenital heart disease(CHD)is the most common major congenital anomaly,affecting approximately one in every 100 live births[1].Among congenital anomalies,66%of preventable deaths are due to CHD,and 58%of the avertable morbidity and mortality due to congenital anomalies would result from scaling congenital heart surgery services[2].Every year,nearly 300,000 children and adults die from CHD,the majority of whom live in low-and middle-income countries(LMICs)[3].Approximately 49%of all individuals with CHD will require surgical or interventional care at some point in their lifetime[4];as a result of advances in access to and the delivery of such services,over 95%of children born with CHD in high-income countries now live into adulthood[3].Here,adults have surpassed children in the number of CHD cases at a ratio of 2:1[5].

关键词： Congenital heart disease pediatric heart disease global health health systems health policy

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Genes & Diseases 2024年第3期11卷 66-68页

作者： Aswathi N Jincy M.Jose Sreelata B.nair Prabha S.N Pappachan S Department of Medical Genetics Lifeline Super Specialty HospitalPathanamthittaKerala 691523India Lifeline Super Specialty Hospital PathanamthittaKerala 691523India

Alagille syndrome(ALGS;OMIM#118450)is a highlyvariable,multi-systemic,autosomal dominant disorder,caused by mutations in the Jagged Canonical Notch Ligand 1(JAG1)gene(20p12.2)or in the Neurogenic locus notch homolog protein 2(NOTCH2)gene(1p13).^(1)It primarily affects the liver,heart,eyes,face,kidney,skin,vertebrae,and skeleton.^(1,2)The JAG1 gene has 26 exons and about 90%of the ALGS cases result from pathogenic variants in the JAG1 and around 7%of cases have deletions in chromosome 20 that include this gene.

关键词： JAG1 cases Notch

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Sammon Quadratic Recurrent Multilayer Deep Classifier for Legal Document Analytics

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Computers, Materials & Continua 2022年第8期72卷 3039-3053页

作者： Divya Mohan Latha Ravindran nair School of Engineering Cochin University of Science and TechnologyKeralaIndia

In recent years,machine learning algorithms and in particular deep learning has shown promising results when used in the field of legal domain.The legal field is strongly affected by the problem of information overload,due to the large amount of legal material stored in textual form.Legal text processing is essential in the legal domain to analyze the texts of the court events to automatically predict smart decisions.With an increasing number of digitally available documents,legal text processing is essential to analyze documents which helps to automate various legal domain tasks.Legal document classification is a valuable tool in legal services for enhancing the quality and efficiency of legal document review.In this paper,we propose Sammon Keyword Mapping-based Quadratic Discriminant Recurrent Multilayer Perceptive Deep Neural Classifier(SKM-QDRMPDNC),a system that applies deep neural methods to the problem of legal document classification.The SKM-QDRMPDNC technique consists of many layers to perform the keyword extraction and classification.First,the set of legal documents are collected from the dataset.Then the keyword extraction is performed using SammonMapping technique based on the distance measure.With the extracted features,Quadratic Discriminant analysis is applied to performthe document classification based on the likelihood ratio test.Finally,the classified legal documents are obtained at the output layer.This process is repeated until minimum error is attained.The experimental assessment is carried out using various performance metrics such as accuracy,precision,recall,F-measure,and computational time based on several legal documents collected from the dataset.The observed results validated that the proposed SKM-QDRMPDNC technique provides improved performance in terms of achieving higher accuracy,precision,recall,and F-measure with minimum computation time when compared to existing methods.

关键词： Legal document data analytics recurrent multilayer perceptive deep neural network sammon mapping quadratic discriminant analysis likelihood ratio test

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