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Stem cell therapy applied for digestive anastomosis: Current state and future perspectives

World Journal of Stem Cells 2022年第1期14卷 117-141页

作者： Jacobo Trébol Tihomir Georgiev-Hristov Isabel Pascual-Miguelañez Hector Guadalajara mariano garcía-arranz Damian garcía-Olmo Servicio de Cirugía General y del Aparato Digestivo Complejo Asistencial Universitario de SalamancaSalamanca 37007Spain Departamento de Anatomía e Histología Humanas Universidad de SalamancaSalamanca 37007Spain Servicio de Cirugía General y del Aparato Digestivo Hospital General Universitario de VillalbaMadrid 28400Spain Servicio de Cirugía General y del Aparato Digestivo Hospital Universitario La PazMadrid 28046Spain Servicio de Cirugía General y del Aparato Digestivo Hospital Universitario Fundación Jiménez DíazMadrid 28040Spain Grupo de Investigación en Nuevas Terapias Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Damian garcía-Olmo Departamento de CirugíaUniversidad Autónoma de MadridMadrid 28029Spain Servicio de Cirugía General y del Aparato Digestivo Hospital Universitario Fundación Jiménez Díaz y Grupo Quiron-Salud MadridMadrid 28040Spain

BACKGROUND Digestive tract resections are usually followed by an *** leakage,normally due to failed healing,is the most feared complication in digestive surgery because it is associated with high morbidity and *** technical and technological advances and focused research,its rates have remained almost unchanged the last *** the last two decades,stem cells(SCs)have been shown to enhance healing in animal and human studies;hence,SCs have emerged since 2008 as an alternative to improve anastomoses *** To summarise the published knowledge of SC utilisation as a preventative tool for hollow digestive viscera anastomotic or suture *** PubMed,Science Direct,Scopus and Cochrane searches were performed using the key words“anastomosis”,“colorectal/colonic anastomoses”,“anastomotic leak”,“stem cells”,“progenitor cells”,“cellular therapy”and“cell therapy”in order to identify relevant articles published in English and Spanish during the years of 2000 to *** employing SCs,performing digestive anastomoses in hollow viscera or digestive perforation sutures and monitoring healing were finally *** lists from the selected articles were reviewed to identify additional pertinent *** Given the great variability in the study designs,anastomotic models,interventions(SCs,doses and vehicles)and outcome measures,performing a reliable meta-analysis was considered impossible,so we present the studies,their results and *** Eighteen preclinical studies and three review papers were identified;no clinical studies have been published and there are no registered clinical *** studies,mainly in rat and porcine models and occasionally in very adverse conditions such as ischaemia or colitis,have been demonstrated SCs as safe and have shown some encouraging morphological,functional and even clinical *** SCs are mostly employed,and delivery routes are mainly local

关键词： Surgical anastomosis Anastomotic leak Digestive system surgical procedure Cell transplantation Cell therapy Stem cells Tissue engineering

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Stem cell therapy for faecal incontinence: Current state and future perspectives

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World Journal of Stem Cells 2018年第7期10卷 82-105页

作者： Jacobo Trébol Ana Carabias-Orgaz mariano garcía-arranz Damián garcía-Olmo General and Digestive Tract Surgery Department Salamanca University Healthcare Centre Anaesthesiology Department Complejo Asistencial de ávila New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez Díaz General and Digestive Tract Surgery Department Quiron-Salud Hospitals Surgery Department Universidad AutónomaMadrid

Faecal continence is a complex function involving different organs and systems. Faecal incontinence is a common disorder with different pathogeneses, disabling consequences and high repercussions for quality of life. Current management modalities are not ideal, and the development of new treatments is needed. Since 2008, stem cell therapies have been validated, 36 publications have appeared(29 in preclinical models and seven in clinical settings), and six registered clinical trials are currently ongoing. Some publications have combined stem cells with bioengineering technologies. The aim of this review is to identify and summarise the existing published knowledge of stem cell utilization as a treatment for faecal incontinence. A narrative or descriptive review is presented. Preclinical studies have demonstrated that cellular therapy, mainly in the form of local injections of muscle-derived(muscle derived stem cells or myoblasts derived from them) or mesenchymal(bone-marrow-or adipose-derived) stem cells, is safe. Cellular therapy has also been shown to stimulate the repair of both acute and subacute anal sphincter injuries, and some encouraging functional results have been obtained. Stem cells combined with normal cells on bioengineered scaffolds have achieved the successful creation and implantation of intrinsically-innervated anal sphincter constructs. The clinical evidence, based on adipose-derived stem cells and myoblasts, is extremely limited yet has yielded some promising results, and appears to be safe. Further investigation in both animal models and clinical settings is necessary to drawing conclusions. Nevertheless, if the preliminary results are confirmed, stem cell therapy for faecal incontinence may well become a clinical reality in the near future.

关键词： Faecal incontinence Anal sphincter Cell implantation Tissue engineering Cell therapy Stem cells

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Rat model of anal sphincter injury and two approaches for stem cell administration

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World Journal of Stem Cells 2018年第1期10卷 1-14页

作者： Jacobo Trébol Tihomir Georgiev-Hristov Luz Vega-Clemente Ignacio garcía-Gómez Ana Carabias-Orgaz mariano garcía-arranz Damián garcía-Olmo Department of General and Digestive Tract Surgery University Hospital“La Paz”Madrid 28046Spain Department of General and Digestive Tract Surgery Villalba General HospitalMadrid 28400Spain New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Hektoen Institute of Medicine ChicagoIL 60612United States Department of Anaesthesiology Complejo Asistencial deávilaávila 05004Spain New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Department of General and Digestive Tract Surgery Quiron-Salud HospitalsMadrid 28040Spain Department of Surgery Madrid Autonomous UniversityMadrid 28029Spain

AIM To establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured *** Adipose-derived stem cells(ASCs) were isolated from BDIX rats and were transfected with green fluorescent protein(GFP) for cell tracking. Biosutures(sutures covered with ASCs) were prepared with 1.5 × 10~6 GFPASCs, and solutions of 10~6 GFP-ASCs in normal saline were prepared for injection. Anorectal normal anatomy was studied on Wistar and BDIX female rats. Then, we designed an anal sphincter injury model consisting of a 1-cm extra-mucosal miotomy beginning at the anal verge in the anterior middle line. The sphincter lesion was confirmed with conventional histology(hematoxylin and eosin) and immunofluorescence with 4', 6-diamidino-2-phenylindole(commonly known as DAPI), GFP and α-actin. Functional effect was assessed with basal anal manometry, prior to and after injury. After sphincter damage, 36 BDIX rats were randomized to three groups for:(1) Cell injection without repair;(2) biosuture repair; and(3) conventional suture repair and cell injection. Functional and safety studies were conducted on all the animals. Rats were sacrificed after 1, 4 or 7 d. Then, histological and immunofluorescence studies were performed on the surgical *** With the described protocol, biosutures had been covered with at least 820000-860000 ASCs, with 100% viability. Our studies demonstrated that some ASCs remained adhered after suture passage through the muscle. Morphological assessment showed that the rat anal anatomy is comparable with human anatomy; two sphincters are present, but the external sphincter is poorly developed. Anal sphincter pressure data showed spontaneous, consistent, rhythmic anal contractions, taking the form of "plateaus" with multiple twitches(peaks) in each pressure wave. These basal contractions were very heterogeneous; their frequency was 0.91-4.17 per min(mean 1.6980, SD 0.57698), their mean duration was 26.67 s and mean numb

关键词： Fecal incontinence Experimental rat model Anal sphincter Cell implantation Cell therapy Stem cells Mesenchymal stem cell

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Detection of KRAS G12D in colorectal cancer stool by droplet digital PCR

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World Journal of Gastroenterology 2017年第39期23卷 7087-7097页

作者： Susana Olmedillas-López Dennis César Lévano-Linares Carmen Laura Aúz Alexandre Luz Vega-Clemente Edurne León Sánchez Alejandro Villagrasa Jaime Ruíz-Tovar mariano garcía-arranz Damián garcía-Olmo Foundation Health Research Institute-Fundación Jiménez Díaz University Hospital Department of Surgery School of Medicine Universidad Autónoma de Madrid Department of Surgery Rey Juan Carlos University Hospital Department of Pathology Fundación Jiménez Díaz University Hospital Department of Biomedicine and Biotechnology Universidad de Alcalá Department of Surgery Fundación Jiménez Díaz University Hospital

AIM To assess KRAS G12 D mutation detection by droplet digital PCR(dd PCR) in stool-derived DNA from colorectal cancer(CRC) *** In this study, tumor tissue and stool samples were collected from 70 patients with stage Ⅰ-Ⅳ CRC diagnosed by preoperative biopsy. KRAS mutational status was determined by pyrosequencing analysis of DNA obtained from formalin-fixed paraffinembedded(FFPE) tumor tissues. The KRAS G12 D mutation was then analyzed by dd PCR in FFPE tumors and stool-derived DNA from patients with this point mutation. Wild-type(WT) tumors, as determined by pyrosequencing, were included as controls; analysis of FFPE tissue and stool-derived DNA by dd PCR was performed for these patients as *** Among the total 70 patients included, KRAS mutations were detected by pyrosequencing in 32(45.71%), whereas 38(54.29%) had WT tumors. The frequency of KRAS mutations was higher in left-sided tumors(11 located in the right colon, 15 in the left, and 6 in the rectum). The predominant point mutation was KRAS G12 D(14.29%, n = 10), which was more frequent in early-stage tumors(I-IIA, n = 7). In agreement with pyrosequencing results, the KRAS G12 D mutation was detected by dd PCR in FFPE tumor-derived DNA, and only a residual number of mutated copies was found in WT controls. The KRAS G12 D mutation was also detected in stool-derived DNA in 80% of all fecal samples from CRC patients with this point mutation. CONCLUSION dd PCR is a reliable and sensitive method to analyze KRAS G12 D mutation in stool-derived DNA from CRC patients, especially at early stages. This non-invasive approach is potentially applicable to other relevant biomarkers for CRC management.

关键词：微滴数字 PCR KRAS 凳子修理福尔马林嵌入石蜡 Pyrosequencing Colorectal 癌症

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A universal additive concept yields record-high efficient organic solar cells

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Science China Materials 2024年第5期67卷 1670-1671页

作者： mariano Campoy Quiles Institute of Materials Science of Barcelona ICMAB-CSICCampus UAB08193BellaterraSpain

Organic photovoltaics(OPVs)are an emerging light-to-electricity conversion technology that promises flexible,lightweight,semitransparent devices based on abundant and non-toxic organic *** power conversion efficiency under one sun has been increasing at an average pace of approximately 1%every year over the past 10 years,up to current values circa 20%.This has been possible through the continuous synthesis of improved semiconductors.

关键词： additive semiconductors approximate

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Quality assessment of the Topo-Iberia CGPS stations and data quality's effects on postfit ionosphere-free phase residuals

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Geodesy and Geodynamics 2024年第2期15卷 189-199页

作者： Juan A.garcía-Armenteros Center for Advanced Studies in Earth Sciences Energy and Environment(CEACTEMA)University of Jaén23071 JaenSpain

This paper analyzed GPS data from the Topo-Iberia network spanning almost 12 years(2008-2020).The data quality information for all 26 Topo-Iberia stations is provided for the first time,complementing the Spanish Geological Survey’s storage *** analyses based on quality indicators obtained using TEQC have been carried *** guidelines and data quality information from the IGS stations have been considered as the quality references,with the stations ALJI,EPCU,and TIOU standing out as the worst stations,while on the contrary,FUEN,PALM,PILA,and TRIA meet the quality requirements to become an IGS *** relationship between the GPS data quality and their GAMIT-and Gipsy X-derived postfit ionosphere-free phase residuals has also been investigated,and the results reveal an inversely proportional *** has been found that the stations showing an increase in elevation of the horizon line,also show an increase in cycle slips and multipath,are among the poorest quality stations,and among those with the highest postfit RMS of phase ***,the evolution of the vegetation around the antenna should be considered as it could cause a progressive loss of quality,which is not complying with the IGS *** quality assessment shows that the Topo-Iberia stations are appropriate for geodetic purposes,but permanent monitoring would be necessary to avoid the least possible loss of data and *** addition,a method to characterize the GNSS data quality is proposed.

关键词： GPS dataquality's effects IGS quality standard Postfit LC phase residual Qualityassessment Topo-Iberia CGPS network

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On the analytical solution of transient friction in channel flows

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Applied Mathematics and Mechanics(English Edition) 2024年第8期45卷 1447-1466页

作者： F.J.garcíA-garcíA P.FARI?AS-ALVARI?O Department of Naval & Industrial Engineering Polytechnic School of EngineeringUniversity of A Coru?a Campus Industrial de Ferrol Integraciones Técnicas de Seguridad S.A. Pol.Ind.Espíritu Santo

The transient friction in channel mean flows is the sum of two contributions,i.e., the underlying laminar flow(ULF) and the purely turbulent component(PTC), and the contributions are analyzed separately by theoretical experiments. It is found that,the transient friction may be higher or remarkably lower than that in equal-Reynolds number steady-state flows. The universal time constant for plane-parallel laminar flows is reported, and the role of the time constant in a turbulent mean flow is examined. It is shown that the time constant is related to the turbulence's frozen time. Finally, a study of the logarithmic layer during the transient flow is accomplished, which shows that the logarithmic layer is destroyed.

关键词： 76D05 76D06 76F55 O361 transient flow transient friction unsteady channel flow

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Myelin histology:a key tool in nervous system research

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Neural Regeneration Research 2024年第2期19卷 277-281页

作者： Óscar Darío garcía-garcía Víctor Carriel Jesús Chato-Astrain Department of Histology Tissue Engineering GroupUniversity of Granada&Instituto de Investigación Biosanitaria ibs.GRANADAGranadaSpain

The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve *** to the complex structure and composition of myelin,various histological techniques have been developed over the centuries to evaluate myelin under normal,pathological or experimental ***,methods to assess myelin integrity or content are key tools in both clinical diagnosis and neuroscience *** this review,we provide an updated summary of the composition and structure of the myelin sheath and discuss some histological procedures,from tissue fixation and processing techniques to the most used and practical myelin histological staining *** the lipoprotein nature of myelin,the main features and technical details of the different available methods that can be used to evaluate the lipid or protein components of myelin are described,as well as the precise ultrastructural techniques.

关键词： fluorescence microscopy histology light microscopy lipid histochemistry metallographic techniques myelin histochemistry myelin immunohistochemistry myelin structure&composition myelin ultrastructural evaluation tissue fixation&processing

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Comparing Fine-Tuning, Zero and Few-Shot Strategies with Large Language Models in Hate Speech Detection in English

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Computer Modeling in Engineering & Sciences 2024年第9期140卷 2849-2868页

作者： Ronghao Pan JoséAntonio garcía-Díaz Rafael Valencia-garcía Departamento de Informática y Sistemas Universidad de MurciaCampus de EspinardoMurcia30100Spain

Large Language Models(LLMs)are increasingly demonstrating their ability to understand natural language and solve complex tasks,especially through text *** of the relevant capabilities is contextual learning,which involves the ability to receive instructions in natural language or task demonstrations to generate expected outputs for test instances without the need for additional training or gradient *** recent years,the popularity of social networking has provided a medium through which some users can engage in offensive and harmful online *** this study,we investigate the ability of different LLMs,ranging from zero-shot and few-shot learning to *** experiments show that LLMs can identify sexist and hateful online texts using zero-shot and few-shot approaches through information ***,it is found that the encoder-decoder model called Zephyr achieves the best results with the fine-tuning approach,scoring 86.811%on the Explainable Detection of Online Sexism(EDOS)test-set and 57.453%on the Multilingual Detection of Hate Speech Against Immigrants and Women in Twitter(HatEval)***,it is confirmed that the evaluated models perform well in hate text detection,as they beat the best result in the HatEval task *** error analysis shows that contextual learning had difficulty distinguishing between types of hate speech and figurative ***,the fine-tuned approach tends to produce many false positives.

关键词： Hate speech detection zero-shot few-shot fine-tuning natural language processing

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Online Demand Response Characterization Based on Variability in Customer Behavior

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Journal of Modern Power Systems and Clean Energy 2024年第3期12卷 936-946页

作者： Lester Marrero Daniel Sbárbaro Luis garcía-Santander the Department of Electrical Engineering University of ConcepciónConcepción 4070409Chile

This paper proposes an online framework to characterize demand response(DR)over *** proposed framework facilitates obtaining and updating the daily consumption patterns of *** essential concept of response profile class(RPC)is introduced for characterization and complemented by the measure of the variability in customer *** paper uses a modified version of the incremental clustering by fast search and find of density peaks(CFSFDP)algorithm for daily profiles,considering the multivariate normal kernel density estimator and incremental forms of the Davies-Bouldin(i DB)and Xie-Beni(i XB)validity *** studies conducted using real-world and simulated daily profiles of residential and commercial Chilean end-users have demonstrated how the proposed framework can continuously characterize *** proposed framework is proven to achieve realistic customer models for effective energy management by estimating the customer response to price signals at the distribution system operator(DSO)level.

关键词： Demand response(DR) incremental indice online characterization online clustering response profile class(RPC)

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