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Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

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World Journal of Stem Cells 2024年第5期16卷 604-614页

作者： Edoardo Agosti Marco Zeppieri Mattia Ghidoni Tamara Ius alessandro Tel Marco Maria Fontanella Pier Paolo Panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy Clinic of Maxillofacial Surgery Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and *** stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and *** studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular *** mechanisms can involve different cellular pathways,most of which have been recently reported in the *** progress,targeted therapeutic approaches lack consensus due to GSCs’high *** To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying *** A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,*** search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text *** them,201 were deemed eligible after excluding 168 for various *** temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma *** analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance *** molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette

关键词： Glioma stem cells Chemoresistance Radioresistance Molecular pathways Targeted therapies Systematic review

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Development of deep-learning-based autonomous agents for low-speed maneuvering in Unity

Journal of Intelligent and Connected Vehicles

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Journal of Intelligent and Connected Vehicles 2024年第3期7卷 229-244页

作者： Riccardo Berta Luca Lazzaroni Alessio Capello Marianna Cossu Luca Forneris alessandro Pighetti Francesco Bellotti Electrical Electronics and Telecommunication Engineering and Naval Architecture Department(DITEN)University of GenoaGenoa 16145Italy

This study provides a systematic analysis of the resource-consuming training of deep reinforcement-learning (DRL) agents for simulated low-speed automated driving (AD). In Unity, this study established two case studies: garage parking and navigating an obstacle-dense area. Our analysis involves training a path-planning agent with real-time-only sensor information. This study addresses research questions insufficiently covered in the literature, exploring curriculum learning (CL), agent generalization (knowledge transfer), computation distribution (CPU vs. GPU), and mapless navigation. CL proved necessary for the garage scenario and beneficial for obstacle avoidance. It involved adjustments at different stages, including terminal conditions, environment complexity, and reward function hyperparameters, guided by their evolution in multiple training attempts. Fine-tuning the simulation tick and decision period parameters was crucial for effective training. The abstraction of high-level concepts (e.g., obstacle avoidance) necessitates training the agent in sufficiently complex environments in terms of the number of obstacles. While blogs and forums discuss training machine learning models in Unity, a lack of scientific articles on DRL agents for AD persists. However, since agent development requires considerable training time and difficult procedures, there is a growing need to support such research through scientific means. In addition to our findings, we contribute to the R&D community by providing our environment with open sources.

关键词： automated driving autonomous agents deep reinforcement learning curriculum learning modeling and simulation

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Lower limb suspension induces threshold-specific alterations of motor units properties that are reversed by active recovery

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Journal of Sport and Health Science 2024年第2期13卷 264-276页

作者： Giacomo Valli Fabio Sarto Andrea Casolo alessandro Del Vecchio Martino V.Franchi Marco V.Narici Giuseppe De Vito Department of Biomedical Sciences University of PadovaPadova 35131Italy Department Artificial Intelligence in Biomedical Engineering Friedrich-Alexander UniversityErlangen-Nurnberg 91052Germany

Purpose:This study aimed to non-invasively test the hypothesis that(a) short-term lower limb unloading would induce changes in the neural control of force production(based on motor units(MUs) properties) in the vastus lateralis muscle and(b) possible changes are reversed by active recovery(AR).Methods:Ten young males underwent 10 days of unilateral lower limb suspension(ULLS) followed by 21 days of *** ULLS,participants walked exclusively on crutches with the dominant leg suspended in a slightly flexed position(15°-20°) and with the contralateral foot raised by an elevated *** AR was based on resistance exercise(leg press and leg extension) and executed at 70% of each participant’s 1repetition maximum,3 times/*** voluntary isometric contraction(MVC) of knee extensors and MUs properties of the vastus lateralis muscle were measured at baseline,after ULLS,and after *** were identified using high-density electromyography during trapezoidal isometric contractions at 10%,25%,and 50% of the current MVC,and individual MUs were tracked across the 3 data collection ***:We identified 1428 unique MUs,and 270 of them(18.9%) were accurately *** ULLS,MVC decreased by 29.77%,MUs absolute recruitment/derecruitment thresholds were reduced at all contraction intensities(with changes between the 2 variables strongly correlated),while discharge rate was reduced at 10% and 25% but not at 50% *** MVC and MUs properties fully recovered to baseline levels after *** changes were observed in the pool of total as well as tracked ***:Our novel results demonstrate,non-invasively,that 10 days of ULLS affected neural control predominantly by altering the discharge rate of lower-threshold but not of higher-threshold MUs,suggesting a preferential impact of disuse on motoneurons with a lower depolarization ***,after 21 days of AR,the impaired MUs properties were fully restored to baseline levels,highlighting the plas

关键词： Disuse High-density EMG Muscle disuse Neural impairment Neuromuscular degeneration

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Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer:A meta-analysis and systematic review

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Asian Journal of Urology 2024年第2期11卷 191-207页

作者： Stefano Salciccia Marco Frisenda Giulio Bevilacqua Pietro Viscuso Paolo Casale Ettore De Berardinis Giovanni Battista Di Pierro Susanna Cattarino Gloria Giorgino Davide Rosati Francesco Del Giudice alessandro Sciarra Gianna Mariotti alessandro Gentilucci Department of Urology Sapienza Rome UniversityPoliclinico Umberto I00161 RomeItaly Department of Urology Humanitas20089 RozzanoMIItaly

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic ***: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect ***: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24).Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

关键词： Prostatic neoplasm Neutrophil-to-lymphocyte ratio Platelet-to-lymphocyteratio Meta-analysis Radical prostatectomy Metastatic

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Exploring the landscape of minimally invasive pancreatic surgery: Progress, challenges, and future directions

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World Journal of Gastrointestinal Surgery 2024年第10期16卷 3094-3103页

作者： Greta Donisi alessandro Zerbi Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20090MilanItaly Department of Pancreatic Surgery IRCCS Humanitas Research HospitalRozzano 20089MilanItaly

Minimally invasive surgery(MI)has become the standard of care for many surgical procedures aimed at reducing the burden on ***,its adoption in pancreatic surgery(PS)has been limited by the pancreas’s unique location and the complexity of the dissection and reconstruction *** factors continue to contribute to PS having one of the highest morbidity and mortality rates in general *** a rough start,MIPS has gained widespread acceptance in clinical practice *** evidence supports MI distal pancreatectomy safety,even in oncological cases,indicating its potential superiority over open ***,definitive evidence of MI pancre-aticoduodenectomy(MIPD)feasibility and safety,particularly for malignant lesions,is still ***,reports from high-volume centers are emer-ging,suggesting outcomes comparable to those of the open *** robotic PS increasing adoption,facilitated by the wider availability of robotic platforms,may further facilitate the transition to MIPD by overcoming the technical con-straints associated with laparoscopy and accelerating the learning ***-ough the MIPS implementation process cannot be stopped in this evolving world,ensuring patient safety through strict outcome monitoring is *** in younger surgeons with structured and recognized training programs can promote safe expansion.

关键词： Minimally invasive surgery Minimally invasive pancreatic surgery Pancreatic surgery Robotic Laparoscopic Pancreaticoduodenectomy Distal pancrea-tectomy

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Cold ischemia time in liver transplantation:An overview

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World Journal of Hepatology 2024年第6期16卷 883-890页

作者： Manuela Cesaretti alessandro Izzo Roberta Anna Pellegrino alessandro Galli Orestes Mavrothalassitis Department of HPB and Liver Transplantation Brotzu HospitalCagliari 09122Italy Department of Nanophysic Istituto Italiano di TecnologiaGenova 16163Italy Department of Critical Care Medicine and Anesthesia ASST Papa Giovanni XXIIIBergamo 24100Italy Department of Anesthesia and Perioperative Care University of California San FranciscoSan FranciscoCA 94143United States

The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time(CIT).This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time,transit time,and recipient surgery time,and is one of the most important donor-related risk factors which may influence the graft and recipient’s ***,the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation *** review details the CIT definition and analyzes its different *** also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.

关键词： Cold ischemia time Liver transplantation Organ donation Donation after cardiac death Warm ischemia time Machine perfusion

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May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients’questions?An evidencecontrolled analysis

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World Journal of Gastroenterology 2024年第1期30卷 17-33页

作者： Antonietta Gerarda Gravina Raffaele Pellegrino Marina Cipullo Giovanna Palladino Giuseppe Imperio Andrea Ventura Salvatore Auletta Paola Ciamarra alessandro Federico Division of Hepatogastroenterology Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy

Artificial intelligence is increasingly entering everyday *** language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM *** hype generated by such systems may lead to unweighted patient trust in these ***,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for *** review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their *** the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some *** studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.

关键词： Crohn’s disease Ulcerative colitis Inflammatory bowel disease Chat Generative Pre-trained Transformer Large language model Artificial intelligence

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The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 71-76页

作者： alessandro Fugazza Matteo Colombo Michel Kahaleh V.Raman Muthusamy Bick Benjamin Wim Laleman Carmelo Barbera Carlo Fabbri Jose Nieto Abed Al-Lehibi Mohan Ramchandani Amy Tyberg Haroon Shahid Avik Sarkar Dean Ehrlich Stuart Shermand Cecilia Binda Marco Spadaccini Andrea Iannone Kareem Khalaf Nageshwar Reddy Andrea Anderloni alessandro Repici Division of Gastroenterology and Digestive Endoscopy Humanitas Research Hospital-IRCCSVia Manzoni 5620089RozzanoMilanoItaly Gastroenterology Rutgers Robert Wood JohnsonNew BrunswickNew JerseyUSA Vatche and Tamar Manoukian Division of Digestive Diseases University of CaliforniaLos Angeles School of Medicine at UCLALos AngelesCaliforniaUSA Division of Digestive and Liver Disorders Indiana University School of MedicineIndianapolisINUSA Department of Gastroenterology and Hepatology University Hospitals LeuvenKU Leuven3000 LeuvenBelgium U.O.C.di Gastroenterologia ed Endoscopia Digestiva Ospedale Giuseppe MazziniASL TeramoItaly Gastroenterology and Digestive Endoscopy Unit Forlì-Cesena HospitalsAUSL RomagnaForlì-CesenaItaly Borland Groover Clinic JacksonvilleFloridaUSA Department of Gastroenterology and Hepatology King Fahad Medical CityRiyadhSaudi Arabia Asian Institute of Gastroenterology HyderabadIndia Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy Department of Biomedical Sciences Humanitas UniversityVia Rita Levi Montalcini 420090Pieve EmanueleMilanItaly

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 ***: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

关键词： Single-operator cholangioscopy Single-use duodenoscope Endoscopic retrograde cholangiopancreatography Indeterminate biliary stricture Difficult biliary stones

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Device-assisted enteroscopy: Are we ready to dismiss the spiral?

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World Journal of Gastroenterology 2024年第26期30卷 3185-3192页

作者： alessandro Mussetto Elettra Merola Cesare Casadei Daniele Salvi Fabiola Fornaroli Silvia Cocca Margherita Trebbi Armando Gabbrielli Cristiano Spada Andrea Michielan Department of Gastroenterology S Maria della Croci HospRavenna 48121Italy Department of Gastroenterology Unit G.B.Grassi Hospital(ASL Roma 3)Roma 00122Italy Section of Digestive Endoscopy and Gastroenterology Fondazione PoliambulanzaBrescia 25124Italy Gastroenterology and Endoscopy Unit Department of Medicine and SurgeryUniversity of ParmaParma 43125Italy Gastroenterology and Endoscopy Unit Azienda Ospedaliero Universitaria Policlinico di ModenaModena 41121Italy Center for Medical Sciences(CISMed) University of TrentoTrento 38122Italy Gastroenterology and Digestive Endoscopy Unit Santa Chiara HospitalAzienda Provinciale per i Servizi SanitariTrento 38122Italy Digestive Endoscopy Unit Fondazione Policlinico Universitario A.Gemelli IRCSSRoma 00168Italy

Motorized spiral enteroscopy(MSE)is the latest advance in device-assisted *** events related to MSE were discussed in a recent large systematic review and meta-analysis and were directly compared with those of balloon enteroscopy in a case-matched study and a randomized controlled *** the real-life application of MSE,an unexpected safety issue emerged regarding esophageal injury and the technique has been withdrawn from the global market,despite encouraging results in terms of diagnostic and therapeutic *** conducted an Italian multicenter real-life prospective study,which was prematurely terminated after the withdrawal of MSE from the *** primary goals were the evaluation of MSE performance(both diagnostic and therapeutic)and its safety in routine endoscopic practice,particularly in the early phase of introduction in the endoscopic unit.A subanalysis,which involved patients who underwent MSE after unsuccessful balloon enteroscopy,demonstrated,for the first time,the promising performance of MSE as a rescue *** its remarkable performance in clinical practice and its potential role as a backup technique following a previously failed enteroscopy,it may be more appropriate to refine and enhance MSE in the future rather than completely abandoning it.

关键词： Motorized spiral enteroscopy Rescue enteroscopy Diagnostic yield Adverse events AGREE classification

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Sarcopenic obesity in patients awaiting liver transplant: Unique challenges for nutritional recommendations

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World Journal of Transplantation 2024年第2期14卷 40-47页

作者： Darya M Herscovici Katherine M Cooper alessandro Colletta Michelle Rightmyer Alexandra Shingina Lauren D Feld Department of Medicine UMass Chan Medical SchoolWorcesterMA 01655United States Division of Transplant Nutrition UMass Chan Medical SchoolWorcesterMA 01655United States Department of Medicine Vanderbilt University Medical CenterNashvilleTN 37215United States Division of Gastroenterology UMass Chan Medical SchoolWorcesterMA 01655United States

Sarcopenic obesity increases the risk of mortality in patients with liver disease awaiting liver transplantation and in the post-transplant *** recommendations for individuals with sarcopenia differ from recommendations for patients with obesity or sarcopenic *** these nutrition guidelines have been established in non-cirrhotic patients,established guidelines for liver transplant candidates with sarcopenic obesity are *** this paper,we review existing literature on sarcopenic obesity in patients with chronic liver disease and address opportunities to improve nutritional counseling in patients awaiting liver transplantation.

关键词： Nutrition Sarcopenia Sarcopenic obesity Liver transplant Cirrhosis Chronic liver disease Body composition Myostatin

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