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Facing ethical concerns in the age of precise gene therapy:Outlook on inherited arrhythmias

World Journal of Cardiology 2024年第2期16卷 64-66页

作者： federico Carbone Fabrizio Montecucco Department of Internal Medicine University of GenoaGenoa 16132Italy IRCCS Ospedale Policlinico San Martino Genoa Italian Cardiovascular NetworkGenoa 16132Italy

This editorial,comments on the article by Spartalis et al published in the recent issue of the World Journal of Cardiology.We here provide an outlook on potential ethical concerns related to the future application of gene therapy in the field of inherited arrhythmias.As monogenic diseases with no or few therapeutic options available through standard care,inherited arrhythmias are ideal candidates to gene therapy in their treatment.Patients with inherited arrhythmias typically have a poor quality of life,especially young people engaged in agonistic sports.While genome editing for treatment of inherited arrhythmias still has theoretical application,advances in CRISPR/Cas9 technology now allows the generation of knock-in animal models of the disease.However,clinical translation is somehow expected soon and this make consistent discussing about ethical concerns related to gene editing in inherited arrhythmias.Genomic off-target activity is a known technical issue,but its relationship with ethnical and individual genetical diversity raises concerns about an equitable accessibility.Meanwhile,the costeffectiveness may further limit an equal distribution of gene therapies.The economic burden of gene therapies on healthcare systems is is increasingly recognized as a pressing concern.A growing body of studies are reporting uncertainty in payback periods with intuitive short-term effects for insurance-based healthcare systems,but potential concerns for universal healthcare systems in the long term as well.Altogether,those aspects strongly indicate a need of regulatory entities to manage those issues.

关键词： Ethics Inherited arrhythmias CRISPR/Cas9 Gene therapy Equitable accessibility

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CBE Clima Tool:A free and open-source web application for climate analysis tailored to sustainable building design

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Building Simulation 2024年第3期17卷 493-508页

作者： Giovanni Betti federico Tartarini Christine Nguyen Stefano Schiavon Center for the Built Environment University of California BerkeleyBerkeleyUSA Berkeley Education Alliance for Research in Singapore SingaporeSingapore Heat and Health Research Incubator Faculty of Medicine and HealthThe University of SydneyCamperdownAustralia College of Letters and Sciences University of California BerkeleyBerkeleyUSA

Climate-responsive building design holds immense potential for enhancing comfort,energy efficiency,and environmental sustainability.However,many social,cultural,and economic obstacles might prevent the wide adoption of designing climate-adapted buildings.One of these obstacles can be removed by enabling practitioners to easily access,visualize and analyze local climate data.The CBE Clima Tool(Clima)is a free and open-source web application that offers easy access to publicly available weather files and has been created for building energy simulation and design.It provides a series of interactive visualizations of the variables contained in the EnergyPlus Weather Files and several derived ones like the UTCI or the adaptive comfort indices.It is aimed at students,educators,and practitioners in the architecture and engineering fields.Since its inception,Clima’s user base has exhibited robust growth,attracting over 25,000 unique users annually from across 70 countries.Our tool is poised to revolutionize climate-adaptive building design,transcending geographical boundaries and fostering innovation in the architecture and engineering fields.

关键词： architectural design climate analysis sustainable building design web application building energy simulation open-source software

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Distinct vibrational signatures and complex phase behavior in metallic oxygen

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Matter and Radiation at Extremes 2024年第2期9卷 4-11页

作者： Philip Dalladay-Simpson Bartomeu Monserrat Li Zhang federico Gorelli Center for High Pressure Science Technology Advanced Research 1690 Cailun RoadShanghai 201203China Department of Materials Science and Metallurgy University of Cambridge27 Charles Babbage RoadCambridge CB3 OFSUnited Kingdom Cavendish Laboratory University of CambridgeJ.J.Thomson AvenueCambridge CB3 OHEUnited Kingdom Istituto Nazionale di Ottica Consiglio Nazionale delle Ricerche(CNR-INO)50125 FlorenceItaly Shanghai Advanced Research in Physical Sciences(SHARPS) ShanghaiChina

Evidence for metallization in dense oxygen has been reported for over 30 years[Desgreniers et al.,J.Phys.Chem.94,1117(1990)]at a now routinely accessible 95 GPa[Shimizu et al.,Nature 393,767(1998)].However,despite the longevity of this result and the technological advances since,the nature of the metallic phase remains poorly constrained[Akahama et al.,Phys.Rev.Lett.74,4690(1995);Goncharov et al.,Phys.Rev.B 68,224108(2003);Ma,Phys.Rev.B 76,064101(2007);and Weck et al.,Phys.Rev.Lett.102,255503(2009)].In this work,through Raman spectroscopy,we report the distinct vibrational characteristics of metallicζ-O_(2) from 85 to 225 GPa.In comparison with numerical simulations,weﬁnd reasonable agreement with the candidate structure up to about 150 GPa.At higher pressures,the C2/mstructure is found to be unstable and incompatible with experimental observations.Alternative candidate structures,and Ci,with C2/m C2/conly two molecules in the primitive unit cell,are found to be stable and more compatible with measurements above 175 GPa,indicative of the dissociation of(O_(2))4 units.Further,we report and discuss a strong hysteresis and metastability with the precursory phaseϵ-O_(2).Theseﬁndings will reinvigorate experimental and theoretical work into the dense oxygen system,which will have importance for oxygen-bearing chemistry,prevalent in the deep Earth,as well as fundamental physics.

关键词： metallic phase vibrational

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Aspirin interruption before neurosurgical interventions:A controversial problem

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World Journal of Cardiology 2024年第4期16卷 191-198页

作者： Alexander Kulikov Anton Konovalov Pier Paolo Pugnaloni federico Bilotta Department of Anesthesiology Burdenko National Medical Research Center of NeurosurgeryMoscow 125047Russia Department of Vascular Neurosurgery Burdenko National Medical Research Center of NeurosurgeryMoscow 125047Russia Department of Anesthesiology Critical Care and Pain MedicineUniversity of Rome“Sapienza”Rome 00161Italy

Aspirin is widely used for primary or secondary prevention of ischemic events.At the same time,chronic aspirin consumption can affect blood clot formation during surgical intervention and increase intraoperative blood loss.This is especially important for high-risk surgery,including neurosurgery.Current European Society of Cardiology guidelines recommend aspirin interruption for at least 7 d before neurosurgical intervention,but this suggestion is not supported by clinical evidence.This narrative review presents evidence that challenges the necessity for aspirin interruption in neurosurgical patients,describes options for aspirin effect monitoring and the clinical implication of these methods,and summarizes current clinical data on bleeding risk associated with chronic aspirin therapy in neurosurgical patients,including brain tumor surgery,cerebrovascular procedures,and spinal surgery.

关键词： Aspirin Neurosurgery Postoperative complications Bleeding risk Brain tumor surgery Cerebrovascular surgery Spinal surgery

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Thermoelectrocatalysis: an emerging strategy for converting waste heat into chemical energy

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National Science Review 2024年第4期11卷 19-21页

作者： Yuqiao Zhang Shun Li Jianming Zhang Li-Dong Zhao Yuanhua Lin Weishu Liu federico Rosei Institute of Quantum and Sustainable Technology(IQST) School of Chemistry and Chemical Engineering Jiangsu University School of Materials Science and Engineering Beihang University State Key Laboratory of New Ceramics and Fine Processing School of Materials Science and Engineering Tsinghua University Department of Materials Science and Engineering Southern University of Science and Technology Centre for Energy Materials and Telecommunications Institut national de la recherche scientifique

Waste heat emissions are universally present in the environment and industrial production. Innovations aimed at efficiently utilizing low-grade thermal energy have long been desired. Among these, thermoelectric materi...

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Stem cell technology for antitumor drug loading and delivery in oncology

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Oncology Research 2024年第3期32卷 433-437页

作者： FRANCESCO PETRELLA ENRICO MARIO CASSINA LIDIA LIBRETTI EMANUELE PIRONDINI federico RAVEGLIA ANTONIO TUORO Department of Thoracic Surgery Fondazione IRCCSS an Gerardo dei TintoriMonza20900Italy

The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.

关键词： Mesenchymal stromal cell Drug loading Drug delivery Mesothelioma Melanoma Glioblastoma Pancreatic ductal adenocarcinoma Multiple myeloma

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Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

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Neural Regeneration Research 2024年第8期19卷 1671-1677页

作者： Yolanda Diz-Chaves Zainab Maastor Carlos Spuch José Antonio Lamas Lucas C.González-Matías federico Mallo Biomedical Research Centre(CINBIO) Laboratory of EndocrinologyUniversity of VigoGalicia Sur Health Research InstituteVigoSpain Translational Neuroscience Research Group Galicia Sur Health Research InstituteCIBERSAMHospitalÁlvaro CunqueiroSala InvestigaciónEstrada Clara CampoamorVigoSpain Biomedical Research Centre(CINBIO) Laboratory of NeuroscienceUniversity of VigoGalicia Sur Health Research InstituteVigoSpain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migrai

关键词： astrocytes brain glucagon-like peptide 1 receptor inflammation microglia

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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 healthcare.Large 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 tools.The hype generated by such systems may lead to unweighted patient trust in these systems.Therefore,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for patients.This review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists.From 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 cases.Further 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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Experimental and Finite Element Analysis of Corroded High-Pressure Pipeline Repaired by Laminated Composite

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 1783-1806页

作者： Seyed Mohammad Reza Abtahi Saeid Ansari Sadrabadi Gholam Hosein Rahimi Gaurav Singh Hamid Abyar Daniele Amato Luigi federico Faculty of Mechanical Engineering Tarbiat Modares UniversityTehran***Iran A.Leon Linton Department of Mechanical Robotics and Industrial EngineeringLawrence Technological UniversitySouthfieldMI48075USA Department of Mechanical Engineering Faculty of EngineeringMeybod UniversityYazd***Iran Department of Industrial Engineering University of SalernoVia Giovanni PaoloⅡFiscianoItaly Italian Aerospace Research Center(C.I.R.A.) Via MaioriseCapuaCE81043Italy

Repairs of corroded high-pressure pipelines are essential for fluids transportation under high pressure.One of the methods used in their repairs is the use of layered composites.The composite used must have the necessary strength.Therefore,the experiments and analytical solutions presented in this paper are performed according to the relevant standards and codes,including ASME PCC-2,ASME B31.8S,ASME B31.4,ISO 24817 and ASME B31.G.In addition,the experimental tests are replicated numerically using the finite element method.Setting the strain gauges at different distances from the defect location,can reduce the nonlinear effects,deformation,and fluctuations due to the high pressure.The direct relationship between the depth of an axial defect and the stress concentration is observed at the inner side edges of the defect.Composite reparation reduces the non-linearities related to the sharp variation of the geometry and a more reliable numerical simulation could be performed.

关键词： High-pressure pipeline composite repair ASME PCC-2 ISO 24817

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Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

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World Journal of Gastroenterology 2024年第7期30卷 685-704页

作者： Marcello Dallio Mario Romeo Paolo Vaia Salvatore Auletta Simone Mammone Marina Cipullo Luigi Sapio Angela Ragone Marco Niosi Silvio Naviglio Alessandro federico Department of Precision Medicine Hepatogastroenterology DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Precision Medicine Clinical Biochemistry DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P0.472 and>0.894 as the best

关键词： Liver cirrhosis Red blood cell distribution width Red blood cell distribution width to platelet ratio Translational Medicine Prognostic biomarker

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