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endosomal trafficking defects in patient cells with KIAA1109 biallelic variants

Genes & Diseases 2019年第1期6卷 56-67页

作者： Megan S.Kane Callie J.Diamonstein Natalie Hauser john F.Deeken john e.niederhuber Thierry Vilboux Inova Translational Medicine Institute Inova Health SystemFairfaxVAUnited States Department of Medicine Virginia Commonwealth UniversityRichmondVAUnited States Department of Public Health Sciences University of Virginia School of MedicineCharlottesvilleVAUnited States Department of Oncology and Surgery Johns Hopkins University School of MedicineBaltimoreMDUnited States

The uncharacterized gene KIAA1109 has recently been associated with a congenital neurological malformation disorder that variably presents with arthrogryposis,craniofacial and/or cardiac *** have identified two additional patients with compound heterozygous KIAA1109 variants presenting with the same neurological *** mechanism whereby KIAA1109 loss of function causes this spectrum of disorders was the primary focus of our *** hypothesized that KIAA1109 function could be conserved relative to the fly gene tweek and examined endocytosis and endosome recycling in patient ***,we examined the structure of the cytoskeleton and cilia based on functional overlap with endocytosis and several known etiologies for neuronal migration *** primary dermal fibroblasts from one patient and a healthy donor,we performed immunofluorescence and endocytosis assays to examine the endosomal,cytoskeletal,and ciliary cellular *** found notable abnormalities in endosomal trafficking and endosome recycling *** also observed changes in the actin cytoskeleton and cilia structural *** conclude that the function of KIAA1109 in humans may indeed overlap with the function of the Drosophila ortholog,resulting in perturbations to endosomal trafficking and the actin *** alterations have ripple effects,altering many pathways that are critical for proper neuronal migration and embryonic development.

关键词： Cilia endocytosis KIAA1109 Neurological malformation Vesicular trafficking

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Immunotherapy of gastric cancer:Present status and future perspectives

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World Journal of Gastroenterology 2024年第8期30卷 779-793页

作者： john K Triantafillidis Manousos M Konstadoulakis Apostolos e Papalois Inflammatory Bowel Disease Unit “Metropolitan General”HospitalHolargos 15562AtticaGreece.Hellenic Society for Gastrointestinal Oncology354 Iera OdosChaidari 12461AtticaGreece Second Department of Surgery University of Athens School of MedicineAretaieion HospitalAthens 11528AtticaGreece Unit of Surgical Research and Training Second Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528AtticaGreece

In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of *** focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 *** that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the *** then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant *** describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)*** attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with *** is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in ***,an attempt is made to draw some conclusions and to point out possible future directions.

关键词： Gastric cancer Chemotherapy Immunotherapy Immune checkpoint inhibitors Bibliometrics Scientometrics

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A holistic approach to improving safety for battery energy storage systems

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Journal of energy Chemistry 2024年第5期92卷 422-439页

作者： James Close Jonathan e.Barnard Y.M.john Chew Semali Perera Department of Chemical engineering Centre for DigitalManufacturing&DesignUniversity of BathBath BA27AYUK ioMosaic International Limited 16-18 Queen SquareBath BA12HNUK

The integration of battery energy storage systems(BeSS)throughout our energy chain poses concerns regarding safety,especially since batteries have high energy density and numerous BeSS failure events have *** spread adoption will only increase the prevalence of these failure events unless there is a step change in the management and design of *** understand the causes of failure,the main challenges of BeSS safety are *** consequences and failure events are discussed,including specific focus on the chain of events causing thermal runaway,and a case study of a BeSS explosion in Surprise Arizona is *** on the technology and past events,a paradigm shift is required to improve BeSS *** this review,a holistic approach is *** combines currently adopted approaches including battery cell testing,lumped cell mathematical modelling,and calorimetry,alongside additional measures taken to ensure BeSS safety including the requirement for computational fluid dynamics and kinetic modelling,assessment of installation level testing of the full BeSS system and not simply a single cell battery test,hazard and layers of protection analysis,gas chromatography,and composition *** holistic approach proposed in this study aims to address challenges of BeSS safety and form the basis of a paradigm shift in the safety management and design of these systems.

关键词： energy storagesystems Process safety Battery safety Thermal safety

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Combination treatment of inflammatory bowel disease:Present status and future perspectives

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World Journal of Gastroenterology 2024年第15期30卷 2068-2080页

作者： john K Triantafillidis Constantinos G Zografos Manousos M Konstadoulakis Apostolos e Papalois Inflammatory Bowel Disease Unit "Metropolitan General"HospitalHolargos 15562AtticaGreece Hellenic Society for Gastrointestinal Oncology 354 Iera OdosChaidari 12461AtticaGreece The 2^(nd)Department of Surgery University of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece Unit of Surgical Research and Training The 2^(nd)Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical *** seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the *** daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical *** combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment ***,a part of these patients are going to *** recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe *** our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very *** mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal *** appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research *** this

关键词： Biologics for immune-mediated conditions Dual-targeted treatment Combination treatment Inflammatory bowel disease Crohn’s

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extractable and kerogen-bound hopanoids from typical eocene oil shales in China

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energy Geoscience 2024年第2期5卷 171-179页

作者： Changbo Zhai Zhirong Zhang john K.Volkman Hong Lu Yan'e Chen SINOPeC Key Laboratory of Petroleum Accumulation Mechanisms Wuxi Institute of Petroleum GeologySINOPEC2060 Lihu RoadWuxiJiangsu213126China SINOPeC Petroleum exploration and Production Research Institute 31 Xueyuan RoadBeijing100083China State Key Laboratory of Organic Geochemistry Guangzhou Institute of GeochemistryChinese Academy of ScienceGuangzhou510640GuangdongChina

This study conducted a comparative analysis of extractable hopanoid hydrocarbons and those released via stepwise pyrolysis of typical eocene immature oil shales in China,namely the Huadian,Maoming,and Fushun *** the Huadian and Maoming shales exhibit immature indicators in extractable and kerogen-bound hopanoids(notably,high abundance of C_(29)to C_(32)17β,21β-hopanes and unsaturated hopenes).In contrast,the Fushun oil shale's hopanoids from extracts and pyrolyzates suggest a higher maturity *** absence of neohopenes in the pyrolyzates of the shales underpins that the kerogenbound hopanoid skeletons resist ***,the Huadian oil shale's asymmetric distribution of C_(29)and C_(30)hopenes and neohopenes hints at the presence of an additional *** unsaturated hopenes,such as hop-20(21)-enes,identified in pyrolyzates of the three kerogens at various pyrolysis temperatures,reveal the occurrence of double bonds in kerogen-bound hopanoid skeletons without methyl *** absence of hop-20-(21)-ene in extracts suggests that it might act as an intermediate of these novel hopenes during the epimerization of hopanoid skeletons within *** extractable and pyrolytic hopanoids'stereochemical alignment indicates that epimerization may occur in both ring systems and alkyl side chains of kerogen-bound hopanoid *** stepwise pyrolysis proves to be a quick screening method for geological hopanoids without causing any significant alteration to the original skeletons even when cracking multiple covalent bonds is necessary.

关键词： Hopanoid Hopane Hopene Neohopene Stepwise pyrolysis Kerogen eocene oil shale

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Review of Networked Microgrid Protection:Architectures,Challenges,Solutions,and Future Trends

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CSee Journal of Power and energy Systems 2024年第2期10卷 448-467页

作者： Jorge de la Cruz Ying Wu john e.Candelo-Becerra Juan C.Vasquez Josep M.Guerrero Center for Research on Microgrids(CROM) Department of Energy TechnologyAalborg University9220 AalborgDenmark Facultad de Minas Departamento de Energia Eléctrica y AutomaticaUniversidad Nacional de ColombiaSede MedellinCarrera 80 No.65-223RobledoMedellin 050041Colombia. Center for Research on Microgrids at UPC(UPC CROM) Department of Electronic EngineeringTechnical University of Catalonia(UPC)08019 Barcelona Spain ICReA Pg.Lluis Companys 2308010 BarcelonaSpain Center for Research on Microgrids at AAU(AAU CROM) AAU EnergyAalborg University(AAU)9220 Aalborg EastDenmark

Design and selection of advanced protection schemes have become essential for reliable and secure operation of networked *** protection schemes that allow correct operation of microgrids have been proposed for individual systems in different topologies and ***,protection schemes for networked microgrids are still in devel-opment,and further research is required to design and operate advanced protection in interconnected *** of these microgrids in different nodes with various intercon-nection technologies increases fault occurrence and complicates protection *** paper aims to point out challenges in developing protection for networked microgrids,potential solutions,and research areas that need to be addressed for their ***,this article presents a systematic analysis of different microgrid clusters proposed since 2016,including several architectures of networked microgrids,operation modes,components,and utilization of renewable sources,which have not been widely explored in previous review ***,the paper presents a discussion on protection systems currently available for microgrid clusters,current challenges,and solutions that have been proposed for these ***,it discusses the trend of protection schemes in networked microgrids and presents some conclusions related to ***—Adaptive eprotection,microgrid cluster,microgrid,multiple microgrid,networked microgrid,real-time simulation,smart grid.

关键词： Adaptive eprotection microgrid cluster microgrid multiple microgrid networked microgrid real-time simulation smart grid

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Latest updates on structure and recommendations of cardiac rehabilitation programs in chronic heart failure

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World Journal of Clinical Cases 2024年第8期12卷 1382-1387页

作者： Christos Kourek Alexandros Briasoulis Dimitrios e Magouliotis john Skoularigis Andrew Xanthopoulos Medical School of Athens National and Kapodistrian University of AthensAthens 15772Greece Department of Clinical Therapeutics Alexandra HospitalFaculty of MedicineNational and Kapodistrian University of AthensAthens 11528Greece Department of Surgery University Hospital of LarissaLarissa 41110Greece of Cardiology University Hospital of LarissaLarissa 41110Greece

Chronic heart failure(HF)is a clinical syndrome with high morbidity and mor-tality *** rehabilitation(CR)is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF,recommended by both American and european guidelines.A CR program con-sists of a multispecialty group including physicians,nurses,physiotherapists,trainers,nutritionists,and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF *** activity,lifestyle,and psychological support are core components of a successful CR *** has been shown to be beneficial in all ejection fraction categories in HF and most patients,who are stable under medication,are capable of *** individualized exercise prescription should be developed on the basis of a baseline evaluation in all *** main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and *** is important to set the appropriate clinical outcomes from the beginning,in order to assess the effectiveness of a CR *** are still significant limitations that prevent patients from participating in these programs and need to be solved.A significant limitation is the generally low quality of research in CR and the presence of negative trials,such as the rehabilitation after myocardial infarction trial,where comprehensive rehabilitation following myocardial infraction had no important effect on mortality,morbidity,risk factors,or health-related quality of life or *** the present editorial,we present all the updated knowledge and recommendations in CR programs.

关键词： Cardiac rehabilitation Heart failure Outcomes exercise protocols Prescription Future perspectives Limitations

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early-onset gastrointestinal cancer:An epidemiological reality with great significance and implications

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 583-597页

作者： john K Triantafillidis Konstantinos Georgiou Manousos M Konstadoulakis Apostolos e Papalois Department of IBD and GI endoscopy Metropolitan General HospitalHolargos 15562AthensGreece.Hellenic Society for Gastrointestinal Oncology354 Iera OdosChaidari 12461AtticaGreece 2nd Department of Surgery University of Athens School of MedicineAretaieion HospitalAthens 11528Greece

During the last few years,epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages,the so-called“early-onset cancer”.This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms,mainly stomach and in a lesser degree pancreas,and biliary *** should be emphasized that data concerning digestive neoplasms,except for those referring to the colon and stomach,could be characterized as rather *** exact magnitude of the shift in younger ages is expected to become clearer shortly,as long as relevant epidemiological data from many parts of the world would be *** most important question concerns the etiology of this phenomenon,since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many *** existing data support the assumption that a number of environ-mental factors may play a primary role in influencing carcinogenesis,sometimes from *** that have appeared in the last decades related mainly to eating habits,consistency of gut microbiome and an increase of obese people interacting with genetic factors,ultimately favor the process of *** these factors however,are not entirely sufficient to explain the age-related changes in the frequency of digestive *** of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are *** this article,we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible ***,we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

关键词： Gastrointestinal cancer endoscopy epidemiology early-onset environment

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Metal-metal bonds in Zintl clusters:Synthesis,structure and bonding in[Fe_(2)Sn_(4)Bi_(8)]^(3-)and[Cr_(2)Sb_(12)]^(3-)

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Chinese Chemical Letters 2024年第8期35卷 558-566页

作者： Ya-Nan Yang Zi-Sheng Li Sourav Mondal Lei Qiao Cui-Cui Wang Wen-Juan Tian Zhong-Ming Sun john e.McGrady State Key Laboratory of element-Organic Chemistry Tianjin Key Lab for Rare Earth Materials and ApplicationsSchool of Materials Science and EngineeringNankai UniversityTianjin 300350China Department of Chemistry University of OxfordInorganic Chemistry LaboratoryOxfordOX13QRUnited Kingdom

We report here the synthesis and characterization of two new members of the M2 e 12 family of endohe-dral Zintl clusters,[Fe_(2)Sn_(4)Bi_(8)]^(3-)and[Cr_(2)Sb_(12)]^(3-),both of which contain open-shell metal dimers encap-sulated inside a triple-decker cluster of main-group *** 75-electron[Fe_(2)Sn_(4)Bi_(8)]^(3-)cluster has a D4h-symmetric structure,while[Cr_(2)Sb_(12)]^(3-),despite having the same 75-electron count,is strongly dis-torted to a geometry that resembles a CrSb_(8)crown capped by a CrSb_(4)*** structural differences between the two are driven by the increasing availability of 3d electron density in the earlier transi-tion metal,which leads,ultimately,to different electronic configurations in the two *** trends precisely mirror those observed in the Me_(10)and Me_(12)families containing a single transition metal ion.

关键词： Zintl anions endohedral clusters Metal-metal bond Second-order Jahn-Teller effect DFT calculation

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Development and characterization of 3D-printed electroconductive pHeMA-co-MAA NP-laden hydrogels for tissue engineering

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Bio-Design and Manufacturing 2024年第3期7卷 262-276页

作者： Sara De Nitto Aleksandra Serafin Alexandra Karadimou Achim Schmalenberger john J.eMulvihill Maurice N.Collins DIBRIS Polytechnic Inter-School Section University of Genoa16126 GenoaItaly School of engineering Bernal InstituteUniversity of LimerickLimerick V94 T9PXIreland School of Natural Sciences Department of Biological SciencesUniversity of LimerickLimerick V94 T9PXIreland Health Research Institute University of LimerickLimerick V94 T9PXIreland AMBeR University of LimerickLimerick V94 T9PXIreland

Tissue engineering(Te)continues to be widely explored as a potential solution to meet critical clinical needs for diseased tissue replacement and tissue *** this study,we developed a poly(2-hydroxyethyl methacrylate-co-methacrylic acid)(pHeMA-co-MAA)based hydrogel loaded with newly synthesized conductive poly(3,4-ethylene-dioxythiophene)(PeDOT)and polypyrrole(PPy)nanoparticles(NPs),and subsequently processed these hydrogels into tissue engineered constructs via three-dimensional(3D)*** presence of the NPs was critical as they altered the rheological properties during ***,all samples exhibited suitable shear thinning properties,allowing for the development of an optimized processing window for 3D *** were 3D printed into pre-determined disk-shaped configurations of 2 and 10 mm in height and diameter,*** observed that the NPs disrupted the gel crosslinking efficiencies,leading to shorter degradation times and compressive mechanical properties ranging between 450 and 550 *** conductivity of the printed hydrogels increased along with the NP concentration to(5.10±0.37)×10^(−7)S/*** vitro studies with cortical astrocyte cell cultures demonstrated that exposure to the pHeMA-co-MAA NP hydrogels yielded high cellular viability and proliferation ***,hydrogel antimicrobial studies with staphylococcus epidermidis bacteria revealed that the developed hydrogels affected bacterial *** together,these materials show promise for various Te strategies.

关键词： Conductive nanoparticles Hydroxyethyl methacrylate(HeMA) Ultraviolet(UV)polymerization 3D printing

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