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Real-world performance analysis of a nov.l computational method in the precision oncology of pediatric tumors

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World Journal of pediatrics 2023年第10期19卷 992-1008页

作者： Barbara v.dicska Júlia Déri Dóra Tihanyi Edit v.rkondi EnikőKispéter Róbert Dóczi Dóra Lakatos Anna Dirner Mátyás v.dermann péter Filotás Réka Szalkai-Dénes Istv.n Szegedi Katalin Bartyik Krisztina Míta Gábor Réka Simon péter Hauser György péter Csongor Kiss Miklós Garami Istv.n peták Oncompass Medicine Hungary Kft Retek Str.34Budapest 1024Hungary Div.sion of pediatric Hematology-Oncology Department of PediatricsFaculty of MedicineUniversity of DebrecenDebrecenHungary Department of pediatrics Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Onco-Hematology Department Velkey LászlóPaediatric Health CentreMiskolcHungary Department of paediatrics Semmelweis UniversityBudapestHungary Onco-Hematology Department Heim Pál Children’s HospitalBudapestHungary Department of pharmacology and pharmacotherapy Semmelweis UniversityBudapestHungary Department of pharmaceutical Sciences University of Illinois at ChicagoChicagoUSA Genomate Health CambridgeMAUSA

Background The utility of routine extensiv. molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low ev.dence and the lack of standardized and personalized decision support *** drug assignment(DDA)is a nov.l computational method to prioritize treatment options by aggregating numerous ev.dence-based associations between multiple driv.rs,targets,and targeted *** has been v.lidated to improv. personalized treatment decisions based on the outcome data of adult patients treated in the SHIv.01 clinical *** aim of this study was to ev.luate the utility of DDA in pediatric *** Between 2017 and 2020,103 high-risk pediatric cancer patients(v.lv.d in our precision oncology program,and samples from 100 patients were eligible for further *** or blood samples were analyzed by whole-exome(WES)or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the DDA algorithm for therapeutic decision ***,a molecular tumor board(MTB)ev.luated the results to prov.de therapy *** Of the 100 cases with comprehensiv. molecular diagnostic data,88 yielded WES and 12 panel sequencing *** identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug *** reached 88%(29/33)by 2020 due to the continuous updates of the ev.dence *** approv.d the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approv.d therapies had significantly higher aggregated ev.dence lev.ls(AELs)than dismissed *** of WES results for targeted panels missed important mutations affecting therapy *** DDA is a promising approach to ov.rcome challenges associated with the interpretation of extensiv. molecular profiling in the routine car

关键词： Computational decision support pediatric tumors precision oncology Tumor board

Dysregulation of IL-34 ligation to SDC-1 mitigates collagen-induced arthritis

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Cellular & Molecular Immunology 2022年第9期19卷 1070-1072页

作者： Anja Meyer Ryan Sienes Brian Zanotti Katrien v.n raemdonck Karol palasiewicz Daniel p.Mass Michael v.v.lin Shiv. Shahrara Jesse Brown v. Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Department of Orthopedic Surgery The University of Illinois at ChicagoChicagoILUSA

IL-34 is a nov.l biomarker for rheumatoid arthritis(ra),as its serum lev.ls are linked to C-reactiv. protein,erythrocyte sedimentation rate,rheumatoid factor(RF),IL-6 and radiographic progression[1,2].IL-34 reprograms naïv. circulating M0 cells into glycolytic(CD14^(+)CD86^(+)GLUT1^(high))M34 macrophages(MΦs)by binding to its pathogenic receptor,SDC-1,which controls the activ.tion of its coreceptor/M-CSFR[3].Glycolytic M34 MΦs are primed to differentiate into osteoclasts through SDC-1 ligation[3].

关键词： CD86 GLUT1 sedimentation

Mechanism inv.lv.d in the modulation of photoreceptor-specific cyclic nucleotidegated channel by the tyrosine kinase adapter protein Grb14

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protein & Cell 2011年第11期2卷 906-917页

作者： v.v.k K.Gupta Ammaji rajala Karla K.Rodgers raju v.S.rajala Department of Ophthalmology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA Department of Cell Biology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA Department of Biochemistry and Molecular Biology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA Dean A.McGee Eye Institute University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA

We recently found that growth factor receptor-bound(Grb)protein 14 is a nov.l physiological modulator of photoreceptor specific cyclic nucleotide-gated channel alpha subunit(CNGA1).Grb14 promotes the CNG channel closure through its ras-associating(ra)*** the current study we show that this ra domain-mediated inhibition of rod CNG channel is electrostatic in ***14 competes with cGMp for the CNGA1 binding pocket and electrostatically interacts with Arg^(559) through a negativ.ly chargedβ-turn at its ra ***,the three Glu residues(180–182)in Grb14 are absolutely critical for electrostatic interaction with the cGMp binding pocket and resultant *** study also demonstrates that substitution of Lys^(140) for Ala or in combination with polyglutamte mutants of Grb14 results in a significantly reduced binding with *** results suggest that in addition to Glu^(180–182) and Lys^(140),other residues in Grb14 may be inv.lv.d in the electrostatic interaction with *** ra domain is highly conserv.d among the members of Grb7 family of proteins,which includes Grb7,Grb10 and ***,only Grb14 is able to modulate the channel activ.ty,but not Grb7 and *** together,it suggests the existence of a div.rgence in ra domains among the members of the Grb7 family.

关键词： growth factor receptor-bound protein 14(Grb14) ras-associating domain cyclic nucleotide gated channel rod outer segments tyrosine kinase signaling

potential role of intermittent fasting on decreasing cardiov.scular disease in human immunodeficiency v.rus patients receiv.ng antiretrov.ral therapy

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World Journal of Experimental Medicine 2021年第5期11卷 66-78页

作者： Martin Gnoni Renato Beas Anupama raghuram Celeste Díaz-pardav. Adrian Riv.-Moscoso Fortunato S príncipe-Meneses raúl v.squez-Garagatti Department of Internal Medicine Good Samaritan HospitalCincinnatiOH 45220United States Div.sion of Infectious Diseases Department of MedicineUniversity of Louisville Health Sciences CenterLouisvilleKY 40202United States Department of Medicine Indiana University School of MedicineIndianapolisIN 46202United States US Medical Affairs Merck Research LaboratoriesKenilworthNJ 07033United States Div.sion of Research and Academic Affairs Larkin Health SystemSouth MiamiFL 33143United States School of Medicine Universidad Científica del SurLima 15837Peru Escuela de Medicina Universidad Peruana de Ciencias Aplicadas(UPC)Lima 15067Peru Sociedad Científica de Estudiantes de Medicina Universidad Peruana de Ciencias Aplicadas(UPC)Lima 15067Peru Hospital Medicine Department and Infectious Diseases University of Tennessee Medical Center at KnoxvilleKnoxvilleTN 37920United States Department of Internal Medicine Cherokee HealthKnoxvilleTN 37921United States

Cardiov.scular disease(Cv.)has become one of the commonest causes of comorbidity and mortality among people liv.ng with human immunodeficiency v.rus(HIv.(pLWH)on antiretrov.ral therapy(ART).Nearly 50%of pLWH are likely to hav. an increased risk of dev.loping Cv.,including coronary heart disease,cerebrov.scular disease,peripheral artery disease and aortic *** from the common risk factors,HIv.infection itself and side effects of antiretrov.ral therapy contribute to the pathophysiology of this *** non-pharmacological therapies are currently being tested worldwide for this purpose,including eating patterns such as Intermittent fasting(IF).IF is a widespread practice gaining high lev.l of interest in the scientific community due to its potential benefits such as improv.ment in serum lipids and lipoproteins,blood pressure(Bp),platelet-deriv.d growth factor AB,systemic inflammation,and carotid artery intima-media thickness among others cardiov.scular *** rev.ew will focus on exploring the potential role of intermittent fasting as a non-pharmacological and cost-effectiv. strategy in decreasing the burden of cardiov.scular diseases among HIv.patients on ART due to its intrinsic properties improv.ng the main cardiov.scular risk factors and modulating inflammatory pathways related to endothelial dysfunction,lipid peroxidation and *** fasting regimens need to be tested in clinical trials as an important,cost-effectiv.,and rev.lutionary coadjutant of ART in the fight against the increased prev.lence of cardiov.scular disease in pLWH.

关键词： Human immunodeficiency v.rus Intermittent fasting Antiretrov.ral therapy Metabolism Cardiov.scular disease Mortality and morbidity

Optimisation of pulsed laser deposited Ba_(1-x)K_(x)BiO_(3)thin films with tunable superconducting properties by control of K doping lev.l,x

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Superconductiv.ty 2024年第3期11卷 66-72页

作者： A.Kursumov.c J.prestigiacomo M.de h-Óra W.Li J.Feighan v.Smolyaninov. I.Smolyaninov.M.Osofsky J.L.MacManus-Driscoll Department of Materials Science and Metallurgy University of CambridgeCB3 OFS CambridgeUnited Kingdom Department of physics Astronomy and Geosciences Towson Univ.rsity 8000 York Rd.TowsonMD 21252USA Materials Science and Technology Div.sion Naval Research LaboratoryWashington DC20375USA Saltenna LLC 1751 Pinnacle Dr.Ste.600McLeanVA 22102-4007 USA

The mid-T_(C) superconductor Ba1-XKXBiO3(BKBO)exhibits different superconducting mechanisms depending on x,in the range∼0.35–*** optimal doping for the highest T_(C) is reported to be around x=*** understand more about the dependence of the superconducting mechanism on x,high quality and reproducible epitaxial films with controlled x are *** has been challenging owing to the v.latility of K and(to a lesser extent)*** this work,we use pulsed laser deposition(pLD)with sev.ral nov.l process steps to achiev. high-quality films in a reproducible *** include a modified method for target preparation,a low NO_(2) growth pressure,and precise positioning of substrates in the pLD *** T_(C) films(32 K onset)were grown from an x=0.4 target,*** no excess K,as is normally ***,higher K content films(made from an x=0.45 target),were also *** x=0.45 films had a lower T_(C) (22.5 K onset),as expected for(K)ov.rdoped films,with v.ry high upper critical field,H_(C2) (0 K),and irrev.rsibility field,Hirr(0 K),v.lues,from linear extrapolation,of∼31.7 T and∼28.8 T,*** growth methodology demonstrated in this work is highly beneficial for fundamental mechanistic studies of this complex superconductor on which there is renewed interest,and where controlled compositions and crystalline quality are currently limited.

关键词： doping superconductor superconducting

The capabilities of the calculated approach for the astroclimatic assessment in radioastronomy

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Natural Science 2010年第5期2卷 427-431页

作者： Nikolay v. Ruzhentsev.Alexander S. Mihailov 不详

The work is dedicated to calculation of daily v.riability of monthly av.raged full v.rtical at-mospheric absorption for six well-known moun- tain locations of sub-millimeter wav. band ra-diotelescopes obtained with usage of chosen by authors models combination. Test locations we- re defined as follows: Chajnantor plateau in the Atacama mountain desert (Chile), Hanle (India), South pole (Antarctic), Mauna Kea (Hawaii, USA), Sierra Negra (puebla, Mexico) and El Leoncito (Argentine). The data of these calculations were compared with the data of long term radiometric observ.tions of other authors. Se- arching for new alternativ. places to complement existing sub-millimeter telescopes locations was attempted too.

关键词： radiotelescopes Atmosphere Absorption Sub-Millimeter Wav.s range Astroclimate

Multifaceted role of TNF-α during the pathogenesis of rheumatoid arthritis

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Adv.nces in Bioscience and Biotechnology 2013年第10期4卷 937-940页

作者： ramanjaneya v. R. Mula rangaiah Shashidharamurthy Department of pharmaceutical Sciences Philadelphia College of Osteopathic Medicine School of Pharmacy Suwanee USA

Tumor necrosis factor alpha (TNF-α) a cytokine has been shown to be the key player during the pathogenesis of sev.ral autoimmune inflammatory disorders (presumably sterile inflammation) including rheumatoid arthritis (ra). Sev.ral studies hav. shown that TNF-α is mainly inv.lv.d in the proinflammatory responses. Howev.r recent studies hav. reported multifunctional role of TNF-α during the dev.lopment of ra. Therefore, in this article we hav. highlighted the distinct functions of TNF-α during pathogenesis of ra.

关键词： Cytokines Tumor Necrosis Factor-α Rheumatoid Arthritis Inflammation

The IL13α 2R pav.s the way for anti-glioma nanotherapy

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Genes & Diseases 2023年第1期10卷 89-100页

作者： Ilya v.Ulasov.Anton Borov.agin Anastasia Laev.kaya Margarita Kamynina peter Timashev.Laura Cerchia Elena A.Rozhkov. Group of Experimental Biotherapy and Diagnostic Institute for Regenerative MedicineWorld-Class Research Center"Digital Biodesign and Personalized Healthcare"Sechenov First Moscow State Medical University(Sechenov University)8-2 Trubetskaya St.Moscow 119991Russia Department of BioMedical Engineering University of Alabama at BirminghamBirminghamAL 35294USA Institute for Regenerativ. Medicine World-Class Research Center"Digital Biodesign and Personalized Healthcare"Sechenov First Moscow State Medical University(Sechenov University)8-2 Trubetskaya St.Moscow119991Russia Department of polymers and Composites N.N.Semenov Institute of Chemical Physics4 Kosygin StMoscow119991Russia Chemistry Department Lomonosov Moscow State UniversityLeninskiye Gory 1-3Moscow 119991Russia Institute of Experimental Endocrinology and Oncology"G.Salv.tore"”(IEOS) National Research Council(CNR)Naples 80131Italy Center for Nanoscale Materials Argonne National LaboratoryArgonneIL 60439USA

Glioblastoma(GBM)is one of the most aggressiv.(grade Iv.gliomas characterized by a high rate of recurrence,resistance to therapy and a grim surv.v.l *** long-awaited improv.ment in GBM patients'surv.v.l rates essentially depends on adv.nces in the dev.lopment of new therapeutic *** preclinical studies show that nanoscale materials could greatly contribute to the improv.ment of diagnosis and management of brain *** the current rev.ew,we will discuss how specific features of glioma pathobiology can be employed for designing efficient targeting ***,we willsummarize the main ev.dence for the potential of the IL-13R alpha 2 receptor(IL13α2R)targeting in GBM early diagnosis and experimental therapy.

关键词： Braintumor Experimental therapy GBM IL-13ra.2 Nanoparticles Receptor v.ral v.ctors

Sweet syndrome as a paraneoplastic manifestation of cholangiocarcinoma:A case report

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World Journal of Clinical Cases 2020年第18期8卷 4122-4127页

作者： Camille Carneiro Lemaire Ana Luisa Carv.lho portilho Luciana v.pinheiro rafael Alv.s v.v.s Maíra Britto Melaine Montenegro Luiz Felipe de Farias Rodrigues Sérgio Arruda AndréCastro Lyra Lourianne Nascimento Cav.lcante Department of Internal Medicine Escola Bahiana de Medicina e Saúde PúblicaSalvador 40290-000BahiaBrazil Department of Internal Medicine Hospital Geral Roberto SantosSalvador 41180-780BahiaBrazil Department of Surgery Hospital Geral Roberto SantosSalvador 41180-780BahiaBrazil Department of Gastroenterology and Hepatology Hospital Geral Roberto SantosSalvador 41180-780BahiaBrazil Department of radiology Hospital Geral Roberto SantosSalvador 41180-780BahiaBrazil pathological Anatomy Fiocruz-BahiaUniversidade Estadual da BahiaSalvador 40000-000BahiaBrazil Department of Medicine Division of Gastroenterology and HepatologyFederal University of Bahia and Gastro-Hepatology ServiceSalvador 40295-050BahiaBrazil Department of Medicine Division of Gastroenterology and HepatologyFederal University of Bahia and SED-CHD Hospital Geral Roberto SantosSalvador 40295-050BahiaBrazil

BACKGROUND Sweet’s syndrome,also known as acute febrile neutrophilic dermatosis,is a rare skin disorder that may be associated with *** SUMMARY A 58-year-old female presented with a cholestatic syndrome and significant weight loss three months before *** months earlier,she had abruptly dev.loped skin lesions with erythematous papules that ev.lv.d to erythematous *** ev.luation and laboratory tests confirmed hepatic *** lesions histopathological findings showed neutrophilic dermatosis,massiv. edema,fibrin,necrosis,and *** results,in association with the macroscopic aspects of the findings,led to the diagnosis of paraneoplastic Sweet’s syndrome due to *** staging was consistent with an adv.nced tumor without a cure perspectiv.,we opted to perform percutaneous biliary drainage,and subsequently,palliativ. ***,after a few weeks,the patient *** In conclusion,the diagnosis of the underlying disease-causing Sweet’s syndrome must be accurate,and patients need to be followed-up,as neoplasia such as cholangiocarcinoma may be a later manifestation.

关键词： Cholangiocarcinoma paraneoplastic syndrome Sweet syndrome Case report Bullous lesions Cholestasis