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Real-world performance analysis of a novel 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 Vodicska Júlia Déri Dóra Tihanyi Edit Várkondi EnikőKispéter Róbert Dóczi Dóra Lakatos Anna Dirner mátyás Vidermann Péter Filotás Réka Szalkai-Dénes István Szegedi katalin Bartyik Krisztina míta Gábor Réka Simon Péter hauser György Péter Csongor Kiss miklós Garami István Peták Oncompass medicine Hungary Kft Retek Str.34Budapest 1024Hungary Division 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 extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support *** drug assignment(DDA)is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers,targets,and targeted *** has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical *** aim of this study was to evaluate the utility of DDA in pediatric *** Between 2017 and 2020,103 high-risk pediatric cancer patients(nvolved 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)evaluated the results to provide therapy *** Of the 100 cases with comprehensive 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 evidence *** approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approved therapies had significantly higher aggregated evidence levels(AELs)than dismissed *** of WES results for targeted panels missed important mutations affecting therapy *** DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine car

关键词： Computational decision support Pediatric tumors Precision oncology Tumor board

Increased duodenal expression of mi R-146a and-155 in pediatric Crohn's disease

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World Journal of Gastroenterology 2016年第26期22卷 6027-6035页

作者： Dániel Szucs nóra Judit Béres Réka Rokonay Kriszta Boros katalin Borka Zoltán Kiss András Arató Attila J Szabó ádám Vannay Erna Sziksz Csaba Bereczki Gábor Veres Department of Pediatrics and Pediatric Health Care Center University of Szeged H-6725 Szeged Hungary 1st Department of Pediatrics Semmelweis University H-1083 Budapest Hungary 2nd Department of Pathology Semmelweis University H-1091 Budapest Hungary 1st Department of Pediatrics Semmelweis University and MTA-SE Pediatrics and Nephrology Research Group H-1083 Budapest Hungary

AIm: To evaluate the role of microRna (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn’s disease (CD) and the effect of transforming growth factor-β (TGF-β) on these miRs in duodenal epithelial and fibroblast ***: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-β (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as ***: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, P ≤ 0.01) and to the control group (CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P ≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 ± 1.02 vs Control: 1.00 ± 0.40, P ≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, P ≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, P ≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, P ≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated control

关键词： Inflammatory bowel disease Crohn’ s disease Pediatric microRnas Transforming growth factor-β

Evolution of X-pinch loads for pulsed power generators with current from 50 to 5000 ka

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matter and radiation at Extremes 2018年第6期3卷 267-277页

作者： T.A.Shelkovenko S.A.Pikuz I.n.Tilikin m.D.mitchell S.n.Bland D.A.hammer Cornell University IthacaNY14850USA P.n.Lebedev Institute Moscow119991Russia Blackett Laboratory Imperial College LondonLondonSW72AZUK University of Evansville EvansvilleINUSA

A review of X-pinches of various configurations and of different materials as an X-ray source for various applications is presented. Theadvantages and disadvantages of different designs of X-pinches as a load for generators with a wide range of output parameters and as a sourceof X-ray radiation for X-ray point-projection imaging were analyzed.

关键词： X-pinch X-ray source X-ray point-projection imaging

Thermal bleaching of optical absorption and photoluminescence spectra of γ-irradiated CaF_2:Dy:Pb:na single crystals

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Journal of rare Earths 2010年第4期28卷 493-497页

作者： S.m. moses Kennedy Department of Physics S.S.N. College of Engineering Rajiv Gandhi Salai Kalavakkam-603 110 Chennai Tamil Nadu India

The variation of the optical absorption (OA) and photoluminescence (PL) spectra with temperature was studied on γ-irradiated CaF2:Dy:Pb:na single crystals. The OA spectrum showed bands around 2.05, 3.20, 3.82 and 6.20 eV which could be attributed to different sodium associated (SA) colour centres (CCs) such as mna and ra+ . Heating the crystal indicated the annihilation and formation of different SACCs. The excitation spectrum for the characteristic Dy3+ emission at 2.14 eV immediately after irradiation was...

关键词： calcium fluoride optical absorption photoluminescence colour centres dysprosium lead sodium rare earths

On the diversity of fungi from soda soils

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Fungal Diversity 2016年第1期76卷 27-74页

作者： Alexey A.Grum-Grzhimaylo marina L.Georgieva Sofiya A.Bondarenko Alfons J.m.Debets Elena n.Bilanenko Laboratory of Genetics Plant Sciences GroupWageningen UniversityDroevendaalsesteeg 16708 PB WageningenThe Netherlands Gause Institute of new Antibiotics Federal State Budgetary Scientific InstitutionBol’shaya Pirogovskaya 11119021 MoscowRussia Faculty of Biology Lomonosov Moscow State UniversityLeninskie Gory 1-12119234 MoscowRussia

The diversity of filamentous fungi that can grow at high ambient pH values(i.e.,8–11)remains largely *** we study 100 alkalitolerant and alkaliphilic isolates from the soils around the basin of soda lakes in Asia and Africa to assess the major evolutionary lineages and morphologies pertinent to the alkaliphilic trait in filamentous *** Emericellopsis lineage(Hypocreales,Hypocreomycetidae),along with Plectosphaerellaceae(Hypocreomycetidae),Pleosporaceae(Dothideomycetes),Chaetomiaceae(Sordariomycetidae)families appeared to be overrepresented with strong alkalitolerants and effective *** particular,Sodiomyces species(Plectosphaerellaceae),Acrostalagmus luteoalbus(Plectosphaerellaceae),Emericellopsis alkalina(Hypocreales),Thielavia sp.(Chaetomiaceae),and Alternaria ***(Pleosporaceae)grew best at high ambient *** pH tolerance of Chordomyces antarcticum,Acrostalagmus luteoalbus and some other species was largely affected by the presence of extra na+in the growth *** alkalitolerants included Scopulariopsis members(microascales),Fusarium,Cladosporium,and many asexual acremonium-like species from *** alkalitolerants were represented by sporadic isolates of Penicillium,Purpureocillium lilacinum,and Alternaria alternata species,with the growth optimum at neutral or acidic *** alkalitolerants develop loose dry chains of spores easily dispersed by *** presence at low frequency with the growth optimum at neutral or acidic pH leads us to treat them as transient species in the alkaline soils,as those are also ubiquitous saprobes in normal *** phylogenetic analyses show that the alkaliphilic trait in filamentous fungi has evolved several *** lineages harboring strong alkalitolerants derived from the known marine-borne fungi(Emericellopsis,Alternaria ***),or fall within the fungi associated with halophytic grasses(Pleosporaceae).Soda soils contain a diversity of fungi that ra

关键词： Alkaliphilic fungi pH Soda soils Extremophile Sodiomyces Acrostalagmus Chordomyces Verticillium Emericellopsis Acremonium Scopulariopsis Alternaria Thielavia Plectosphaerellaceae Pleosporaceae

Processing and characterization of lead-free ceramics on the base of sodium-potassium niobate

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Journal of Advanced Dielectrics 2018年第1期8卷 29-36页

作者： E.D.Politova n.V.Golubko G.m.kaleva A.V.mosunov n.V.Sadovskaya S.Yu.Stefanovich D.A.Kiselev A.m.Kislyuk P.K.Panda L.Ya.karpov Institute of Physical Chemistry Vorontsovo Pole 10Moscow 105064Russia national University of Science and Technology“mISiS”Leninskii pr.4 Moscow 119991Russia Kotelnikov Institute of radio Engineering and Electronics Russian Academy of Sciences(Fryazino Branch)pl.Vvedenskogo 1 FryazinoMoscow Region 141190Russia national Aerospace Laboratories Kodihalli Bangalore 560017India

Lead-free sodium-potassium niobate-based piezoelectric materials are most intensively studied in order to replace the widely used Pb-based *** this work,the effects of modification of compositions by donor and acceptor dopants in the A-and B-sites of perovskite lattice on structure,dielectric,ferroelectric,and piezoelectric properties of ceramics from morphotropic Phase Boundary in the(1-x)(K_(0.5)na_(0.5))nbO_(3)-xBaTiO_(3) system and in compositions with x=0.05 and 0.06 additionally doped by ni^(3+) cations have been studied.

关键词： (ka_(0.5)na_(0.5))nbO_(3) BaTiO_(3) perovskite structure solid solutions phase transitions dielectric ferroelectric piezoelectric properties

Geochemistry of Sediments from the Lopare Basin(Bosnia and Herzegovina):Implications for Paleoclimate,Paleosalinity,Paleoredox and Provenance

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Acta Geologica Sinica(English Edition) 2020年第5期94卷 1591-1618页

作者： AleksandraŠAJnOVIĆ nenad GRBA Franz nEUBAUER milica kaŠAnIn-GRUBIn Ksenija STOJAnOVIĆ nenad PETKOVIĆ Branimir JOVAnČIĆEVIĆ University of Belgrade Center of ChemistryICTMStudentski trg 12-1611000 BelgradeSerbia University of novi Sad Faculty of SciencesDepartment of ChemistryBiochemistry and Environmental ProtectionTrg Dositeja Obradovica 321000 Novi SadSerbia Paris Lodron University of Salzburg Department of Geography and GeologyHellbrunnerstrasse 345020 SalzburgAustria University of Belgrade Faculty of ChemistryStudentski trg 12-1611000 BelgradeSerbia Rio Tinto–Rio Sava Exploration Takovska 4511000 BelgradeSerbia

A combined inorganic and organic geochemical study was carried out on marls and mudstones collected from the Lower miocene Lopare Basin,Bosnia and Herzegovina.A total of 46 samples collected from two boreholes,Pot 1(depth of 193 m)and Pot 3(depth of 344 m),showed that element abundances like boron(B),lithium(Li),strontium(Sr),uranium(U),chromium(Cr),nickel(ni),magnesium(mg),sodium(na)and calcium(Ca)are much higher than average than in the upper continental crust(UCC).Chemical composition indicates at least two sources:(i)mesozoic ophiolites occurring in the north of the investigated area,and(ii)dacito-andesitic pyroclastics(mesozoic to Cenozoic).Lopare Basin sedimentation was influenced by strong evaporation resulting in a partly hypersaline lake,which formed during a warm climatic period,probably during the miocene Climatic Optimum.A brief episode of humid climate conditions resulted in the basin fillingup and deposition of felsic sediments enriched in thorium(Th).Organic geochemistry shows that the majority of studied sediments contains predominantly immature to marginally mature algal organic matter(Om).The biomarker patterns are generally in agreement with the geological history of the Lopare Basin and inorganic and mineralogical ***,the molecular distribution of n-alkanes as reliable climatic andδ-mTTC as paleosalinity indicators do not support this conclusion.

关键词： geochemistry provenance analysis paleoenvironmental conditions salinity/hypersalinity biomarker Lopare Basin Bosnia and Herzegovina

Resin infiltration of deproteinised natural occlusal subsurface lesions improves initial quality of fissure sealing

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International Journal of Oral Science 2017年第2期9卷 117-124页

作者： Andrej m Kielbassa Ina Ulrich Rita Schmidl Christoph Schuller Wilhelm Frank Vanessa D Werth Centre for Operative Dentistry Periodontology and Endodontology University of Dental Medicine and Oral Health Danube Private University (DPU) Krems Austria Department of Applied Genetics and Cell Biology UFT-Campus Tulln University of Natural Resources and Life Sciences (BOKU) Vienna Austria Centre for Preclinical Education Department of Biostatistics University of Dental Medicine and Oral Health Danube Private University (DPU) Krems Austria

The aim of this ex vivo study was to evaluate the infiltration capability and rate of microleakage of a low-viscous resin infiltrant combined with a flowable composite resin(RI/CR) when used with deproteinised and etched occlusal subsurface lesions(International Caries Detection and Assessment System code 2). This combined treatment procedure was compared with the exclusive use of flowable composite resin(CR) for fissure sealing. Twenty premolars and 20 molars revealing non-cavitated occlusal carious lesions were randomly divided into two groups and were meticulously cleaned and deproteinised using na OCl(2%). After etching with HCl(15%), 10 premolar and 10 molar lesions were infiltrated(Icon/DmG; rhodamine B isothiocyanate(RITC)-labelled) followed by fissure sealing(G-?nial Flo/GC; experimental group, RI/CR). In the control group(CR), the carious fissures were only sealed. Specimens were cut perpendicular to the occlusal surface and through the area of the highest demineralisation(DIAGnOdent pen, ka Vo). Using confocal laser-scanning microscopy, the specimens were assessed with regard to the percentage of caries infiltration, marginal adaption and internal integrity. Within the CR group, the carious lesions were not infiltrated. Both premolar(57.9% ± 23.1%) and molar lesions(35.3% ± 22.1%) of the RI/CR group were uniformly infiltrated to a substantial extent, albeit with significant differences(P = 0.034). moreover, microleakage(n = 1) and the occurrence of voids(n = 2) were reduced in the RI/CR group compared with the CR group(5 and 17 specimens,respectively). The RI/CR approach increases the initial quality of fissure sealing and is recommended for the clinical control of occlusal caries.

关键词： aprismatic enamel fissure sealing occlusal caries resin infiltration sodium hypochlorite

Explosion dynamics of thin flat foils at high current density

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matter and radiation at Extremes 2022年第5期7卷 39-46页

作者： T.A.Shelkovenko I.n.Tilikin S.A.Pikuz A.R.mingaleev V.m.Romanova L.Atoyan D.A.hammer P.n.Lebedev Institute RASMoscow 119991Russia Cornell University IthacaNew York 14853USA

This paper presents characteristic features of the explosion of thin flat foils for currents and pulse risetimes ranging from 8 ka at 350 ns to1000 ka at ∼100 ns. Foils made of aluminum, copper, nickel, and titanium with thicknesses of 1–100 μm are tested. Various diagnostics inthe optical, UV, and x-ray spectral ranges are used to image the exploding foils from initial breakdown to complete destruction or *** is shown that foil explosion is a complex process that depends on many factors, but features common to all foils are found that do notdepend on the parameters of the generators or, accordingly, on the energy deposited in the foil: for example, the breakdown of flat foils underdifferent conditions occurs at the edges of the foil. For the first time, the formation of a precursor over the central part of the foil is shown,which significantly changes the dynamics of the foil explosion.

关键词： foils dynamics nickel