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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

Sustainable Biomass Conversion: Food or Fuels or Chemicals?

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Sustainable Biomass Conversion: Food or Fuels or Chemicals?

3D tomographic analysis of equatorial plasma bubble using GnSS-TEC data from Indonesian GnSS network

中国化学会第26届学术年会绿色化学分会场

作者： istván T. Horváth Etvs University Institute of Chemistry Pázmány Péter sétány 1/AH-1117 BudapestHungary

＜正＞The sustainability of mankind depends whether we can supply the increasing population with enough energy, food, and chemicals, including carbon-based consumer products, simultaneously without compromising the lo...

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Earth and Planetary Physics 2025年第1期9卷 127-136页

作者： Ihsan naufal Muafiry Prayitno Abadi Teguh n.Pratama Dyah R.Martiningrum Sri Ekawati Yuandhika GWismaya Febrylian FChabibi Gatot HPramono Research Center for Climate and Atmosphere Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia Indonesian Geospatial Information Agency(BIG) JakartaIndonesia Dept.of Physics Faculty of ScienceUniversiti Teknologi MalaysiaJohor BahruMalaysia Dept.Earth Planet Sci. Hokkaido UniversitySapporoJapan School of Electrical Engineering Telkom UniversityBandungIndonesia

Equatorial Plasma Bubbles(EPBs)are ionospheric irregularities that take place near the magnetic *** most commonly occur after sunset during the equinox months,although they can also be observed during other *** phenomenon significantly disrupts radio wave signals essential to communication and navigation *** national network of Global navigation Satellite System(GnSS)receivers in Indonesia(>30°longitudinal range)provides an opportunity for detailed EPB *** explore this,we conducted preliminary 3D tomography of total electron content(TEC)data captured by GnSS receivers following a geomagnetic storm on December 3,2023,when at least four EPB clusters occurred in the Southeast Asian *** and extracted TEC depletion with a 120-minute running average were then used as inputs for a 3D tomography *** 2D spatial distribution consistently captured the four EPB clusters over *** tomography results were validated through a classical checkerboard test and comparisons with other ionospheric data sources,such as the Global Ionospheric Map(GIM)and International Reference Ionosphere(IRI)*** of the results demonstrates the capability of the Indonesian GnSS network to measure peak ionospheric *** findings highlight the potential for future three-dimensional research of plasma bubbles in low-latitude regions using existing GnSS networks,with extensive longitudinal coverage.

关键词： EPB Indonesian GnSS network 3D tomography

Arterial stiffness, vascular calcification and bone metabolism in chronic kidney disease

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World Journal of nephrology 2012年第1期1卷 25-34页

作者： János nemcsik istván Kiss András Tislér Department of Family Medicine Semmelweis University 1125 Budapest Hungary Division of Angiology and nephrology Department of Medicine St. Imre Teaching Hospital 1115 BudapestHungary 1st Department of Medicine Semmelweis University 1125 Budapest Hungary

Patients with chronic kidney disease （CKD） have an extremely poor cardiovascular outcome. Arterial stiff-ness, a strong independent predictor of survival in CKD, is connected to arterial media calcification. A huge number of different factors contribute to the increased arterial calcification and stiffening in CKD, a process which is in parallel with impaired bone metabolism. This coincidence was demonstrated to be part of the direct inhibition of calcifcation in the vessels, which is a counterbalancing effect but also leads to low bone turnover. Due to the growing evidence, the defnition of “CKD mineral bone disorder” was created recently, un-derlining the strong connection of the two phenomena. In this review, we aim to demonstrate the mechanisms leading to increased arterial stiffness and the up-to date data of the bone-vascular axis in CKD. We over-view a list of the different factors, including inhibitors of bone metabolism like osteoprotegerin, fetuin-A, pyro-phosphates, matrix Gla protein, osteopontin, fbroblast growth factor 23 and bone morphogenic protein, which seem to play role in the progression of vascular calcif-cation and we evaluate their connection to impaired ar-terial stiffness in the mirror of recent scientifc results.

关键词： Arterial stiffness Vascular calcification Bone metabolism Chronic kidney disease

Tyrosine isomers and hormonal signaling:A possible role for the hydroxyl free radical in insulin resistance

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World Journal of Diabetes 2015年第3期6卷 500-507页

作者： Gerg A Molnár Esztella Zsóka Mikolás istván András Szijártó Szilárd Kun Eszter Sélley istván Wittmann 2nd Department of Medicine and nephrological Center University of Pécs

Oxidative stress processes play a major role in the development of the complications associated with diabetes and other diseases via non-enzymatic glycation,the hexosamine pathway,the polyol pathway and diacylglycerol-protein kinase *** stress may lead to the production of hydroxyl free radicals,which can attack macromolecules,such as lipids,nucleic acids or amino ***(Phe) can be enzymatically converted to the physiological para-tyrosine(p-Tyr);however,a hydroxyl free radical attack on Phe may yield meta-and ortho-tyrosine(m-and o-Tyr,respectively) in addition to ***,m-and o-Tyr may be regarded as markers of hydroxyl free radical-induced *** accumulation has been described;e.g.,this accumulation has been found in the urine of patients with diabetes mellitus(DM) and/or chronic kidney disease,in cataract lenses,in vessel walls,in irradiated food and in amniotic fluid,and it may serve as an indicator of oxidative *** use of resveratrol to treat patients with type 2 DM led to a decrease in the urinary excretion of o-Tyr and concomitantly led to an improvement in insulin signaling and insulin *** data also suggest that m-and o-Tyr may interfere with intracellular *** group has shown that erythropoietin(EPO) has insulin-like metabolic effects on fat cells in addition to its ability to promote the proliferation of erythroid precursor *** have shown that the supplementation of cell culture medium with m-and o-Tyr inhibits erythroblast cell proliferation,which could be ameliorated by ***,in vivo,the o-Tyr/p-Tyr ratio is higher in patients with renal replacement therapy and a greater need for ***,the o-Tyr/p-Tyr ratio was an independent determinant of EPO-resistance indices in our human *** o-Tyr content of blood vessel walls inversely correlates with insulin-and acetylcholineinduced vasodilation,which could be further impaired by artificial oxidative stress and impr

关键词： Acetylcholine Insulin resistance Hormoneresistance Oxidative stress Para-tyrosine Orthotyrosine Meta-tyrosine Erythropoietin

Alleviated mucosal and neuronal damage in a rat model of Crohn's disease

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World Journal of Gastroenterology 2014年第44期20卷 16690-16697页

作者： Petra Talapka Lajos istván nagy Alexandra Pál Marietta Zita Poles Anikó Berkó Mária Bagyánszki László Géza Puskás éva Fekete nikolett Bódi Department of Physiology Anatomy and Neuroscience Faculty of Sciences and Informatics University of Szeged Avidin Ltd.

AIM:To establish a rat model suitable to investigate the repetitive relapsing inflammations(RRI)characteristic to Crohn’s ***:Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid(TnBS).RRI were mimicked by repeating administrations of *** samples were taken from control,once,twice and three times treated rats from the inflamed and adjacent non-inflamed colonic segments at different timepoints during the acute intestinal *** means of the ulcerated area were measured to evaluate the macroscopic mu-cosal *** density of myenteric neurons was determined on whole mounts by Hu C/Hu D *** oxygenase-1(HO-1)expression was evaluated by molecular biological ***:TnBS-treated rats displayed severe colitis,but the mortality was negligible,and an increase of body weight was characteristic throughout the experimental *** widespread loss of myenteric neurons,and marked but transient HO-1 up-regulation were demonstrated after the first TnBS *** repeated doses the length of the recovery time and extent of the ulcerous colonic segments were markedly decreased,and the neuronal loss was on a smaller scale and was limited to the inflamed ***-1 m RnA level was notably greater than after a single dose and overexpression was sustained throughout the timepoints ***,the HO-1protein up-regulation after the second TnBS treatment proved to be *** the third treatment HO-1 protein expression could not be ***:Experimentally provoked RRI may exert a protective preconditioning effect against the mucosal and neuronal *** persistent up-regulation of HO-1 m RnA expression may correlate with this.

关键词： Crohn's disease Experimental rat model Heme oxygenase-1 Myenteric neurons Repetitive re-lapsing inflammation

The Effect of Speech Fragmentation and Audio Encodings on Automatic Parkinson’s Disease Recognition

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Journal of Biomedical Science and Engineering 2022年第1期15卷 6-25页

作者： Dávid Sztahó Attila Zoltán Jenei istván Valálik Klára Vicsi Department of Telecommunications and Media Informatics Budapest University of Technology and Economics Budapest Hungary Department of neurosurgery St. John’s Hospital Budapest Hungary

Parkinson’s disease is a neurological disease which is incurable according to current clinical knowledge. Therefore, early detection and provision of appropriate treatment are of primary importance. Speech is one of the biomarkers that enable the detection of Parkinson’s disease affection. numerous researches are based on recordings from controlled environments;nonetheless fewer apply real circumstances. In the present study, three objectives were examined: recording fragmentation (paragraph, sentences, time-based), variable encodings (Pulse-Code Modulation [PCM], GSM-Full Rate [FR], G.723.1) and majority voting on 8 kHz records using multiple classifiers. Support Vector Machine (SVM), Long Short-Term Memory (LSTM), i-vector and x-vector classifiers were evaluated in contrast with SVM as baseline. The highest results in accuracy and F1-score were achieved using i-vector models. Although variable encodings generally caused decrease in Parkinson-disease recognition, decline was within 2% - 3% at best. Moreover, fragmentation did not yield a clear outcome though some classifiers performed with the very similar efficiency along the differently fragmented sets. Majority voting did produce a slight increase in classification performance compared to as if no aggregation is used.

关键词： Parkinson’s Disease Speech Support Vector Machine neural network i-Vector x-Vector

Seroreactivity against Saccharomyces cerevisiae in patients with Crohn's disease and celiac disease

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World Journal of Gastroenterology 2003年第10期9卷 2308-2312页

作者： Zsolt Barta istván Csíp■ Gábor G.Szabó Gyula Szegedi 3~(nd) Department of Medicine University of DebrecenMóricz Zs.Krt.22.4004 DebrecenHungary

AIM:To explore whether there was anti-Saccharomyces cerevisiae antibodies (ASCA) positivity in our patients with biopsy-confirmed celiac disease. METHODS:A cohort of patients with inflammatory bowel diseases (42 patients with Crohn's disease and 10 patients with ulcerative colitis) and gluten sensitive enteropathy (16 patients) from Debrecen,Hungary were enrolled in the study. The diagnosis was made using the formally accepted criteria. Perinuclear antineutrophil cytoplasmic antibodies (pAnCA) and anti-Saccharomyces cerevisiae antibodies (ASCA), antiendomysium antibodies (EMA),antigliadin antibodies (AGA) and anti human tissue transglutaminase antibodies (tTGA) were investigated. RESULTS:The results showed that ASCA positivity occurred not only in Crohn's disease but also in Celiac disease and in these cases both the IgG and IgA type antibodies were proved. COnCLUSIOn:It is conceivable that ASCA positivity correlates with the (auto-) immune inflammation of small intestines and it is a specific marker of Crohn's disease.

关键词： Adult Antibodies, Antineutrophil Cytoplasmic Antibodies, Fungal Celiac Disease Cohort Studies Crohn Disease Female Gliadin Humans Immunoglobulin A Immunoglobulin G Male Middle Aged Saccharomyces cerevisiae Seroepidemiologic Studies

Catheter-directed thrombolysis in inflammatory bowel diseases:Report of a case

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World Journal of Gastroenterology 2012年第34期18卷 4791-4793页

作者： Péter Ilonczai Judit Tóth László Tóth istván Altorjay Zoltán Boda Károly Palatka Division of Haemostasis 2nd Department of MedicineMedical and Health Science CentreUniversity of Debrecen4032 DebrecenHungary Euromedic Diagnostics Hungary Ltd. Medical and Health Science CentreUniversity of Debrecen4032 DebrecenHungary Department of Pathology Medical and Health Science CentreUniversity of Debrecen4032 DebrecenHungary Division of Gastroenterology 2nd Department of MedicineMedical and Health Science CentreUniversity of Debrecen4032 DebrecenHungary

In patients with inflammatory bowel diseases (IBD) the prevalence of thrombosis is 6.2%, the average incidence of thromboembolism (TE) is 3.6 times higher compared to normal population. The TE is a common extraintestinal complication of IBD, squarely associated with the IBD activity. The application of antico-agulant and thrombolytic therapy in severe IBD is an unresolved issue. Herein we report the first case in literature of an active IBD patient with an upper limb acute arterial occlusion and successful catheter-directed thrombolysis (CDT). A 46-year-old male patient is reported who had Crohn's disease for 10 years. His right hand suddenly became cold and painful. Angiography proved acute occlusion of the brachial and radial artery. Vascular surgery intervention was not applicable. Endoscopy showed extended, severe inflammation of the colon. Despite the severe endoscopic findings, frequent bloody stools and moderate anaemia, CDT with recombinant tissue plasminogen activator was performed. The control angiography proved improvement, the radial artery pulse appeared. no bleeding complication was observed. This case supports that CDT-after careful estimation of the bleeding risk-can be effective and safe in patients with severe or life-threatening TE and active IBD.

关键词： Inflammatory bowel disease Crohn's dis-ease Thromboembolism Catheter-directed thromboly-sis Gastrointestinal haemorrhage