TY - JOUR AU - Balog, József Ágoston AU - Zvara, Ágnes AU - Bukovinszki, Vivien AU - Puskás, László AU - Balog, Attila AU - Szebeni, Gábor TI - Comparative single-cell multiplex immunophenotyping of therapy-naive patients with rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus shed light on disease-specific composition of the peripheral immune system JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 15 PY - 2024 SN - 1664-3224 DO - 10.3389/fimmu.2024.1376933 UR - https://m2.mtmt.hu/api/publication/34829278 ID - 34829278 LA - English DB - MTMT ER - TY - JOUR AU - Gémes, Nikolett AU - Balog, József Ágoston AU - Neuperger, Patricia AU - Schlegl, Erzsébet AU - Barta, Imre AU - Fillinger, János AU - Antus, Balázs AU - Zvara, Ágnes AU - Hegedűs, Zoltán AU - Czimmerer, Zsolt AU - Manczinger, Máté AU - Balogh, Gergő Mihály AU - Tóvári, József AU - Puskás, László AU - Szebeni, Gábor TI - Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC. JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 14 PY - 2023 PG - 16 SN - 1664-3224 DO - 10.3389/fimmu.2023.1297577 UR - https://m2.mtmt.hu/api/publication/34486293 ID - 34486293 N1 - * Megosztott szerzőség AB - Tobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC).Smoker controls without chronic illness were recruited as controls. Through extensive mapping of single cells, surface receptor quantification was achieved by single-cell mass cytometry (CyTOF) with 29 antibodies. The CyTOF characterized 14 main immune subsets such as CD4+, CD8+, CD4+/CD8+, CD4-/CD8-, and γ/δ T cells and other subsets such as CD4+ or CD8+ NKT cells, NK cells, B cells, plasmablasts, monocytes, CD11cdim, mDCs, and pDCs. The CD4+ central memory (CM) T cells (CD4+/CD45RA-/CD45RO+/CD197+) and CD4+ effector memory (EM) T cells (CD4+/CD45RA-/CD45RO+/CD197-) were FACS-sorted for RNA-Seq analysis. Plasma samples were assayed by Luminex MAGPIX® for the quantitative measurement of 17 soluble immuno-oncology mediators (BTLA, CD28, CD80, CD27, CD40, CD86, CTLA-4, GITR, GITRL, HVEM, ICOS, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, TLR-2) in the four studied groups.Our focus was on T-cell-dependent differences in COPD and NSCLC, where peripheral CD4+ central memory and CD4+ effector memory cells showed a significant reduction in exCOPD and CD4+ CM showed elevation in NSCLC. The transcriptome analysis delineated a perfect correlation of differentially expressed genes between exacerbating COPD and NSCLC-derived peripheral CD4+ CM or CD4+ EM cells. The measurement of 17 immuno-oncology soluble mediators revealed a disease-associated phenotype in the peripheral blood of stCOPD, exCOPD, and NSCLC patients.The applied single-cell mass cytometry, the whole transcriptome profiling of peripheral CD4+ memory cells, and the quantification of 17 plasma mediators provided complex data that may contribute to the understanding of the disbalance in immune homeostasis generated or sustained by tobacco smoking in COPD and NSCLC. LA - English DB - MTMT ER - TY - JOUR AU - Neuperger, Patricia AU - Szalontai, Klára Margit AU - Gémes, Nikolett AU - Balog, József Ágoston AU - Tiszlavicz, László AU - Furák, József AU - Lázár, György ifj AU - Puskás, László AU - Szebeni, Gábor TI - Single-cell mass cytometric analysis of peripheral immunity and multiplex plasma marker profiling of non-small cell lung cancer patients receiving PD-1 targeting immune checkpoint inhibitors in comparison with platinum-based chemotherapy JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 14 PY - 2023 PG - 14 SN - 1664-3224 DO - 10.3389/fimmu.2023.1243233 UR - https://m2.mtmt.hu/api/publication/34199166 ID - 34199166 N1 - Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary PhD School in Biology, University of Szeged, Szeged, Hungary Csongrád County Hospital of Chest Diseases, Deszk, Hungary Department of Pathology, University of Szeged, Szeged, Hungary Department of Surgery, University of Szeged, Szeged, Hungary Avicor Ltd, Szeged, Hungary Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary CS-Smartlab Devices Ltd, Kozármisleny, Hungary Export Date: 7 November 2023 Correspondence Address: Puskás, L.G.; Laboratory of Functional Genomics, Hungary; email: laszlo@avidinbiotech.com Correspondence Address: Szebeni, G.J.; Laboratory of Functional Genomics, Hungary; email: szebeni.gabor@brc.hu Funding details: Magyar Tudományos Akadémia, MTA, BO/00582/22/8, ÚNKP-23-5 -SZTE-694 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFI Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, C1764415 Funding details: Innovációs és Technológiai Minisztérium Funding details: National Research, Development and Innovation Office Funding text 1: This research was funded by the 2020‐1.1.6‐JÖVŐ−2021‐00003 and 142877 FK22, KFI_16-1-2017-0105 grant from the National Research, Development, and Innovation Office (NKFI), Hungary. This work was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GS) and by the by the ÚNKP-23-5 -SZTE-694 New National Excellence Program of the Ministry for Innovation and Technology (GS). This manuscript was supported by the KDP-2021 Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund for NG (C1764415). LA - English DB - MTMT ER - TY - THES AU - Balog, József Ágoston TI - Terápia naiv autoimmun betegek perifériás immunrendszerének multiplex jellemzése [Multiplex characterization of the peripheral immune system of therapy naive autoimmune patients] PB - Szegedi Tudományegyetem PY - 2023 SP - 93 DO - 10.14232/phd.11572 UR - https://m2.mtmt.hu/api/publication/34108405 ID - 34108405 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Szebeni, Gábor AU - Alföldi, Róbert AU - Nagy, Lajos I. AU - Neuperger, Patricia AU - Gémes, Nikolett AU - Balog, József Ágoston AU - Tiszlavicz, László AU - Puskás, László TI - Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model JF - VACCINES (BASEL) J2 - VACCINES-BASEL VL - 11 PY - 2023 IS - 7 PG - 18 SN - 2076-393X DO - 10.3390/vaccines11071254 UR - https://m2.mtmt.hu/api/publication/34076543 ID - 34076543 N1 - Laboratory of Functional Genomics, Biological Research Centre, Temesvári krt. 62, Szeged, H6726, Hungary Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, Szeged, H6726, Hungary CS-Smartlab Devices Ltd., Ady E. u. 14, Kozármisleny, H7761, Hungary AstridBio Technologies Ltd., Wimmer Fülöp utca 1, Szeged, H6728, Hungary Avidin Ltd, Alsó Kikötő sor 11/D, Szeged, H6726, Hungary Department of Pathology, University of Szeged, Állomás u. 2, Szeged, H6725, Hungary Export Date: 20 October 2023 Correspondence Address: Szebeni, G.J.; Laboratory of Functional Genomics, Temesvári krt. 62, Hungary; email: szebeni.gabor@brc.hu Correspondence Address: Puskás, L.G.; Laboratory of Functional Genomics, Temesvári krt. 62, Hungary; email: laszlo@avidinbiotech.com Chemicals/CAS: cyclophosphamide, 50-18-0, 6055-19-2; immunoglobulin G, 97794-27-9, 308067-58-5; interleukin 2, 85898-30-2; propidium iodide, 25535-16-4; resazurin, 550-82-3; streptomycin, 57-92-1 Manufacturers: Thermo, United States Funding details: Magyar Tudományos Akadémia, MTA, BO/00582/22/8 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH Funding details: National Research, Development and Innovation Office Funding text 1: This research was funded by the 2020-1.1.6-JÖVŐ−2021-00003 and 142877 FK22 grants from the National Research, Development, and Innovation Office (NKFI), Hungary. This work was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GJS). AB - The advent of immunotherapy has revolutionized cancer treatments. However, the application of immune checkpoint inhibitors may entail severe side effects, with the risk of therapeutic resistance. The generation of chimeric antigen receptor (CAR) T-cells or CAR-NK cells requires specialized molecular laboratories, is costly, and is difficult to adapt to the rapidly growing number of cancer patients. To provide a simpler but effective immune therapy, a whole-cell tumor vaccine protocol was established based on ultraviolet C (UCV)-irradiated 4T1 triple-negative breast cancer cells. The apoptosis of tumor cells after UVC irradiation was verified using resazurin and Annexin V/propidium iodide flow cytometric assays. Protective immunity was achieved in immunized BALB/c mice, showing partial remission. Adoptive transfer of splenocytes or plasma from the mice in remission showed a protective effect in the naive BALB/c mice that received a living 4T1 tumor cell injection. 4T1-specific IgG antibodies were recorded in the plasma of the mice following immunization with the whole-cell vaccine. Interleukin-2 (IL-2) and oligonucleotide 2006 (ODN2006) adjuvants were used for the transfer of splenocytes from C57BL/6 mice into cyclophosphamide-treated BALB/c mice, resulting in prolonged survival, reduced tumor growth, and remission in 33% of the cases, without the development of the graft-versus-host disease. Our approach offers a simple, cost-effective whole-cell vaccine protocol that can be administered to immunocompetent healthy organisms. The plasma or the adoptive transfer of HLA-matching immunized donor-derived leukocytes could be used as an immune cell therapy for cancer patients. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Enikő AU - Modok, Szabolcs AU - Rónaszéki, Benedek AU - Faragó, Anna AU - Gémes, Nikolett AU - Nagy, Lajos I. AU - Hackler, László AU - Farkas, Katalin AU - Neuperger, Patricia AU - Balog, József Ágoston AU - Balog, Attila AU - Puskás, László AU - Szebeni, Gábor TI - Comparison of humoral and cellular immune responses in hematologic diseases following completed vaccination protocol with BBIBP-CorV, or AZD1222, or BNT162b2 vaccines against SARS-CoV-2 JF - FRONTIERS IN MEDICINE J2 - FRONT MED VL - 10 PY - 2023 PG - 11 SN - 2296-858X DO - 10.3389/fmed.2023.1176168 UR - https://m2.mtmt.hu/api/publication/34069256 ID - 34069256 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Office (NKFI), Hungary [2020-1.1.6-JOVO-2021-00003, 142877 FK22, KFI_16-1-2017-0105]; KDP-2021 Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund [C1764415]; Jnos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00582/22/8]; Ministry of Culture and Innovation; New National Excellence Program [NTP-NFTOE-21-B-0164] Funding text: This research was funded by the 2020-1.1.6-JOEVO-2021-00003 and 142877 FK22, KFI_16-1-2017-0105 grant from the National Research, Development, and Innovation Office (NKFI), Hungary. This work was supported by the UNKP-22-5-SZTE-535 New National Excellence Program for GS, and by the KDP-2021 Program for NG (C1764415) of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. This work was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GS). This manuscript was prepared with the professional support of SZTE AOK-KKA Hetenyi Geza Scholarship_5S726 (AB). This manuscript was prepared with the support of the National Young Talent Scholarship for ES (NTP-NFTOE-21-B-0164) by the Ministry of Culture and Innovation. LA - English DB - MTMT ER - TY - JOUR AU - Gémes, Nikolett AU - Makra, Zsófia AU - Neuperger, Patricia AU - Szabó, Enikő AU - Balog, József Ágoston AU - Flink, Lili Borbála AU - Kari, Beáta AU - Hackler, László AU - Puskás, László AU - Kanizsai, Iván AU - Szebeni, Gábor TI - A cytotoxic survey on 2-amino-1H-imidazol based synthetic marine sponge alkaloid analogues JF - DRUG DEVELOPMENT RESEARCH J2 - DRUG DEVELOP RES VL - 83 PY - 2022 IS - 8 SP - 1906 EP - 1922 PG - 17 SN - 0272-4391 DO - 10.1002/ddr.22006 UR - https://m2.mtmt.hu/api/publication/33211172 ID - 33211172 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Office (NKFI), Hungary [2020-1.1.6-JOVO-2021-00003, 142877 FK22]; New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund [UNKP-22-5 -SZTE-535]; [BO/00582/22/8] Funding text: This research was funded by the 2020-1.1.6-JOVO-2021-00003 and 142877 FK22 (GJS) grant from the National Research, Development, and Innovation Office (NKFI), Hungary. This work was supported by the UNKP-22-5 -SZTE-535 (GJS) New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. This work was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GJS). AB - Here, we describe the synthesis and biologic activity evaluation of 20 novel synthetic marine sponge alkaloid analogues with 2-amino-1H-imidazol (2-AI) core. Cytotoxicity was tested on murine 4T1 breast cancer, A549 human lung cancer, and HL-60 human myeloid leukemia cells by the resazurin assay. A total of 18 of 20 compounds showed cytotoxic effect on the cancer cell lines with different potential. Viability of healthy human fibroblasts and peripheral blood mononuclear cells upon treatment was less hampered compared to cancer cell lines supporting tumor cell specific cytotoxicity of our compounds. The most cytotoxic compounds resulted the following IC50 values 28: 2.91 µM on HL-60 cells, and 29: 3.1 µM on 4T1 cells. The A549 cells were less sensitive to the treatments with IC50 15 µM for both 28 and 29. Flow cytometry demonstrated the apoptotic effect of the most active seven compounds inducing phosphatidylserine exposure and sub-G1 fragmentation of nuclear DNA. Cell cycle arrest was also observed. Four compounds caused depolarization of the mitochondrial membrane potential as an early event of apoptosis. Two lead compounds inhibited tumor growth in vivo in the 4T1 triple negative breast cancer and A549 human lung adenocarcinoma xenograft models. Novel marine sponge alkaloid analogues are demonstrated as potential anticancer agents for further development. LA - English DB - MTMT ER - TY - JOUR AU - Honfi, Dániel György AU - Gémes, Nikolett AU - Szabó, Enikő AU - Neuperger, Patricia AU - Balog, József Ágoston AU - Nagy, Lajos I. AU - Toldi, Gergely AU - Puskás, László AU - Szebeni, Gábor AU - Balog, Attila TI - Comparison of Homologous and Heterologous Booster SARS-CoV-2 Vaccination in Autoimmune Rheumatic and Musculoskeletal Patients JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 19 PG - 15 SN - 1661-6596 DO - 10.3390/ijms231911411 UR - https://m2.mtmt.hu/api/publication/33115577 ID - 33115577 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Office (NKFIH), Hungary [2020-1.1.6-JOVO -2021-00003, 142877 FK22OTKA]; SZTE AOK-KKA Hetenyi 2020 grant; Ministry of Innovation and Technology - National Research, Development, and Innovation Fund [C1764415]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00582/22/8] Funding text: This research was funded by the grants 2020-1.1.6-JOVO -2021-00003 and 142877 FK22OTKA (GJS) from the National Research, Development, and Innovation Office (NKFIH), Hungary. This work was supported by the SZTE AOK-KKA Hetenyi 2020 grant (AB). This manuscript was prepared with the professional support of the doctoral student scholarship program of the Ministry of Innovation and Technology, financed by the National Research, Development, and Innovation Fund for NG (C1764415). This paper was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00582/22/8 for GJS). AB - Vaccination against SARS-CoV-2 to prevent COVID-19 is highly recommended for immunocompromised patients with autoimmune rheumatic and musculoskeletal diseases (aiRMDs). Little is known about the effect of booster vaccination or infection followed by previously completed two-dose vaccination in aiRMDs. We determined neutralizing anti-SARS-CoV-2 antibody levels and applied flow cytometric immunophenotyping to quantify the SARS-CoV-2 reactive B- and T-cell mediated immunity in aiRMDs receiving homologous or heterologous boosters or acquired infection following vaccination. Patients receiving a heterologous booster had a higher proportion of IgM+ SARS-CoV-2 S+ CD19+CD27+ peripheral memory B-cells in comparison to those who acquired infection. Biologic therapy decreased the number of S+CD19+; S+CD19+CD27+IgG+; and S+CD19+CD27+IgM+ B-cells. The response rate to a booster event in cellular immunity was the highest in the S-, M-, and N-reactive CD4+CD40L+ T-cell subset. Patients with a disease duration of more than 10 years had higher proportions of CD8+TNF-α+ and CD8+IFN-γ+ T-cells in comparison to patients who were diagnosed less than 10 years ago. We detected neutralizing antibodies, S+ reactive peripheral memory B-cells, and five S-, M-, and N-reactive T-cells subsets in our patient cohort showing the importance of booster events. Biologic therapy and <10 years disease duration may confound anti-SARS-CoV-2 specific immunity in aiRMDs. LA - English DB - MTMT ER - TY - JOUR AU - Szebeni, Gábor AU - Gémes, Nikolett AU - Honfi, Dániel György AU - Szabó, Enikő AU - Neuperger, Patricia AU - Balog, József Ágoston AU - Nagy, LI AU - Szekanecz, Zoltán AU - Puskás, László AU - Toldi, Gergely AU - Balog, Attila TI - Humoral and cellular immunogenicity and safety of five different SARS-CoV-2 vaccines in patients with autoimmune rheumatic and musculoskeletal diseases in remission or with low disease activity and in healthy controls: a single center study JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 13 PY - 2022 PG - 11 SN - 1664-3224 DO - 10.3389/fimmu.2022.846248 UR - https://m2.mtmt.hu/api/publication/32728646 ID - 32728646 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Office (NKFIH), Hungary [2020-1.1.6-JOVO-2021-00003]; National Research, Development, and Innovation Fund [KDP-17-4/PALY-2021, 1000464] Funding text: This study was supported by the grant 2020-1.1.6-JOVO-2021-00003 from the National Research, Development, and Innovation Office (NKFIH), Hungary. This manuscript was prepared with the professional support of the doctoral student scholarship program of the Ministry of Innovation and Technology, financed by the National Research, Development, and Innovation Fund for JB (KDP-17-4/PALY-2021, 1000464). AB - Background: Vaccine-induced immunity is essential for controlling the COVID-19 pandemic. Data on humoral and cellular immunogenicity and safety of different SARS-CoV-2 vaccines in patients with autoimmune rheumatic and musculoskeletal diseases (RMDs) are limited. Methods: A single center observational study evaluated the immunogenicity and safety of the two-dose regimen of the BBIBP-CorV inactivated, Gam-COVID-Vac and AZD1222 adenovirus-based, and BNT162b2 and mRNA-1273 mRNA-based vaccines in patients with RMDs (n = 89) compared with healthy controls (n = 74). Neutralizing anti-RBD (receptor binding domain) specific antibodies and SARS-CoV-2 specific T-cell response were measured one and four months after the second vaccine dose in parallel with vaccination efficacy and safety. Results: Disease-specific comparison showed that antibody response at four months was higher in spondylarthropathies compared to rheumatoid arthritis and autoimmune RMDs. Risk factors for reduced immunogenicity included longer disease duration, positive immunoserological profile and anti-CD20 therapy of patients. The rate of positive anti-RBD antibody response for healthy controls versus patients after 4 months post vaccination was 69% vs. 55% for the inactivated viral vaccine BBIBP-CorV, 97% vs. 53% for the pooled data of adenovirus vector-based vaccines Gam-COVID-Vac and AZD1222, or 100% vs. 81% for the pooled data of mRNA vaccines BNT162b2 and mRNA-1273, respectively. Patients who received the Gam-COVID-Vac or mRNA-1273 vaccines had a higher proportion of TNF-alpha producing CD4+ T-cells upon SARS-CoV-2 antigen stimulation compared to the inactivated viral vaccine. Conclusion: All five investigated vaccines were immunogenic in the majority of patients and healthy controls with variable antibody and T-cell response and an acceptable safety profile. LA - English DB - MTMT ER - TY - JOUR AU - Neuperger, Patricia AU - Balog, József Ágoston AU - Tiszlavicz, László AU - Furák, József AU - Gémes, Nikolett AU - Kotogány, Edit AU - Szalontai, Klára Margit AU - Puskás, László AU - Szebeni, Gábor TI - Analysis of the Single-Cell Heterogeneity of Adenocarcinoma Cell Lines and the Investigation of Intratumor Heterogeneity Reveals the Expression of Transmembrane Protein 45A (TMEM45A) in Lung Adenocarcinoma Cancer Patients JF - CANCERS J2 - CANCERS VL - 14 PY - 2022 IS - 1 PG - 22 SN - 2072-6694 DO - 10.3390/cancers14010144 UR - https://m2.mtmt.hu/api/publication/32558299 ID - 32558299 N1 - Laboratory of Functional Genomics, Biological Research Centre, Temesvári krt. 62, Szeged, H6726, Hungary Ph.D. School in Biology, University of Szeged, Szeged, H6726, Hungary Department of Pathology, University of Szeged, Állomás u. 2, Szeged, H6725, Hungary Department of Surgery, University of Szeged, Semmelweis u. 8, Szeged, H6725, Hungary Csongrád County Hospital of Chest Diseases, Alkotmány u. 36, Szeged, H6772, Hungary Avicor Ltd, Alsó kikötő sor 11/D, Szeged, H6726, Hungary Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, Szeged, H6726, Hungary CS-Smartlab Devices, Ady E. u. 14, Kozármisleny, H7761, Hungary Export Date: 7 January 2022 Correspondence Address: Puskás, L.G.; Laboratory of Functional Genomics, Temesvári krt. 62, Hungary; email: puskas.laszlo@brc.hu Correspondence Address: Szebeni, G.J.; Laboratory of Functional Genomics, Temesvári krt. 62, Hungary; email: szebeni.gabor@brc.hu Funding details: GINOP-2.3.2-15-2016-00001, GINOP-2.3.2-15-2016-00030 Funding details: National Research, Development and Innovation Office, 1000464, KDP-17-4/PALY-2021 Funding text 1: This research was supported by the following grants: 2020-1.1.6-J?V?-2021-00003 (BRC), 2017-1.3.1-VKE-2017-00028 (Avicor Ltd.), GINOP-2.3.2-15-2016-00030 (BRC), and GINOP-2.3.2-15-2016-00001 (BRC) by the National Research, Development, and Innovation Office, Hungary. This study was prepared with the professional support of the doctoral student scholarship program of the co-operative doctoral program of the Ministry of Innovation and Technology financed by the National Research, Development, and Innovation Fund for J?zsef ?. Balog (KDP-17-4/PALY-2021, 1000464). Funding text 2: Funding: This research was supported by the following grants: 2020-1.1.6-JÖVO˝ -2021-00003 (BRC), 2017-1.3.1-VKE-2017-00028 (Avicor Ltd.), GINOP-2.3.2-15-2016-00030 (BRC), and GINOP-2.3.2-15-2016-00001 (BRC) by the National Research, Development, and Innovation Office, Hungary. This study was prepared with the professional support of the doctoral student scholarship program of the co-operative doctoral program of the Ministry of Innovation and Technology financed by the National Research, Development, and Innovation Fund for József Á. Balog (KDP-17-4/PALY-2021, 1000464). LA - English DB - MTMT ER -