Valós idejű polimeráz láncreakció alkalmazása cytomegalovirus-fertőzés és -reaktiváció nyomon követésére malignus hematológiai betegségek kemoterápiás kezelése során és autológ őssejt-transzplantációt követően | Monitoring cytomegalovirus infection and reactivation using quantitative real-time polymerase chain reaction in patients with haematological malignancies during chemotherapy and after autologous stem cell transplantation

Absztrakt Bevezetés: A hematológiai betegek kemo-immun terápiás kezelése és az őssejt-transzplantáció során fellépő fertőzéses komplikációk egyikét képezi a cytomegalovirus-infekció és -reaktiváció. Célkitűzés: A szerzők célja a cytomegalovirus-fertőzés és -reaktiváció követése kvantitatív valós idejű polimeráz láncreakció módszerével. Módszer: A szerzők intézetében 2012–2014 között kezelt 96 beteg dokumentációját elemezték retrospektív vizsgálatban. A betegeket az alapbetegség szerint csoportosították (lymphoproliferativ betegségek, akut leukaemiák), valamint megkülönböztették aszerint, hogy történt-e autológ őssejt-transzplantáció vagy sem. Eredmények: Lymphoproliferativ betegség miatt kezeltek 83 beteget, közülük 63 (76%) részesült autológ őssejt-transzplantációban. A 604 plazmamintából 46 mintában (7,6%) igazolódott valós idejű polimeráz láncreakcióval cytomegalovirus-pozitivitás összesen 25 betegből (6 nem transzplantált [18%], 19 transzplantált [30,2%]). A valós idejű polimeráz láncreakcióval cytomegalovirus-pozitivitás kétszeres gyakorisággal fordult elő a transzplantált betegcsoportban, azonban 68%-ukban a reaktiváció tünetmentes volt és spontán oldódott. Következtetések: Rutinszerű cytomegalovirus-monitorozás nem szükséges a fenti betegcsoportban, azonban jól meghatározott betegcsoportban klinikai gyanú esetén elvégzett molekuláris teszt lehetővé teszi a korai preemptív kezelést, ezáltal csökkentve a mortalitást. Orv. Hetil., 2016, 157(35), 1403–1409. | Abstract Introduction: Because of the use of chemo-immunotherapeutic drugs, cytomegalovirus infection is one of the most important infectious complications among patients with haematological malignancies. Aim: The aim of the authors was to detect cytomegalovirus infection and reactivation using quantitative real-time polymerase chain reaction. Method: Between 2012 and 2014, the authors retrospectively analysed 96 patient’s medical history hospitalised in haematology Unit. Patients were grouped on the basis of their underlying diseases (lymphoprolipherative malignancies, acute leukaemias), and the following groups were created: autologous stem cell transplanted and non-transplanted groups. Results: Eighty-three patients were treated with lymphoprolipherative disorders, and 63 (76%) of them underwent autologous stem cell transplantation. Out of the 604 plasma specimens 46 (7.6%) were positive for the cytomegalovirus desoxyribonucleic acid collected from 25 patients [6 non-transplanted (18%) and 19 from the transplanted group (30.2%)]. The frequency of cytomegalovirus positivity was doubled in the transplanted patient group, however, reactivation was asymptomatic in 68% of the cases. Conclusions: The routine use of cytomegalovirus monitoring is not necessary in this patient group. In case of suspected cytomegalovirus infection, molecular tests allow early preemptive antiviral therapy, which may decrease the mortality attributed to cytomegalovirus infection. Orv. Hetil., 2016, 157(35), 1403–1409

Mobile platforms and multi-mobile platform development

Mobile devices and mobile applications have a significant effect on the present and on the future of the software industry. The diversity of mobile platforms necessitates the development of the same mobile application for all major mobile platforms, which requires considerable development effort. Mobile application developers are multiplatform developers, but they prioritize the platforms, therefore, not all platforms are equally important for them. Appropriate methods, processes and tools are required to support the development in order to achieve better productivity. The main motivation of our research activity is to provide a method, which increases the development productivity and the quality of the applications and also reduces the time to market. The paper discusses our model-driven results on the field of multi-mobile platform development

Genomic Landscape of Normal and Breast Cancer Tissues in a Hungarian Pilot Cohort

A limited number of studies have focused on the mutational landscape of breast cancer in different ethnic populations within Europe and compared the data with other ethnic groups and databases. We performed whole-genome sequencing of 63 samples from 29 Hungarian breast cancer patients. We validated a subset of the identified variants at the DNA level using the Illumina TruSight Oncology (TSO) 500 assay. Canonical breast-cancer-associated genes with pathogenic germline mutations were CHEK2 and ATM. Nearly all the observed germline mutations were as frequent in the Hungarian breast cancer cohort as in independent European populations. The majority of the detected somatic short variants were single-nucleotide polymorphisms (SNPs), and only 8% and 6% of them were deletions or insertions, respectively. The genes most frequently affected by somatic mutations were KMT2C (31%), MUC4 (34%), PIK3CA (18%), and TP53 (34%). Copy number alterations were most common in the NBN, RAD51C, BRIP1, and CDH1 genes. For many samples, the somatic mutational landscape was dominated by mutational processes associated with homologous recombination deficiency (HRD). Our study, as the first breast tumor/normal sequencing study in Hungary, revealed several aspects of the significantly mutated genes and mutational signatures, and some of the copy number variations and somatic fusion events. Multiple signs of HRD were detected, highlighting the value of the comprehensive genomic characterization of breast cancer patient populations

Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212

Chronic kidney disease (CKD) is a public health problem that increases the risk of cardiovascular morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction is a common cardiovascular complication of CKD. MicroRNA-212 (miR-212) has been demonstrated previously to be a crucial regulator of pathologic LVH in pressure-overload-induced heart failure via regulating the forkhead box O3 (FOXO3)/calcineurin/nuclear factor of activated T-cells (NFAT) pathway. Here we aimed to investigate whether miR-212 and its hypertrophy-associated targets including FOXO3, extracellular signal-regulated kinase 2 (ERK2), and AMP-activated protein kinase (AMPK) play a role in the development of HFpEF in CKD. CKD was induced by 5/6 nephrectomy in male Wistar rats. Echocardiography and histology revealed LVH, fibrosis, preserved systolic function, and diastolic dysfunction in the CKD group as compared to sham-operated animals eight and/or nine weeks later. Left ventricular miR-212 was significantly overexpressed in CKD. However, expressions of FOXO3, AMPK, and ERK2 failed to change significantly at the mRNA or protein level. The protein kinase B (AKT)/FOXO3 and AKT/mammalian target of rapamycin (mTOR) pathways are also proposed regulators of LVH induced by pressure-overload. Interestingly, phospho-AKT/total-AKT ratio was increased in CKD without significantly affecting phosphorylation of FOXO3 or mTOR. In summary, cardiac overexpression of miR-212 in CKD failed to affect its previously implicated hypertrophy-associated downstream targets. Thus, the molecular mechanism of the development of LVH in CKD seems to be independent of the FOXO3, ERK1/2, AMPK, and AKT/mTOR-mediated pathways indicating unique features in this form of LVH

Syntaxin 1: A Novel Robust Immunophenotypic Marker of Neuroendocrine Tumors

Considering the specific clinical management of neuroendocrine (NE) neoplasms (NENs), immunohistochemistry (IHC) is required to confirm their diagnosis. Nowadays, synaptophysin (SYP), chromogranin A (CHGA), and CD56 are the most frequently used NE immunohistochemical markers; however, their sensitivity and specificity are less than optimal. Syntaxin 1 (STX1) is a member of a membrane-integrated protein family involved in neuromediator release, and its expression has been reported to be restricted to neuronal and NE tissues. In this study, we evaluated STX1 as an immunohistochemical marker of NE differentiation. STX1, SYP, CHGA, and CD56 expression was analyzed in a diverse series of NE tumors (NETs), NE carcinomas (NECs), and non-NE tumors. All but one (64/65; 98%) NETs and all (54/54; 100%) NECs revealed STX1 positivity in at least 50% of the tumor cells. STX1 showed the highest sensitivity both in NETs (99%) and NECs (100%) compared to CHGA (98% and 91%), SYP (96% and 89%), and CD56 (70% and 93%), respectively. A wide variety of non-NE tumors were tested and found to be uniformly negative, yielding a perfect specificity. We established that STX1 is a robust NE marker with an outstanding sensitivity and specificity. Its expression is independent of the site and grade of the NENs

A Hősök tere kulturális földrajzi szempontú vizsgálata

Szakdolgozatomban a Millenniumi Emlékmű szobrainak fizikai és ideológiai szempontú változásait, és a Hősök terén zajló fontosabb eseményeket mutatom be a kulturális földrajz különböző kultúra-értelmezéseinek és a trialektika térelméletének segítségével. Bemutatom, hogy az ideológiák és a társadalom hogyan befolyásolják a szobrok változásait és a tér fejlődését, továbbá javaslatot teszek a Hősök tere fejlesztésére és jövőbeni használatára