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Introduction
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January 2015 - present
Publications
Publications (120)
Motivation
Identifying disease modules within molecular interaction networks is an essential exploratory step in computational biology, offering insights into disease mechanisms and potential therapeutic targets. Traditional methods often struggle with the inherent complexity and overlapping nature of biological networks, and they are limited in ef...
The heterogeneity and complexity of symptom presentation, comorbidities and genetic factors pose challenges to the identification of biological mechanisms underlying complex diseases. Current approaches used to identify biological subtypes of major depressive disorder (MDD) mainly focus on clinical characteristics that cannot be linked to specific...
We present a male patient carrying a pathogenic MECP2 p. Arg179Trp variant with predominant negative psychiatric features and multilevel evidence of mitochondrial dysfunction who responded to the cariprazine treatment. He had delayed speech development and later experienced severe social anxiety, learning disabilities, cognitive slowing, and predom...
Depression is a highly prevalent and debilitating condition, yet we still lack both in-depth knowledge concerning its etiopathology and sufficiently efficacious treatment options. With approximately one third of patients resistant to currently available antidepressants there is a pressing need for a better understanding of depression, identifying s...
Background:
Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-...
Background
Comprehensive management of multimorbidity can significantly benefit from advanced health risk assessment tools that facilitate value-based interventions, allowing for the assessment and prediction of disease progression. Our study proposes a novel methodology, the Multimorbidity-Adjusted Disability Score (MADS), which integrates disease...
In the EU project TRAJECTOME, we used a novel methodology to identify temporal disease maps of depression and highly prevalent co-occurring disease conditions. This information was combined with disability weights established by the Global Burden of Disease Study 2019 to create a depression-related health risk assessment tool, the Multimorbidity Ad...
The heterogeneity and complexity of symptom presentation, comorbidities and genetic factors pose challenges to the identification of biological mechanisms underlying complex diseases. Current approaches used to identify biological subtypes of major depressive disorder (MDD) mainly focus on clinical characteristics that cannot be linked to specific...
Background
Minimal residual disease (MRD) is one of the most valuable independent prognostic factors in acute lymphoblastic leukemia (ALL). Bone marrow (BM) aspiration, however, is an invasive process. Previous studies have shown that microRNAs (miR) and extracellular vesicle (EV)-related miRs show different expression profiles at the presence of m...
Health(span)-related gene clusters/modules were recently identified based on knowledge about the cross-species genetic basis of health, to interpret transcriptomic datasets describing health-related interventions. However, the cross-species comparison of health-related observations reveals a lot of heterogeneity, not least due to widely varying hea...
Introduction
Early-onset dementias (EOD) are predominantly genetically determined, but the underlying disease-causing alterations are often unknown. The most frequent forms of EODs are early-onset Alzheimer’s disease (EOAD) and frontotemporal dementia (FTD).
Patients
This study included 120 Hungarian patients with EOD (48 familial and 72 sporadic)...
Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and pr...
A kiskorú betegek életvégi dilemmái a legnehezebb döntések egyikét jelentik. A technológia fejlődésének köszönhetően jelentősen javult a koraszülöttek túlélési esélye. Magyarországon a jelenleg hatályos jogi szabályozásban azonban nem jelenik meg szempontként a kiskorúak életminősége. Közleményünk célkitűzése, hogy összehasonlítsa a neonatológi...
Összefoglaló. Manapság, a COVID-19-járvány közepette, a megfelelő kézmosás segít megelőzni vagy legalábbis lassítani a fertőző betegségek, például a SARS-CoV-2-fertőzés terjedését. A kézmosás rutinjának megfelelő oktatás multilaterális tevékenységet igényel, amely a fiatalok ismeretén, egészségmagatartásán, attitűdjein, tapasztalatain és motivációj...
Összefoglaló. A fejlett társadalmak egészségügyi rendszereinek legnagyobb kihívását az öregedéssel összefüggő, korfüggő betegségek jelentik. Annak megértéséhez, hogy az egyes genetikai variánsoknak mi a szerepük egy korfüggő betegség kialakulásában, meg kell ismerkednünk magával az öregedési folyamattal, az egészséges hosszú élettel asszociált, val...
Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were ge...
Health(span)-related gene clusters/modules were recently identified based on knowledge about the cross-species genetic basis of health, to interpret transcriptomic datasets describing health-related interventions. However, the cross-species comparison of health-related observations reveals a lot of heterogeneity, not least due to widely varying hea...
There is increasing evidence that several mitochondrial abnormalities are present in the brains of patients with Alzheimer’s disease (AD). Decreased alpha-ketoglutarate dehydrogenase complex (αKGDHc) activity was identified in some patients with AD. The αKGDHc is a key enzyme in the Krebs cycle. This enzyme is very sensitive to the harmful effect o...
Extracellular vesicles (EV) are considered as a promising diagnostic tool for pancreatic ductal adenocarcinoma (PDAC), a disease with a poor 5-year survival that has not improved in the past years. PDAC patient-derived 3D organoids maintain the intratumoral cellular heterogeneity, characteristic for the tumor in vivo.Thus, they represent an ideal i...
Aims
Asparaginase (ASP) hypersensitivity is a well‐known challenge in the treatment of lymphoblastic malignancies. In terms of cost considerations, the cheap native Escherichia coli ASP, the most immunogenic form of this medication, is used in the first line in middle‐income countries. Previously, the role of the HLA‐DRB1*07:01–DQA1*02:01–DQB1*02:0...
Purpose
Proper handwashing helps prevent the spread of communicable diseases. The aim of our study was to analyse and compare children's knowledge and skills in hand hygiene before and after school interventions in order to evaluate the effectiveness of our peer education programme.
Materials/methods
In our longitudinal study, short- and long-term...
Background
In the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding RNAs (lncRNAs) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases.
Methods
In the discovery cohort, the gene expression level...
Context
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Five-year survival rate is nearly 90%. Measurement of minimal residual disease (MRD) at set time points has become a fundamental part of stratified treatment in ALL. Treatment response is assessed using bone marrow samples. Exosomal microRNAs are putative biomarkers...
Context
Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. In order to further improve results, gaining a better understanding of its complications is needed. Central nervous system (CNS) is an important site of relapse in ALL. In this study, the incidence of CNS relapse (REL) was investigated.
Objective
CNS-REL...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
[This corrects the article DOI: 10.3389/fgene.2020.00128.].
Background:
Refractory central nervous system (CNS) involvement is among the major causes of therapy failure in childhood acute leukemia. Applying contemporary diagnostic methods, CNS disease is often underdiagnosed. To explore more sensitive and less invasive CNS status indicators, we examined microRNA (miR) expressions and extracellular vesicle...
Background:
Severe asthma (SA) database was established in Hungary to estimate the prevalence of SA and to define and analyze clinical phenotypes of the patients.
Methods:
SA questionnaires were sent out to 143 public pulmonary dispensaries specialized for diagnosing and caring pulmonary patients. Data of 520 SA patients were evaluated.
Results...
Absztrakt
A nukleárisan kódolt POLG -gén fehérjeterméke kulcsszerepet játszik a mitokondriális DNS replikációjának fenntartásában, és hibája különböző súlyosságú, több szervrendszert érintő betegségeket okoz. A klinikai spektrum rendkívül tág, a leggyakrabban előforduló tünetek közé tartozik többek között a ptosis, a myoclonus, az epilepszia, a myo...
A flow cytometry-based method was developed to quantify in vivo circulating neutrophil extracellular trap (NET) levels in plasma and compare them in patients with different chronic inflammatory lung diseases. Seventeen asthmatic and 11 control children, 12 adult controls, 46 asthmatic, 6 COPD and 6 adult patients with asthma-COPD overlap syndrome (...
Tie2, coded by the TEK gene, is a tyrosine kinase receptor and plays a central role in vascular stability. It was suggested that variations in the TEK gene might influence the susceptibility to asthma and allergic conjunctivitis. The aim of this study was to further investigate these suggestions, involving different populations and to study the Tie...
The paper introduces the multidisciplinary HUNIC project, which is partly based on the EURONIC study. The objective of the HUNIC study is to assess the attitude and opinion of healthcare providers in Hungarian NICUs about end-of-life decisions, the decision-making process, parental communication, to analyse the differences between HUNIC results in...
Background:
Treatment stratification based on bone marrow minimal residual disease (MRD) at set time points has resulted in considerably improved survival in pediatric acute lymphoblastic leukemia (ALL). Treatment response is assessed using bone marrow samples. MicroRNAs (miRs) easily traffic among fluid spaces and are more stable than most other...
The genetic analysis of early-onset Parkinsonian disorder (EOPD) is part of the clinical diagnostics. Several genes have been implicated in the genetic background of Parkinsonism, which is clinically indistinguishable from idiopathic Parkinson’s disease. The identification of patient’s genotype could support clinical decision-making process and als...
Pediatric acute lymphoblastic leukemia (ALL) has a favorable prognosis thanks to the combined chemotherapy, however,
relapsed disease and serious adverse effects caused by the treatment
still needs to take in consideration. Objective: We focused on the
central nervous system (CNS) in pediatric ALL investigating relapsed
ALL recurring in the CNS and...
Background
Autism spectrum disorder (ASD) is genetically and phenotypically heterogeneous. Former genetic studies suggested that both common and rare genetic variants play a role in the etiology. In this study, we aimed to analyze rare variants detected by next generation sequencing (NGS) in an autism cohort from Hungary.
Methods
We investigated t...
Number of variants in the investigated genes. Table summarizes the number of different variant types, detected in the investigated genes. Table only includes rare variants, as defined in the Section “Materials and Methods.” n/a, not applicable. Next generation sequencing is not suitable for detection of repeat expansion events. Repeat expansions we...
Extracellular vesicles (EVs) are membrane-enclosed structures secreted by cells. In the past decade, EVs have attracted substantial attention as carriers of complex intercellular information. They have been implicated in a wide variety of biological processes in health and disease. They are also considered to hold promise for future diagnostics and...
Background:
The etiology of autism spectrum disorders (ASD) is very heterogeneous. Mitochondrial dysfunction has been described in ASD; however, primary mitochondrial disease has been genetically proven in a small subset of patients. The main goal of the present study was to investigate correlations between mitochondrial DNA (mtDNA) changes and al...
Background: NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The core features are various movement disorders, characteristically chorea, less frequently myoclonus, dystonia, ataxia; thyroid disease; and lung involvement. The full triad is present in...
Genes represented on commercial dystonia panels.
Neurological examination of patient II/2.
Neurological examination of patient III/1.
Background:
The treatment of acute lymphoblastic leukemia (ALL) and osteosarcoma (OSC) is very effective: the vast majority of patients recover and survive for decades. However, they still need to face serious adverse effects of chemotherapy. One of these is cardiotoxicity which may lead to progressive heart failure in the long term. Cardiotoxicit...
Next generation sequencing (NGS) technologies reshape the diagnostics of rare neurological diseases. In the background of certain neurological symptoms, such as ataxia, many acquired and genetic causes may be present. Variations in a given gene can present with variable phenotypes, too. Because of this phenomenon, the conventional one gene sequenci...
The Tie2 receptor is an important player in angiogenesis. The Tie2 mRNA and protein are abundantly expressed in the lungs and the associated pathway also has an important role in the development and function of the eye. Tie2 is encoded by the TEK gene in humans. Recently, variations in the TEK gene have been found associated with asthma. The object...
During the last decades, the prevalence of allergy has dramatically increased. Allergen-specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease, but there are still many questions and unmet needs hindering its widespread use to fulfill its treatment potential and...
BRAF inhibitor vemurafenib achieved improved overall survival over chemotherapy and have been approved by the FDA and EMA for the treatment of BRAF-mutated metastatic melanoma. The aim of our retrospective analysis was to determine the efficacy and safety of vemurafenib therapy for BRAF mutated metastatic melanoma and subsequently to prove the clin...
Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to Escherichia coli-derived asparaginase in pediatric acute lymphoblastic leukemia patients. The aim of the present study was to identify associations between sequence-based Human Leukocyte Antigen Class II region alleles and asparaginase hypersensitivity in a Hungaria...
Dabrafenib is a potent BRAF inhibitor, which showed intracranial tumor activity. The purpose of our retrospective analysis was to evaluate the efficacy of dabrafenib for patients with melanoma brain metastasis (BM). We studied 30 BRAF mutant melanoma patients with BM, who received dabrafenib after local control of the brain between 2014 and 2017. E...
Purpose:
Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes.
Methods:
The levels of gene expressions of the members of the Hippo/YAP1 were compared. Th...
Verification of Bayesian results by logistic regression regarding exercise-induced asthma and rs9671722 as variables, and allergic rhinitis as a target variable
Diagram showing a significant difference in the haplotype ACGTCAC of SNPs rs1820453, rs7106388, rs10895257, rs1426398, rs11225138, rs1426394, and rs948737 of YAP1 between the mild (GINA 2) and moderate (GINA 3) asthma severity groups. SNP, single nucleotide polymorphism; GINA, Global Initiative for Asthma.
Summary of all SNPs included in the BN-BMLA statistical analysis
YAP1 haplotypes which showed the association with asthma severity
(A) Pie chart of SNP rs2846836 in the non-exercise- and exercise-induced asthma groups; P=0.004, OR=2.01 (1.26-3.43). (B) Pie chart of SNP rs11225138 in the mild and moderate-to-severe asthma groups: P=0.003, OR=2.80 (1.40-5.57). The percentages were calculated from case numbers. SNP, single nucleotide polymorphism; OR, odds ratio.
Dendrogram of the subsets of strongly relevant variables with respect to allergic rhinitis. The nodes in the dendrogram represent strongly relevant subsets of all variables, and the arrows denote the broadening of the subsets. The numbers in the nodes show the a posteriori probability that all variables in a given subset are strongly relevant.
Western blot analysis of YAP1 and GAPDH proteins. HeLa, HeLa cell extract.
Inter-individual differences in toxic symptoms and pharmacokinetics of high-dose methotrexate (MTX) treatment may be caused by genetic variants in the MTX pathway. Correlations between polymorphisms and pharmacokinetic parameters and the occurrence of hepato- and myelotoxicity were studied. Single nucleotide polymorphisms (SNPs) of the ABCB1, ABCC1...
Anthracyclines constitute a fundamental part of the chemotherapy regimens utilized to treat a number of different malignancies both in pediatric and adult patients. These drugs are one of the most efficacious anticancer agents ever invented. On the other hand, anthracyclines are cardiotoxic. Childhood cancer survivors treated with anthracyclines of...
Background/aim:
The frequency of brain metastasis (BM) is up to 45-50% in patients with advanced melanoma. Our aim was to identify the risk factors for the early occurrence of BM.
Patients and methods:
A total of 333 patients with BM were identified from our database of 2,972 patients with melanoma between 2003-2015.
Results:
The median elapse...
The low concordance between different variant calling methods still poses a challenge for the wide-spread application of next-generation sequencing in research and clinical practice. A wide range of variant annotations can be used for filtering call sets in order to improve the precision of the variant calls, but the choice of the appropriate filte...
L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data co...
Purpose
Based on a previous gene expression study in a mouse model of asthma, we selected 60 candidate genes and investigated their possible roles in human asthma.
Methods
In these candidate genes, 90 SNPs were genotyped using MassARRAY technology from 311 asthmatic children and 360 healthy controls of the Hungarian (Caucasian) population. Moreove...
CYP3A4 has an important role in the metabolisms of many drugs used in acute lymphoblastic leukemia (ALL) therapy; still, there are practically no publications about the role of CYP3A4 polymorphisms in ALL pharmacogenomics. We genotyped eight common single-nucleotide polymorphisms (SNPs) in the CYP3A4 and CYP3A5 genes in 511 children with ALL and in...