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Nearly half of the refugee and asylum seeking population in Europe is under the age of 18, and many of these individuals are unaccompanied children and adolescents.The aim of this systematic review is both to summarize findings regarding the prevalence of mental health disorders among unaccompanied refugee minors (URM) in European countries since the last available systematic review (October 2017), and to describe associated risk factors.Five databases were systematically searched for articles published between October 1, 2017 and May 1, 2022.The findings from 23 studies conducted in 9 countries which examined 80,651 child and adolescent URM are explained. Afghanistan was the most common country of origin in the majority of studies and75 % of the subjects were boys. Most of the studies (N = 13, 56.5 %) assessed posttraumatic stress disorder (PTSD) prevalence. We found a high prevalence of mental health disorders among URM children and adolescents, which varied considerably between studies, ranging from 4.6 % to 43 % for (PTSD), 2.9 % to 61.6 % for depression, 32.6 % to 38.2 % for anxiety and 4 to14.3 % for behavioral problems. Two studies looking at suicide attempts and deaths, also observed higher rates in URM compared to the host population of the same age. The studies looking at mental health risk factors suggest that levels of social support in the host country, rearing environment, and other factors are associated with psychopathology. Moreover, a meta-analysis of four studies regarding PTSD in URM and accompanied refugee minors (ARM) showed a lower prevalence among ARM: -1.14 (95%CI:-1.56-0.72).PTSD, depression and anxiety are the most prevalent problems among the URM population in Europe. Early intervention in host countries is needed in order to improve mental health outcomes for this vulnerable population and avoid possible neglect.

Objective:Hungary has one of the highest incidences and mortality rates of lung cancer (LC), therefore the objective of this study was to analyse and compare LC incidence and mortality rates between the main Hungarian regions.Methods:This nationwide, retrospective study used data from the National Health Insurance Fund and included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between Jan 1, 2011 and Dec 31, 2016. Age-standardized incidence and mortality rates were calculated and compared for the main regions.Results:The highest incidence rate in males was recorded in Northern Hungary (146.8/100,000 person-years [PY]), while the lowest rate was found in Western Transdanubia (94.7/100,000 PY in 2011). All rates showed a declining trend between 2011 and 2016, with the largest decrease in the Northern Great Plain (−20.0%;p= 0.008). LC incidence and mortality rates in women both showed a rising tendency in all regions of Hungary, reaching the highest in Central Hungary (59.86/100,000 PY in 2016). Lung cancer incidence and mortality rates in males correlated with the level of education and smoking prevalence (p= 0.006 andp= 0.01, respectively) in the regions. A correlation with GDP per capita and Health Development Index (HDI) index could also be observed in the Hungarian regions, although these associations were not statistically significant. No correlations could be detected between these parameters among females.Conclusion:This analysis revealed considerable differences in the epidemiology of LC between the 7 main Hungarian regions. LC incidence and mortality rates significantly correlated with smoking and certain socioeconomic factors in men, but not in women. Further research is needed to explain the regional differences.

Background: No assessment was conducted describing the age and gender specific epidemiology of lung cancer (LC) prior to 2018 in Hungary, thus the objective of this study was to appraise the detailed epidemiology of lung cancer (ICD-10 C34) in Hungary based on a retrospective analysis of the National Health Insurance Fund database.Methods: This longitudinal study included patients aged ≥20 years with LC diagnosis (ICD-10 C34) between 1th January 2011 and 31th December 2016. Patients with different cancer-related codes 6 months before or 12 months after LC diagnosis or having any anti-cancer treatment different from lung cancer protocols were excluded. Results: Lung cancer incidence and mortality increases with age, peaking in the 70–79 age group (375.0/100,000 person-years) among males, while at 60–69 age group for females (148.1/100,000 person-years). The male-to-female incidence rate ratio reached 2.46 to 3.01 (p60) annually during the study period.Conclusion: This nationwide epidemiology study demonstrated that LC incidence and mortality in Hungary is decreasing in younger male and female population, however we found significant increase of incidence in older female population, similar to international trends. Incidence rates peaked in younger age-groups compared to Western countries, most likely due to higher smoking prevalence in these cohorts, while lower age LC incidence could be attributed to higher competing cardiovascular risk resulting in earlier mortality in smoking population.

Objective: Lung cancer is one of the most common cancers worldwide and its survival is still poor. The objective of our study was to estimate long-term survival of Hungarian lung cancer patients at first time based on a nationwide review of the National Health Insurance Fund database.Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between January 1, 2011 and December 31, 2016. Survival rates were evaluated by year of diagnosis, patient gender and age, and morphology of lung cancer.Results: 41,854 newly diagnosed lung cancer patients were recorded. Mean age at diagnosis varied between 64.7 and 65.9 years during study period. One- and 5-year overall survival rates for the total population were 42.2 and 17.9%, respectively. Survival was statistically associated with gender, age and type of lung cancer. Female patients (n = 16,362) had 23% better survival (HR: 0.77, 95% confidence interval (CI): 0.75–0.79; p < 0.001) than males (n = 25,492). The highest survival rates were found in the 20–49 age cohort (5Y = 31.3%) and if the cancer type was adenocarcinoma (5Y = 20.5%). We measured 5.3% improvement (9.2% adjusted) in lung cancer survival comparing the period 2015–2016 to 2011–2012 (HR: 0.95 95% CI: 0.92–0.97; p = 0.003), the highest at females Conclusion: Our study provided long-term Lung cancer survival data in Hungary for the first time. We found a 5.3% improvement in 5-year survival in 4 years. Women and young patients had better survival. Survival rates were comparable to–and at the higher end of–rates registered in other East-Central European countries (7.7%–15.7%).

Genetic studies robustly implicate perturbation of DLG2-scaffolded mature postsynaptic signalling complexes in schizophrenia. Here we study in vitro cortical differentiation of DLG2 -/- human embryonic stem cells via integrated phenotypic, gene expression and disease genetic analyses. This uncovers a developmental role for DLG2 in the regulation of neural stem cell proliferation and adhesion, and the activation of transcriptional programs during early excitatory corticoneurogenesis. Down-regulation of these programs in DLG2 -/- lines delays expression of cell-type identity and causes marked deficits in neuronal migration, morphology and active properties. Genetic risk factors for neuropsychiatric and neurodevelopmental disorders converge on these neurogenic programs, each disorder displaying a distinct pattern of enrichment. These data unveil an intimate link between neurodevelopmental and mature signalling deficits contributing to disease - suggesting a dual role for known synaptic risk genes - and reveal a common pathophysiological framework for studying the neurodevelopmental origins of Mendelian and genetically complex mental disorders.

e21582 Background: Lung cancer is one of the most common cancers worldwide, however, 5-year survival is poor, only 10-20% of pataients survive this period. To date, no long-term study has been conducted to evaluate long-term survival rates in Hungary. Therefore, the objective of our study was to assess the 6-year survival of lung cancer patients (ICD-10 C34) based on a nationwide review of the National Health Insurance Fund (NHIF) database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between 1 January 2011 and 31 December 2016. Screening period was set for 2009-2010. Patients with other cancer-related ICD-10 codes 6 months before or 12 months after lung cancer diagnosis and those who received any anticancer treatment different from lung cancer protocols were excluded. Survival rates were evaluated according to year of diagnosis, patient gender and age, and morphology of lung cancer and main treatment type. Results: 41,854 newly diagnosed lung cancer patients were recorded. Mean age at diagnosis varied between 64.66 and 65.88 years during study period. One- and 5-year crude survival rates for the total population were 42.23% and 17.85%, respectively. Survival was significantly associated with gender, age and type of lung cancer based on statistical association. Female patients (n = 16,362) had 23% better survival (HR: 0.77 CI95% 0.75-0.79; p < 0.001) than males (n = 25,492). The highest survival rates were found in the 20–49 age cohort (5Y = 31.3%) and if the cancer type was adenocarcinoma (5Y = 20.48%). We measured 5.3 % improvement in lung cancer survival between cases diagnosed in 2015-2016 vs. 2011-2012 (HR: 0.947 CI95% 0.92-0.97; p = 0.003). Survival of those lung cancer patients, whom had surgery in first line treatment without adjuvant therapy (3,120) reached 64.18%, those with adjuvant treatment (n = 2,675) 54.47% 5 year survival, while patients with chemotherapy (n = 11,780) had only 7.9% crude survival. Conclusions: Our study provided long-term LC survival data in Hungary for the first time. We found a 6% improvement in survival by the end of the study period in females and in the younger age groups. Survival rates were comparable to – and at the higher end of – rates registered in other East-Central European countries. Better survival rate of females could be attributed to a higher incidence rate of adenocarcinoma in women. Lung cancer patients diagnosed in early stage had 7-8 times better survival than those found in late stage.

Oil pipelines and gas pipelines operations result in very different pressure fluctuation schemes due to different compressive properties of liquids and gases. Liquid fluids such as oil are less compressible and pressure fluctuations during oil pipelines operations are more frequent and vary over a wide range of magnitudes and frequencies, compared with those during gas pipelines operations. Despite the differences in operating conditions indicated above, both oil pipelines and gas pipelines are susceptible to stress corrosion cracking and corrosion fatigue failures. This investigation was initiated to understand the different crack growth rate behavior of pipeline steels characteristic to the type of pressure fluctuation schemes in near-neutral pH environment, that is, oil pipelines vs. gas pipelines. It was suspected that the similar range of service life between oil pipeline steels and gas pipeline steels could be attributed to a higher rate of direct dissolution at the tip of a crack during gas pipeline operation because of much higher mean pressures, despite their lower crack growth caused by corrosion fatigue. In the case of near-neutral pH stress corrosion cracking, corrosion makes minor contribution to crack growth but produces diffusible hydrogen that interacts with cyclic loading to make cracks grow. This study was performed using specimens with surface cracks, which simulated the following two environmental conditions: 1) fully exposed to the environment, 2) shielded from the environment, exposed to hydrogen only. In Case 1), the specimen surface, on which the surface cracks were made, was fully exposed to a near-neutral pH solution, allowing the occurrence of corrosion at the crack tip. In Case 2), a narrow strip of a coating was applied to prevent the cracks from direct contact with the corrosive solution; however, the cracks were affected by diffusible hydrogen which had been generated as a by-product of corrosion on the adjacent steel surface free of coatings. These specimens were mechanically loaded under different pressure schemes typical of both oil and gas pipeline operations. It has been found that crack growth caused by direct dissolution of crack tip materials is insignificant, regardless of pipeline operating conditions. A much higher crack growth rate, attributed to hydrogen embrittlement, was found under gas transmission conditions, while a higher corrosion fatigue crack growth was found under oil transmission conditions. Based on these findings, strategies on crack growth mitigation, characteristic to each type of pipeline operation are also proposed.

Background The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV. Results ChIP-Seq high throughput sequencing of HBx-bound fragments was used to obtain a high-resolution, unbiased, mapping of HBx binding sites across the genome in HBV replicating cells. Protein-coding genes and ncRNAs involved in cell metabolism, chromatin dynamics and cancer were enriched among HBx targets together with genes/ncRNAs known to modulate HBV replication. The direct transcriptional activation of genes/miRNAs that potentiate endocytosis (Ras-related in brain (RAB) GTPase family) and autophagy (autophagy related (ATG) genes, beclin-1, miR-33a) and the transcriptional repression of microRNAs (miR-138, miR-224, miR-576, miR-596) that directly target the HBV pgRNA and would inhibit HBV replication, contribute to HBx-mediated increase of HBV replication. Conclusions Our ChIP-Seq analysis of HBx genome wide chromatin recruitment defined the repertoire of genes and ncRNAs directly targeted by HBx and led to the identification of new mechanisms by which HBx positively regulates cccDNA transcription and HBV replication. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-3561-5) contains supplementary material, which is available to authorized users.

HBx ChIP-Seq experiments analysis. Figure S2. HBx occupancy on cellular promoters. Figure S3. HBx occupancy on the control RFP2 promoter. Figure S4. HBx occupancy on cellular promoters in NTCP-HepG2 cells infected with wild-type and mt-HBx HBV. Figure S5. HBx occupancy on miRNAs promoters in NTCP-HepG2 cells and PHHs infected with HBV-wt virus. Figure S6. ChIP validation of high P value HBx peak. Figure S7. HBx targeted miRNAs expression in HBV-infected Primary Human Hepatocytes. Table S1. Rab family and ATG family. Table S2. HBx targeted miRNAs functions (PubMed). Table S3. TF binding sites overlapping HBx peaks (Genomatix MatInspector). Table S4. miRNAs that activate or repress HBV replication HBV replication. Table S5. miRNA seeds predicted in HBV pgRNA sequence and conserved across HBV genotypes. Table S6. List of primers used thoughout the manuscript. (PDF 647 kb)

Constitutive NF ?B signaling promotes survival in multiple myeloma (MM) and other cancers; however current NF ?B targeting strategies lack cancer cell specificity. Here we identify the interaction between the NF ?B regulated antiapoptotic factor GADD45ß and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug discovery strategy we developed DTP3 a D tripeptide which disrupts the GADD45ß/MKK7 complex kills MM cells effectively and importantly lacks toxicity to normal cells. DTP3 has similar anticancer potency to the clinical standard bortezomib but more than 100 fold higher cancer cell specificity in vitro. Notably DTP3 ablates myeloma xenografts in mice with no apparent side effects at the effective doses. Hence cancer selective targeting of the NF ?B pathway is possible and at least for myeloma patients promises a profound benefit.