| 1. |
- Biurrun, Idoia, et al.
(author)
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Benchmarking plant diversity of Palaearctic grasslands and other open habitats
- 2021
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In: Journal of Vegetation Science. - Oxford : John Wiley & Sons. - 1100-9233 .- 1654-1103. ; 32:4
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Journal article (peer-reviewed)abstract
- Journal of Vegetation Science published by John Wiley & Sons Ltd on behalf of International Association for Vegetation Science.Aims: Understanding fine-grain diversity patterns across large spatial extents is fundamental for macroecological research and biodiversity conservation. Using the GrassPlot database, we provide benchmarks of fine-grain richness values of Palaearctic open habitats for vascular plants, bryophytes, lichens and complete vegetation (i.e., the sum of the former three groups). Location: Palaearctic biogeographic realm. Methods: We used 126,524 plots of eight standard grain sizes from the GrassPlot database: 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 and 1,000 m2 and calculated the mean richness and standard deviations, as well as maximum, minimum, median, and first and third quartiles for each combination of grain size, taxonomic group, biome, region, vegetation type and phytosociological class. Results: Patterns of plant diversity in vegetation types and biomes differ across grain sizes and taxonomic groups. Overall, secondary (mostly semi-natural) grasslands and natural grasslands are the richest vegetation type. The open-access file ”GrassPlot Diversity Benchmarks” and the web tool “GrassPlot Diversity Explorer” are now available online (https://edgg.org/databases/GrasslandDiversityExplorer) and provide more insights into species richness patterns in the Palaearctic open habitats. Conclusions: The GrassPlot Diversity Benchmarks provide high-quality data on species richness in open habitat types across the Palaearctic. These benchmark data can be used in vegetation ecology, macroecology, biodiversity conservation and data quality checking. While the amount of data in the underlying GrassPlot database and their spatial coverage are smaller than in other extensive vegetation-plot databases, species recordings in GrassPlot are on average more complete, making it a valuable complementary data source in macroecology. © 2021 The Authors.
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| 2. |
- Dora, David, et al.
(author)
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Computed Tomography-Based Quantitative Texture Analysis and Gut Microbial Community Signatures Predict Survival in Non-Small Cell Lung Cancer
- 2023
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In: Cancers. - 2072-6694. ; 15:20
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Journal article (peer-reviewed)abstract
- This study aims to combine computed tomography (CT)-based texture analysis (QTA) and a microbiome-based biomarker signature to predict the overall survival (OS) of immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients by analyzing their CT scans (n = 129) and fecal microbiome (n = 58). One hundred and five continuous CT parameters were obtained, where principal component analysis (PCA) identified seven major components that explained 80% of the data variation. Shotgun metagenomics (MG) and ITS analysis were performed to reveal the abundance of bacterial and fungal species. The relative abundance of Bacteroides dorei and Parabacteroides distasonis was associated with long OS (>6 mo), whereas the bacteria Clostridium perfringens and Enterococcus faecium and the fungal taxa Cortinarius davemallochii, Helotiales, Chaetosphaeriales, and Tremellomycetes were associated with short OS (≤6 mo). Hymenoscyphus immutabilis and Clavulinopsis fusiformis were more abundant in patients with high (≥50%) PD-L1-expressing tumors, whereas Thelephoraceae and Lachnospiraceae bacterium were enriched in patients with ICI-related toxicities. An artificial intelligence (AI) approach based on extreme gradient boosting evaluated the associations between the outcomes and various clinicopathological parameters. AI identified MG signatures for patients with a favorable ICI response and high PD-L1 expression, with 84% and 79% accuracy, respectively. The combination of QTA parameters and MG had a positive predictive value of 90% for both therapeutic response and OS. According to our hypothesis, the QTA parameters and gut microbiome signatures can predict OS, the response to therapy, the PD-L1 expression, and toxicity in NSCLC patients treated with ICI, and a machine learning approach can combine these variables to create a reliable predictive model, as we suggest in this research.
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| 3. |
- Radeczky, Peter, et al.
(author)
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Bone-Specific Metastasis Pattern of Advanced-Stage Lung Adenocarcinoma According to the Localization of the Primary Tumor
- 2021
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In: Pathology and Oncology Research. - : Frontiers Media SA. - 1219-4956 .- 1532-2807. ; 27
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Journal article (peer-reviewed)abstract
- Background: Patients with advanced-stage lung adenocarcinoma (LADC) often develop distant metastases in the skeletal system. Yet, the bone-specific metastasis pattern is still controversial. We, therefore, aimed to examine how the primary tumor location affects bone specificity and survival in LADC patients diagnosed with skeletal metastases. Methods: In total, 209 bone-metastatic Caucasian LADC patients from two thoracic centers were included in this study. Focusing on the specific location of primary tumors and bone metastatic sites, clinicopathological variables were included in a common database and analyzed retrospectively. Skeletal metastases were diagnosed according to the contemporary diagnostic guidelines and confirmed by bone scintigraphy. Besides region- and side-specific localization, primary tumors were also classified as central or peripheral tumors based on their bronchoscopic visibility. Results: The most common sites for metastasis were the spine (n = 103) and the ribs (n = 60), followed by the pelvis (n = 36) and the femur (n = 22). Importantly, femoral (p = 0.022) and rib (p = 0.012) metastases were more frequently associated with peripheral tumors, whereas centrally located LADCs were associated with humeral metastases (p = 0.018). Moreover, we deduced that left-sided tumors give rise to skull metastases more often than right-sided primary tumors (p = 0.018). Of note, however, the localization of the primary tumor did not significantly influence the type of affected bones. Multivariate Cox regression analysis adjusted for clinical parameters demonstrated that central localization of the primary tumor was an independent negative prognostic factor for overall survival (OS). Additionally, as expected, both chemotherapy and bisphosphonate therapy conferred a significant benefit for OS. Conclusion: The present study demonstrates unique bone-specific metastasis patterns concerning primary tumor location. Peripherally located LADCs are associated with rib and femoral metastases and improved survival outcomes. Our findings might contribute to the development of individualized follow‐up strategies in bone-metastatic LADC patients and warrant further clinical investigations on a larger sample size.
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| 4. |
- Rozsas, Anita, et al.
(author)
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Erythropoietin Receptor Expression Is a Potential Prognostic Factor in Human Lung Adenocarcinoma
- 2013
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
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Journal article (peer-reviewed)abstract
- Recombinant human erythropoietins (rHuEPOs) are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR) signaling in human non-small cell lung cancer (NSCLC) also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC) and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPO alpha were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPO alpha with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC) proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPO alpha treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPO alpha significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPO alpha treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.
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| 5. |
- Berta, Judit, et al.
(author)
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Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.
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| 6. |
- Berta, Judit, et al.
(author)
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Thoracic irradiation as consolidation therapy in patients with extensive-stage small cell lung cancer
- 2023
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In: Current Opinion in Oncology. - 1040-8746. ; 35:1, s. 54-60
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Research review (peer-reviewed)abstract
- Purpose of reviewSmall cell lung cancer (SCLC) is marked by an exceptionally high proliferative rate and poor prognosis. Given its high propensity to metastasize, nearly two-thirds of SCLC patients are diagnosed with extensive-stage (ES) disease when surgery is not a treatment option anymore. Over several decades, only minimal changes have been made in the therapeutic armamentarium of ES-SCLC. Recently, however, several new therapeutic avenues were defined, thus renewing the hope for patients with this recalcitrant cancer. Here, we present an overview of the most current therapeutic advances in ES-SCLC focusing in particular on consolidative thoracic radiation therapy (cTRT) and chemo-immunotherapy.Recent findingsThe incorporation of immunotherapy in the standard-of-care of ES-SCLC patients and the resulting outcomes are both a remarkable hallmark of progress and a disappointment. Indeed, chemo-immunotherapy with or without cTRT and prophylactic cranial irradiation contributes to longer survival outcomes with minimal toxicity rates in well selected and properly monitored patients. Nevertheless, the gain in overall survival is still modest relative to that seen in many other solid tumors.SummaryDespite the encouraging results, further clinical trials are needed to determine the efficacy and safety of these therapeutic approaches, and moreover, to identify new predictive biomarkers of response.
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| 7. |
- Biswas, Dhruva, et al.
(author)
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A clonal expression biomarker associates with lung cancer mortality
- 2019
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:10, s. 1540-1548
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Journal article (peer-reviewed)abstract
- An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage(1). Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types(2-6). Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types.
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| 8. |
- Ferencz, Bence, et al.
(author)
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Comparative expression analysis of immune-related markers in surgically resected lung neuroendocrine neoplasms
- 2023
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In: Lung Cancer. - 0169-5002. ; 181
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Journal article (peer-reviewed)abstract
- Background: Although immunotherapy has led to a paradigm shift in the treatment of lung cancer, the therapeutic approaches for lung neuroendocrine neoplasms (LNENs) are still limited. Our aim was to explore the immunological landscape and the expression of immune checkpoint markers in LNENs. Methods: Surgically removed tumor samples of 26 atypical carcinoid (AC), 30 large cell neuroendocrine carcinoma (LCNEC) and 29 small cell lung cancer (SCLC) patients were included. The immune phenotype of each tumor type was assessed by using a panel of 15 immune-related markers. As these markers are potentially expressed by immune cells and/or tumor cells, they might serve as putative targets for immunotherapy. Expression patterns were measured by immunohistochemistry and correlated with clinicopathological parameters and prognosis. Results: Unsupervised hierarchical clustering revealed distinct immunologic profiles across tumor types. Specifically, AC tumors were characterized by high tumor cell CD40 expression and low levels of immune infiltrates whereas SCLC samples had a high CD47 and Inducible T Cell Costimulator (ICOS) expression in tumor cells and immune cells, respectively. High CD70 and CD137 expression by tumor cells as well as elevated expression of CD27, Lymphocyte Activation Gene 3 (LAG3), and CD40 by immune cells were characteristic for LCNEC samples. Overall, SCLC and LCNEC tumors had a more immunogenic phenotype than AC samples. High tumor cell CD47 and CD40 expressions were associated with impaired and improved survival outcomes, respectively. Conclusions: By providing insights into the widely divergent immunologic profiles of LNENs, our results might serve as a basis for the development of novel immunotherapy-related approaches in these devastating malignancies.
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| 9. |
- Gambadauro, Pietro, et al.
(author)
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Psychopathology is associated with reproductive health risk in European adolescents
- 2018
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In: Reproductive Health. - : BMC. - 1742-4755 .- 1742-4755. ; 15:1
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Journal article (peer-reviewed)abstract
- BackgroundReproductive and mental health are key domains of adolescent wellbeing but possible interrelationships are poorly understood. This cross-sectional study evaluated the association between psychopathology and reproductive health risk among European adolescents.MethodsA structured self-report questionnaire was delivered to 12,395 pupils of 179 randomly selected schools in 11 European countries within the EU funded Saving and Empowering Young Lives in Europe (SEYLE) project. The questionnaire included items about sexual initiation and reproductive health risk factors, such as number of sexual partners, frequency of condom use, and pregnancy involvement. Psychopathology was evaluated with validated instruments and/or ad-hoc questions.ResultsOf 11,406 respondents (median age 15; interquartile range [IQR] 14-15; 57% females), 18.8% reported sexual initiation. Sixty percent of them also reported at least one reproductive risk factor. Sexual initiation was significantly more common among pupils older than 15years (38% versus 13.2% younger pupils) and males (21.3% versus 16.9% females). It was also more common among pupils with depression (age/sex-adjusted odds ratio [aOR] 1.871), anxiety (aOR 2.190), severe suicidal ideation (aOR 2.259), self-injurious behaviour (aOR 2.892), and suicide attempts (aOR 3.091). These associations were particularly strong among pupils 15years old and, for overt psychopathology, among pupils with low non-sexual risk behaviour profile and females. Depression (aOR 1.937), anxiety (aOR 2.282), severe suicidal ideation (aOR 2.354), self-injurious behaviour (aOR 3.022), and suicide attempts (aOR 3.284) were associated with higher reproductive health risk, defined by an increasing number of coexisting reproductive risk factors.ConclusionsThese findings suggest an alignment between mental and reproductive health risk and support the value of cross-domain collaboration in adolescent health. The association between psychopathology and reproductive health risk, as well as its variations with age, sex, and associated risk behaviours, should be considered when designing health-promoting or disease-preventing interventions for adolescents.
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| 10. |
- Gambadauro, Pietro, et al.
(author)
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Serious and persistent suicidality among European sexual minority youth
- 2020
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
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Journal article (peer-reviewed)abstract
- BackgroundSuicide is a leading cause of death among adolescents and more knowledge from high risk groups is needed in order to develop effective preventive strategies. The aim of this study was to evaluate the association between sexual minority status and suicidality in a multinational sample of European school pupils.MethodsA self-report questionnaire was delivered to 2046 adolescents (mean age 15.34±1.01; 56.3% females) recruited from 27 randomly selected schools in 6 European countries. Suicidal ideation, measured with the Paykel Suicide Scale (PSS), and lifetime suicide attempts were compared between heterosexual and sexual minority (i.e. those with a non-heterosexual orientation) youth. Poisson regression analyses studied the longitudinal association between sexual minority status and the rate of serious suicidal ideation, measured at three time-points during a 4-month period. Several variables, including alcohol and illegal drugs use, bullying, family interaction, school-related stress, economic status, and religiosity, were included in multivariable analysis. Sex-stratified analyses evaluated the association respectively among females and males.ResultsOf 1958 pupils included in analysis (mean age 15.35±1.00; females 56.8%), 214 (10.9%) were categorized as sexual minority youth (SMY). When compared to heterosexual youth (HSY), SMY were significantly more exposed to substance abuse, bullying, school-related stress, and lower economic status. SMY pupils had significantly higher suicidal ideation scores (p<0.001; r 0.145) as well as higher prevalence of serious suicidal ideation (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.83–3.79) and previous suicide attempts (OR 2.72, 95%CI 1.77–4.18), compared to their HSY peers. The rate of serious suicidal ideation reports during the study was significantly higher among SMY compared to HSY (rate ratio [RR] 2.55, 95%CI 1.90–3.43). A significant difference was found even when controlling for the pupils’ country as well as after adjustment for alcohol and illegal drugs use, bullying, family interaction, school-related stress, economic status, and religiosity (adjusted RR 1.73, 95%CI 1.23–2.48). Stratified analyses showed significant associations between SMY status and persistent serious suicidal ideation for both sexes, with a notably strong association among male pupils (females aRR 1.51, 95%CI 1.01–2.24; males aRR 3.84, 95%CI 1.94–7.59).ConclusionsEuropean sexual minority youth are a high-risk group for suicidality, independently from objective factors such as victimization or substance abuse. There is a need to develop primary and secondary preventive measures for sexual minority youth, including the management of context vulnerabilities and related distal stressors, before the establishment of proximal stressors. Context-targeting interventions may effectively focus on social and economic factors, as well as on the potentially different risk profile of female and male sexual minority youth.
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