98 research outputs found
Integrating environmental and socio-economic indicators to explore the sustainability of food patterns and food security in Lebanon
Abstract Food security is a complex issue whose comprehension requires multidisciplinary research exploring environmental, socio-economic, and policy aspects. World population is expected to continue increasing in the next decades. As a consequence, the global food demand is also expected to increase, exacerbating the contribution of food consumption and production patterns to environmental problems and climate change. In addition, the problem of socio-economic inequalities is also noteworthy, with a very high number of undernourished people at global level. Considering the complex nature of food security, the integration of environmental and socio-economic indicators is much needed for assessing its multiple dimensions. In this study, environmental and socio-economic indicators were assessed to explore the sustainability of food patterns and food security in Lebanon. Environmental indicators were calculated to assess the environmental costs and impacts of the Lebanese and refugee diets. All the environmental indicators calculated for the Lebanese diet resulted higher compared to the refugee diet. The overall contribution of the refugee diet to the investigated impact categories resulted in about 25%, confirming its significance in terms of direct and indirect natural resources consumption and environmental impacts. The socio-economic indicators showed that food security is a critical issue for the Lebanese population and, particularly, for the refugees living in Lebanon. In particular, 59% and 15% of Lebanese and refugee populations resulted having an adequate individual access to food. In conclusion, the outcomes of the study provide scientific information to support policy-makers and a benchmark for future studies aimed at improving food security in Lebanon
Biochar addition in the anaerobic digestion of the organic fraction of municipal solid waste for biogas production
The continuous decline of fossil fuel availability and the ever increasing concern about environmental pollution, expressed by scientists, governments and public at large, are stimulating the research on renewable energy production. In this perspective, anaerobic digestion (AD) of the organic fraction of municipal solid waste (OFMSW) is recently meeting with increasing interest. It is a process viable both from an economic and technological standpoints, capable to combine the environmental friendly re-cycle of large amount of OFMSW combined to the production of methane, an excellent fossil-based fuels substitute (Chatterjee and Mazumder, 2016).
Please click on the file below for full content of the abstract
On the Emergy accounting for the evaluation of road transport systems: an Italian case study
Road transportation is one of the most polluting as well as energy-intensive sectors, and requires planning policies capable to address at the same time several different environmental, social, and economic issues. Cost-benefit analyses are generally carried out with a major focus on fuelling and driving efficiency, whereas a systemic approach appears to be needed for a more comprehensive evaluation of the alternatives that may become available to address any issue, be it intended for either short-term or long-term spans. For instance, building up a new infrastructure might allow for savings in time or fuel per km, but this may require an equivalent or even higher socio-environmental investment. In this work, a short review is presented of some systemic studies on transportation that use the emergy synthesis methodology. A case study is also addressed, concerning recent important expansion works on the Apennine Mountains section of the Italian major highway A1. In particular, the analysis points out the role of time saving, since for a new or renewed transport infrastructure (and when comparing for example road to rail transport) saved time is likely to become crucial in justifying civil enterprises. Nevertheless, the present emergy synthesis and the teaching of H.T. Odum (Odum & Odum, 2001) warn us that such “luxury” highly depends on the abundance of available energy, which is less and less given for granted, whereas a systemic analysis approach may indicate different levels of criticality when oriented towards environmental and well-being issues
Genetics and molecular epidemiology of multiple myeloma : the rationale for the IMMEnSE consortium (review)
There is strong evidence suggesting the presence of a genetic component in the aetiology of multiple myeloma (MM). However no genetic risk factors have been unequivocally established so far. To further our understanding of the genetic determinants of MM risk, a promising strategy is to collect a large set of patients in a consortium, as successfully done for other cancers. In this article, we review the main findings in the genetic susceptibility and pharmacogenetics of MM and present the strategy of the IMMEnSE (International Multiple Myeloma rESEarch) consortium in contributing to determine the role of genetic variation in pharmacogenetics and in MM risk.We acknowledge support by the recruiting hospitals and physicians of the study regions as well as their collaborating nurses and technicians. Collection of blood samples from Spain, patients from Granada area and DNA extraction was partially supported by grants P08-CVI-4116 from Consejeria de Salud de la Junta de Andalucia (Sevilla, Spain) and PI081051 from Fondo de Investigaciones Sanitarias (Madrid, Spain). Collection of blood samples from Polish patients and controls from Lodz area and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. N N402178334)
A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients: results from the IMMEnSE consortium and meta-analysis
Diabetogenic single nucleotide polymorphisms (SNPs) have recently been associated with multiple myeloma (MM) risk but their impact on overall survival (OS) of MM patients has not been analysed yet. In order to investigate the impact of 58 GWAS-identified variants for type 2 diabetes (T2D) on OS of patients with MM, we analysed genotyping data of 936 MM patients collected by the International Multiple Myeloma rESEarch (IMMENSE) consortium and an independent set of 700 MM patients recruited by the University Clinic of Heidelberg. A meta-analysis of the cox regression results of the two sets showed that rs7501939 located in the HNF1B gene negatively impacted OS (HRRec = 1.44, 95% CI = 1.18-1.76, P = 0.0001). The meta-analysis also showed a noteworthy gender-specific association of the SLC30A8(rs13266634) SNP with OS. The presence of each additional copy of the minor allele at rs13266634 was associated with poor OS in men whereas no association was seen in women (HRMen-Add = 1.32, 95% CI 1.13-1.54, P = 0.0003). In conclusion, these data suggest that the HNF1B(rs7501939) SNP confers poor OS in patients with MM and that a SNP in SLC30A8 affect OS in men.This work was supported by grants from the FIBAO foundation (Granada, Spain), from the CRIS foundation against cancer, from the Cancer Network of Excellence (RD12/10 Red de Cáncer), from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688) and from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS [01ZX1309]).FIBAO
foundation (Granada, Spain), from
the
CRIS foundation
against cancer, from the Cancer Network of Excellence
(RD12/10 Red de Cáncer), from the Instituto de Salud
Carlos III (Madrid, Spain; PI12/02688) and from the
Dietmar Hopp Foundation and the German Ministry
of Education and Science (BMBF: CLIOMMICS
[01ZX1309]info:eu-repo/semantics/publishedVersio
Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium
Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case–control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32–2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76–0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10-06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.This work was supported by grants from the FIBAO foundation (Granada, Spain) and the CRIS foundation against cancer, from the Cancer Network of Excellence (RD12/10 Red de Cancer) and from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688)
Identification of miRSNPs associated with the risk of multiple myeloma
Accepted articleMultiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression. MiRSNPs are known to be associated with risk of various types of cancer, but they have never been investigated in MM. We performed an in silico genome-wide search for miRSNPs predicted to alter binding of miRNAs to their target sequences. We selected 12 miRSNPs and tested their association with MM risk. Our study population consisted of 1,832 controls and 2,894 MM cases recruited from seven European countries and Israel in the context of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this population two SNPs showed an association with p<0.05: rs286595 (located in gene MRLP22) and rs14191881 (located in gene TCF19). Results from IMMEnSE were meta-analyzed with data from a previously published genome-wide association study (GWAS). The SNPs rs13409 (located in the 3UTR of the POU5F1 gene), rs1419881 (TCF19), rs1049633, rs1049623 (both in DDR1) showed significant associations with MM risk. In conclusion, we sought to identify genetic polymorphisms associated with MM risk starting from genome-wide prediction of miRSNPs. For some mirSNPs, we have shown promising associations with MM risk.
What's new? Even though deregulation of miRNA expression has been associated with human cancers little information is available regarding their relation with MM susceptibility. We performed an in silico genome-wide search for miRSNPs and selected the most promising ones for an association study. The SNPs with the strongest associations with MM risk are localized in genes which have never been related with MM.This work was partially funded by: intramural funds of German Cancer
Research Center (DKFZ), Grant ref. HUS412A1271 from
the “Gerencia Regional de Salud de la Junta de Castilla y Léon”. This work was supported by grants from the Instituto de Salud Carlos III
(Madrid, Spain; PI12/02688). Catalan Government DURSI grant 2014SGR647 and Instituto de Salud Carlos III, co7funded by FEDER funds –a way to build Europe– grants PI11701439 and PIE13/00022info:eu-repo/semantics/publishedVersio
Polymorphisms within autophagy-related genes as susceptibility biomarkers for multiple myeloma: a meta-analysis of three large cohorts and functional characterization
Functional data used in this project have been meticulously catalogued and archived in the BBMRI-NL data infrastructure (https://hfgp.bbmri.nl/, accessed on 12 February 2020) using the MOLGENIS open-source platform for scientific data.Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the
bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains,
resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a
dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development,
but also ensuring MM cell survival and promoting resistance to treatments. To date no studies
have determined the impact of genetic variation in autophagy-related genes on MM risk. We
performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and
6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms
(SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear
cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy
donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46,
IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14).
Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations
of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of
transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte
hemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP corre lated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+ IgD− cells, IgM− cells, IgD−IgM−
cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4
) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels
of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4
). These results suggest that genetic variants within
these six loci influence MM risk through the modulation of specific subsets of immune cells, as well
as vitamin D3−, MCP-2−, and IL20-dependent pathways.This work was supported by the European Union’s Horizon 2020 research and innovation program, N° 856620 and by grants from the Instituto de Salud Carlos III and FEDER (Madrid, Spain; PI17/02256 and PI20/01845), Consejería de Transformación Económica, Industria, Conocimiento y Universidades and FEDER (PY20/01282), from the CRIS foundation against cancer, from the Cancer Network of Excellence (RD12/10 Red de Cáncer), from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS [01ZX1309]), and from National Cancer Institute of the National Institutes of Health under award numbers: R01CA186646, U01CA249955 (EEB).This work was also funded d by Portuguese National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020 and by the project NORTE-01-0145-FEDER-000055, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)
Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization
Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways.This work was supported by the European Union’s Horizon 2020 research and innovation program, N° 856620 and by grants from the Instituto de Salud Carlos III and FEDER (Madrid, Spain; PI17/02256 and PI20/01845), Consejería de Transformación Económica, Industria, Conocimiento y Universidades and FEDER (PY20/01282), from the CRIS foundation against cancer, from the Cancer Network of Excellence (RD12/10 Red de Cáncer), from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS [01ZX1309]), and from National Cancer Institute of the National Institutes of Health under award numbers: R01CA186646, U01CA249955 (EEB). This work was also funded d by Portuguese National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020 and by the project NORTE-01-0145-FEDER-000055, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).Peer reviewe
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
- …