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News U25

Robust Conditional Independence maps of single-voxel Magnetic Resonance Spectra to elucidate associations between brain tumours and metabolites

Scientists of CIBER-BBN, Ana Paula Candiota and Margarida Juliá managing Nanbiosis ICTS U25 NMR: Biomedical Applications I have participated in the research carried out by Liverpool John Moores University and University of Valencia to elucidate associations between brain tumours and metabolites, published by the journal Plos One.

The aim of the paper is two-fold. First, to show that structure finding with the PC algorithm can be inherently unstable and requires further operational constraints in order to consistently obtain models that are faithful to the data. The authors propose a methodology to stabilise the structure finding process, minimising both false positive and false negative error rates. This is demonstrated with synthetic data. Second, to apply the proposed structure finding methodology to a data set comprising single-voxel Magnetic Resonance Spectra of normal brain and three classes of brain tumours, to elucidate the associations between brain tumour types and a range of observed metabolites that are known to be relevant for their characterisation. The data set is bootstrapped in order to maximise the robustness of feature selection for nominated target variables. Specifically, Conditional Independence maps (CI-maps) built from the data and their derived Bayesian networks have been used. A Directed Acyclic Graph (DAG) is built from CI-maps, being a major challenge the minimization of errors in the graph structure. This work presents empirical evidence on how to reduce false positive errors via the False Discovery Rate, and how to identify appropriate parameter settings to improve the False Negative Reduction. In addition, several node ordering policies are investigated that transform the graph into a DAG. The obtained results show that ordering nodes by strength of mutual information can recover a representative DAG in a reasonable time, although a more accurate graph can be recovered using a random order of samples at the expense of increasing the computation time.

Article of reference:

Robust Conditional Independence maps of single-voxel  Magnetic  Resonance  spectra  to  elucidate  associations  between  brain  tumours  and  metabolites. Raúl Vicente Casaña-Eslava, Sandra Ortega-Martorell, Paulo J. Lisboa, Ana Paula Candiota, Margarida Julià-Sapé, José David Martín-Guerrero, Ian H. Jarman 2020, PLoS ONE  https://doi.org/10.1371/journal.pone.0235057

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The ATTRACT Online Conference open for registration

The on line Conference ATTRACT – Igniting the Deep Tech Revolution will take pace on 22-23 Sep 2020. The ATTRACT Online Conference website is now live! Please register before 28 August at https://attract-eu-conference.cern.b2match.io/

The ATTRACT Conference offers multiple opportunities to understand the dynamics and contribute to the emergence of a strong European deep tech ecosystem for detection and imaging technologies. The ATTRACT Project is an EC funded initiative led by a consortium of leading European research infrastructures and universities.

CIBERBBN and Nanbiosis are involved in MAGRes : Multiparametric MR approaches for non-invasive glioblastoma therapy response follow-up, one of the 170 projects using sensing and imaging technology
to enable breakthrough innovation funded by ATTRACT and headed by Ana Paula Candiota, Scientific Coordinator of NANBIOSIS U25 NMR: Biomedical Applications I

MAGRes Project:

Glioblastoma (GB) is the major aggressive primary brain tumour in adults showing disproportion between high mortality compared to low overall incidence. Survival after detection is below 18 months even after standard aggressive treatment and no cure has been reported. Novel therapies (e.g. immunotherapy) may be very expensive and it may be relevant to have in vivo, early efficiency, non-invasive imaging biomarkers (IB) to halt unsuccessful use of such therapeutic agents and allowing early evidence-based therapy-related decisions.

Researchers involved in Magret project believes that Magnetic Resonance (MR)-derived data (MRI, MRSI, i.e. imaging, spectroscopic imaging) can be translated into IB of successful GB therapy through in vivo monitoring.

MAGRes proposes a breakthrough innovative hashtag combining MRI and MRSI data acquisition. MRSI data will be used as decoding agent to translate MR-derived information into surrogate IB of successful therapeutic outcome, which definitely represents a step beyond in comparison with present follow-up therapy response strategies based in volume changes of the tumour mass.

The extremely large amount of multi-parametric data acquired for each preclinical subject (mice), longitudinal explorations with several acquisitions will allow us to benefit from powerful state-of-the-art multiparametric data analysis methods based on Deep-Learning (DL). This, together with feature selection and interpretation methods will lead to extraction of MR- based significant IB.

At present, there is no software approach allowing both fast, user-friendly post-processing of conventional MRI and MRSI, and encompassing sophisticated developments in the area of pattern recognition (PR), automated MRSI artifact removal, as well as the weighted combination of multi-parametric images.

Accordingly, MAGRes targets the development and implementation of user-friendly software with capabilities to compute 2D and 3D MR-derived parametric images and to visualise them overlaid on high resolution MR structural images. Moreover, this will be implemented in an open-source software imaging platform as a plugin, paving the way to a scalable system, which could also handle clinical patient data in the immediate future.

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The Autonomous University of Barcelona, in the elite of the 300 best universities in the world

The Academic Ranking of World Universities (ARWU), known as Shanghai Ranking, which was made public on August 15, places the Autonomous University of Barcelona among the elite of the 300 best universities in the world and the first of the Spanish universities.

This indicator organizes up to 20,000 university centers worldwide,
based on transparent methodology and objective third-party data. ARWU is regarded as one of the three most influential and widely observed university rankings

The Autonomous University of Barcelona houses two of NANBIOSIS Units:

U1 Protein Production Platform (PPP), led by Toni Villaverde, Neus Ferrer and Paolo Saccardo, offer an “tailored” service for the design, production and purification of recombinant proteins using both prokaryotic and eukaryotic expression systems

U25 NMR: Biomedical Applications I, led by Carles Arús and Ana Paula Candiota, with a recognized research track record in the use of NMR as a tool for biomedical applications, and more especifically to identify biomarkers of different pathologies, the main objective of this unit is the acquisition, processing and/or interpretation of Nuclear Magnetic Resonance data



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Open call for contribution to the Special Issue by MDPI in IJMS about “In Vivo Biomarkers for Immunotherapy Efficacy in Brain Tumours”

Ana Paula Candiota, Scientific Coordinator of NANBIOSIS U25 NMR: Biomedical Applications I Unit (from CIBER-BBN and Autonomous University of Barcelona), is the Guest Editor of a special issue launched by MDPI in the International Journal of Molecular Sciences (IF 4.183). This special issue is about In Vivo Biomarkers for Immunotherapy Efficacy in Brain Tumours

Contributions with papers or reviews to this issue, can be fowarded to the Guest Editor (AnaPaula.Candiota@uab.cat) with a tentative title and/or abstract.

Final deadline for submission: 31/10/2020

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Preclinical brain tumour therapy response assessment with MRSI approaches: Oral presentation awarded to Ana Paula Candiota


NANBIOSIS U25 scientific coordinator, Ana Paula Candiota, has recently presented a scientific work about preclinical brain tumour therapy response assessment with MRSI approaches in the 36th annual meeting of ESMRMB held in Rotterdam, Netherlands, October 3-5. Work was entitled  “Oscillatory pattern of response in MRSI-based Glioblastoma therapy follow-up: an immune system biomarker?” and was awarded an oral presentation in the scientific session of Animal Models: Brain & others

Article of refrence:
L. Villamañan, P. Calero, S. Wu, N. Arias-Ramos, M. Pumarola, S. Ortega-Martorell, M. Julià-Sapé, C. Arús, A.P. Candiota. Oscillatory pattern of response in MRSI-based Glioblastoma therapy follow-up: an immune system biomarker? European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2019. Rotterdam, NL. Oct 2019.

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The Autonomous University of Barcelona, in the elite of the 300 best universities in the world

The Academic Ranking of World Universities (ARWU), known as Shanghai Ranking, which was made public on August 15, places the Autonomous University of Barcelona among the elite of the 300 best universities in the world.

This indicator organizes up to 20,000 university centers worldwide,
based on transparent methodology and objective third-party data. ARWU is regarded as one of the three most influential and widely observed university rankings

The Autonomous University of Barcelona houses two of NANBIOSIS Units:

U1 Protein Production Platform (PPP), led by Toni Villaverde, Neus Ferrer and Paolo Saccardo, offer an “tailored” service for the design, production and purification of recombinant proteins using both prokaryotic and eukaryotic expression systems

U25 NMR: Biomedical Applications I, led by Carles Arús and Ana Paula Candiota, with a recognized research track record in the use of NMR as a tool for biomedical applications, and more especifically to identify biomarkers of different pathologies, the main objective of this unit is the acquisition, processing and/or interpretation of Nuclear Magnetic Resonance data

Here you can check the results of the University of Zaragoza in this year’s Shanghai Ranking:
http://www.shanghairanking.com/World-University-Rankings/Autonomous-University-of-Barcelona.html



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Multiparametric MR approaches for non-invasive glioblastoma therapy response follow-up (MAGRes)


Ana Paula Candiota, Scientific coordinator of U25 of NANBIOSIS, is the IP of the granted project Multiparametric MR approaches for non-invasive Glioblastoma therapy response follow-up (MAGRes), selected for funding in the ATTRACT call https://attract-eu.com/the-project/

The kick-off meeting for is taking place at CERN, Switzerland, days 20-21th May with talks of all selected projects. Unit 25 will have a relevant role in the development of MAGRes. MRI/MRSI from preclinical brain tumors will be acquired at NANBIOSIS U25, NMR: Biomedical Applications I

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NANBIOSIS Scientific Women in the International Day of Women and Girls in Science

Today February 11 is the International Day of Women and Girls in Science, a day to raise awareness of the gender gap in science and technology.

According to the United Nations, while yet women and girls continue to be excluded from participating fully in science, science and gender equality are vital to achieve the internationally agreed development goals, including the 2030 Agenda for Sustainable Development. Thus, in recent years, the international community has made a great effort to inspire and promote the participation of women and girls in science.

NANBIOSIS wants to acknowledge  the efforts made by scientific women who struggle every day to contribute their bit to Science and highlight their essential role in nowadays research. Especially we want to recognize the work of scientists women involved in our units, whatever is the nature of their contribution: technical, scientific development, management, coordination, direction, etc; just to mention some examples:
Neus Ferrer in the Scientific Direction of Unit 1 Protein Production Platform (PPP)
Pilar Marco and Nuria Pascual in the Management and Scientific Coordination of U2 Custom Antibody Service (CAbS) 
Miriam Royo in the Scientific Direction of U3 Synthesis of Peptides Unit
Laura Lechuga and M.Carmen Estevez in the Direction and Scientific Coordination of U4 Biodeposition and Biodetection Unit
Nora Ventosa and Nathaly Segovia in the Scientific Direction and Technical Coordination of U6 Biomaterial Processing and Nanostructuring Unit
Isabel Oliveira and Teresa Galán in the Coordination of U7 Nanotecnology Unit
Rosa Villa and Gemma Gabriel in the Management and Scientific Coordination of U8 Micro – Nano Technology Unit
Gema Martínez in the Scientific Coordination of U9 Synthesis of Nanoparticles Unit
Fany Peña in the Scientific Coordination of U13 Tissue & Scaffold Characterization Unit
Mª Luisa González Martín in the of Direction and Scientific Coordination of U16 Tissue & Scaffold Characterization Unit
Gemma Pascual and Isabel Trabado in the Coordination of the U17 Confocal Microscopy Service
Mª Virtudes Céspedes in the Scientific Coordination of U18 Nanotoxicology Unit
Beatriz Moreno in the Scientific Direction of Unit 19 Clinical tests lab
Ibane Abásolo in the Scientific Coordination of Unit 20 In Vivo Experimental Platformt
Verónica Crisóstomo in the Scientific Direction of Unit 24 Medical Imaging 
Ana Paula Candiota in the Scientific Coordination of Unit 25 Biomedical Applications I 
Maria Luisa García in the Scientific Direction of U28 NanoImaging Unit from Bionand, recently incorporated to NANBIOSIS

Thanks to all of you and your teams!

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NANBIOSIS Against Cancer

The World Health Organization, the International Cancer Research Center (IARC) and the International Union Against Cancer (UICC) celebrate February 4 of each year as World Cancer Day

Every year, 14 million new cases of cancer are diagnosed worldwide and the disease causes 8.2 million deaths.

Thanks to scientific research, great advances have been made in the fight against cancer. Through surgery, chemotherapy or radio therapy and, in the last 20 years, through immunotherapy, hormonal treatment or cell therapies, tools have been obtained to improve early diagnosis and treatments, increasing cancer survival by 20%.

The only way to understand cancer and, someday, eradicate it or eliminate the suffering and death due to this disease, is RESEARCH

NANBIOSIS as an ICTS (Singular Scientific and Technical Infrastructures) for biomedical research plays a very important role in the fight against cancer. Some examples are bellow:

Thanks to a coordinated action between units U1 of Protein Production Platform (PPP), U18 of Nanotoxicology and U29 of Nucleic Acid Synthesis, NANBIOSIS is developing nanopharmaceuticals with a high degree of efficacy for the treatment of metastases in colon cancer, by using of proteins with high specificity of binding to metastatic cells and a high degree of permanence in the blood flow, loaded with anti-cancer drugs that are selectively released inside the tumor cells that are going to form the metastases. Through the public financing of a NEOTEC project and a RETOS-COLABORACION and the company NANOLIGENT SL, the first antimetastatic drug on the market will be developed.

The Protein Production Platform-PPP collaborates with research projects whose objective is the development of new cancer therapies based on recombinant modular proteins with the ability to self-assemble. These multimeric complexes have shown, in animal models, a high stability in serum and an improved biodistribution compared to that observed with drugs for clinical use. These principles have been valued in different types of cancer, including colorectal cancer and breast cancer. The modular design of these constructions allows the incorporation or substitution of direct peptides and therefore they are presented as a transversal tool for more effective treatments against cancer. In addition, the PPP has served the Vall d’Hebron Institute of Oncology (VHIO) of Barcelona, the Josep Vilanueva group (CIBERONC) in the field of biomarker study and new targets associated with triple negative breast cancer (TNBC).

Unit 6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit is working on a project in collaboration with VHIR, financed by the Spanish Goverment and CIBER-BBN, for the development of a new nanomedicine for the treatment of high-risk neuroblastoma, one of the most frequent childhood cancers.

Unit 6 is also working on the project Artificial Lymph Nodes for Cancer ImmunoTherapy (ALYCIA) A project born of a initiative of CIBER-BBN/ CIBERONC to enhance scientific interdisciplinary collaborations between research groups working on oncology and nanomedicine. Researchers of unit 6 will develop Artificial Lymph Nodes (ALN) based on dynamic 3D scaffolds able to promote efficient ex vivo lymphatic cell expansion of relevant phenotypes. Such ALN represent a new approach to lymphocyte expansion, which not only includes artificial Antigen Presenting Cells in suspension like the state-of-the-art expansion techniques, but also mimics the function of the LN ex vivo.

One of the singular capabilities of the U25 of NANBIOSIS NMR: Biomedical Applications I is the acquisition of high quality, high resolution preclinical magnetic resonance imaging/spectroscopy/spectroscopic imaging data. This allows performing leading-edge studies in preclinical cancer models such as noninvasive therapy response follow-up in murine brain tumours, revealing new response biomarkers with translational potential for brain cancer patients.

NANBIOSIS U4 Biodeposition and Biodetection Unit  is currently developing the national project PREDICT Point-of-care Nanoplasmonic Platforms for Novel High-Value Diagnostics and Therapy Follow-Up , which works in the early detection of lung cancer. PREDICT project will use the Unit 4 of Nanbiosis for the multiplexed biofunctionalization of the biosensor chips and their methodology optimisation.

Finally, Unit 20 of NANBIOSIS In Vivo Experimental Platform at VHIR, is the most implicated of the CIBER units on projects in the field of cancer, just to name some of them: H2020-NoCanTher: magnetic nanoparticles against pancreatic cancer through the use of hyperthermia combined with conventional treatment. H2020-Target-4-Cancer: nanotherapy based on polymeric micelles directed against specific receptors of tumor stem cells in colorectal cancer. H2020-DiamStar: nanodiamonds directed against leukemia for the potentiation of chemotherapy. FET-OPEN EvoNano: in silico and tumor-tumor models for the prediction of PK / PD and tumor efficacy of antitumor nanomedicines against tumor stem cells. FIS-ISCIII: polymeric micelles for siRNA and combined therapy against breast cancer tumor stem cells. CarboXigel: hydrogels for the sustained release of chemotherapeutic drugs against the metastatic spread of ovarian cancer. MelanoMir: nanomedicine applied to skin cancer, melanoma, beside other projects promoted by CIBER-BBN.

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Cancer metabolism in a snapshot: MRS(I)

Margarida Julià‐Sapé, Ana Paula Candiota and Carles Arús, Scientific Director and Scientific Coordinators of Nanbiosis U25 NMR: Biomedical Applications I, are the authors of a new article in the journal NMR in Biomedicine: “Cancer metabolism in a snapshot: MRS(I)

The article contains a revision of the contribution of MRS(I) to the in vivo evaluation of cancer‐metabolism‐derived metrics, mostly since 2016. Strategies include the following: (1) quantification of single oncometabolite content such as 2HG; (2) selected metabolite ratios such as total Cho to NAA in gliomas, ratios related to Cho, Cr, citrate and polyamines in prostate cancer or Lac/Pyr in hyperpolarized 13C MRSI; and (3) the whole 1H MRSI(I) pattern, through pattern recognition analysis, allowing detection of response to therapy in preclinical brain tumours before detectable volume changes.

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