Ministry of Science and Higher Education

Science Dissemination Activity (DUN)

"Increasing the information coverage of the online catalog of the Main Library of the Medical University of Warsaw by retrospective development of catalog descriptions of medical journals from 1870-2012." - task financed under Agreement 559/P-DUN/2018 from the funds of the Minister of Science and Higher Education allocated for science dissemination activity ”.

The aim of the work planned for implementation in the proposed task is to extend the online catalog information about the resources of the journals of the Main Library of the Medical University of Warsaw (BG WUM).

It is planned to prepare bibliographic descriptions for 2,100 volumes of journals, from the years 1870-2012, not yet registered in the library system of BG WUM. Catalog work will be carried out in the Aleph integrated library system. Compiled records, with information about library resources, will be made available through the online catalog at a generally accessible address BG WUM: http://aleph.wum.edu.pl. The implementation of the task is part of the systematic process of increasing the range of online catalog information through the retrospective study of the library resources of BG WUM. The requested task is an extension of the scope of catalog information developed under Application No. 351268, co-financed by the DUN, for 2017.

The Main Library of the Medical University of Warsaw, as one of 11 libraries of medical universities in the country, plays an important role in the nationwide medical library and information network. It is the largest library in its group in terms of the number of collections and the second largest library with a medical profile in the Mazowieckie region. This makes it one of the most important institutions for people associated with the health service, interested in access to professional medical literature. In 2017, the libraries of the Medical University of Warsaw recorded over 188,100 user visits, over 327,000 visits to the website, over 62,000 library information was provided, including over 20,000 catalog information.

Pursuant to the provisions of the Act on Libraries of June 27, 1997 (as amended) in Chapter 6 Article 21 point 2, the Main Library of the Medical University of Warsaw, as a unit organized by the university, belongs to the group of scientific libraries. Performing a scientific and didactic function, it provides access to resources that are necessary to conduct scientific and research work. An important element of the ongoing process of sharing scientific sources is providing information about the resources held. The basic tool used for this purpose is the online catalog. Maintained in the integrated Aleph system, the electronic catalog is available at the generally available address: http://aleph.wum.edu.pl from the website of the Main Library, as well as from the level of the National Universal Central Catalog (NUKAT). This makes our catalog a tool with nationwide meta-information about scientific resources, as well as by indexing information from NUKAT in the WorldCat OCLC database, a global search tool. The presence of the MUW library catalog in the above-mentioned Internet locations, will allow the extensive use of descriptive metadata, prepared as part of the implementation of the requested task. This will ensure increased access to information about the collections of BG MUUM, which should translate directly into better use of our book collection, greater popularization of scientific achievements and the intensification of the creation of new publications.

The works will be performed in the Main Library of the Medical University of Warsaw, by a qualified team with many years of experience in the field of developing library collections. Catalog descriptions will be created using Polish standards and recommendations for bibliographic description, based on internationally standardized ISBD (CR) cataloging rules, as well as the MARC 21 data input format.

Receiving the international APHEA accreditation for the Public Health Unit of the Faculty of Health Sciences of the Medical University of Warsaw. 

The aim of the project is to determine whether urine concentrations of CCL2 and CXCL10 chemokines may be an effective, non-invasive tool for monitoring the function of the transplanted kidney and constitute an early marker of acute rejection in renal transplant patients. The project will be implemented at the Clinical Department of Transplantation Medicine, Nephrology and Internal Diseases of the Medical University of Warsaw. The study will include 50 patients who have undergone kidney transplantation. CCL2 and CXCL10 concentrations will be determined by enzyme immunoassay ELISA on frozen urine specimens collected 3 and 12 months post-transplant in the time prior to protocol biopsy. The relationship of the concentrations of the CCL2 and CXCL10 chemokines in the urine with the histopathological changes in the material obtained by protocol biopsy as well as with the factors of increased immunological risk (subsequent transplant, PRA> 80%, the number of HLA incompatibilities) and their change depending on the time after transplantation will be investigated. It will be determined whether CCL2 and CXCL10 chemokine levels could be an effective and non-invasive tool for monitoring transplant function to identify a group of high-risk patients after kidney transplant surgery, resulting in improved long-term outcomes, including better patient survival.

The aim of the project is to determine in a randomized trial whether 3D printed models allow the operator to perform transcatheter aortic valve replacement (TAVI) more efficiently compared to using only traditional imaging methods (CT and cardiac echo). Procedural aspects will be analyzed, such as: treatment time, volume of contrast used, fluoroscopy time, dose of radiation and TAVI results based on endpoints defined by Valve Academic Research Consortium 2 (VARC2). The project will be carried out in the form of a prospective randomized trial involving 60 patients qualified for transcatheter aortic valve implantation (TAVI) due to severe aortic stenosis (AS) at the 1st Academic and Clinical Department of Cardiology of the Medical University of Warsaw. Patients will be randomly divided into two groups, the first of which will be prepared for TAVI based on the standard cardiac echo and CT, and the second, in which the treatment planning will be additionally enriched with a 3D printed heart model. Additionally, the usefulness of the personalized heart model as a tool in the process of patient-doctor communication will be determined. The aim of the work is to show whether the use of 3D printing as an additional method of visualization will allow to improve the course of implantation by influencing procedural aspects and the possibility of translating it, for example, into reducing the risk of acute kidney damage.

The project concerns the establishment of the "CERAD" Center for Design and Synthesis of Molecularly Targeted Radiopharmaceuticals - a strategic research infrastructure included in the list of the Polish Road Map for Research Infrastructure. The planned infrastructure will be used both non-economically and economically. The project is implemented by a consortium headed by the Applicant - the National Center for Nuclear Research (hereinafter NCBJ) - Consortium Leader and the only beneficiary of aid and consortium members - the University of Warsaw, the Institute of Nuclear Chemistry and Technology, the Medical University of Warsaw, the Jagiellonian University, Collegium Medicum and the Medical University of Bialystok. The aim of the project is to create a modern research infrastructure in the field of searching for new radiopharmaceuticals for diagnostics and therapy, based on biologically active ligands operating at the cellular and molecular level. The combination of isotope techniques with molecular markers of the disease state will enable earlier detection of diseases and implementation of appropriate therapeutic procedures. The implemented Project is therefore a response to the global socio-demographic trends and challenges related to the development of effective methods of cancer diagnostics and therapy.

The aim of the project is to identify and stratify Diffuse large D-cdl lymphoma (DLBCL) signal-dependent B-cell receptor (BCR) with low or high activity of the transcription factor NF- KB. As part of the project, it is planned to study the anti-tumor activity of selected BCR signal inhibitors in DLBCL cell lines and primary DLBCL cells, taking into account their division into BCR-dependent and BCR-independent lines as well as with low and high basal activity of the NF-KB transcription factor. At a later stage of the project, it is also planned to develop a comprehensive antibody panel to analyze the signal status of BCR and the response to therapy with BCR inhibitors in established and primary DLBCL cell lines by mass cytometry - CyTOF. In parallel, comprehensive characterization of genetic changes in the BCR signaling pathway in the model of 317 primary DLBCL cell lines with known cell-of-origin (COO) and consensus cluster classification (CCC) status, subjected to exome sequencing, will be carried out. DLBCL is an aggressive lymphoma with a diverse genetic background, and thus - with a varied clinical picture. The project involving research into the molecular mechanisms of DLBCL pathogenesis related to signaling with BCR is important because BCR signal inhibitors have already been registered for the treatment of chronic lymphocytic leukemia (CLL), but not DLBCL, although both diseases are dependent on the signal from the BCR. In DLBCL, morphologically identical cells may rely on completely different pro-life signaling pathways and thus respond differently to chemical inhibition of BCR-associated kinases. A better understanding of the mechanisms leading to neoplastic transformation of DLBCL B cells could contribute to a better understanding of the anti-tumor activity of BCR inhibitors. The effect of inhibitors of BCR-related proximal kinases on DLBCL cells dependent on this receptor signal has not been systematically studied so far. Despite many reports indicating that BCR inhibitors have antitumor effect, it has not been clearly established what the mechanism of their action is and whether there are interactions between various drugs in this group. Preliminary results indicate that a combination of different BCR inhibitors should be used to achieve a more effective anti-tumor activity in DLBCL therapy. Such a strategy would primarily prevent the activation of pro-life compensatory pathways in neoplastic cells. However, this issue requires detailed research, which is planned to be carried out under this project. Despite significant advances in cancer genomics in recent years and the publication of numerous results from the sequencing of the genomes of cells of many types of cancer, genetic data on the primary clinical material from DLBCL patients is still insufficient to identify with a high probability the mutations that play a leading role in pathogenesis of this disease. The expected result of the proposed project will be: a) Identification of the most therapeutically beneficial combinations of BCR inhibitors depending on the molecular basis of DLBCL. b) Development of a comprehensive and convenient CyTOF antibody panel for DLBCL molecular substrate analysis and cell responses to therapy with BCR inhibitors. Analysis of the sequencing data of the exomic pool of 317 primary DLBCL cells to search for new mutations of potential prognostic and therapeutic importance in this disease.

The human intestinal flora is of key importance for health mainly through its influence on the immune system and the metabolism of nutrients and xenobiotics. One of the groups of compounds that undergo significant structural changes under its influence are ellagotanoids, which are macromolecular polyphenols found in walnuts, pomegranate juice, raspberries, strawberries or wine matured in barrels. The positive effects of consuming these products on the circulatory system and non-specific inflammation of the large intestine are particularly emphasized, and due to the metabolism of ellagotanoids by the intestinal flora in recent years, it is postulated that bioavailable urolithins produced in the intestine may be responsible for the observed effects. As a significant role in the pathophysiology of the above diseases is played by disruptions in the functioning of mechanisms related to the active suppression of inflammation, the aim of the project will be to investigate the influence of urolithins on the molecular processes underlying this phenomenon. Comparative in vitro studies of the effect of urolithins and their phase II metabolites: glucuronides and sulphates (obtained from the urine of volunteers consuming ellagotanoid-rich products) on neutrophil apoptosis, phagocytosis of neutrophils by macrophages (eferocytosis) and the secretion of anti-inflammatory factors by macrophages will be carried out. Additionally, the hydrolysis of urolithin glucuronides under the influence of glucuronidase released by stimulated neutrophils and macrophages will be investigated. Demonstrating the effect of urolithines on the active suppression of inflammation will contribute to the confirmation of the therapeutic efficacy of ellagotanoid-rich products in diseases associated with chronic inflammation and will allow to indicate the molecular mechanisms of action responsible for these effects.

Under the agreement, 6 doctoral scholarships are financed as well as the cost of maintaining research infrastructure is co-financed under the 1st edition of the program of the Minister of Science and Higher Education entitled "Implementation doctorate".

Scientific goal: The overall goal of the project is to create a rat model of modified adipose tissue stem cells producing the TRAIL protein with anti-tumor activity, administered to free tissue lobes. Another goal is to develop a complete animal model of biological brachytherapy. State of knowledge: Tumors occurring in the superficial layers of the human body (skin, breast, head and neck area) require, after radical resection, adequate restorative therapy. To date, no easy-to-implement and safe model for creating functional tissue flaps that, in addition to restoring the appearance of the tissue, affects the root cause of the disease, has not been developed. There are few reports on biological brachytherapy - the process of creating modified tissue flaps, exerting an additional, local therapeutic effect on the primary conversion, e.g. anti-cancer, accelerating the healing of chronic wounds, angiogenesis. Until now, genetically engineered adipose tissue stem cells (ADSC) have not been used to develop such tissue flaps. The study is translational, and if the effectiveness of functional tissue flaps is proven, the collected data can be used to implement an analogous solution in breast reconstruction after mastectomy due to breast cancer. Material and methods: The project consists of successive tasks, which, performed sequentially, will allow for the development of a complete rat model of biological brachytherapy. First, the surgical procedure will be optimized - the lifting of the subcutaneous flap from the superficial inferior epigastric vessels and the perfusion of the flap. Subsequently, ADSC cells will be isolated from rat adipose tissue, followed by lentiviral transduction with fluorescent protein vectors. The modified cells will be used to optimize the perfusion of the tissue flaps. In addition, ADSCs will be transduced with the TRAIL protein with lentivirus vectors. The cytotoxic effect of such modified cells on the rat breast cancer cells RBA will be investigated in vitro. Then, the TRAIL-producing ADSCs will be applied to the free skin flap under which the RBA breast cancer tumor will be induced. The effectiveness of administering the modified cells to the flap will be confirmed by: observation of the animals' survival, vivid visualization of the dynamics of tumor growth and microscopy (post mortem). Expected end result: The result of the study will be a complete verification of the effectiveness of modification of free tissue flaps by enriching them with transduced mesenchymal stem cells from adipose tissue. In addition to objectively assessing efficacy, the study will accurately describe the model of rat biological brachytherapy with autologous modified cells. Hence, it will be possible to use the results of the study for comparative studies of other tumors/anti-cancer proteins.

In recent years, cancer immunotherapy has become an effective method of cancer treatment, leading to complete remission of the disease in 20-30% of cases. Nevertheless, this therapy is still ineffective in many patients and the mechanisms of resistance to immunotherapy are being searched for. One such potential mechanism may be the activity of arginase, the enzyme that breaks down L-arginine. The reduced concentration of arginine in the tumor microenvironment or in the lymph nodes draining the tumor area inhibits lymphocyte proliferation by reducing the expression of the CD3Z and CD3s chains, which are components of the T lymphocyte receptor complex (TCR) used for antigen recognition. Our preliminary research indicates that arginase inhibits T cell proliferation, and an arginase inhibitor, developed in collaboration with our team, reverses the suppressive effect of arginase on lymphocytes under cell culture conditions. The main scientific task of the project is to study the effects of arginase inhibitors on the development of antigen-specific T cell immune responses in a completely new research model using transparent lymphoid organs. For this purpose, a method will be developed to obtain transparent lymph nodes, which will enable their quick, microscopic imaging in full, in a natural three-dimensional state. The use of antigen-specific T lymphocytes isolated from double transgenic mice in which the constitutive expression of the DsRed fluorescent protein is used in the research will allow for the localization and creation of a spatial distribution map of all lymphocytes within the entire lymph node, not cut into histological sections. The implementation of the project assumptions will contribute to the development of a lymph node 'transparency' protocol, which does not damage their microscopic structure or degrade fluorescent proteins. The new method may in the future help to solve many research problems, currently limited by the need to image only tissue sections. It is expected that the application of the described novel research model will provide a precise description of the immunostimulatory effect of the arginase-1 inhibitor on the cellular response of T lymphocytes. This result may constitute an important argument justifying attempts to include compounds of this class in clinical trials in combination with cancer immunotherapy.