The Molecular, Cellular and Clinical Approach to Healthy Aging (ENOCH) project focuses on finding treatment for the diseases that most affect aging, such as dementia, cancer and heart disease. Five scientific centers in Moravia cooperate on it, in addition to our center it is the Institute of Molecular and Translational Medicine of Palacký University in Olomouc, RECAMO center of the Masaryk memorial Cancer Institute, the Department of Neurology of the Medical Faculty of Olomouc University Hospital and Blood Cancer Research Group at the University of Ostrava.

The first meeting of all twenty FNUSA-ICRC research teams participating in this project took place on Thursday, April 8. This is two thirds of all teams within our center, so the ENOCH project is given a lot of attention. The course of the meeting also corresponded to this, the program mainly included information on the status of fulfillment of individual tasks and mutual cooperation within the FNUSA-ICRC.

The results of the online meeting were then entirely positive. Meeting the individual milestones of the project should be smooth and there has been a big step forward in the area of research quality. It was also stated that due to the state of work on the ENOCH project, in the future our center could try to apply for a similarly significant grant in cooperation with domestic or foreign research centers. The next meeting should be at the end of June.

Supported by the European Regional Development Fund – Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868).
.

New publication of the Kardiovize research team of the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) deals with visceral fat, ie body fat that is stored around vital organs. “This is the first published study conducted in Central and Eastern Europe,” said Dr. Juan Pablo Gonzalez Rivas, Principal Investigator of Kardiovize team. “It turned out that we can’t use the values of visceral fat defined by colleagues in the USA or Japan to determine cardiovascular risk. The local population has very different values. ” The publication was published in the journal Obesity Research & Clinical Practice and can be found here:

A young researcher, Anna Polcrová, who studied Nutritional Therapy at the Faculty of Medicine of Masaryk University, Social Epidemiology at the Faculty of Science of Charles University and continued her studies at the Masaryk University while working in Kardiovize team. We asked her for a detailed explanation of not only the results of the study:

It is very well known that obesity is dangerous for the health, but it is not common to talk about visceral fat. What is visceral fat? And why is unhealthy?
The body fat can be stored in various areas. We basically distinguish between subcutaneous fat, which is located under the skin, and visceral fat, which is located inside abdominal area and surrounding our organs. The location of fat depot significantly affects its impact on our health. Previous research determined that a subcutaneously located fat depot is not as risky as visceral fat, because excess of visceral fat is related to more metabolic abnormalities, including insulin resistance, type 2 diabetes mellitus, increased risk of thrombosis, or endothelial dysfunction.

How can be measured visceral fat? How do I know that if I have too much?
The gold standard method to measure visceral fat is computed tomography, but this is relatively expensive and exposes individuals to radiation. We can use bioelectrical impedance analysis, which is an advantageous method because it is simple, quick, low cost, non-invasiveness, and showed strong correlation with values measured by computed tomography. Bioimpedance is based on weak electricity flowing through the body and the voltage is measured in order to calculate impedance (resistance), allowing to determine the body composition, including visceral fat area. Although it may sound dangerous, this method is completely painless and can be used for people of any age. The only contraindication is the presence of a pacemaker or pregnancy. High amount of visceral fat is unhealthy, commonly used devices in Czechia use a cut-off of 100 cm2 to define high amount of visceral fat, however, this value came from Asian studies, that does not distinguish between genders, and has not been validated in the European population.

What is the main result of your study? And how this can benefit the European population?
Our results showed that the cut-offs of visceral fat related to cardiometabolic risk in the Czech population are different in comparison to previous studies in different populations. We observed that cut-offs of 90 cm2 for men and 109 cm2 for women were associated with the presence of cardiometabolic risk factors including high waist circumference, elevated blood pressure, reduced HDL-cholesterol, elevated triglycerides, and impaired fasting glucose. Men showed a higher risk of cardiometabolic complication in lower values of visceral fat in comparison to women. In summary, the distinguishment of the high and low level of visceral fat and related cardiometabolic risk need to be based on cut-offs determined for a specific population, respecting gender differences.

You now have one year working with the Kardiovize team, how has been the experience working with them in ICRC? What have your learned?
I am very happy about the opportunity to work in the Kardiovize team. This team is open to share their experience and support junior researchers. Over the past 12 months, I have published 3 articles (1 as a first author), collaborated in a grant proposal, and we are working on an intervention to reduce the cardiometabolic risk of people from Brno with a lifestyle program. Moreover, thanks to my experience in Kardiovize, I started to study Ph.D. program in Environmental health sciences at RECETOX in Masaryk University. This combination is creating an amazing space for me to further develop my research in the fields of my passion – lifestyle, health literacy, and social determinants of health.

Jan Mičan became one of the holders of this year’s Dean’s Award of the Faculty of Medicine, Masaryk University for the best undergraduate students of the faculty. He received it in the Category for outstanding scientific performance, where he took first place. The Dean’s Award is given according to more selective criteria than in previous years – obtaining it is really a very prestigious matter. Jan Mičan is part of the Protein Engineering team of the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC), where, according to the team leader prof. Damborsky was literally raised up. In the Loschmidt laboratories of the Faculty of Science, Masaryk University and the FNUSA-ICRC, he focuses, for example, on the development of new thrombolytics within the Stroke Brno platform.

Congratulations to the Dean’s Award of the Faculty of Medicine, Masaryk University and the first place in the Category for excellent scientific performance. Was it a specific scientific performance or was it an award for a comprehensive work?
It is an award for the overall work, Professor Damborský and I have filled in a number of scientific publications in which I participated. These were, for example, publications from my very first research, which dealt with the development of enzymes for the decomposition of mustard gas. At that time, we developed more efficient enzymes to neutralize this war gas instead of using strong caustics or combustibles, which cannot be used, for example, after some expensive equipment or vehicles are hitted. A number of publications were also from research dealing with the development of new thrombolytics, ie drugs for dissolving blood clots, which we do in cooperation with Professor Mikulík within the Stroke Brno project.

You work in Loschmidt Laboratories of Faculty of Science, Masaryk University and FNUSA-ICRC. Was it your long-term career goal or is it a coincidence?
I would say that it was a coincidence… I met Loschmidt’s laboratories at the grammar school, where I noticed a leaflet that attracted students to the Summer School of Protein Engineering event (this year, June 28-30 https://loschmidt.chemi.muni.cz/school/ ed. note). The scientific environment and science in general have always attracted me a lot, and the event promised to get acquainted with the issues of protein engineering directly in laboratories. I applied, I was selected and I was really interested. After high school, I got to FM MU, and that’s where my hesitation between medicine and science began, which actually lasts to this day. I managed to get into biochemistry and medicine and I couldn’t decide what would be better. Fortunately, I managed to get into the P-PooL program (Undergraduate Program for motivated medical students with extended scientific training), in which I was able to do science from the first year of medicine. I was placed behind the 150th place on the receivers, which would normally close the door to P-PooL, but thanks to the saying ” Nothing is lost for asking ” and many emails, I was included in the selection procedure and fortunately I was selected later. When I had to choose a project in the first year, I remembered my stay in Loschmidt’s laboratories and wrote prof. Damborsky and Dr. Bednar, if they don’t have one. We agreed to start computational research – first these were the already mentioned enzymes for the decomposition of mustard gas. Although the project was not completed, because we were unable to create a better enzyme than those used now, I have learned the extreme number of different methods and procedures that I have used so far. I remember the beginning of the cooperation on the development of thrombolytics exactly, it was the day after the anatomy test, when I was able to attend the meeting of the team members, and I was offered if I did not want to work with the Stroke Research team and prof. Mikulík. So really a coincidence.

What do you plan after studying and what is the specific scope of your work?
When I graduate, I will be a general practitioner, I will specialize only in the attestation. I would very much like to work at a neurological clinic, where patients are treated and recovering after a stroke, but also with other neurological diseases, that is my goal. After I started doing stroke research, my grandmother died of it, so I have unresolved bills with the stroke… I’m still slightly hesitant to be a doctor and stay with research, but now the scales are inclined to work as a doctor, but certainly with research I will stay in the hospital.
When it comes to research, 98 percent of the time it’s computer work. Either on mine or I use supercomputers everywhere in the country and around the world. I am a member of the Metacentrum organization, which enables this in the Czech Republic. There are times when I use, for example, a thousand computers at once, to calculate complex chemical reactions or to process statistical data on genetic or protein sequences from all possible animals and protein variants that exist in nature, when I try to find various useful connections between them. I also worked in the laboratory when I tested the enzymes I developed for the decomposition of mustard gas. I wanted to try it and learn techniques like protein purification, cultivation in bacteria, genetic modification of bacteria… I spent the whole summer and winter on it, but I wouldn’t change it for computer work… There, if something goes wrong, then follow the steps you can find and fix a bug in the program, while in that lab you sometimes don’t know what and why it went wrong. That life is simply unpredictable and even though we know a lot about it, it is still not enough… To do that, you have to sit it down, weld it, wash it off, dose it, stir it up. Computational biology and chemistry, on the other hand, are purely creative work, and if you don’t like to do something a third time, you write a program and it will do it for you. And with an internet connection, you can do it, for example, from the Jeseníky Mountains.
Then I dealt with the issue of thrombolytics for a really long time, a number of new drug candidates emerged from the research. Now it is up to colleagues from the Veterinary Research Institute in Brno or the Institute of Biophysics of the AV CR to test them on animal and fluid models. Specifically, there are eleven new enzymes (so-called Ocean’s eleven) with different properties and approaches to the treatment of stroke and four thrombolytics based on staphylokinase, which I developed in Israel. Of course, I pay close attention to how the tests are evolving, but now I am fully committed to finding enzymes for more efficient degradation of plastics for industrial and environmental purposes. If successful, this would be a new way of recycling, which would help to make more and cheaper use of recycled plastics. I also now have several other strategies to further improve thrombolytics by analyzing coevolution or modeling the interaction with fibrin, so hopefully there will be time for them later, I’m looking forward to it.

Do staphylokinases have anything to do with the dreaded staphylococci?
Yes, we try to take advantage of the unique properties of these bacteria. Staphylokinase is a substance with which staphylococci literally make their way through the human body. The defenses that every person has try to stop their progress by using fibrin barriers that build around the bacteria. However, staphylococci can dissolve these clots with the enzyme staphylokinase, and this is exactly what we want to use in the treatment.

What are your other goals? What is the scientific holy grail you would like to achieve for you?
So this is probably the hardest question I’ve ever had… Of course, I would like to develop a new universal remedy for ischemic stroke, myocardial infarction and embolism in general – everything is caused by blood clots… But the Holy Grail is something else for me, I imagine it like it as an effective interconnection of various scientific disciplines and disciplines. For example, medicine, biochemistry, computer technology, data visualization… All this can be beautifully put together in medical practice and I am terribly fascinated by it. I would like to somehow blur the boundaries between these fields and find new uses for their interconnection. For example, using biochemical methods, develop a new drug, get it to the pediatric patient’s bedside, and then compile an effective visually comprehensible treatment plan to understand what is happening to it and why doctors are doing what they are doing with it. And that will calm him down and allow him to manage his diagnosis and treatment well.
Another thing that I am very interested in is from the field of computational-chemical, it is the breaking of the so-called Anfinsen’s dogma (This hypothesis states that, at least for small spherical proteins, the native structure of the proteins is determined only by the amino acid sequence. In the environmental conditions in which association occurs, the original structure is unique, stable and kinetically with minimal free energy. Three conditions apply to this: 1. Uniqueness – requires that the sequence has no other possibilities of comparable free energy, therefore the free energy must be unique. small changes in the environment cannot lead to changes in the model with the minimum possible free energy 3. Kinetic availability – means that the bond on the surface with free energy from uncoupled to associated must be sufficiently balanced. shape ed. note). It is a question of what those proteins actually look like, how we all de facto look on this microscopic scale. The standard protein has about 300 amino acids, of which there are twenty species. There are astronomical numbers of those combinations, here 20 to three hundred, which is a huge number, more than there are atoms in the universe. But how and according to which laws is it put together? Google’s AlphaFold2 project, which is now much talked about, is a great hope for solving this problem. It is based on machine learning, which is extremely complex in itself, machines sometimes learn completely on their own, combine different properties, so-called properties and metaproperties, but the weakness is the lack of intelligibility for humans – the project may tell us that some sequence amino acids fold into exactly this shape – a protein, which is extremely useful, but it does not create a theory that one can understand. And that’s exactly what I want. Understanding how proteins are put together.

Now that we’re interested in interdisciplinary collaboration – the media has recently said that physicists are on the verge of finding the fifth fundamental force in the universe – this also interests you, could it help in the field of biochemistry or machine learning and artificial intelligence?
This probably doesn’t upset me, given that this force is so “strong” that we had to create a special accelerator in which we observe muons, particles smaller than atoms, and only then were we able to notice it… If it were to be a force that should have some significance in biochemistry, for example, would not escape us for so long. I don’t think this will affect much in the medical world. Although the human body can perceive quantum effects with the basic senses – for example, you will know the difference between water and heavy water, which has a neutron more by taste, but this is extreme and this new force will probably have no effect. But I have heard that this discovery could fundamentally change communication between people and allow very fast transmission of information. And this could significantly improve the calculations and thus the machine learning.

Do you have any free time left in your work? If so, then how do you like to spend it the most?
I like to spend my free time outside, thank God the weather is a bit more acceptable, so it will be even more intense again. Sometimes it’s “just” walks or trips, I would like to invite you to the shores of Svitava, where we or our friends do such improvised guitar concerts. I also really like such more special walks, it’s called urban exploration and it’s a visit to old abandoned buildings created by human activity, which are somehow forgotten, unused, intended for demolition and at the same time interesting and beautiful. It’s on the edge and I don’t encourage anyone else to do it, but I don’t do any destructive or harmful activities there, it’s just about discovering places that are connected with the history of this or that place.
I will not report it anywhere and thank you for the interview!

Non-alcoholic fatty liver disease (NAFLD) is a disease in which fat accumulates in the liver without excessive alcohol consumption. It is related, among other things, to the development of diabetes II. type, obesity and also genetic predisposition and is therefore an increasingly common diagnosis. It is estimated that more than a quarter of the world’s population suffers from NAFLD.

An international research team, whose members were also scientists from The International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC), focused in its work on how NAFLD is affected by genetic variations. Their article entitled “Pediatric Non-Alcoholic Fatty Liver Disease is Affected by Genetic Variants Involved in Lifespan / Healthspan” was published in the Journal of Pediatric Gastroenterology and Nutrition.

“We investigated the impact of single nucleotide polymorphisms (SNPs), which are related to lifespan,” said Manlio Vinciguerra, Ph.D. MSc, Principal Investigatorof Epigenetics, Metabolism and Aging research team of FNUSA-ICRC. Single nucleotide polymorphisms are variations in a single nucleotide in the human genome and are the basis of differences in our susceptibility to various diseases.

The research was performed on a sample of 177 patients with this diagnosis with an average age of 13.7 years. As a control, there were 146 healthy individuals. 10 single nucleotide polymorphism were selected, which are demonstrably related to metabolism and also to liver function. “We used multidimensional reduction analysis and control of SNP-SNP interactions on the obtained samples in order to identify the effect of the examined SNPs in the prediction of NAFLD and related complications,” described Dr. Vinciguerra.

The results showed that all examined SNPs are related to individual metabolic features of NAFLD, however, none was significantly associated with its diagnosis. Subsequent testing of potential synergies revealed that the combination of IL-6 rs1800795 and ANRIL rs1556516 could be used to diagnose NAFLD and to estimate their life expectancy. “To confirm whether the genetic interaction between the two genes affects the development of this disease in children, another, larger, study will be needed,” added Dr. Vinciguerra.

You can find the article here:

At the beginning of March, the University of Cape Town organized a workshop called CCP4 Crystallographic School in South Africa. Due to the current situation, it was of course in the online environment and Ing. Andrea Schenkmayerová Ph.D. from Loschmidt laboratories of Faculty of Science MU and the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) achieved great success. The researcher of the Protein Engineering reserach team won the award for the best poster entitled Structural analysis of a haloalkane dehalogenase from subfamily HLD-III.

In general, crystallography is a scientific discipline that deals primarily with the study of the arrangement and bonding of atoms in crystals and the study of the geometric structure of crystal lattices. Although most of us imagine a crystal such as a grain of salt, the modern concept of a crystal is based directly on the characteristics of the internal structure at the level of atoms and not on its external shape. The crystalline state of matter is more energetically advantageous and at present we can get not only minerals but also metal alloys or organic molecules into this state. The importance of crystallography is also underlined by the fact that 32 Nobel Prizes have so far been awarded for research and related results.

Macromolecular crystallography deals with the study of the structure and spatial arrangement of biological macromolecules (eg proteins, DNA) and their complexes, which is key to understanding their function in organisms. A detailed understanding of the structure and function of biological macromolecules is then key to understanding complex cellular processes, their homeostasis but also their pathological manifestations.

Crystallography is also used to research new proteins and their inhibitors, which could be used, for example, as drugs. The therapeutic effect is influenced, inter alia, by the shape of the molecules of the therapeutic component, so that crystallography functions here as a tool for obtaining information about the shape of the molecules. However, we would not find a classic optical microscope in this area, the light has too long wavelength – for microscopy at the molecular level devices using for example, X-rays. In general, the best drug is one whose molecule fits into a suitable binding site in the macromolecule and thus affects its biological activity.

Ing. Andrea Schenkmayerová Ph.D. in her work focused on hitherto structurally unexplored enzymes from the haloalkane dehalogenase family. These enzymes have an interesting property – they catalyze the cleavage of carbon-halogen bonds to form the corresponding alcohol, halogen anion and proton. Due to these properties, these enzymes are used in various biotechnological applications. In addition to haloalkane dehalogenase activity, lactone decarboxylase activity has been found in some of these enzymes in recent years, prompting a broad scientific discussion of the natural biological function of these enzymes and how they evolved during evolution.

“It was started by my colleague Ing. Klaudia Chmelová and after she left for maternity, I started doing it, “said Schenkmayerová. “It was a real challenge, because so far no one in the world has been able to determine the structure of the enzyme from the HLD-III subgroup, because it forms heterogeneous oligomeric structures, which makes their structural analysis very impossible. In our laboratory, systematic work has succeeded in developing a method by which we are able to prepare relatively homogeneous enzyme preparations, which opened the way for their structural analysis using cryo-electron microscopy and X-ray crystallography. Although we eventually managed to prepare crystals of this enzyme and collect quality crystallographic data, we still had trouble solving the structure due to the atypical internal arrangement of the crystal and the lower resolution of the obtained crystallographic data.”

She signed up for the workshop with work that still needed to be completed, and with the help of lecturers, she finally succeeded. It was a truly international collaboration, on the result contributed for example, professor Kay Diederichs from the University of Konstanz or professor Randy J. Read and Dr. Tristan Croll from the University of Cambridge. Important data were obtained in CEITEC laboratories and measurements were also performed on a Swiss Light Source synchotron device in Switzerland.

“This is a perfect example of an integrated approach in structural biology, which combines several experimental approaches at the same time so that it is possible to solve the structure of biomolecules when one technique is not enough. The original, say, wild-type protein formed various types of oligomers and we failed to crystallize for a long time. Using protein engineering methods, we prepared a stabilized form of the enzyme that did not produce so many different types of oligomers, and we were able to crystallize it. Despite all the difficulties, the workshop managed to solve the crystal structure of this unexplored enzyme, which will help us understand the biological function of these very interesting biocatalysts, “described Schenkmayerová.
A manuscript of the publication is currently being prepared, we will inform you as soon as it is ready.

Fig. 1: Ing. Andrea Schenkmayerová PhD. with her leader RNDr. Ing. Martin Marek Ph.D.
Fig. 2: Photo of protein crystal

The international journal Frontiers in Psychiatry published the work of the Translational Neuroscience and Aging Program Research Group in collaboration with the research group Kardiovize led by Dr. Juan Pablo Gonzalez Rivas – both from the International Clinical Research Center of St. Anne’s University Hospital Brno – and the Mayo Clinic in the United States.

A multidisciplinary team led by dr. Stokin focused on the analysis of the impact of the COVID-19 pandemic and related anti-epidemic measures in the spring of 2020 on the mental health of the Kardiovize study population and on the role of selected risk factors on mental health changes.

“The results showed that the prevalence of increased stress and the presence of depressive symptoms increased 1.4-fold to 5.5-fold compared to the period before the COVID-19 pandemic,” said the first author of the study, Dr. Novotný. This deterioration was seen in all age groups and was more pronounced in women. The main risk factors associated with this increased prevalence have been feelings of loneliness, perceptions of COVID-19 as threatening, and some negative lifestyle effects (sleep quality, exercise, financial implications). On the contrary, a higher level of resilience proved to be a protective factor.

The results of this study support previous findings about the significant impact of the COVID-19 pandemic not only on the physical health of the population (or its economic and social functionality), but also on mental health and point to the need to respond to this threat in a timely and targeted manner. to reduce the risk of a subsequent pandemic of mental disorders in the population. The study’s research team continues this study in an effort to capture long-term changes in mental health as the COVID-19 pandemic continues to grow.

The article can be found here:

An inconspicuous and slightly underestimated disease, however, every twelfth Czech suffers from. It is the fourth most common cause of death in our country, with the number of deaths from diabetes worldwide rising by 70 percent since 2000. In addition, it is one of the comorbidities that can cause serious complications of COVID-19. Nevertheless, awareness of the dangers of diabetes and the prevention of this disease is at a very low level. Scientists from the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC).

Diabetes mellitus, is a disease in which the body is unable to produce enough insulin. Most of the food we consume is broken down in the body into simple sugar – glucose. The human body uses glucose as a source of energy. Glucose is transported in the body by the blood, and in order for cells to use glucose from the blood, they need insulin. Without this hormone, therefore, cells cannot obtain energy from food. People with diabetes cannot use their blood glucose, which leads to an increase in blood sugar (hyperglycemia) and other serious consequences, such as visual impairment, kidney disease or damage to the nerves, circulatory system and others. There are two main types of diabetes, with approximately 95% of patients suffering from type 2 diabetes.

One of the main obstacles to halting the rise in diabetes is the fact that patients are often diagnosed at later stages of the disease. There are a number of risk factors that can contribute to the development of the disease and which can be prevented by proper prevention. The highest degree of risk means the so-called prediabetes, which is a slight increase in glucose values above normal. Patients with this diagnosis have a consistently high risk (up to 70%) of developing type 2 diabetes, which can occur at any time. And it is the period of prediabetes that is the ideal time for an effective campaign to prevent and inform the population about the dangers they may face.

However, this is hampered by the absence of this information among the general population. “For example, there is no diabetes prevention program in Brno yet and it is difficult to set one if 8 out of 10 people ignore the risk associated with prediabetes,” said Juan Pablo Gonzalez Rivas MD, head of the Kardiovize research team. At the same time, it is a fact that patients with type 2 diabetes who have been able to reduce their weight radically may experience long-term remission of diabetes. “If the patient meets the criteria, this reduction can be achieved by surgery, if not, then by an intensive lifestyle change program,” said Dr. Gonzalez Rivas.

When evaluating more than 2,000 inhabitants of Brno and the surrounding area aged 25-64, researchers from Kardiovize found that 64.7% of them have a high risk of developing type 2 diabetes in the following years. They are currently working so intensively on a preventive strategy that would target this high-risk group. It will be a combination of important changes that will lead to an improvement in lifestyle. First, the individual’s current condition, such as physical activity, medical history, or eating habits, is evaluated, and the risk of developing type 2 diabetes is determined based on this information. This will be followed by a consultation with a doctor, nutritional counselor and coach in order to draw up an individual plan. Its goal will be to motivate the patient to lose weight and related improvements in glucose, lipids and blood pressure – in short, to improve his health and quality of life.

“We plan to conduct a pilot study in July, we want to have the final version of the prevention program for volunteers, which we will monitor for six months,” added Dr. Gonzalez Rivas. “It is really a challenge for us, and if it succeeds on a local scale, we would like to expand this program for the entire Czech population. We want to help as many people as possible. ”

With the increasing power of supercomputers, artificial intelligence is penetrating more and more areas of scientific life and helping to solve the problem that scientific leaders have been struggling with for decades. A necessary prerequisite for successfully finding a solution is the availability of a sufficient amount of quality source data, based on which the algorithm analyzes the problem. Without data, finding the right solution is much more difficult or impossible. Many scientific communities have not dealt with historically systematic data collection and management, and their current acquisition from thousands of published studies is very time consuming and laborious.

One of the attractive areas for the application of artificial intelligence is the analysis of the effect of mutations on the thermal stability of a protein, as this mechanism is not well understood. This area also suffers from a lack of quality data, and therefore data analysts and programmers from the Loschmidt Laboratories of the Faculty of Science, Masaryk University and the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) under the guidance of molecular biologist Mgr. David Bednář Ph.D. and Mathematics Stanislav Mazurenko Ph.D. from the FNUSA-ICRC Protein Engineering research team decided to create a new database FireProtDB, which would systematically collect and maintain this data for a long time.

“The database currently contains 16,000 experimental values obtained from own measurements, available scientific literature and no longer maintained databases, which have been thoroughly filtered and verified,” said Mgr. Jan Štourač, who is one of the creators of the database. To access the data, it offers users a simple web interface, which has been visited by more than 500 scientists from around the world since its publication in October 2020. The data were also provided to the worldwide PDBe-KB database, which serves as a global repository of information for biological and biomedical research and is managed by the European Institute of Bioinformatics. The FireProtDB database was published in the prestigious scientific journal Nucleic Acids Research.

Link to the database here.
.

… and it has awarded 20 stroke centers, 11 study nurses and coordinators and 5 academic studies.

More than 8 years ago, we started working on the idea of ​​creating a research network of clinical workplaces for the implementation of joint projects in the field of stroke. 4 years ago, we started trying to raise funds, and when we succeeded in cooperation with the CZECRIN research infrastructure, we were finally able to start building the network from last year. Today, after one year of solution, we can celebrate the first fruits of our efforts. To the network, which is initiated and led by prof. Robert Mikulík, head of the FNUSA-ICRC Cerebrovascular Research Program, involved 20 stroke centers, created a network of study coordinators and nurses at the participating hospitals, and began work on five academic studies. This with the support of the parent platform, the CZECRIN research infrastructure.

The idea of ​​the newly established STROCZECH network is to connect a well-functioning network of clinical stroke workplaces, which have patients, physicians and knowledge in the field of stroke research and care, with the CZECRIN research infrastructure, which brings know-how for academic clinical studies in the Czech Republic. The aim of the STROCZECH network is to raise the research of cerebrovascular diseases in the Czech Republic to the highest possible level with the possibility of conducting randomized clinical trials. At the same time, the National Research Stroke Network has become a model for other Disease Oriented Networks, which will continue to emerge within the CZECRIN research infrastructure (eg epilepsy or mental health).

To the STROCZECH network, which is coordinated by the Cerebrovascular Research Team of the St. Anne’s University Hospital Brno, the following hospitals also participated: University Hospital Brno, Hospital Jihlava, Hospital České Budějovice, Hospital Písek, General University Hospital in Prague, Military University Hospital, Hospital Na Homolce, University Hospital in Motol, Thomayer University Hospital, University Hospital Královské Vinohrady, Regional Hospital Liberec, University Hospital Hradec Králové, Hospital Pardubice, Hospital Vyškov, University Hospital Olomouc, Tomas Bata´s Regional Hospital Zlín, Hospital Karviná, University Hospital Ostrava and Hospital Vítkovice.

Last year, the scientific council of the network was established, which consists of elected members of the Committee of the Cerebrovascular Section of the Czech Neurological Society of the Czech Medical Association JEP. It includes 13 experts in the field of stroke in the Czech Republic and also representatives of Czech stroke centers. The members of the Scientific Council prepare research protocols and plan the implementation of national academic studies as well as participation in international studies. However, ideas for scientific projects implemented within the network may also be submitted by other researchers, not only members of the Scientific Council.

The STROCZECH network has also become a member of the global alliance of stroke networks GAINS. Thanks to this, STROCZECH will have the opportunity to participate in international academic studies and also access to new knowledge.

However, not all centers of the network have been activated yet, for some partners we are in the contracting phase and in the phase of recruiting other research nurses. In particular, the legislative processes were a challenging point in the creation of the network, as was the pandemic, which, of course, paralyzed the network. So we still have a long way to go before we carry out our own multicenter academic studies throughout our network.

How do we prepare a generation of research coordinators and study nurses?

Last year, we also organized a workshop for research nurses and coordinators of our STROCZECH network. The two-day fully-fledged program was designed to present the workload of research nurses and their contribution to clinical research and patients, as well as the planned first academic clinical trials within the network.
The workshop program also involved experts from the CZECRIN research infrastructure, who presented work in the preparatory, evaluation and monitoring phases of clinical trials, ie start-up, project management, monitoring, pharmacovigilance, data management and statistics.
One of the blocks of the workshop was focused on increasing knowledge about strokes and the latest trends in their treatment. In the simulation center, participants could try out how to inform the patient together with the doctor about his possibility to participate in the clinical study and how to communicate with different types of patients. Professor Mikulík and MUDr. Ondřej Volný contributed their invaluable personal experience.

And how did our study nurses and coordinators like the workshop?

“Clinical trials are a completely new area for me, so the meeting was extremely interesting and beneficial for me from start to finish. I was most interested in the lecture on monitoring clinical trials and also the opportunity to participate in educational projects such as the HOBIT program implemented by the Cerebrovascular Research Team, “says Pavla, a research nurse from Liberec.

“I was most impressed by the interactive training room, where we tried to get informed consent from the patient using a simulated situation, and I appreciated the great acting performance of all members of the simulation team,” says David, a medical brother from Písek.

Kristýna, a research nurse for Prague hospitals, summed up the event as follows: “The workshop was fully loaded with information. I will draw from it on a daily basis in my research work. I consider the most useful information about the individual phases of the preparation of a clinical trial, about communication with regulatory authorities and about the monitoring of studies. ”

We wish our network in the coming years to grow with new projects and other enthusiastic members and to gain in its importance, because its results will be beneficial both for the hospitals themselves and especially for patients.

Veronika Svobodová, Martina Sittová and Kristýna Znamenáčková
for the STROCZECH research network
Cerebrovascular research program FNUSA-ICRC

The new head of the Biostatistics team is MUDr. Michal Šitina Ph.D. MSc. We talked in a short interview about his plans for the future, but also about the services that this department can offer not only to other research teams within the FNUSA-ICRC, but also to individual clinics of the hospital and external subjects.

A brief introduction at the beginning, what was your professional journey to the head of the Biostatistics department?
I used to hesitate to study medicine or physical chemistry or physics, because I was both very interested. I chose medicine and I still work as a doctor, internist with an interest in intensive care medicine. Later, I lived for about 8 years and worked as a doctor in Jena, Germany. In Jena because there is an extensive sepsis research program that I was going to get involved in. There is also  a large old university in Jena. Eventually, I succumbed to the urge to enroll in the Faculty of Mathematics and Computer Science, studying first bioinformatics and later a Master’s degree in Computational and Data Science (basically Numerical Mathematics and Data Analysis), as well as a basic course in theoretical physics. After returning to the Czech Republic in 2019, I did not want to leave medicine, but also mathematical disciplines. FNUSA-ICRC made it possible to combine the two – I work for the most part at ARK (Department of Anaesthesiology and Resuscitation) as a doctor and a smaller one in the Biostatistics department. After Mrs. Mgr. Bělašková left FNUSA-ICRC, I became the head of the department. I have the slight advantage over others that I can be a mediator between statistics / mathematicians on the one hand and doctors / biologists on the other. The downside is that I can’t do either properly.

You were actively involved in the fight against COVID-19 last spring, are you continuing to do so?
In the first wave of the pandemic, we helped the hospital monitor data on hospitalized patients and bed capacity. Because the hospital information system (NIS) does not easily provide all the necessary data, we have developed a new solution in the REDCap system. In the autumn, we adapted this solution for the needs of the entire South Moravian Region – every day the individual hospitals of the South Moravian Region update the condition of their beds of various types so that they can be available at any time, for example for the regional coordinator prof. Šrámek for managing patient routing and planning hospital capacity adjustments.

Biostatistics is a so-called Core Facility, what does it mean from your point of view?
A Core Facility is generally a central laboratory or unit that offers its expert services to other departments within a center, hospital, or external entity. It offers the services that most others need, such as statistics. I believe that we will be a sought-after and valuable partner for research teams. This year, we have hired three new colleagues, graduates of mathematical biology, so we can guarantee the delivery of serious results in a reasonably short time.

What services do you offer?
We offer several services. First of all data analysis. From easy analyzes that teams would probably be able to do without us, they just don’t have the time to do so, through exploratory analyzes, which means searching for knowledge and context in data, to complex regression models, survival analysis, time series analysis, bioinformatics analysis, etc. We can also help with the preparation of projects or grants, such as estimating the required sample size of the study or consulting with its design. We will also help prepare professional charts for the needs of presentations or articles. Another important activity is the creation (fitted to a specific study) and management of a database in the REDCap system, which is easy to use. As a novelty, we offer support in the use of the OpenProject project application (https://project-icrc.fnusa.cz), which facilitates the planning and management of clinical trials or project management.
Why should research teams use the services of ours and not external suppliers? We offer an understanding of the problem – we are oriented not only in statistics, but also in medicine. We try to make the results not only statistically exact, but also give medical or biological meaning and answer the questions that the researcher asks.

So it’s an IT job, how do you relax?
Unfortunately, I have a minimum time to relax. I still hope it gets better. But many are even more busy. I play piano. Classical music. I would like to actively improve my piano playing. Brno makes it possible, there is, for example, a conservatory and JAMU, unfortunately not a coronavirus situation at the moment.