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A genetikai adatok szerepe a járványok elleni küzdelemben

Genetic data in the fight against pandemics

Scientia et Securitas
Authors: Ágnes Becsei, Orsolya Anna Pipek, Péter Pollner, and István Csabai

Összefoglaló. A COVID–19-járvány alatt bizonyossá vált, hogy az adattudományok, az adatok gyors megosztása és a nemzetközi összefogás a hatékony járványkezelés kulcsfontosságú eszközei. A járvány előtt létrejött Újonnan Felbukkanó fertőző betegségek Obszervatóriuma (Versatile Emerging infectious disease Observatory, VEO) nevű nemzetközi konzorcium célja egy olyan monitorozó rendszer kiépítése, amely a potenciálisan veszélyes kórokozókat még az előtt azonosítja, mielőtt azok tömeges megbetegedéseket okoznának, lehetőséget adva ezzel a gyors reagálásra. A járványok megelőzésére és kezelésére létrejött nemzetközi együttműködésekben, így a VEO-ban is a kórokozók, vagy a fertőzésnek kitett személyek genetikai szekvencia adatai kiemelkedő fontosságúak. Az ilyen típusú adatok kezelésével kapcsolatban az Európai Unióban többek között a Nagojai Jegyzőkönyv és a GDPR fogalmaz meg elveket, szabályokat.

Summary. Data science is proved to be a key tool in the fight against the ongoing COVID-19 pandemic, but it requires a huge amount of data shared between international research groups. The Versatile Emerging infectious disease Observatory (VEO) EU collaboration was established to generate and distribute high quality data for an evidence-based early warning system for emerging infectious diseases. Through an iterative process between data scientists, disease experts, social scientists and citizen scientists, a collaborative platform will be created for storing, secure sharing and analyses of traditional and new data sources. Next generation sequencing (NGS) has revolutionized genomic research. This versatile technology is broadly applicable to pathogens and human hosts. Rapid sharing of pathogen genetic resources, including physical samples of cultured pathogens and additionally genetic sequencing data of pathogens, is crucial in support of research and outbreak response. Access to genetic resources is regulated by the Nagoya protocol which is an internationally binding treaty to ensure equal sharing of benefits arising from the use of genetic resources. So far the Nagoya protocol has been applied only to biological samples, but digital data from genetic sequencing doesn’t necessarily fall under the treaty. Effects of diseases can differ based on genetic backgrounds, as certain gene variants may provide protection against or susceptibility to viral diseases. Human genomic data is an important resource for medical research. The General Data Protection Regulation (GDPR) lists identifiable human genetic data as sensitive, which is a subset of personal data. Sharing and analysis of this kind of data are strictly regulated and they are also subject to ethical challenges. These concerns become less pronounced when analyzing environmental samples like sewage. Samples collected from wastewater treatment plants can be used as pooled samples, containing naturally anonymized genetic information of the human population, near the wastewater treatment plant.

Open access

Segmentation is one of important methods in medical images processing, particularly as it allows images to be analysed. The method used for segmentation depends on the image problem to be resolved. In this research, knee cartilage needs to be segmented to determine the level of the Osteoarthritis (OA) and for further treatment. Knee cartilage is a soft hyline sponge that is located at the end of the femur, tibia and patella bone to release friction during movement. OA is a knee cartilage problem wherein there is a thinning of the cartilage that results in a shift especially happening between femur and tibia bone causing discomfort and pain. Thinning of the knee cartilage is due to many factors such as age, body weight, genetic, accident, sport injury and extreme use such as physical work. OA can occur to a male or female, child or adult. The effects experienced by patients with OA are such as difficulty to walk, limited movement, and pain in the thin cartilage areas. Monitoring of patients' condition needs to be done to help reduce the problem and thereby enable specialists to perform the appropriate treatment. Imaging is a method used today to monitor the condition of patients with OA. Previous studies showed that MRI is a suitable method for monitoring the condition of patients with OA because of its advantages in visualising knee cartilage more clearly than other imaging methods. Thus, for segmenting the knee cartilage which as mentioned before is an important process in medical images processing, the MR images were selected based on many factors. Segmentation in this study was aimed to obtain the cartilage region to diagnose patient OA level. Various segmentation techniques have been developed by researchers in segmenting the knee cartilage region but they have been unable to segment precisely due to the thin structure of the knee cartilage, especially for patients with intermediate and severe OA. COMSeg technique was developed to segment knee cartilage, especially for those experiencing a normal and intermediate OA and try to implement it to severe OA. The development of this new technique takes into account the imaging method used, the images feature obtained so it can be suitable to process knee image and then selection of an appropriate technique to be applied to the selected images as input.

Open access

Buildings are the largest consumers of energy, accounting for nearly 40% of all energy used. Therefore, an effective method of reducing energy consumption is to create and design more efficient buildings. In this paper details of a sustainable and green building design for a small residential home are presented. This design is unique in that it is built to Passive house standards, and using shipping containers. The structure will use four 20 ft. (6.1 m) high and one 40 ft. (12.2 m) high cube containers, with the four 20 ft. (6.1 m) making up the main floor and the 40 ft. (12.2 m) forming the second floor. The size is a modest 820 sq. ft. (76.2 m2) designed for a family with one or two children.

The goal for the building is to be as self-sufficient as possible which makes it ideally suited to an ‘off-grid’ rural setting. However, it can be adapted to be ‘on-grid’ as well. Solar energy will provide all the electricity needs through a photovoltaic battery system, and warm water with a solar water heater. The site will be water neutral by utilising rainwater harvesting and on site waste water treatment. The results from energy modelling, using HOT2000, are presented, as well as an in-depth analysis on different insulation types and strategies. Finally, a cost estimate exercise is conducted and results compared to other passive houses and traditional code compliance buildings.

Open access
Scientia et Securitas
Author: György Miklós Keserű

Összefoglaló. A COVID–19-járvány egyre növekvő számú fertőzött betegének ellátása érdekében rövid időn belül szükség mutatkozott vírusellenes terápiás lehetőségekre. A gyors reagálás szempontját figyelembe véve erre a célra elsősorban más vírusok ellen már kifejlesztett vírusellenes szerek jöhetnek szóba. A magyar betegek ellátásbiztonsága szempontjából különösen fontos a hatóanyagok és gyógyszerkészítmények hazai gyártása. Ezt a cél tűzte ki a favipiravir, egy széles spektrumú antivirális hatóanyag hazai fejlesztése, amely sikeresen befejeződött, a gyógyszerkészítmény klinikai vizsgálata folyamatban van.

Summary. Increasing impact of COVID-19 on the healthcare system prompted the identification of potential antiviral therapies. Due to the immediate demand, known drugs were subjected to repositioning attempts. These drugs include agents inhibiting the viral entry into the host cells, drugs potentially blocking the release of the viral RNA from the endosomes, antivirals inhibiting the replication of the viral RNA and finally compounds that might prevent the assembly of the new virion. Since there is less experience with camostat and nafamostat, the entry inhibitors tested in Japan, and due to the ambiguous data collected with the endosome blocking chloroquine and hydroxyl-chloroquine, we focused on the actual antiviral treatment options for COVID-19 infections. In addition to favipiravir and remdesivir that were used early, at the onset of the pandemic, we discuss novel candidates including molnupiravir, a promising antiviral actually investigated in clinical trials. Considering the needs of Hungarian COVID patients and the security of supply as first priority, we selected favipiravir and developed a convenient process for the industry-scale production of the active pharmaceutical ingredient (API). At the end of this review we summarize the development and clinical investigation of favipiravir, a wide spectrum antiviral drug used for the treatment of mild and moderate COVID patients in Hungary in both ambulant and clinical settings. The Hungarian COVID Task Force set up two consortia, one for the development and the other for the clinical investigations of favipiravir. The objective of the favipiravir development consortium was to develop processes for the production of Favipiravir API and dosage forms. The consortium completed the pilot plant scale industrial production of the API and produced clinical samples for the upcoming trials. The selection and laboratory scale optimization of the synthesis route was performed at the Medicinal Chemistry Research Group of the Research Center for Natural Sciences. The laboratory scale synthesis was scaled up for pilot plant production at EVI plc and Gedeon Richter plc. GMP production was realized at the facilities of Gedeon Richter plc. Finished dosage forms were developed at Meditop Ltd who produced the clinical samples under GMP conditions. The clinical consortium is headed by the Hungarian section of the European Clinical Research Infrastructure Network (ECRIN) and organized two trials. One of these trials investigates favipiravir produced in Hungary while the other trial is performed with favipiravir produced in Japan. Both studies were approved by the Hungarian regulatory agency (OGYÉI) and are ongoing.

Open access

Chakaiya variety of amla was investigated for its phenolic contents, and extracted phenolics from amla powder were evaluated for their antioxidant activity. RSM (response surface methodology) was used to determine the optimum conditions for maximum recovery of total phenolic content (TPC) and 2,6-diphenyl picryl hydrazil free radical (DPPH*) scavenging activity. The gelatine coating on banana slices before frying significantly reduced (approximately 60%) the fat uptake from oil during frying in comparison to control. The reduction of particle size to the nano range was found to be effective to load the antioxidants effectively. Antioxidant extracted from amla reduced the rate of oxidation of oil during frying and so it may be a better alternative of synthetic antioxidant in food products.

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. Influence of various chemical treatments on the interactions between hemp fibers and a lime matrix Journal of the European Ceramic Society 2009 29 10 1861 1868

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A szennyvíz alapú epidemiológia jelentősége a COVID–19 járványban és azon túl

The importance of wastewater-based epidemiology in the COVID-19 pandemic and beyond

Scientia et Securitas
Authors: Tamás Pándics, Eszter Róka, Bernadett Khayer, Zoltán Kis, Luca Bella Kovács, Nóra Magyar, Tibor Málnási, Orsolya Oravecz, Bernadett Pályi, Eszter Schuler, and Márta Vargha

Összefoglaló. A szennyvízalapú epidemiológia módszere a jelenlegi világjárványban egyre inkább előtérbe kerül. Mivel a szennyvízhálózatot szinte mindenki használja, ezzel a módszerrel gyorsan és olcsón lehet reprezentatív egészségügyi információhoz jutni, az így keletkező adatok pedig támogatást és visszajelzést nyújthatnak a döntéshozatalban. A Nemzeti Népegészségügyi Központ 2020 júniusa óta működteti a COVID–19 előrejelző rendszert. A mintavételek hetente történnek Budapest három szennyvíztisztítójából, valamint a megyeszékhelyekről. A kapott adatok hazánkban is előrejelzik az esetszám alakulását, az eredmények gyors kommunikációja pedig lehetővé teszi a járványhelyzetre történő felkészülést. A szennyvízalapú epidemiológia alkalmazása a jövőben más területeken is megfontolandó hazánkban is.

Summary. Wastewater based epidemiology (WBE) is an emerging method in the current COVID-19 pandemic. Since almost everyone uses the sewerage system, wastewater is technically a composite sample representing the entire population of the area serviced by a wastewater plant. This community sample contains pathogens and compounds excreted by the human body through feces or urine, and can be used to obtain information on the health status of the community. It was successfully used previously for confirming the eradication of poliovirus and tracking legal and illegal drug consumption.

The etiological agent of COVID-19, the SARS-CoV-2 virus is an enveloped, single strand RNA coronavirus. Although it is a respiratory virus, it is also shed in feces both in symptomatic and asymptomatic infections. Wastewater therefore can be used to estimate outbreak trends and support outbreak management.

Wastewater monitoring efforts in Hungary started in June 2020, first in Budapest, then gradually extended to a national surveillance system. Weekly samples are collected in the three wastewater treatment plants servicing Budapest, and from every county seat. The analyzed 22 samples represent approximately 40 % of the population. Raw sewage samples are centrifuged to remove the debris and concentrated by membrane ultrafiltration. RNA is extracted from the concentrate and SARS-CoV-2 is quantified by RT-qPCR. Results are normalized to Enterococcus counts to correct for the bias of dilution from precipitation.

The first results in June reflected the decline of the first wave of the outbreak. During the summer, viral RNA concentrations were low, mainly below the limit of detection. The increase of RNA in the sewage preceded the resurge of cases by 2 weeks. Trends of viral concentration followed the same pattern as the number of infections in the second and third wave. SARS-CoV in sewage shows statistically significant association with the number of new cases in the following weeks, thus it can be used as an early warning system.

Results are communicated weekly to the governance board responsible for outbreak management, or more frequently in case of outstanding results or when it is necessary for decision support. Weekly information is also made available to the public. To inform the public, concentration categories (low, medium, elevated and high) were defined, representing orders of magnitude of the viral RNA concentration. Trends (increasing, stagnating or decreasing) are also indicated.

The establishment of a long-term wastewater surveillance system would provide an opportunity for early recognition of future emerging infections, tracking seasonal influenza, drug use or even the detection of certain bioterror attacks. It would be an important addition to maintaining the health and safety of the Hungarian population.

Open access

A COVID–19 patológiája.

Halálok SARS-CoV-2-fertőzésben: vírusfertőzésben vagy vírusfertőzéssel?

Pathology of COVID-19.

Cause of death in SARS-CoV-2 infection: viral infection or other chronic diseases with SARS-CoV-2 (death “in” or “with” COVID-19)
Scientia et Securitas
Authors: Zsuzsa Schaff, Krisztina Danics, Adrián Pesti, Gábor Lotz, Tibor Várkonyi, Deján Dobi, István Vályi-Nagy, Klára Törő, Tibor Glasz, and András Kiss

Összefoglaló. A SARS-CoV-2-pandémia óta a Semmelweis Egyetemen és egyéb intézményekben rendszeresen végeznek boncolásokat, melyek feltárták a COVID–19 jellegzetességeit. A legsúlyosabb kép a tüdőben mutatkozik, melynek légtelensége változó kiterjedésű, oka összetett, így tüdővizenyő, fehérjében gazdag izzadmány, az erek vérrög okozta elzáródása és gyulladás. A szív, a vese, az agy és a máj változó mértékben érintett, érrögösödés, elhalás, degeneratív elváltozások mutatkoznak. A SARS-CoV-2-vírus fehérjéi (tüske, nukleokapszid) és a vírus genetikai anyaga (RNS) kimutatható az egyes szervekben, leginkább a tüdőben. Klinikopatológiai elemzéssel megállapítható, hogy a halál a SARS-CoV-2-fertőzés mint közvetlen kórok következménye, vagy egyéb krónikus megbetegedés, melyet súlyosbított a SARS-CoV-2-fertőzés, vagy a halál a vírusfertőzéstől függetlenül következett be.

Summary. Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic with substantial mortality, serial autopsies at the Semmelweis University Budapest Hungary and other institutions revealed the most characteristic pathological changes and cause of death of patients in Coronavirus Disease-19 (COVID-19). The virus primarily affects the respiratory system and the most severe alterations can be seen in the lungs. The most characteristic changes, however, are non-specific, as the atelectasis of various extents and severe congestion. The alveoli are filled with edema fluid, protein-rich alveolar exudates, often forming hyalin membranes. Diffuse alveolar damage (DAD) can be noted, which have exudative and fibroproliferative forms. The desquamated alveolar epithelial and inflammatory cells which fill the alveolar spaces further block the oxygen transportation, causing hypoxia and induces ventilation problems. Vascular thrombosis and emboli coming from thrombotic vessels from other organs, might involve the small and larger vessels are common findings in COVID-19 sometimes associated with vasculitis. Extended hemorrhages and giant cells are common findings too. Superimposed bacterial infection might cause purulent bronchopneumonia. Aspiration pneumonia, in which remnant of food and parts of filters etc might be present in the bronchi, causing acute bronchopneumonia, occurs specially in intubated patients. Other organs such as the heart, kidneys, the central nervous system and the liver are similarly, though less severely involved by thrombosis, necrotic and degenerative changes. Myocardial fibrosis is common, however usually associated with previous chronic diseases similarly to the findings in the kidneys. Liver steatosis is common, partly as the result of infection, however treatment and previous liver diseases could be in the background too. Smaller and larger cerebral bleedings, cerebral infarcts of various sizes are detected often. The protein components (spike and nucleocapside) of the SARS-CoV-2 could be demonstrated by immunohistochemical methods and the RNA genome of the SARS-CoV-2 by in situ hybridization in several organs, with highest amounts in the lungs. Clinicopathological analyses effectively determine whether the cause of death in SARS-CoV-2 infection had been the direct result of the infection, or any other previously known chronic disease, which had been superposed by the viral infection. However, in certain cases, the death might not be associated with the SARS-CoV-2 infection. The correct determination of the cause of death of the patients with COVID-19 is by consultation between clinicians and pathologists.

Open access

Összefoglaló. A klinikai orvosbiológiai vizsgálatok elkezdéséhez a kutatásban részt vevők biztonságát ellenőrző Egészségügyi Tudományos Tanács (ETT) kutatásetikai bizottságainak hozzájárulása szükséges. A járványt csak tudományos eredményekkel lehet legyőzni, ezért kitörésekor gyorsították a COVID–19 kutatási protokollok bírálatát. A koronavírus világjárvány szükségessé tett egy megváltozott kutatási adatkezelést is. A járványok megoldása a megelőzés. Bár a vírusellenes vakcinák adása hamar megkezdődött, ami jelentős tudományos teljesítmény, mégis tudományellenes hullám söpör végig a világon, és a kötelező védőoltások körüli jogi, etikai viták fellángoltak. Áltudományos érvelésekkel félrevezetnek embereket. Az ETT nemzeti kutatásfejlesztési programot javasolt a járvány következményeinek leküzdésére.

Summary. Biomedical research activities are subjects to prior professional-ethical approval. ETT (the Medical Research Council in Hungary) through its research-ethics committees ensures the safety of people and protects their interests and health in various clinical investigations and trials. Thus, science, ethics, and safety cannot be separated in biomedical research. The ETT operates three national ethics committees. The opinions of ethical bodies are binding; clinical and biomedical research may not be initiated without the consent of the relevant ETT committees. This is in line with international regulations. The ETT has published the “Codex of Bioethics. On the concepts and practice of biomedical research” on its website.

When the epidemic broke out, the ETT Presidency initiated immediate legislative changes that allowed for online meetings as well as digital consent to investigations, in addition to the previously exclusive personal ones. In the epidemic, time became the determining dimension, but this and the aim of the research could not be combined with such “lightening” that would endanger the safety and interests of the participants in the COVID studies. Thus, under the still strict requirements, the time for reviewing the COVID-19 protocols had to be radically shortened. However, the ETT research ethics committees also rejected submissions during the epidemic. A total of 171 COVID-19-related research protocols were approved in Hungary in 2020. The ETT Presidency initiated a national Research and Development program on infectious diseases, a call for scientific clinical R&D proposals on COVID-19, and also elaborated its priorities.

Throughout human history, the solution to epidemics has always been to prevent the spread of disease through vaccinations. The average production time for traditional vaccines is about 15 years, whereas in the year of the SARS-CoV-2 virus pandemic outbreak, mass vaccinations began with completely new coronavirus vaccines partly made using brand new molecular biology technology that had never been used before. Despite the tremendous professional scientific achievements, a wave of hostilities is sweeping across the world, and the ethos and successes of science, and scientific communities in research are being questioned when their roles are dominant and outstanding. The concept of compulsory vaccination has been arguably classified as a human right. With this, the world of vaccinations was tied to concepts that it really had nothing to do with. Arbitrary pairing and joint treatment of remote concepts favours the spread of fatal diseases such as measles and poliomyelitis, for which there are already vaccines. Meanwhile, pseudosciences are misleading the public.

The coronavirus pandemic has also necessitated changes in data management. The ETT has previously initiated a number of legal and professional proposals on health data management and access to research data, and has developed its own data protection rules following the introduction of the GDPR.

Open access

A. Anton 2010 Stabilization of toxic element contaminated soil with water treatment sludge Fresenius Environmental Bulletin 19 1774 – 1783

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