Modern Biomedical Technologies Research Articles

CLEVER assay: A visual and rapid RNA extraction-free detection of SARS-CoV-2 based on CRISPR-Cas integrated RT-LAMP technology.

AimThe current scenario of COVID‐19 pandemic has presented an almost insurmountable challenge even for the most sophisticated hospitals equipped with modern biomedical technology. There is an urgency to develop simple, fast and highly accurate methods for the rapid identification and isolation of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infected patients. To address the ongoing challenge, the present study offers a CLEVER assay (CRISPR‐Cas integrated RT‐LAMP Easy, Visual and Extraction‐free RNA) which will allow RNA extraction‐free method to visually diagnose COVID‐19. RNA extraction is a major hurdle in preventing rapid and large‐scale screening of samples particularly in low‐resource regions because of the logistics and costs involved.Method and ResultHerein, the visual SARS‐CoV‐2 detection method consists of RNA extraction‐free method directly utilizing the patient's nasopharyngeal and oropharyngeal samples for reverse transcription loop‐mediated isothermal amplification (RT‐LAMP). Additionally, the assay also utilizes the integration of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)‐Cas12‐based system using different guide RNAs of N, E and an internal control POP7 (human RNase P) genes along with visual detection via lateral flow readout‐based dip sticks with unaided eye (~100 min). Overall, the clinical sensitivity and specificity of the CLEVER assay were 89.6% and 100%, respectively.ConclusionTogether, our CLEVER assay offers a point‐of‐care tool with no equipment dependency and minimum technical expertise requirement for COVID‐19 diagnosis.Significance and Impact of the StudyTo address the challenges associated with COVID‐19 diagnosis, we need a faster, direct and more versatile detection method for an efficient epidemiological management of the COVID‐19 outbreak. The present study involves developing a method for detection of SARS‐CoV‐2 in human body without RNA isolation step that can visually be detected with unaided eye. Taken together, our assay offers to overcome one major defect of the prior art, that is, RNA extraction step, which could limit the deployment of the previous assays in a testing site having limited lab infrastructure.

Representation Theorem and Functional CLT for RKHS-Based Function-on-Function Regressions

We investigate a nonparametric, varying coefficient regression approach for modeling and estimating the regression effects caused by two functionally correlated datasets. Due to modern biomedical technology to measure multiple patient features during a time interval or intermittently at several discrete time points to review underlying biological mechanisms, statistical models that do not properly incorporate interventions and their dynamic responses may lead to biased estimates of the intervention effects. We propose a shared parameter change point function-on-function regression model to evaluate the pre- and post-intervention time trends and develop a likelihood-based method for estimating the intervention effects and other parameters. We also propose new methods for estimating and hypothesis testing regression parameters for functional data via reproducing kernel Hilbert space. The estimators of regression parameters are closed-form without computation of the inverse of a large matrix, and hence are less computationally demanding and more applicable. By establishing a representation theorem and a functional central limit theorem, the asymptotic properties of the proposed estimators are obtained, and the corresponding hypothesis tests are proposed. Application and the statistical properties of our method are demonstrated through an immunotherapy clinical trial of advanced myeloma and simulation studies.

Evaluation of disorders of adaptive mechanisms in heart failure by microwave dielectrometry

Differential diagnosis of stress adaptive mechanisms is one of the areas of modern biomedical engineering and the most complex part of the pre-nosological diagnosis of cardiac pathology. One of the manifestations of disadaptation in heart failure is a violation of the mechanisms of realization of the intracellular chain "signal-function". The concept of imbalance in the functioning of the adenylate cyclase system and β-adrenergic receptors of the erythrocytes membrane and cardiomyocytes is considered in the pathogenesis of the heart.
 The study of the dielectric constant (ε՜) of erythrocytes of patients with heart failure was performed using an instrument-recording complex based on microwave dielectrometry of the γ-dispersion region of free water dielectric permittivity. Testing of the β-adrenergic complex of the erythrocyte membrane by specific stimulators, blockers, and modulators was implemented at a fixed frequency of microwave radiofrequency generation (f = 37,7 GHz). Interpretation of the obtained experimental data was that the process of interaction of bioregulators with the biological system is accompanied by an increase or decrease in the relative amount of free water, which leads to a change in the real part of ε՜ complex dielectric constant. This allowed us to visualize the violation of the signal cell system at the molecular level, which manifested itself in the change of integral hydration by ε՜ parameter. It was shown that the change in the dielectric constant of the erythrocyte suspension at risk (patients with hereditary predisposition to dilated and ischemic cardiomyopathy) was significant relative to the dielectric parameters of erythrocyte samples from healthy donors; there was a tendency to block β-adrenergic receptors, with the combined action of adrenaline, PGE2 and cordanum, with Δε՜ = 0,009 ± 0,008 х 10-12 F/m. It should be noted the formation of preconditions for changes in the functioning of the adenylate cyclase system and the development of heart failure in the group at risk, is accompanied by dilated and ischemic cardiomyopathy.
 The effectiveness of the microwave dielectrometry method for the assessment of violations of adaptation mechanisms through the adenylate cyclase system of the erythrocyte membrane in dilated and ischemic forms of cardiomyopathies is shown. The results of the study are the basis for the introduction of the dielectric constant criterion in the general algorithm of pre-nosological diagnosis of heart failure.

THE INDIVIDUAL EXISTENTIAL SECURITY IN THE CONTEXT OF THE CRISIS OF THE HUMANISTIC PHILOSOPHY

Personal security is one of the important components of Russian national security. A serious challenge to the existential security of the individual comes from modern biomedical and information technologies, the use of which creates opportunities for changing the biosocial nature of a person. The distortion of the moral content of the philosophical principle of humanism in the conditions of the Fourth Industrial Revolution gave rise to the spread of the philosophy and ideology of transhumanism and post-humanism. The introduction of Trans-human and Post-human images into the public consciousness is a global threat to the continued existence of mankind.
 Purpose is to trace the historical transformation of the philosophy of humanism, which led to the formation of modern concepts of Trans-human and Post-human.
 Methodology: the article uses the methodology of historical and philosophical research approaches.
 Results:
 1) A brief overview of the evolution of understanding of the essence of man and the principle of humanism in the history of philosophical thought is given.
 2) The danger of deepening the gap between man and the technologies he creates is shown, especially in the conditions of the Fourth Industrial Revolution.
 3) The content of the ideology and philosophy of transhumanism is revealed.
 4) Various images of the Post-human, replacing Homo Sapiens, are considered.
 5) The possible negative consequences for humanity of attempts to artificially change human nature are indicated.
 Practical implications: scientific discussions, expert activity, educational process.
 Conclusions:
 1) A serious challenge to the security of the individual in modern society is the implementation in practice of the ideas of «cybernetic evolution», which call into question the continuation of human existence as a biological species.
 2) The philosophy of classical humanism, based on the recognition of human life as the highest ethical value, is being blurred and distorted today.
 3) Advances in the development of biomedical and information technologies have created favorable opportunities for attempts to revise the very nature of man in order to prolong life expectancy and overcome mortality, which was expressed in the concepts of Trans-human and Post-human.
 4) The philosophy of transhumanism and post-humanism consistently leads to the destruction of the human personality.
 5) The task of global management of post-humanity is greatly facilitated by the use of genetic and information technologies.

Интернистика ХХI века: проблемы и перспективы

Развитие современных биомедицинских технологий, углубление и расширение специализации медицинских профессий оказывают неоднозначное влияние на интернистику, клиническое мышление врача, этику взаимоотношений врача и пациента. В статье обсуждаются перспективы возрождения внутренней медицины на современном интегральном уровне, пути оптимизации подготовки будущих врачей на принципах проблемно-личностно-практически-ориентированной парадигмы, непрерывного образования.

Human metabolite detection by surface-enhanced Raman spectroscopy.

Metabolites are important biomarkers in human body fluids, conveying direct information of cellular activities and physical conditions. Metabolite detection has long been a research hotspot in the field of biology and medicine. Surface-enhanced Raman spectroscopy (SERS), based on the molecular “fingerprint” of Raman spectrum and the enormous signal enhancement (down to a single-molecule level) by plasmonic nanomaterials, has proven to be a novel and powerful tool for metabolite detection. SERS provides favorable properties such as ultra-sensitive, label-free, rapid, specific, and non-destructive detection processes. In this review, we summarized the progress in recent 10 years on SERS-based sensing of endogenous metabolites at the cellular level, in tissues, and in biofluids, as well as drug metabolites in biofluids. We made detailed discussions on the challenges and optimization methods of SERS technique in metabolite detection. The combination of SERS with modern biomedical technology were also anticipated.

Human rights and modern biomedicine: problems and perspectives

The article is devoted to the emerging threats to human rights in the context of the development of biomedical technologies, as well as to the identification of social risks requiring legal resolution in this area. It suggests a human rights model for regulating innovative methods of diagnosis and treatment. The purpose of the article is to analyze legislation in the field of modern biomedicine, genetic engineering, and related innovative technologies. A comparative legal study applied in the work made it possible to substantiate a framework model for regulating modern biomedicine. The main task of such a model is to identify risks affecting fundamental human and civil rights and freedoms. With this approach, the details of regulation are the subject of bylaws or the corresponding prescriptions of professional medical organizations. Methods . The basis of this research was formed by such research methods as analysis of legal regulation, formal legal and comparative legal methods. The main results of the study are to determine the legal links between modern biomedical technologies and the concept of personalized medicine. In fact, the lack of interaction of new advances in biomedicine with the basic provisions of medical care has been revealed. The article proves the need to impose restrictions on the alleged popularization of innovative technologies by persons without medical education, using them for dubious social purposes. The risks of developing updated eugenics have been outlined. The tendency of relativism in consolidating the principles of mutual relations between a person, state, and society has been identified. Conclusions. The development of biomedicine requires an adequate response from the Russian legislation, which does not yet take into account most of its achievements. This creates certain risks for human and civil rights and freedoms. The article substantiates the introduction of bans on the most ethically questionable technologies and experiments. It is proposed to expand the powers of professional medical organizations (including the transfer of some of the regulatory powers to them).

Using Simulation-Based Active Learning Strategies for Teaching Biofluids Concepts.

Biofluids comprises a core topical domain for modern biomedical engineering education. Like other biomedical topic areas, biofluids education must address highly interdisciplinary and applied topics. Concept/problem-based active learning approaches can provide effective avenues to teach such diverse and applied topics. However, with the heterogeneity within biofluids topics across cellular, physiological, and/or extra-organismal scales, it is important to develop active learning content that enables students to explore concepts with appropriate context. This challenge is further complicated by the need to administer such content remotely (due to the Covid-19 pandemic). Here, we outline our design process and implementation experience for simulation-based active learning modules for a newly developed physiological biofluids course. We share the overall design approach, with two example cases of simulation-based concept exploration: (a) arterial Windkessel effects and lumped parameter hemodynamic analysis; and (b) curvature-induced helical flow in human aorta illustrated using four-dimensional (4D) flow magnetic resonance imaging (MRI). Evidence from student survey ratings, student comments and feedback, and monitoring student performance for course deliverables indicate positive student response toward these modules, and efficacy of the modules in enabling student learning. Based on our design and implementation experience, we argue that simulation-based approaches can enable active learning of biofluids through remote and online learning modalities.

Complex reconstructions in the facial and cranial regions

Posttraumatic reconstruction of the neurocranium and viscerocranium is an essential part of modern oral and maxillofacial surgery, in addition to oncological surgery, surgery of congenital craniofacial deformities and dental surgery. Due to the complex anatomy of the facial skull and significant esthetic and functional demands on its reconstruction, reconstructive trauma surgery in this area places the highest demands on the surgeon. This is all the more true if definitive craniomaxillofacial surgical treatment can sometimes only be performed with considerable delays for the benefit of other life-threatening injuries. In order to take these prerequisites into account, achievements of modern biomedical technology, such as intraoperative real-time navigation, computer-assisted planning and computer-assisted manufacturing (CAD/CAM) of patient-specific biomodels and implants, came up early for use in oral and maxillofacial surgery. In combination with intraoperative three-dimensional imaging, these methods result in atreatment pathway tailored to the individual patient, which is directly checked for quality at every step and thus ensures the best possible result for the patient. The use of these technologies extends far beyond the original indications in the area of orbital reconstruction and restoration of bony defects with simple geometry, such as skull defects. Nowadays, even the most complex pan-facial fractures can be restored esthetically and functionally by means of digitalized preliminary planning and individualized skull, orbital and zygomatic implants as well as total temporomandibular joint prostheses.

Государственный научный центр Российской Федерации – Федеральный медицинский биофизический центр имени А.И.Бурназяна ФМБА России: 75 лет на страже здоровья людей

The article presents the history of creation, formation and development of the State Scientific Center of the Russian Federation — Federal Medical Biophysical Center named after A.I. Burnazyan of the Federal Medical and Biological Agency of Russia (A.I. Burnazyan Federal Biophysical Center, the Center). The Institute of Biophysics of USSR Ministry of Health and Clinical Hospital № 6, predecessors of the Center, were engaged in the elimination of medical and sanitary consequences of Chernobyl Radiation Accident (1986). The main directions of activities of the A.I. Burnazian Federal Medical Biophysical Center — the flagship institution of Russian health care in the field of biophysics, radiation and nuclear medicine are considered. The perspectives of scientific activity of the Center related to solving actual problems of modern radiobiology, radiation safety and biomedical technologies are outlined. It is concluded that it is expedient to create the Disaster Medicine Service of the Federal Medical and Biomedical Agency of Russia.

Anti-tumour drugs of marine origin currently at various stages of clinical trials (review)

Oncological diseases for a long time have remained one of the most significant health problems of modern society, which causes great losses in its labour and vital potential. Contemporary oncology still faces unsolved issues as insufficient efficacy of treatment of progressing and metastatic cancer, chemoresistance, and side-effects of the traditional therapy which lead to disabilities among or death of a high number of patients. Development of new anti-tumour preparations with a broad range of pharmaceutical properties and low toxicity is becoming increasingly relevant every year. The objective of the study was to provide a review of the recent data about anti-tumour preparations of marine origin currently being at various phases of clinical trials in order to present the biological value of marine organisms – producers of cytotoxic compounds, and the perspectives of their use in modern biomedical technologies. Unlike the synthetic oncological preparations, natural compounds are safer, have broader range of cytotoxic activity, can inhibit the processes of tumour development and metastasis, and at the same time have effects on several etiopathogenic links of carcinogenesis. Currently, practical oncology uses 12 anti-tumour preparations of marine origin (Fludarabine, Cytarabine, Midostaurin, Nelarabine, Eribulin mesylate, Brentuximab vedotin, Trabectedin, Plitidepsin, Enfortumab vedotin, Polatuzumab vedotin, Belantamab mafodotin, Lurbinectedin), 27 substances are at different stages of clinical trials. Contemporary approaches to the treatment of oncological diseases are based on targeted methods such as immune and genetic therapies, antibody-drug conjugates, nanoparticles of biopolymers, and metals. All those methods employ bioactive compounds of marine origin. Numerous literature data from recent years indicate heightened attention to the marine pharmacology and the high potential of marine organisms for the biomedicinal and pharmaceutic industries.

Artificial intelligence using for medical diagnosis via implementation of expert systems

Modern biomedical technologies development affords to provide the doctor with colossal amount of information about patients organism condition. However, the opportunity of using this data for medical diagnosis fully now is a distantive perspective only. The reason is a humans limited ability in assessment and interpretation this data arrays. The solution seems in artificial intelligence and expert systems wide introduction to medicine. Currently, almost all authors consider various options for constructing artificial neural networks as a way to implement artificial intelligence. This approach, which goes back to the fundamental theorem of A.N. Kolmogorov, the works of V.I. Arnold and Hecht-Nielsen [3], demonstrates excellent capabilities in a number of pattern recognition problems, which are reduced to revealing hidden details against the background of input noises. Much less often is mentioned such a method of modeling formal thinking as expert systems, which arose in the 1960s and then went into the shadows. Since the inception of cybernetics, computer programmers have tried to reproduce the mechanism of human thinking, that is, the task was to teach the computer to "think". The first known results in the field of creating and using intelligent systems were laid by the work of Norbert Wiener and G.S. Altshuller. At the same time, the creation of intelligent systems was reduced to the development of programs that solve problems using a variety of heuristic methods based on the property of human thinking to generalize.

Human respiratory monitoring during sleep using a two-channel bioradar

permanent sleep deprivation and a decrease in sleep quality. Currently, in clinical practice, the method of polysomnography is used to detect sleep disorders. This method is expensive, labor and time-consuming, as well as uncomfortable for the patient. Therefore, at present, the problem of creating accurate, reliable and comfortable for the patients methods for assessing the sleep quality, as well as identifying and monitoring various sleep disorders, remains an up-to-date task of modern biomedical engineering. One of these methods is bioradiolocation, which allows detecting sleep disorders based on the variability of the breathing pattern of a sleeping person. However, because the amplitude of chest movements during breathing in different directions differs by an order of magnitude, the quality of the signal received by the bioradar during sleep also varies depending on the orientation of the sleeping person relative to the bioradar. To overcome this problem, in this article we propose a combined use of two bioradars oriented at different angles towards to the sleeping person. Thus, the aim of this work was to develop a bioradar system that provides reliable registration of the breathing pattern for various positions of a sleeping person. During the experiments, we used two monochromatic bioradars "BioRASCAN-24" with probing frequencies in the range of 24.0 and 24.1 GHz, located at an angle of 90 ° to each other. In this work, we used bioradar data recorded for seven volunteers who underwent polysomnographic research at the sleep laboratory of Almazov National Medical Research Centre. During the night, a parallel recording of bioradar signals and polysomnographic data was carried out for each subject using the Embla N7000 system (Natus Neurology Inc., USA). The duration of the experimental recording for each subject was from 7 to 9 hours. An algorithm was developed to extract a breathing pattern from a bioradar signal and estimate the respiratory rate of a sleeping person. It consisted of the following stages: synchronization of the bioradar and polysomnographic signals, demodulation, exclusion from consideration of signal fragments containing motion artifacts, signal filtering in order to isolate the breathing pattern, assessment of respiration rate in the inter-artifact periods for each of the bioradars separately, the final estimation of the respiration rate for the inter-artifact periods, taking into account the combination of data for both radars. Bioradar signal processing algorithms were done utilizing Matlab 2020b. To assess the accuracy of the proposed algorithm, we compared the respiratory rates calculated for each 30-second epoch using bioradar data with similar parameters calculated by the abdominal belt polysomnography sensor. The efficiency of the proposed algorithm was estimated by the accuracy and the mean absolute error. The results obtained for seven volunteers showed that the developed two-channel bioradar system turned out to be more accurate and reliable than a single bioradar. In the course of further research, it is planned to expand the dataset to include data from volunteers not only with sleep-related breathing disorders, but also with other sleep disorders. Although this work was carried out with the involvement of only seven volunteers, it is nevertheless an important step towards the development of a reliable view-independent bioradar system for assessing breathing rate during sleep.

Правовое оформление евгеники и современные правовые тенденции в свете новейших биотехнологий

The article examines the historical retrospective of the legal confirmation of eugenic practices in a number of states: Germany, Denmark, Iceland, Canada, Norway, Singapore, the USSR and the Russian Federation, the USA, Finland and Sweden. Attention is drawn to the implementation of eugenic practices through migration and marriage legislation. The spread of theories of genetics in a number of states is reflected. The article provides examples of modern biomedical technologies that can be considered within the framework of eugenic practices and require appropriate legal regulation.

LEGAL REGULATION OF GENOMIC TECHNOLOGIES, GENODIAGNOSTICS AND GENE THERAPY AND IMPLEMENTATION OF THEIR RESULTS IN MEDICAL PRACTICE

At the present stage of formation and progressive development of the socially-oriented policy of the Russian state and developed civil society, the possibility of using modern genomic technologies, genodiagnostics and gene therapy in medical practice becomes particularly relevant in order to ensure the physical and mental health of the population and protect the rights of citizens in the field of medicine, effective treatment of patients with genetic and other diseases. The practice of implementing such developments is aimed at implementing the rights of a citizen of the Russian Federation in the field of health care, genetic «improvement» of the human body for medical purposes. The article analyzes some features of legal regulation and the possibility of using modern biomedical technologies, genodiagnostics and gene therapy in medical practice in order to ensure the physical and mental health of the population, effective treatment of severe diseases.

КОНСТРУИРОВАНИЕ ЧЕЛОВЕКА В РАКУРСЕ СОВРЕМЕННОЙ БИОМЕДИЦИНЫ: ПАНИЧЕСКИЕ ОЖИДАНИЯ, ЭЙФОРИЯ И ОСТОРОЖНЫЕ ПРОГНОЗЫ

The article attempts to conduct a balanced analysis of the impact of modern biomedical technologies on human corporeality from the perspective of its formation processes. On the one hand, there is a panic mood about the loss of the human proper in man due to the rapid development of biomedical technolo-gies and the construction of human corporeality using them, and as a result, the adoption of measures to prevent radical modification of such corporeality. On the other hand, there are also excessive expecta-tions for modern biomedical technologies that are ultimately, as supposed, to be able to make humans immortal. The task of the author of the article is to show that the scientists involved in biomedical are rather cautious about radical changes in human body, seeing the real risks from such intervention and the lack of clarity about the long-term consequences. At the same time, any interference with a person 's body must be based on respect for and observance of human rights and human dignity.

Clinical effectiveness of cognitive behavioural therapy on alcohol-dependent patients: an observation with the WeChat platform

BackgroundWith the continuous improvement of people’s material living standards, the consumption of alcoholic beverages is increasing. Alcohol dependence caused by alcohol addiction has become a widespread concern in society. As...

Islam, ethics and bioethics

The article discusses the influence of Sharia, as mandatory rules of behavior of Muslims, on ethical and bioethical norms of life. Based on the sources of Islam, the Koran and the Sunnah, rather than their various interpretations, the article deals with a number of problems of medical bioethics. It is noted that, despite the influence of modern biomedical technologies on modern world cultures, their moral and ethical comprehension is the least in Islam. All of these issues are considered solely on the basis of the provisions of the Koran and the Sunnah. From the various ethical positions that contain the Qur'an and the Sunnah, it can be concluded that the physician, as a true Muslim, must demonstrate the qualities prescribed by Islam to the individual. It is shown that discussions in Islamic countries in a number of areas of modern bioethics do not conflict with the sources of Islam. It is concluded that in the Islamic world the norms of medical bioethics are determined by religious beliefs, which are the dominant of all social life.

Synthesis of α-(R)-/γ-(S)-Dimethyl Substituted Peptide Nucleic Acid Submonomer Using Mitsunobu Reaction

One of the major challenges facing modern biochemical and biomedical technologies are finding molecular tools for diagnosis and detection of genetic diseases. In this connection, several classes of oligonucleotides have been developed that can recognize and bind to DNA and RNA with high affinity and sequence selectivity and withstand enzymatic degradation by proteases and nucleases; however, few can traverse the cell membrane on their own. One such promising class of nucleic acid mimics developed in the last two decades which showed good results in vitro, are the peptide nucleic acids (PNAs). New chiral α- and γ-peptide Nucleic Acid (PNA) submonomer with methyl substituents in pseudopeptide backbone were synthesized via Mitsunobu reaction. The α-(R)-/γ-(S)-configuration of the chiral centres will ensure the preorganization of the PNA oligomer into a right-handed helix. The results obtained showed that Boc/Fmoc-submonomer compatible with Boc-protocol PNAs solid-phase synthesis on an MBHA resin. We synthesized simple and efficient α-R-, γ-S-disubstituted PNA submonomer based on L-Ala and D-Ala with the construction of the intermediate pseudopeptide moiety by Mitsunobu reaction for subsequent use in the Boc-Protocol of solid phase PNA synthesis.

An Efficient Nonparametric Estimate for Spatially Correlated Functional Data

Functional data are often generated by modern biomedical technologies where features related to the pathophysiology and pathogenesis of a disease are interrogated repeatedly over time and at multiple spatially interdependent regions. To reduce model complexity and simplify the resulting inference, possible spatial correlation among neighboring regions is often neglected. In this article, we propose a weighted kernel smoothing estimate of the mean function that leverages the spatial and temporal correlation. We also address the companion problem of developing a simultaneous prediction method for individual curves using discrete samples. We establish the asymptotic properties of the proposed estimate, including its unique maximum efficiency achieving minimum asymptotic variance. The proposed method improves estimation and prediction in the presence of sparse observations, and therefore, is advantageous to biomedical applications that utilize markers to identify features intrinsic to a particular disease at multiple interdependent sites within an organ. Our simulation and case studies show that the proposed method outperforms conventional approaches for characterizing the dynamic functional imaging data, with the maximum benefit achieved in the presence of a small number of repeated scans.