Biomedical Experiments Research Articles

Improving Pure Titanium's Biological and Mechanical Characteristics through ECAP and Micro-Arc Oxidation Processes.

Pure titanium is limited to be used in biomedical applications due to its lower mechanical strength compared to its alloy counterpart. To enhance its properties and improve medical implants feasibility, advancements in titanium processing technologies are necessary. One such technique is equal-channel angular pressing (ECAP) for its severe plastic deformation (SPD). This study aims to surface modify commercially pure titanium using micro-arc oxidation (MAO) or plasma electrolytic oxidation (PEO) technologies, and mineral solutions containing Ca and P. The composition, metallography, and shape of the changed surface were characterized using X-ray diffraction (XRD), digital optical microscopy (OM), and scanning electron microscope (SEM), respectively. A microhardness test is conducted to assess each sample's mechanical strength. The weight % of Ca and P in the coating was determined using energy dispersive spectroscopy (EDS), and the corrosion resistance was evaluated through potentiodynamic measurement. The behavior of human dental pulp cell and periodontal cell behavior was also studied through a biomedical experiment over a period of 1-, 3-, and 7-days using culture medium, and the cell death and viability can be inferred with the help of enzyme-linked immunosorbent assay (ELISA) since it can detect proteins or biomarkers secreted by cells undergoing apoptosis or necrosis. This study shows that the mechanical grain refinement method and surface modification might improve the mechanical and biomechanical properties of commercially pure (CP) titanium. According to the results of the corrosion loss measurements, 2PassMAO had the lowest corrosion rate, which is determined to be 0.495 mmpy. The electrode potentials for the 1-pass and 2-pass coated samples are 1.44 V and 1.47 V, respectively. This suggests that the coating is highly effective in reducing the corrosion rate of the metallic CP Ti sample. Changes in the grain size and the presence of a high number of grain boundaries have a significant impact on the corrosion resistance of CP Ti. For ECAPED and surface-modified titanium samples in a 3.6% NaCl electrolyte solution, electrochemical impedance spectroscopy (EIS) properties are similar to Nyquist and Bode plot fitting. In light of ISO 10993-5 guidelines for assessing in vitro cytotoxicity, this study contributes valuable insights into pulp and periodontal cell behavior, focusing specifically on material cytotoxicity, a critical factor determined by a 30% decrease in cell viability.

Deformation and motion of the mesh shaped robot driven by the magnet

Magnetic field driven robots have a wide spectrum of applications in many areas, such as in biomedical experiment, surgical tools, aerospace and mechanical engineering. In the present study, we make a comprehensive investigation on the deformation and motion of a mesh shaped robot controlled by the magnet. First we have prepared the matrix material of the robot, which is a mixture of silica gel and NdFeB powders. Then the deformation and motion of the robot driven by the magnet are recorded, and the warping and arching configurations are analyzed. The experimental phenomena have been compared with the numerical simulation and theoretical analysis, and the results are in excellent agreement. These findings are beneficial to engineer new types of intelligent robots, as well as to put them in various industrial settings.

A novel qPCR-based technique for identifying avian sex: An illustration within embryonic craniofacial bone.

Sex is a biological variable important to consider in all biomedical experiments. However, doing so in avian embryos can be challenging as sex can be morphologically indistinguishable. Unlike humans, female birds are the heterogametic sex with Z and W sex chromosomes. The female-specific W chromosome has previously been identified in chick using a species-specific polymerase chain reaction (PCR) technique. We developed a novel reverse transcription quantitative PCR (RT-qPCR) technique that amplifies the W chromosome gene histidine triad nucleotide-binding protein W (HINTW) in chick, quail, and duck. Accuracy of the HINTW RT-qPCR primer set was confirmed in all three species using species-specific PCR, including a novel quail-specific HINTW PCR primer set. Bone development-related gene expression was then analyzed by sex in embryonic lower jaws of duck and quail, as adult duck beak size is known to be sexually dimorphic while quail beak size is not. Trends toward sex differences were found in duck gene expression but not in quail, as expected. With these novel RT-qPCR and PCR embryo sexing methods, sex of chick, quail, and duck embryos can now be assessed by either/both RNA and DNA, which facilitates analysis of sex as a biological variable in studies using these model organisms.

Certain Bioethical Aspects of Personal Dignity in Genomics

The paper deals with the constitutionalism and constitutionalization of certain provisions of genomics and bioethics at the present stage. The author analyzes constitutional domestic and foreign normative acts, the subject of which are relations in the field of genomics and the correlation of these relations with bioethics. The paper presents the opinions of Russian and foreign scientists regarding bioethics and related phenomena. The paper examines individual bioethical aspects, potential risks and threats, and searches for elements of the scientific concept of bioethical and somatic dignity of the individual in Russian legislation. The paper discusses the general issues of the legal regime of the human genome and the issues of genetic, genomic, biomedical research. The author raises the question of the balance of private and public interests as an optimal combination of personal interest and scientific ones. Having studied the legislation, the author speaks about the need to legally consolidate the definition of the concepts «genetic research with human participation» and «genomic research with human participation» at the federal level. The author expresses the opinion that the introduction of this conceptual apparatus into medical legislation would help to unify value-based legal approaches and models of legal regulation, and would also be the most important guarantee of the inviolability of human somatic dignity, eliminating unjustified risk and potential threats of subsequent biomedical research and experiments with human participation.The author concludes: the categories of bioethical and somatic dignity require further disclosure in Russian legislation and state policy in the field of biomedicine.

Production and separation of positron emitters for hadron therapy at FRS-Cave M

The FRagment Separator FRS at GSI is a versatile spectrometer and separator for experiments with relativistic in-flight separated short-lived exotic beams. One branch of the FRS is connected to the target hall where the bio-medical cave (Cave M) is located. Recently a joint activity between the experimental groups of the FRS and the biophysics at the GSI and Department of physics at LMU was started to perform biomedical experiments relevant for hadron therapy with positron emitting carbon and oxygen beams. This paper presents the new ion-optical mode and commissioning results of the FRS-Cave M branch where positron emitting 15O-ions were provided to the medical cave for the first time. An overall conversion efficiency of 2.9±0.2×10−415O fragments per primary 16O ion accelerated in the synchrotron SIS18 was reached.

AWARENESS AND CONSUMPTION OF PREBIOTICS AND PROBIOTICS AMONG ADULT (MALE/FEMALE) IN AL AHSA REGION

Introduction: Public awareness and interest in food that is highly related to their health benefits are flourishing. Even though there is a gap between the biomedical sciences experiments and the business of marketing, the accessibility of health-promoting channels/media leads the consumer to seek healthier food and drinks. Pre/probiotics have a big role in management and protection of gastrointestinal infection, allergic disease. The aim of study is to find out the awareness and consumption of prebiotics and probiotics among adults (male/female) in Al-Ahsa region. Method: Cross sectional study was conducted in Al Ahsa, KSA among adults using structured questionnaire which included questions related to demographic, anthropometric, frequency of consumption of prebiotics and probiotics and about health status. A clear inclusion and exclusion criteria data was set before the data collection. Arabic version of Questionnaire along with ethical consent form was distributed through social media total of 450 participated in the study with their consent, based on inclusion and exclusion criteria data of 384 respondents was included for statistical analysis, Data was collected, checked for completeness, and further analysis of the data was done by using (SPSS) software version 20, Descriptive statistics was calculated including frequencies and proportions for categorical variables. Approval for this study was obtained from KAIMRC and IRB Result: Majority of the participants are not aware of the term prebiotic (64.3%) and probiotic (61.2%). However, pre/probiotics products (apples, leeks, garlic, yogurt) are available in all the supermarkets which (kefir and yakult) are rarely available, also the consumption of these products are in high percentage on regular basis (28% & 35%) daily and weekly basis, respectively. Significant association of age, gender, and educational level for awareness & consumption. Conclusion: Pre/probiotics products are available abundantly in all the Al-Ahsa supermarket also the consumption rate, most of them aware of the health benefits of these products. However, the term Pre/probiotics is not very familiar to the population of al Ahsa indicating need for increasing awareness about these products also its health benefits.

A maximum kernel-based association test to detect the pleiotropic genetic effects on multiple phenotypes.

Testing the association between multiple phenotypes with a set of genetic variants simultaneously, rather than analyzing one trait at a time, is receiving increasing attention for its high statistical power and easy explanation on pleiotropic effects. The kernel-based association test (KAT), being free of data dimensions and structures, has proven to be a good alternative method for genetic association analysis with multiple phenotypes. However, KAT suffers from substantial power loss when multiple phenotypes have moderate to strong correlations. To handle this issue, we propose a maximum KAT (MaxKAT) and suggest using the generalized extreme value distribution to calculate its statistical significance under the null hypothesis. We show that MaxKAT reduces computational intensity greatly while maintaining high accuracy. Extensive simulations demonstrate that MaxKAT can properly control type I error rates and obtain remarkably higher power than KAT under most of the considered scenarios. Application to a porcine dataset used in biomedical experiments of human disease further illustrates its practical utility. The R package MaxKAT that implements the proposed method is available on Github https://github.com/WangJJ-xrk/MaxKAT.

Substrate colour guides turquoise killifish's (Nothobranchius furzeri) choice of preferred spawning habitat.

Turquoise killifish (Nothobranchius furzeri) is a promising new model species used in biomedical and ecological laboratory experiments, and should be kept under optimal conditions to ensure fish welfare and the quality of science. While the popularity of this model species is rapidly increasing, we need to improve our understanding of how the species interacts with its environment in order to optimise its husbandry. Specifically, turquoise killifish are substrate spawners that bury their eggs in the sediment which can be accommodated under captive conditions, but it is not yet known whether or not turquoise killifish have a preference for a specific sediment colour. Here, we performed a laboratory experiment in which fish could choose between white, orange, and black sand for spawning, colours of which are relevant in both laboratory and field conditions. We assessed their preference in the context of single breeding pairs, as well as in a social group setting. Additionally, we also assessed preference of individuals for a white vs. black background in a non-mating context. Single breeding pairs deposited over 3.5× more eggs in black compared to orange or white sand. Similarly, fish in social groups deposited over 3.5× more eggs in black compared to orange sand, which in turn was over 2× times higher than that in white sand. Fish showed a slight preference for the black compared to the white zone in a non-mating context but this did not correlate with substrate choice during the spawning tests. The results suggest that turquoise killifish select their preferred spawning location based on the colour of the substrate. These findings contribute to our understanding of the species' biology and can help to guide good welfare and scientific practice. This article is protected by copyright. All rights reserved.

Designing microplate layouts using artificial intelligence

Microplates are indispensable in large-scale biomedical experiments but the physical location of samples and controls on the microplate can significantly affect the resulting data and quality metric values. We introduce a new method based on constraint programming for designing microplate layouts that reduces unwanted bias and limits the impact of batch effects after error correction and normalisation. We demonstrate that our method applied to dose-response experiments leads to more accurate regression curves and lower errors when estimating IC50/EC50, and for drug screening leads to increased precision, when compared to random layouts. It also reduces the risk of inflated scores from common microplate quality assessment metrics such as Z′ factor and SSMD. We make our method available via a suite of tools (PLAID) including a reference constraint model, a web application, and Python notebooks to evaluate and compare designs when planning microplate experiments.

Particle count estimation in dilution series experiments

AbstractEstimation of microorganism concentration in samples (bacterial cells or viral particles) has been a focal point in biomedical experiments for more than a century. Serial dilution of the samples is often used to estimate the target concentrations in immunology, virology, and pharmaceutical industry. A new methodology, called joint likelihood estimation (JLE), is proposed to estimate particles such as the number of microorganisms in a sample from counts obtained by serially diluting the sample. It models count data from the entire single dilution series rather than using only specific dilutions. The theoretical framework is based on the binomial and the Poisson distributions and is consistent with the actual experimental process. The estimator of the target concentration is obtained by MLE with derived joint likelihood functions of the observed counts including right‐censored values. Simulations demonstrated that the new JLE method significantly increases precision and accuracy of the estimate compared to the existing methods. It can be applied to a variety of studies with similar experimental designs, especially when the number of particles in the neat sample is very large.

A Silicon-Based Radio Platform for Integrated Edge Sensing and Communication Toward Sustainable Healthcare

Faced with COVID-19 and the trend of aging, it is demanding to develop an online health metrics sensing solution for sustainable healthcare. An edge radio platform owning the function of integrated sensing and communications is promising to address the challenge. Radar demonstrates the capability for noncontact healthcare with high sensitivity and excellent privacy protection. Beyond conventional radar, this article presents a unique silicon-based radio platform for health status monitoring supported by coherent frequency-modulated continuous-wave (FMCW) radar at Ku-band and communication chip. The radar chip is fabricated by a 65-nm complementary metal–oxide–semiconductor (CMOS) process and demonstrates a 1.5-GHz chirp bandwidth with a 15-GHz center frequency in 220-mW power consumption. A specific small-volume antenna with modified Vivaldi architecture is utilized for emitting and receiving radar beams. Biomedical experiments were implemented based on the radio platform cooperating with the antenna and system-on-chip (SoC) field-programmable gate array (FPGA) edge unit. An industrial, scientific, and medical (ISM)-band frequency-shift keying (FSK) communication chip in 915-MHz center frequency with microwatt-level power consumption is used to attain communications on radar-detected health information. Through unified integration of radar chip, management software, and communication unit, the integrated radio platform featuring −72-dBm sensitivity with a 500-kb/s FSK data rate is exploited to drastically empower sustainable healthcare applications.

Feasibility of Magneto-Encephalography Scan under Color-Tailored Illumination

Color plays an important part in human activities, and it also affects circadian cycle and the decision making process. Therefore, it is important to investigate human judgment under different color of illumination, especially because color perception is subjective. In this study, we developed required instrumentation to control the red (R), green (G), blue (B), and amber (A) colored light emitting diode (LED) lamp for carrying out magneto-encephalography (MEG) brain scans. We developed a software to generate all the colors in the visual spectrum, predefined white light combinations and saturation of an illuminated objects by using RGBA color pallet. The lamp is required to control from outside of the MEG electromagnetically shielded room with the LED lamp located inside the MEG room. Hence, USB is used for the communication mode. The feasibility of using LED lamp with MEG brain scanner has been validated for bio-medical and psychological MEG experiments.

The Mongolian Gerbil as a Useful Experimental Model in Reproductive Biology.

Ultimately, the Mongolian gerbils (Meriones unguiculatus) have acquired a relevant role in biological and biomedical experiments alongside other rodents. The use of gerbils in research has been mainly oriented to physiological and pharmacological studies, with special attention to nervous, digestive, and auditory systems as well as microbiology and parasitology. Ultimately, gerbils have also been applied for studying carcinogenesis in different organs and systems, since these animals show a natural propensity to develop spontaneous proliferative lesions, especially in steroid-responsive organs. This characteristic shed light on the reproductive aspects of this rodent model regarding morphological features in male and female individuals. This review of literature summarizes the significance of this model as an alternative to the use of inbred mice and rats in reproductive experimental research, highlighting recent findings. Gerbils have contributed to the expansion of knowledge in prostate biology in male and female individuals, providing studies related to prostatic morphogenesis and neoplasia. In the testes, spermiogenesis occurs in 15 steps, differently from other experimental models. Also, the complete maturation of the testis-epididymal complex occurs between the second and third months. Mammary gland alterations related to the estrous cycle and pregnancy were described, as well as its modulation under endogenous and exogenous estrogenic compounds. The ovaries frequently present ovarian cysts. Furthermore, this organ shows predominantly interstitial steroidogenic glands in the stroma, especially at aging. Adrenal gland shows a large size compared to other animals, presenting three distinct zones with a remarkable role in steroidogenesis.

Predicting circRNA-drug sensitivity associations by learning multimodal networks using graph auto-encoders and attention mechanism.

Recent studies have shown that the expression of circRNAs would affect drug sensitivity of cells and thus significantly influence the efficacy of drugs. Traditional biomedical experiments to validate such relationships are time-consuming and costly. Therefore, developing effective computational methods to predict potential associations between circRNAs and drug sensitivity is an important and urgent task. In this study, we propose a novel method, called MNGACDA, to predict possible circRNA-drug sensitivity associations for further biomedical screening. First, MNGACDA uses multiple sources of information from circRNAs and drugs to construct multimodal networks. It then employs node-level attention graph auto-encoders to obtain low-dimensional embeddings for circRNAs and drugs from the multimodal networks. Finally, an inner product decoder is applied to predict the association scores between circRNAs and drug sensitivity based on the embedding representations of circRNAs and drugs. Extensive experimental results based on cross-validations show that MNGACDA outperforms six other state-of-the-art methods. Furthermore, excellent performance in case studies demonstrates that MNGACDA is an effective tool for predicting circRNA-drug sensitivity associations in real situations. These results confirm the reliable prediction ability of MNGACDA in revealing circRNA-drug sensitivity associations.

CONSTITUTIONAL AND LEGAL PRINCIPLES OF THE LIMITS OF PERMISSIBLE INTERVENTION IN CONDUCTING BIOMEDICAL RESEARCH WITH HUMAN PARTICIPATION.

The aim: To find out the peculiarities of constitutional and legal principles of the limits of permissible intervention in conducting biomedical research with human participation. Materials and methods: The methodological basis of the study was worldview dialectical, general scientific and specific scientific methods of learning the phenomena of state and legal reality. Common ones were widely used in the work principles of scientific knowledge - comprehensiveness, objectivity, historicism, unity of theory and practice and others. The most important methodological prerequisite was a systemic approach to the issue of protecting human rights when conducting biomedical experiments with his participation, which made it possible to form a holistic view of the object and subject of research. With its help, the human rights affected by biomedical research in the context of the general legal principle of humanism were analyzed, the limits of permissible intervention in the human body were identified, and conclusions were drawn regarding the need for the separation and normative legal regulation of the complex branch of medical law. In the study, general scientific methods were widely used: historical, systematic analysis of the studied phenomena and syn¬thesis of the obtained results, inductive and deductive reasoning; special: formal-logical, sociological, statistical; and also private-scientific: comparative-legal, normative-legal, and others. Conclusions: 1) A key point in the mechanism of protection of the subject's rights in the process of conducting biomedical research is the establishment of a number of limits (maxims) that allow interference in the human body and can limit the researcher and protect the subject. These maxims should be integral elements of the process of biomedical research with human participation and determine the basic criteria for the protection of citizens' rights when conducting biomedical research. 2) The limits of permissible intervention in the conduct of biomedical research with human participation are the legal and factual consequences of the activity of bodies authorized to conduct biomedical research, which is based on the law and aimed at achieving the goals set by the researcher for conducting biomedical research with human participation, as a result of which the options for permitted by the norms of the law of behavior of the subjects of biomedical research by establishing various limits of such behavior, which necessarily have an exclusively temporary and subjective nature.

Design of Multi-Cell Cooperative Control Algorithm Based on Fuzzy Brain Emotional Learning

Multi-cell cooperative control can be competent for the current increasingly complex biomedical experiments, greatly improving the efficiency of cell manipulation experiments. At present, this kind of multi-cell cooperative control algorithm is becoming more and more important. In this study, holographic optical tweezers are used to capture multiple cells, and a cell manipulation controller is designed based on the Fuzzy Brain Emotional Learning (FBEL) neural network. Firstly, the dynamic model of trapping yeast cells by optical tweezers is analyzed. The distance between the trap position and the cell position is constrained to avoid cell detachment due to the trap moving too fast. Then, the design cell manipulation controller is relied upon to realize single transport trajectory tracking control. Finally, a multi-cell cooperative control algorithm is designed, and combined with the cell manipulation controller, a multi-cell cooperative controller based on the FBEL neural network is formed. The error between the cell position and the desired trajectory is the input of the multi-cell cooperative controller. The output of the multi-cell cooperative controller is the optical trap position, which is used to realize the cooperative control of multiple cells by holographic optical tweezers. The simulation results showed that the multi-cell cooperative controller based on the FBEL neural network can effectively control multiple yeast cells and quickly converge the cell formation, while ensuring a higher control accuracy than other traditional cell manipulation controllers. It provides a new solution for the efficient and precise automatic manipulation of multiple cells.

Highly efficient near-IR cyclohexene cyanine photosensitizers for antibacterial photodynamic therapy

In spite of significant progress in the development of novel photosensitizers for photodynamic therapy (PDT) applications, the search for new approaches for designing organic dyes exhibiting high cytotoxicity upon biologically relevant near-IR light irradiation is still ongoing. Organic dyes such as porphyrins are widely used as photosensitizers, while cyanine dyes exhibiting much better absorption in the near-IR region have been only moderately explored. Herein, we report on a new series of cyclohexene-based cyanine dyes containing two and three indolenine, benzothiazole, and benzoselenazole terminal end-groups. These dyes are investigated for photodynamic inactivation of pathogenic S. aureus and E. coli bacteria. Both di-substituted benzothiazole and benzoselenazole cyanines were found to efficiently eradicate S. aureus and E. coli at nanomolar and micromolar dye concentrations, respectively, and at a low near-IR light dose, while exhibiting tolerable dark toxicity. The commercially available di-indolenine based dye IR786 that is used in many assays and imaging applications exhibits pronounced dark toxicity and phototoxicity to the cells which can substantially affect biomedical experiments utilizing this dye.

The multi-aspect tests in the presence of ties

The two-sample problem is one of the most important topics in various fields, such as biomedical experiments and product quality maintenance. The Lepage-type test, which is the sum of squares of standardized linear rank statistics, has often been used in the location-scale shift model. Recently, the Lepage-type test has been applied to the joint location-scale and joint location-scale-shape problems. In this study, the test statistics based on the Euclidean distance and Mahalanobis distance of standardized linear rank statistics are considered in the presence of ties. The moments of these test statistics are calculated by deriving the moment-generating function of the vector of linear rank statistics. Moreover, the gamma approximation based on these moments is compared with the chi-square approximation based on the limiting null distribution. Simulation studies and data examples demonstrate the usefulness of gamma approximation in the case of small sample sizes.

Design and Development of an Automatic Microinjection System for High-Throughput Injection of Zebrafish Larvae

The microinjection of zebrafish larvae is a complicated work due to their small size and shape variations. In this article, for the first time, we design an automatic microinjection system dedicated to high-throughput injection of zebrafish larvae. The proposed custom-built microarray Petri dish combined with machine vision-based motion control enables high-efficiency automatic identification and injection of a batch of zebrafish larvae. The feasibility of the developed system is demonstrated by experimental testing on live zebrafish larvae. Results show that the developed system works fast with more stable injection success rate and higher survival rate than the skilled experimenter. The proposed system offers a good working efficiency and maintains a consistent success rate and stability in the process of high-throughput injection. It can be applied in various biomedical experiments based on zebrafish microinjection. Note to Practitioners—Zebrafish is widely used in biomedical experiments due to its obvious advantages. At present, the batch injection task of larvae is mainly conducted by experimenters manually. As the number of injections increases, experimenters will get tired, which makes it difficult for manual injection to maintain a stable success rate. This article reports the first automatic microinjection system for high-throughput batch injection of zebrafish larvae. A new microarray Petri dish has been proposed to fix the larvae, facilitating the microinjection process. Experimental results show that the system can complete a large number of injection tasks quickly while ensuring a stable success rate and survival rate of the larvae. It can free experimenters from repeated and tedious injection work. It also enables efficient zebrafish larvae microinjection for inexperienced experimenters.

Design and energy research of terahertz optical systems for cell stimulation

AbstractTerahertz technology has its unique advantages in the field of biomedicine and is increasingly used in modern medical applications. In this study, to research the responding of biological tissues (cells or nerve nuclei) to various terahertz energy stimulation, an automatic terahertz energy control optical system is designed. The ray tracing simulation of the selfdesigned optical lens model is conducted and the results show that the system can achieve the focusing arrangement within 90 mm and control the strength of terahertz energy on image plane. In addition, an automatic control system with nanometer‐level precision is designed using a stepper motor subdivision scheme to coordinate with the image plane (target point) energy and morphology adjustment. Then biomedical experiments based on this system are carried out. Through adjusting the system, terahertz intensity on cells is changed, so that the cells show various cell viabilities. The optimized experimental results show that the terahertz energy automatic control optical system designed in this study is qualified for terahertz energy irradiation research with biological cells.