bluuebunny/crossref_metadata_2025 huggingface dataset:
THERMAL MODEL OF THE "INDUCTION GENERATOR–INDUCTION MOTOR" SYSTEM WITH NON–SYMMETRY IN THE STATOR WINDINGS
Authors:   Kremenchuk Mykhailo Ostrohradskyi National University, Chenchevoi V. , Zachepa Iu. , Chornyi O. , Yatsiuk R. , Chencheva O. , Nekrasov A. , Kropyvnyi I.
Published: January 2022

Purpose. Development of the IG model for estimation of influence of variations of parameters of the generator on quality of process of self–excitation at definition of the basic and boundary operating modes and system of initial excitation at invariable parameters of the generator. Result. The article presents studies of the system "asynchronous generator-asynchronous motor" with parametric asymmetry to determine the quality of generated electricity in load modes of operation on a mathematical model. The assessment of the thermal state in steady-state conditions was carried out using an equivalent thermal equivalent circuit. Thermal transients were investigated when starting an asynchronous electric motor from an autonomous power source based on an asynchronous generator. On a thermal mathematical model, a study of the influence of the asymmetry of the output voltage and its deviation from the nominal value on the heating of the connected asynchronous motor was carried out. A regression model has been developed for studying the operating conditions of electricity consumers when powered by an asynchronous generator with an asymmetry of the stator windings. Practical value. The use of the obtained equations will make it possible to determine the most rational combination of factors affecting the heating of the stator windings of asynchronous machines, at which they will not overheat in excess of the maximum permissible temperature values of the corresponding insulation classes. Figures 9, tables 2, references 23.
SYNTHESIS OF A FUZZY TWO-LINKED REGULATOR FOR FREQUENCY ELECTRIC DRIVES OF A GRAIN MACHINE WITH A FOCUS OF THE GRAIN FLOW
Authors:   Kremenchuk Mykhailo Ostrohradskyi National University, Burdilna E. , Konokh І. , Serhiienko S.
Published: January 2022

Purpose. A control system for grain overloading during post-harvest processing with grain throwers has been proposed, the use of which will reduce damage and grain loss. An automated electromechanical system is presented that can be installed on agricultural machinery without additional modernization of the working bodies. Methodology. As a result of the analysis of control systems, a system with elements of fuzzy logic was selected, which will clearly define the necessary control actions and take into account additional parameters that can affect the overload process. A functional diagram of a microprocessor control system for an electric drive using a fuzzy system is proposed. The result of the system operation will be the definition of the control task for the frequency converters of the drive motors of the grain thrower mechanisms. Originality. Based on the simulation of grain flight trajectories, the dependences of the flight range on the conveyor speed and additional blowing were formed, which were used to determine the settings of the fuzzy controller. Results. Fuzzy system settings are performed: a set of input and output variables is defined; the number and location of terms are selected; a set of production rules for the system is formulated. As a result of experimental modeling, graphs of the formation of mastering influences by a fuzzy controller under the condition of the appearance and disappearance of the headwind for different given distances of movement were obtained. Practical value. Practical application of the offered system will allow to reduce material losses from injury of the overloaded grain and to increase efficiency of work of the grain thrower. Figures 8, references 21.
RESEARCH OF ENERGY IMBALANCE OF STOCHASTIC PROCESSES AND SYSTEMS IN ORDER TO INCREASE THEIR ENERGY EFFICIENCY
Authors:   Lviv Polytechnic National University, Bratiuk P.
Published: January 2022

Purpose. The results are based on the study of the paradox of disturbed energy balance and the introduction of the virial theorem on the initial state of equilibrium energy and the formalized physical mechanism of energy accumulation due to the violation of its equilibrium. Methodology. According to the results of the analysis of the mathematical apparatus of the model of energy accumulation dynamics on the basis of the energy paradox of the disturbed lever equilibrium, the previously undescribed property of the probability of occurrence of random events is revealed. This property is related to the concept of entropy in its information and energy interpretations, and this makes it possible to establish information criteria for assessing the energy performance of processes and systems of different nature, and vice versa. Results. A positive result of qualitative assessment of general opportunities to increase energy efficiency of stochastic processes and systems by violating their energy balance was obtained by creating conditions to improve energy efficiency of information transmission systems by quality assessment, which combines information and energy performance indicators based on the concept of entropy, namely - the signal/noise ratio. Originality. The previously described property of the probability of occurrence of random events, which quantitatively describes the relationship of information and energy performance of stochastic processes and systems. Practical value. The set of obtained results and previous researches testifies that the property of probability of dynamics of random events revealed by results of the analysis of mathematical device of model of dynamics of accumulation of energy, is display of the fundamental principle of imbalance, and provides a way of management of indicators and criteria increasing the energy efficiency of deterministic and stochastic processes and systems of different physical nature. Based on the identified property of the probability of random events, a method of controlling the probability of occurrence of random events is proposed, which is that to double the increase in the difference of probabilities of opposite random events it is enough to increase the probability of only one of these events. W. Pauli's hypothesis about the reduction of symmetry serves in favor of the concept of energy imbalance. There is good reason to believe that, regardless of whether Pauli considered the reduction of symmetry by division at the level of the particle or not, the nature and mechanism of the reduction of symmetry reflects the paradox of energies of disturbed lever equilibrium. Figures 14, references 11.
MODEL AND ALGORITHM OF OPERATION OF THE ORIGINAL ELECTROMECHANICAL SYSTEM FOR ACCUMULATING KINETIC ENERGY FOR ELECTRIC CAR
Authors:   Odessa Polytechnic State University, Matkovsky M. , Semenov K. ,   Odessa National University of I. І. Mechnikov
Published: January 2022

Purpose. The further introduction of electric transport is largely constrained by the insufficient energy capacity of existing energy storage devices. One of the possible replacements for the chemical accumulator is the flywheel energy storage, which has important advantages. This advantage is its potentially huge storage capacity. One of the disadvantages of flywheel drives is the presence of a gyroscopic moment, which leads to a deterioration in vehicle handling. Methodology. The authors of the work in their development of the flywheel drive have eliminated a number of shortcomings, but to use the drive, it is necessary to develop an operation algorithm and a mathematical model. A mathematical model of electrical and mechanical processes in the author’s electromechanical energy storage system is presented. It is shown that the charging and discharging currents of a storage device change exponentially with time, which should be taken into account when developing a specific implementation of drivers for storage motors. The algorithm of operation of the proposed electromechanical energy storage system in the modes of energy storage and energy withdrawal has been developed. Results. The verbal and graphical form of the algorithm is presented. It is noted that in the presence of an electromechanical transmission on a vehicle, the advantages of such a drive increase even more, which prompted the authors of this work to develop a new electromechanical transmission, which the authors plan to combine in the future with the developed drive based on one vehicle. Originality. In the direction of further increasing the efficiency of using the proposed storage device, as well as, incidentally, of their other types, it is also planned to use the electromechanical system for transmitting electricity to the vehicle, developed by the authors. Practical value. In the future, it is also planned to expand and clarify the algorithm of the drive, in order to take into account the types of charger, energy source, the presence of batteries on board the car, depending on the characteristics of the vehicle, road conditions, driver qualities, weather conditions, etc. (at the limit, go to an intelligent control system). It is planned to create a more detailed model of the drive. Figures 4, references 21.
SYSTEM OF AUTOMATIC CONTROL OF MEASUREMENT OF INDUSTRIAL CONTROLLED PARAMETERS OF SILICON FOR POROUS SUBSTRATES
Authors:   Kremenchuk Mykhailo Ostrohradskyi National University, Pritchin S. , Dragobetsky V. , Shevchenko І. , Palagin V. , Lomonos А. , Naida V.
Published: January 2022

Purpose. Certification of silicon ingots intended for the manufacture of porous silicon substrates, which includes many operations for measuring silicon parameters. Some measurement operations are automated and some are not automated. The aim of the work is to fully automate the process of creating a quality certificate for monocrystalline silicon by developing an automatic control system for measuring controlled silicon parameters for porous linings. Methodology. We have performed an analysis of existing methods and methods of industrially controlled parameters of silicon. We have performed the analysis of standards for the measurement of parameters and the measurement process in the factory. Results. In this work, the authors performed the classification of industrially controlled parameters in accordance with the methods and measurement equipment. On the basis of the obtained analysis, the authors developed a scheme of the procedure for performing the operations of measuring the parameters of monocrystalline silicon. The authors proposed a block diagram of an automatic control system for measuring industrially controlled parameters of silicon. All equipment included in the sites is integrated into an industrial local area network, which is controlled by an industrial controller. The work shows the system software developed by the authors, developed in the LabView environment. The program allows you to generate a quality certificate for a monocrystalline silicon ingot for porous substrates, to analyze data for a selected period of time. Originality. For the first time, a classification of methods and means of measured parameters of monocrystalline silicon was carried out according to the criterion of measurement automation. The scheme of the order of performing of measurement operations has been improved in order to optimize it for automating the generation of a quality certificate. Practical value. The proposed automatic control system for measuring industrially controlled parameters of silicon is used at the plant “Pure Metals” that produces ingots of monocrystalline silicon. It can be used in factories where product quality certificates are used based on the measurement of many parameters. Figures 3, tables 1, references 11.
ELECTROMAGNETIC PROCESSES IN A SYSTEM WITH A PLANE CIRCULAR SOLENOID BETWEEN MASSIVE BIFILARY COILS
Authors:   Kharkiv National Automobile and Highway University, Batygin Yu. , Gavrilova T. , Chaplygin Ev. , Shinderuk S. , Shcherbinina Yu.
Published: January 2022

Purpose. Currently, in order to save materials and energy costs, devices have been developed using inductor systems with bifilar coils used in equipment for magnetic-pulse processing of metals. The purpose of this work is to obtain design relations based on a rigorous solution of the edge electrodynamics for the analysis of electromagnetic processes in a real metal of a circular solenoid of finite thickness placed between massive multi-turn coils of a bifilar with unidirectional currents in a flat inductor system. Methodology. To solve this problem, Maxwell’s equations with appropriate boundary conditions and Laplace transforms were used. Results. Based on the exact solution of the boundary value problem, the space-time function of the density of the induced current, which arises in a flat solenoid when the system is excited by harmonic unidirectional currents in massive bifilar windings, is obtained. On the basis of numerical calculations, it was found that in the low-frequency mode, the transverse distribution of the induced current is linear, symmetric about the central axis of the inductor. In the high-frequency mode, the transverse distribution of the induced current is characteristic of the case of a sharp surface effect. The conditions for the minimum influence of the fields of the external bifilar on the processes in the internal inductor are revealed. Originality. The novelty of this work lies in proposing the idea of the design of the inductor system, as well as in the exact solution of the electrodynamics problem and obtaining the calculated expressions for the analysis of electromagnetic processes. Practical value. On the basis of the obtained formulas and the performed calculations, the efficiency of the proposed calculation model has been proved, which makes it possible to use it as a basic model for similar inductor systems in determining the real conditions of their maximum efficiency. Figures 2, references 17.
“The Lightest Ones of the World and the Greatest Ones of the World” in the Palestinian Traditions of the Mishnaic and Talmudic Periods
Authors: Elitzur Brachi
Published: January 2022

This article discusses the development of a rabbinic tradition that draws on verses from Samuel’s speech dealing with the authority of leaders (1 Sam 12:6–11) against the backdrop of rabbinic political circumstances. In its earliest manifestations, this tradition is integrated into a story describing one of the confrontations concerning the determination of the Jewish calendar. These confrontations occurred in the Beit Midrash in Yavne under the leadership of Rabban Gamliel. The article traces the changes the confrontation underwent during the transitions between the different literary genres and suggests that these changes were influenced by the character of the social tension that existed when each genre was redacted. This article deals with the question of authority, power, and leadership in Palestine in the period of the Sages.
A novel complementary method for ultrasonographic screening of deep endometriosis: a case series of 5 patients diagnosed with transvaginal strain elastography
Authors: Szabó Gábor , Madár István , . János Rigó , Dobó Noémi , Ács Nándor , Bokor Attila
Published: January 2022

Background: Ultrasound elastography displays information on tissue stiffness. Deep endometriotic nodules are hard fibrotic tissues. Patients are recognized as having deep endometriosis only after several years from the onset of symptoms, therefore it is important to improve diagnostic capabilities. Cases: In this case series, our purpose was to present the applicability and feasibility of transvaginal strain elastography. Five patients with various complaints compatible with endometriosis underwent transvaginal ultrasound with strain elastography. Using the ‘International Deep Endometriosis Analysis’ group (IDEA) protocol along with transvaginal strain elastography, preoperative examination clearly demonstrated the size and extent of deep endometriosis. Conclusion: This ultrasonographic technique was effective regardless of whether the ligaments of the female reproductive tract, or the organs of the urinary and intestinal tract were infiltrated.
Isolated tubal torsion associated with hydrosalpinx
Authors: Tamburaci Esra
Published: January 2022

Background: Isolated tubal torsion associated with hydrosalpinx is a rare pathology. Our aim was to analyze clinical and imaging features. Case: A 15-year-old girl was admitted to the gynecological emergency department with lower abdominal pain. She was virgin and did not have gynecological examination. In ultrasonography a 10 cm cystic lumen was observed in the right tube. Right salpingectomy was performed. In the pathological examination, there was ischemic changes due to torsion. Conclusion: Isolated tubal torsion is extremely rare in early adolescent period. Early surgical intervention after diagnosis is important for fertility.
Impact of the COVID-19 pandemic on the policies and practices of delivery facilities in Japan
Authors: Ebina Yasuhiko , Takeuchi Mizuki , Nakamura Maya
Published: January 2022

Background: To clarify the impact of the COVID-19 pandemic on the policies and practices of delivery facilities in Japan from April 2020 to March 2021. Methods: We conducted an online survey of midwives working in obstetric wards nationwide between May 15, 2021, and July 31, 2021. We analyzed the 376 valid responses. Results: With the COVID-19 pandemic, most facilities have barred or partially restricted families and other visitors from being present (patient companions) in outpatient clinics, prenatal classes, during delivery, inpatient care, and inpatient visits. These changes were implemented nationwide, regardless of regional differences in the pandemic state of COVID-19. Meanwhile, by facility classification, prenatal classes, companion at birth, and inpatient visits were more likely to be canceled at perinatal centers than at clinics. The acceptance of “satogaeri deliveries” (a custom in Japan where pregnant women return to their natal homes for labor and childbirth) was partially restricted to about 40% of facilities, although this rate was lower in the four Kanto prefectures (Tokyo, Kanagawa, Saitama, and Chiba). Conclusions: With the COVID-19 pandemic, the differences in Japan’s policies and practices of delivery facilities were attributed more to the role played by facilities in the regional perinatal system than to regional pandemic status.
COUP-TFI deletion affects angiogenesis and apoptosis related gene expression in mouse placenta: results of an explorative study
Authors: Viola Luigi , Marzinotto Stefania , Bertacchi Michele , Londero Ambrogio P , Orsaria Maria , Bertozzi Serena , Driul Lorenza , Di
						Loreto Carla , Studer Michèle , Mariuzzi Laura , Fruscalzo Arrigo
Published: January 2022

Background: Chicken Ovalbumin Upstream Promoter-Transcription Factor I (COUP-TFI) is a member of the steroid/thyroid nuclear receptor superfamily. The aim of this study was to investigate whether absence of this gene affects placental development and fetal growth in a COUP-TFI knockout mouse model. Methods: Placentas of COUP-TFI-knockout (COUP-TFI KO) and wild-type (WT) were collected at 18.5 days post-coitum. The expression level of the following genes known to be involved in different key molecular pathways was evaluated: BCL2 Associated X (Bax) and B-cell lymphoma 2 (Bcl-2) (apoptosis), p21, p53 and α subunit of inhibin (INHA) (proliferation and apoptosis), vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), hypoxia-inducible factor 1-alpha (HIF1α), Fms related receptor tyrosine kinase 1 (Flt-1), and endoglin (ENG) (angiogenesis). Mouse litter weight at birth was also assessed. Results: RT-qPCR analysis showed increased mRNA expression of VEGF-A and Bax in placental tissue of COUP-TFI KO mice compared to WT mice. We also found a loss in the positive correlation between Bcl-2 and INHA, p21 and ENG, as well as HIF1α and Flt-1 mRNA expression in COUP-TFI mutants. Finally, KO mice were lighter than WT littermates (respectively, the mean weight of COUP-TFI KO mice was 1.3 grams, ± 0.13, compared to 1.6 g, ± 0.14 of WT mice, p < 0.05). Conclusions: Our results show that COUP-TFI deletion is associated with a lower birth weight in mice and increased placental transcript expression of pro-apoptotic Bax and pro-angiogenetic VEGF-A genes.
Long term use of oral contraceptives comprising synthetic estrogens induces an excessive breast cancer risk in BRCA mutation carrier women: a meta-analysis
Authors: Peng Hongling , Qi Xiaorong , Wang Qiao
Published: January 2022

Background: The relationship between oral contraceptive (OC) use and breast cancer risk is highly debated. Recent publications support a slight increase in overall breast cancer risk among OC user women, in particular among the current users. Women with inherited BRCA1 (Breast cancer type 1) or BRCA2 (Breast cancer type 2) gene mutations are at increased risk of breast and ovarian cancers, which is often mistakenly attributed to their elevated endogenous estrogen levels. The aim of presented meta-analysis was to assess the effects of OC use on breast cancer risk in BRCA mutation carrier women with minimal bias. Methods: A systematic search strategy was used to identify relevant studies, Stata (version 15) was used for meta-analysis. Results: Individual datasets from 13 studies totaling 20,202 patients were analyzed. The combined results showed no significant increase in risk of breast cancer in BRCA mutation carriers who had ever used oral contraceptive (HR = 1.09, 95% CI: 0.71–1.69 among BRCA1 mutation carriers and HR = 1.19, 95% CI: 0.73–1.95 among BRCA2 mutation carriers, respectively). However, in correlation with long-term (>5 years) OC users, the breast cancer risk was significantly increased in both BRCA1 mutation carriers (HR = 1.39, 95% CI: 1.19–1.60) and BRCA1 mutation carriers (HR = 1.61, 95% CI: 1.25–1.96). Conclusion: The presented results indicate that in BRCA mutation carriers women who have defective liganded activation of estrogen receptors (ERs), the use of synthetic estrogens means an additive factor for ER deregulation further increasing the risk for breast cancer. Long term OC use in BRCA mutation carriers results in a significantly increased risk for breast cancer by exhausting the compensatory genome defending process.
Can hysteroscopy be substituted to hysterosalpingography in the assessment of infertility? Methods of showing tubal transition as hysteroscopic
Authors: Yanar Buket Aydın , Pek Eren , Unsal Mesut A.
Published: January 2022

Background: The main goal of this study was to prove that hysteroscopy is a superior method compared to hysterosalpingography in the evaluation of tubal passage and the uterine cavity in infertile women. Methods: The study was carried out on 30 volunteer women for whom evaluation of the uterine cavity and transit through the tubules was required due to infertility. In the evaluation of the hysteroscopic tubal passage, a 6Fr feeding cannula was advanced from the hysteroscope barrel, and firstly methylene blue and then an air bubble were applied to the fluid-filled uterine cavity through this flexible cannula. Results: When the reference method was taken as hysterosalpingography, the specificity of hysteroscopy was found to be 85.71% (95% CI (confidence interval): 42.13%–99.64%), sensitivity 94.74% (95% CI: 85.38–98.90%). The positive predictive value of hysteroscopy was calculated as 98.18% (95% CI: 89.78%–99.70%) and the negative predictive value was 66.67% (95% CI: 38.96%–86.24%). Observing the bubble and swirl effect together in the evaluation of the tube opening increases the diagnostic accuracy. And benefit of hysteroscopy in the evaluation of tubal passage was statistically significantly higher than hysterosalpingography. Conclusion: Considering the cellular damages that can be caused by hysterosalpingraphy and the real observation power provided by hysteroscopy, simultaneous evaluation and the comfort of making intervention possible, hysteroscopy will be a more useful and useful application.
A 15-year comprehensive literature review of 99 primary ovarian carcinoid tumors
Authors: Georgescu Tiberiu-Augustin , Bohiltea Roxana Elena , Varlas Valentin , Munteanu Octavian , Furtunescu Florentina , Lisievici Antonia-Carmen , Grigoriu Corina
Published: January 2022

Objective: Primary ovarian carcinoids are neuroendocrine tumors, representing up to 1% of all ovarian tumors. In this paper, the authors aimed at analyzing the clinical and pathological aspects of all recently published ovarian carcinoid, providing new correlations regarding them. Mechanism: The authors have reviewed all cases of primary ovarian carcinoid reported in international journals since 2005 to date. A total of 99 cases published in 68 articles have been found and analyzed. Findings in brief: Our results up to 29.31% of patients presented with carcinoid heart disease, and 17.24% had an abdominal mass, which caused them to present to the physician. Patients presenting with metastases had more frequently the insular subtype (33.33%) and had similar median age as those without metastases. A teratoma component was noticed in 58.9% of cases and was also associated with the insular pattern of carcinoid. To our best knowledge, this paper includes the largest review of primary ovarian carcinoid to date. Conclusions: The incidence of carcinoid heart disease might have been underestimated up to this moment, thus, requiring further imagistic investigations of patients presenting with these symptoms. Additionally, the insular variant was most frequently associated with the presence of both teratoma (52.94%) and metastases (33.33%), although previous reports have noticed a higher incidence of teratoma in the mucinous variant. In our opinion, these apparently divergent results warrant further studies of this rare subtype of ovarian tumor.
Uterine fibroids and infertility: a controverse but concrete link
Authors: Sparić Radmila , Andjić Mladen , Nejković Lazar , Štulić Jelena , Dmitrović Aleksandar , Aničić Radomir , Milovanović Zagorka , Tomašević Đina , Tinelli Andrea
Published: January 2022

Background: Uterine fibroids (UFs) are the most common female benign tumors linked to significant morbidity. There are large literature data connecting UFs with infertility and adverse pregnancy outcome. In this research, authors reviewed literature on UFs, analyzing their relationship with infertility, influence of different therapeutic approaches of UFs on fertility and the possible mechanisms related to UFs and infertility. Methods: MEDLINE and PubMed search, during the years 1990–2020 was performed using a combination of keywords on such topic. Peer-reviewed, systematic review, meta-analysis and prospective trials, examining relationship between UFs and infertility were included in this investigation. According to authors evaluation, additional articles were also identified from the retrieved papers references and included in this narrative review. Results: UFs, especially the submucous and intramural types, with related treatments are linked to impairment of fertility and adverse pregnancy outcome, but many data are conflicting. Molecular mechanisms investigations could explain relationship between UFs and infertility. Conclusion: UFs are linked to infertility and interventions improve fertility. However, many studies conflict in the final results, so further investigations on UFs and infertility should clarify the exact role of molecular mechanisms of this association.
High concordance between next-generation sequencing and single-nucleotide polymorphism array in preimplantation genetic testing for aneuploidy
Authors: Ou Zhanhui , Chen Zhiheng , Deng Yu , Sun Ling
Published: January 2022

Background: This study aimed to compare the use of next-generation sequencing (NGS) and single-nucleotide polymorphism (SNP) array in preimplantation genetic testing for aneuploidy (PGT-A) in the same blastocyst. Methods: We performed a retrospective study on 67 embryos (from 23 couples), where PGT-A was carried out. A trophectoderm (TE) biopsy was performed on the blastocyst, and the 24-chromosomal ploidy status was analyzed. Initially, 28 blastocysts with unknown ploidy were analyzed using both NGS and SNP array. Thereafter, 39 blastocysts with euploidy detected via NGS were re-analyzed using SNP array. Results: In the first stage, the concordance rate was 92.9% (26/28). Among the 28 blastocysts, 16 were abnormal, and 12 were euploid when analyzed using NGS. Among the 16 abnormal blastocysts, two showed mosaicisms when analyzed using NGS but were found to be euploid using the SNP array. In the second stage, the concordance rate was 100% (39/39) when analyzing the normal blastocysts. After single blastocyst transfer in 29 frozen embryo transfer cycles, the clinical pregnancy rate was 75.9% (22/29), the ongoing pregnancy rate was 69.0% (20/29), and the live birth rate was 69.0% (20/29). Nineteen couples (20 babies) had healthy babies. Their prenatal diagnosis results and karyotype analysis after delivery were concordant with the PGT results. Two cycles miscarried, and the abortion villus exhibited euploidy. Conclusions: There was a high concordance rate between NGS and SNP array. TE biopsy combined with NGS for PGT was an efficient strategy to identify the suitability of embryos for transfer.
Identification of differentially expressed genes and pathways for risk stratification in HPV-associated cancers governing different anatomical sites
Authors: Kwon Eun Jung , Lee Hye Ran , Lee Ju Ho , Seo Chorong , Ha Mihyang , Roh Jin , Kim Yun Hak , Jang Jeon Yeob
Published: January 2022

Background: Human papillomavirus (HPV) is the major cause of cervical cancer (CC) etiology; its contribution to head and neck cancer (HNC) incidence is steadily increasing. As individual patients’ response to the treatment of HPV-associated cancer is variable, there is a pressing need for the identification of biomarkers for risk stratification that can help determine the intensity of treatment. Methods: We have previously reported a novel prognostic and predictive indicator (HPPI) scoring system in HPV-associated cancers regardless of anatomical location by analyzing The Cancer Genome Atlas and Gene Expression Omnibus databases. In the present study, we comprehensively investigated the association of group-specific expression patterns of common differentially expressed genes (DEGs) between high- and low-risk groups in HPV-associated CC and HNC, identifying molecular biomarkers and pathways for risk stratification. Results: Among the 174 identified DEGs, the expression of genes associated with extracellular matrix (ECM)-receptor interaction pathway (ITGA5, ITGB1, LAMB1, and LAMC1) was increased in high-risk groups in both HPV-associated CC and HNC, while the expression of genes associated with T-cell immunity (CD3D, CD3E, CD8B, LCK, and ZAP70) was decreased and vice versa. The individual genes showed significant prognostic impact on HPV-associated cancers but not on HPV-negative cancers. The expression levels of identified genes were similar between HPV-negative and HPV-associated high-risk groups with distinct expression patterns only in HPV-associated low-risk groups. Each group of genes showed negative correlations and distinct patterns of immune cell infiltration in tumor microenvironments. Conclusions: These results allowed us to identify molecular biomarkers and pathways for risk stratification in HPV-associated cancers regardless of anatomical location. The identified targets were found to be selectively working in only HPV-associated cancers and not in HPV-negative cancers, indicating the possibility of selective targets governing HPV-infective tumor microenvironments.
UV-4B potently inhibits replication of multiple SARS-CoV-2 strains in clinically relevant human cell lines
Authors: Franco Evelyn J. , Warfield Kelly L. , Brown Ashley N.
Published: January 2022

Background: SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Although it poses a substantial public health threat, antiviral regimens against SARS-CoV-2 remain scarce. Here, we evaluated the antiviral potential of UV-4B, a host targeting antiviral, against SARS-CoV-2 in clinically relevant human cell lines. Methods: Cells derived from human lung (A549 cells transfected with human angiotensin converting enzyme 2 receptor (ACE2; ACE2-A549)) and colon (Caco-2) were infected with either a wild type or beta variant strain of SARS-CoV-2 and exposed to various concentrations of UV-4B. Supernatant was sampled daily and viral burden was quantified by plaque assay on Vero E6 cells. Results: Therapeutically feasible concentrations of UV-4B inhibited the replication of the wild type strain in ACE2-A549 and Caco-2 cells yielding EC50 values of 2.694 and 2.489 μM, respectively. UV-4B’s antiviral effect was also robust against the beta variant in both cell lines (ACE2-A549 EC50: 4.369 μM; Caco-2 EC50: 6.816 μM). Conclusions: These results highlight UV-4B’s antiviral potential against several strains of SARS-CoV-2.
An animal study on the effect of topically administered ambroxol for dry eye
Authors: Wang Zixuan , Yu Li , Zhang Shaochong , Wang Zhenhan , Wang Mingwu
Published: January 2022

Objective: To evaluate the effect of 0.2% ambroxol eye drop on tear secretion and corneal healing on a rabbit dry eye model, and to delineate potential underlying mechanisms. Materials and method: A mixed mechanism dry eye model was created using 12 healthy New Zealand rabbits by excision of the main lacrimal glands, Harderian gland and nictitating membrane. Establishment of the model was confirmed by the decrease of Schirmer I and increase of corneal fluorescein staining scores. Two weeks after model creation, the rabbits were randomly and evenly divided into NaCl, 0.1% sodium hyaluronate and 0.2% ambroxol groups. Each group was administered the respective eye drops 4 times a day for four weeks. The Schirmer I test and corneal fluorescein staining were performed at two and four weeks. After four weeks of treatment, the animals were sacrificed and the conjunctiva and eyelid specimens collected. Inflammatory factors IL-8, TNF-α, and goblet cell specific mucin MUC5AC were measured by ELISA while the lid meibomian gland was evaluated by oil red O staining. Results: Compared with the baseline, 2 weeks after the surgery, Schirmer I test value decreased significantly (20.35 ± 5.18 mm/5 min vs 13.95 ± 4.64 mm/5 min, p < 0.01), and the fluorescein staining score increased significantly (0.5 ± 0.6 vs 5.5 ± 1.4, p < 0.01). After four weeks of treatment, compared with the NaCl and sodium hyaluronate groups, tear secretion in ambroxol group increased significantly (p < 0.01), while the corneal fluorescence staining score decreased significantly (p < 0.01). In the conjunctival tissue, significant decrease was seen in TNF-α (p < 0.01) and IL-8 [p (unilateral) < 0.05] concentrations in ambroxol group, and significant increase in MUC5AC concentration (p < 0.01) in ambroxol group as well. The lipid content in the lid meibomian glands appeared increased after the administration of ambroxol. Conclusion: The present rabbit dry eye model study demonstrated potentials of topically administered 0.2% ambroxol in stimulating tear and mucin secretion, inhibiting ocular surface inflammation, promoting corneal healing, and possibly augmenting meibomian gland lipid production.
ABCB1 limits the cytotoxic activity of TAK-243, an inhibitor of the ubiquitin-activating enzyme UBA1
Authors: Wu Zhuoxun , Yang Yuqi , Lei Zining , Narayanan Silpa , Wang Jingquan , Teng Qiuxu , Murakami Megumi , Ambudkar Suresh V. , Ping Fengfeng , Chen Zhesheng
Published: January 2022

Background: One of the major concerns of cancer therapy is the emergence of multidrug resistance (MDR). The MDR-associated ATP-binding cassette sub-family B member 1 (ABCB1) transporter is established to mediate resistance against numerous anticancer drugs. In this study, we demonstrated that the Ubiquitin-like modifier activating enzyme 1 (UBA1) inhibitor TAK-243 is transported by the ABCB1. Methods: MTT assay was performed to evaluate the cytotoxicity of TAK-243. Western blot was carried out to investigate if TAK-243 affect to ABCB1 protein expression in cancer cells. High Performance Liquid Chromatography (HPLC) and ATPase assay were carried out to confirm TAK-243 as an ABCB1 substrate. [3H]-paclitaxel accumulation assay was used to determine the MDR reversal effect of TAK-243. Computational docking analysis was performed to investigate the drug-transporter binding position. Results: The cytotoxicity profile showed that TAK-243 was less effective in ABCB1-overexpressing cells than in the parental cells, but pharmacological inhibition or knockout the gene of ABCB1 was able to reverse TAK-243 resistance. Furthermore, TAK-243 potently stimulated ABCB1 ATPase activity and the HPLC analysis revealed that TAK-243 accumulation was significantly reduced in ABCB1-overexpressing cells. Finally, the computational docking analysis indicates a high binding affinity between TAK-243 and human ABCB1 transporter. Conclusions: Our in vitro data characterized TAK-243 as a substrate of ABCB1, which may predict limited anticancer effect of this compound in drug resistant tumors.
David Hunter Hubel, the ‘Circe effect’, and SARS-CoV-2 infection of the human visual system
Authors: Lukiw Walter J.
Published: January 2022

David Hunter Hubel (1926–2013) was an internationally recognized neurophysiologist and vision neuroscientist noted for his life-long studies on the columnar structure and highly integrated function of the brain’s primary and secondary visual cortex. He was co-recipient with the American neuropsychologist and neurobiologist Roger Wolcott Sperry (1913–1994) and the Swedish neurophysiologist Torsten Nils Wiesel (1924-present) of the 1981 Nobel Prize in Physiology or Medicine, for their significant discoveries concerning the functional specialization of the cerebral hemispheres, the layered structure of the human cerebral visual cortex and information processing in the visual system, how the human visual cortex is organized into columns, and how this remarkable cellular organization and connectivity for the human visual system can be modified by lifestyle, experience, aging and disease. This commentary integrates these significant findings with current observations on SARS-CoV-2, the causative agent of COVID-19, and its invasion of the human visual system via the angiotensin converting enzyme 2 (ACE2) receptor.
Study of the genus Torreya (Taxaceae) based on chloroplast genomes
Authors: Miao Zhen-Peng , Niu Xiang-Na , Wang Rong-Bin , Huang Long , Ma Bei-Bei , Li Jian-Hui , Hong Xin
Published: January 2022

Background: Species of the genus Torreya are similar in morphology, and their morphological taxonomic characteristics are not stable because of environmentally induced changes. Therefore, morphology is insufficient for understanding their relationships. Chloroplast genome sequencing technology provides a powerful tool for molecular analysis to get more infomation for classification and identification of Torreya genus. Methods: A total of 4 chloroplast genome of Torreya, including T. Parvifolia, T. nucifera, T. fargesii var. Yunnanensis and T. grandis var. jiulongshanensis, were sequenced and annotated. Campartive genome and phylogenetic tree were provided for variation analysis. Results: The chloroplast genome size of the four samples is about 137 kb, the inverted repeat (IR) regions are identified in the genus Torreya. Genome comparison using mVISTA showed high sequence similarity among different species. Regions with divergence in exon regions include accD, ndhB, ndhF, psbA, psbJ, rpl2, rps3, rps16, rps18, ycf1, and ycf2. The phylogenetic tree based on 73 single-copy genes showed a clearer relationships among different species of Torreya. Conclusions: All genomes of the four Torreya species consist of two short IR regions, and results of the phylogenetic analysis concluded that T. parvifolia should be considered as T. fargesii var. yunnanensis or treated as a sister species. T. grandis var. jiulongshanensis should be treated as a variety of T. grandis according to molecular evidence, supporting the originally published proposal.
Combinatorial approach of vitamin C derivative and anti-HIV drug-darunavir against SARS-CoV-2
Authors: Sahoo Alaka , Swain Shasank S. , Paital Biswaranjan , Panda Maitreyee
Published: January 2022

Background: Coronavirus disease-2019 (COVID-19) has become a pandemic around the globe due to the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2), a new variant of the Coronavirus (CoV) family. The rapid transmission of the infectious disease, 135,646,617 positive cases from which 2,930,732 mortality cases were recorded until 11 April 2021. In an emergency, several existing anti-viral, anti-malarial, and anti-HIV drugs have been used on a repurposing basis. However, without proper clinical evidence, it may create several side effects for the patient. Thus, recommending potential and less-toxic regimens at this emergency stage is the most crucial aspect for any physician. Methods: We have hypothesized a combinatorial drug approach against COVID-19 and to select potential combinations from ten anti-HIV drugs and ten vitamin C derivatives were systematically validated using advanced bioinformatic tools. Initially, the chemical structures used as ligands from PubChem and the target protein, SARS-CoV-2 main protease (PDB ID: 6Y84) from the protein data bank were retrieved for this study. Further, assess the potency, toxicity, drug-ability, and pharmacokinetics profiles using several bioinformatics tools, viz., molecular docking by the AutoDock 4.1 software with predicting activity spectra for substances, Molsoft, ProTox, and SwissADME tools. Molecular dynamics simulation was also employed for most potential candidates to assess their binding stability using GROMACS 5.1.4 software. Results: The above computational investigation indicated that ‘darunavir with L-ascorbyl-2,6-dibutyrate or ascorbic acid-2-sulfate’ combinations strongly inhibit the SARS-CoV-2-main protease as a potential treatment option against COVID-19. Mostly, vitamin C derivatives enhanced the anti-COVID activity and might reduce the post-treatment side effects of darunavir in combination. Conclusions: Overall, the present work suggests that bioinformatics tools are suitable for recognizing potential candidates in an emergency, and herein the selected ‘anti-HIV-drug-vitamin c derivatives’ cocktails may potential-cum-fewer toxic regimens against COVID-19 treatment.
ET-MSF: a model stacking framework to identify electron transport proteins
Authors: Wang Yizheng , Pan Qingfeng , Liu Xiaobin , Ding Yijie
Published: January 2022

Introduction: The electron transport chain is closely related to cellular respiration and has been implicated in various human diseases. However, the traditional “wet” experimental method is time consuming. Therefore, it is key to identify electron transport proteins by computational methods. Many approaches have been proposed, but performance of them still has room for further improvement. Methodological issues: In our study, we propose a model stacking framework, which combines multiple base models. The protein features are extracted via PsePSSM from protein sequences. Features are fed into the base model including support vector machines (SVM), random forest (RF), XGBoost, etc. The results of base model are entered into logistic regression model for final process. Results: On the independent dataset, the accuracy and Matthew’s correlation coefficient (MCC) of proposed method are 95.70% and 0.8756, respectively. Furthermore, we show that the model stacking framework outperforms single machine learning classifiers statistically. Conclusion: Our models are better than most known strategies for identifying electron transport proteins. Our model can be used to more precisely identify electron transport proteins.
Temporal evolution and adaptation of SARS-CoV-2 codon usage
Authors: Posani Elisa , Dilucca Maddalena , Forcelloni Sergio , Pavlopoulou Athanasia , Georgakilas Alexandros G. , Giansanti Andrea
Published: January 2022

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first occurred in Wuhan (China) in December of 2019. Since the outbreak, it has accumulated mutations on its coding sequences to optimize its adaptation to the human host. The identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. Methods: In this study, we compared 320,338 SARS-CoV-2 genomes isolated from all over the world to the first sequenced genome in Wuhan, China. To this end, we analysed over time the codon usage patterns of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), RNA-dependent RNA polymerase (RdRp) and ORF1ab. Results: We found that genes coding for the proteins N and S diverged more rapidly since the outbreak by accumulating mutations. Interestingly, all genes show a deoptimization of their codon usage with respect to the human host. Our findings suggest a general evolutionary trend of SARS-CoV-2, which evolves towards a sub-optimal codon usage bias to favour the host survival and its spread. Furthermore, we found that S protein and RdRp are more subject to an increasing purifying pressure over time, which implies that these proteins will reach a lower tendency to accept mutations. In contrast, proteins N and M tend to evolve more under the action of mutational bias, thus exploring a large region of their sequence space. Conclusions: Overall, our study shed more light on the evolution of SARS-CoV-2 genes and their adaptation to humans, helping to foresee their mutation patterns and the emergence of new variants.
The systems medicine of cannabinoids in pediatrics: the case for more pediatric studies
Authors: O’Dell Chloe P. , Tuell Dawn S. , Shah Darshan S. , Stone William L.
Published: January 2022

Introduction: The legal and illicit use of cannabinoid-containing products is accelerating worldwide and is accompanied by increasing abuse problems. Due to legal issues, the USA will be entering a period of rapidly expanding recreational use of cannabinoids without the benefit of needed basic or clinical research. Most clinical cannabinoid research is focused on adults. However, the pediatric population is particularly vulnerable since the central nervous system is still undergoing developmental changes and is potentially susceptible to cannabinoid-induced alterations. Research design and methods: This review focuses on the systems medicine of cannabinoids with emphasis on the need for future studies to include pediatric populations and mother-infant dyads. Results and conclusion: Systems medicine integrates omics-derived data with traditional clinical medicine with the long-term goal of optimizing individualized patient care and providing proactive medical advice. Omics refers to large-scale data sets primarily derived from genomics, epigenomics, proteomics, and metabolomics.