bluuebunny/crossref_metadata_2025 huggingface dataset:
TO THE QUESTION OF THE CHOICE OF MOBILE COMPOSITION IN THE BRT SYSTEM
Authors:   National Transport University, Kyiv, Ukraine, V Poliakov , D Yaschenko ,   National Transport University, Kyiv, Ukraine, S Sharai ,   National Transport University, Kyiv, Ukraine
Published: October 2021

In article the question at the choice of the rolling stock of passenger motor transport in the BRT system which provides movements of buses on specially allocated and often obgorodzheny strips, that is its full isolation on the road from other means of transport is considered. For increase in passenger capacity in the BRT system use three-link buses and trolleybuses. Along with indisputable advantages of three-link buses and trolleybuses also shortcomings - the worst maneuverability and stability of the movement in comparison with two-link are inherent in them. Besides, the efficiency of operation of such cars is provided with a passenger traffic which during the day can change many times. Therefore the road train as a part of two (or three) the buses or trolleybuses working in connection, і which passenger capacity similar to the jointed buses and trolleybuses can become perspective. In rush hours the bus train, and in interpeak the period - each bus separately works (the possible parking of one bus at allocated to the platform). In view of restriction of the maximum length of the bus train at the level of 24.26 m, as buses as making road trains, we will accept the 8th meter buses MAZ 206. Passenger capacity of such bus is 72 passenger, the power of the traction engine - 160 kW. The expediency of use of three-link hook-on road train is proved by the conducted researches that MAZ 206 with a total length up to 26 m and with a passenger capacity up to 220 passengers in the BRT system consists of three same buses. It is shown that the total power of engines is necessary for the movement of such bus train with a speed of 25 m/s has to make 300 kW while for one bus at the movement with the same speed it has to be at the level of 135 kW. It demonstrates about economic feasibility of use of the bus train from three buses working in connection because for their movement in all range of speeds there is enough power of two engines, that is one of buses can be used as the passive trailer that will lead to improvement of fuel profitability of the bus train. It is established that on maneuverability indicators three links the hook-on road train considerably exceeds three links pivotally - the jointed bus. So, the dimensional lane of the hook-on bus train at execution of the most typical maneuvers by it during the work on a city route does not exceed 3.9 and 4.1 m at turns respectively on 900 and 1800 that it is much less, than for three links pivotally the jointed bus 24 m long respectively of 6.8 and 8.2 m. KEYWORDS: THREE-UNIT THE ROAD TRAIN, THE BUS, PIVOTALLY-THE JOINTED BUS, THE BRT SYSTEM, POWER, MANEUVERABILITY, A TRAJECTORY, OVERALL STRIP
INCREASING THE OPERATING PROPERTIES OF THE MACHINE PARTS BY THE SURFACE RELIEFS
Authors:   National Transport University, Kyiv, Ukraine, E Posviatenko , N Posviatenko ,   National Transport University, Kyiv, Ukraine, I Rybak ,   National Transport University, Kyiv, Ukraine
Published: October 2021

The article discusses the direction of improving the operational properties of machine parts by applying regular reliefs to the surface/ Purpose - to develop a model, plan and methodology for experimental studies of regular reliefs and create their classification by purpose and methods of obtaining. The object of research - regular reliefs on the surface of machine parts. The hierarchy of the main factors that affect the profile of reliefs formed by triangular grooves is determined. This is the normal penetration force of a linear indenter, hardness and elongation of the experimental material. The optimization parameter is the groove depth. A mathematical model and research plan have been developed 23. The methodology and devices for conducting experiments are determined. These are hydraulic presses, linear indenters, optical microscopes, microhardness testers, test materials, instruments, and measuring instruments. Materials for research: alloyed and stainless steel, gray and malleable cast irons, bronze and brass, aluminum and titanium alloys. Classifications of reliefs according to the methods of obtaining and destination are developed. Production methods are based on cold plastic deformation and cutting. The basic methods for the study are static methods: the introduction of a dividing element with discrete drawing and a single protrusion of the shaped mandrel during reduction. The dependence of the depth and double angle of the relief groove on the normal force is shown. A new method for obtaining the surface of a part, including the alternation of supporting platforms and grooves is proposed. The method is carried out using machining and subsequent deformation pulling. A distinctive feature of the method is the use of an intermediate elastic sleeve. KEYWORDS: REGULAR RELIEF, COLD PLASTIC DEFORMATION, LINEAR INDUCTOR, SURFACE OF PARTS, COATING, MODEL OF FORMATION OF RELIEF.
MODELING OF ROUTE FUNCTIONING OF THE PASSENGER TRANSPORT SYSTEM TAKING INTO ACCOUNT THE QUALITY CRITERIAS OF PASSENGER SERVICES AND QUARANTINE RESTRICTIONS
Authors:   National Technical University of Ukraine «Igor Sikorsky Kyiv Polytechnic Institute» Kyiv, Ukraine, O Sokulskyi , K Hilevska ,   National Transport University, Kyiv, Ukraine, N Vasiltsova ,   National Transport University, Kyiv, Ukraine
Published: October 2021

This article examines the analysis of the functioning of the urban passenger transport system in the context of the COVID-19 pandemic. Parameters of indicators of passengers' quality of services on routes flights are defined by means of software of discrete-event simulation modeling. The proposed simulation model of the system «passenger - stop - passenger vehicle» is considered in terms of the theory of queuing systems. The object of study - aspects of the functioning of the urban passenger transport system in pandemic conditions. The purpose of the work is to investigate the requirements for the organization and functioning of the urban passenger transport system in pandemic conditions to increase the efficiency of the transport complex of the country. The research method - research and analysis of the urban passenger transport system functioning in different conditions. The operation of the urban passenger transport system in the context of the COVID-19 pandemic requires its revision and compliance with current safety standards, which will create a competitive transport system and efficient infrastructure, scientifically justify the construction of schedules and calculation of fares. It is proposed to determine the parameters of passenger service quality on flights of passenger routes using software discrete-event simulation, where the proposed simulation model of the system «passenger - stop - passenger vehicle» is considered in terms of the theory of queuing systems. To take into account the conditions of quarantine restrictions on the occupancy of the passenger vehicle, it is necessary to take into account the restrictions on the maximum number of passengers in the simulation models. Performing a series of runs of the simulation model determine the interval between flights on the route of urban passenger transport system, which meets the quality of passenger service, and, accordingly, does not violate the rights of citizens while receiving transport services. KEYWORDS: RIDERSHIP, ROUTES, FLIGHT, PASSENGER VEHICLE, PASSENGER TRANSPORT SYSTEM, QUALITY OF PASSENGER SERVICE, QUARANTINE, QUEUING SYSTEM, EVENT DISCRETE SIMULATION
THE INFLUENCE OF FUNCTIONAL ELEMENT «AUTO SERVICE ENTERPRISE» PARAMETERS OF THE AUTO SERVICE SYSTEM ON THE Q
Authors:   Cherkasy State Technological University, Cherkasy, Ukraine, L Tarandushka , N Kostian ,   Cherkasy State Technological University, Cherkasy, Ukraine
Published: October 2021

The methodology of determination optimal values of independent parameters for model of car-service system on macrolevels of center that simply answer morphological signs her functional element «Autoservice enterprise» is offered in the article. Methodology is based on the results of analysis statistical and forecast indexes of quality, that it is got after a nonlinear model as Sugeno. Realization of model is carried out with application of the module Fuzzy Logic Toolbox in the package of Matlab. Nonlinear dependences are investigational to the coefficient of quality of technological processes from possible combinations of entry parameters the system for the typical domestic enterprises of car-service center: point of technical service, car repair service workshop, technical service station, authorized technical service station, specialized autoservice enterprise and complex autoservice enterprise. Power of enterprise (amount of posts), level of personnel provision, form of production organization, is taken into account. Level of personnel provision certainly as a complex index, that characterizes the amount of personnel, that is needed for implementation of the pre-arranged technological processes, level of qualification of personnel and level of material well-being technological discipline of personnel. The flow-chart of algorithm sequence of implementation of the stages of methodology is offered is built. An algorithm consists of eight stages and contains a subroutine call of determination optimal form of production. On the basis of computer experiment the maximal values of level quality of technological processes are certain and it is calculated the expected increase at the optimal values of descriptions autoservice enterprise and permanent values of parameters of subsystems «Cars» and «Environment». The offered methodology it is expedient to apply for determination of ways optimization car-service enterprises on micro- and macrolevels. KEYWORDS: AUTOSERVICE ENTERPRISE, PRODUCTION PROCESS, QUALITY.
SCIENTIFIC AND PRACTICAL PROBLEM OF MOTOR TRANSPORT TECHNOLOGY AND SYSTEM CONCEPT OF TECHNO-INNOVATIVE MANAGEMENT ON MOTOR TRANSPORT
Authors:   National Transport University, Kyiv, Ukraine, R Khabutdinov
Published: October 2021

The article deals with the problem of managing techno-innovative development of motor transport technology as an important component of the resource-technological and product-reproduction basis of motor transport. It is shown, that using of this basis, motor transport processes and five reproductive functions of motor transport are materially realized within the framework of the structural and functional organization of the motor transport system. Scientific definitions and concepts of important categories of motor transport science are presented: functional structures of motor transport and systems, motor transport technology, techno-innovative management of motor transport, processes of road transport and delivery, theoretical axioms of the transport process, principles of technical and innovative development of motor transport technology, as well as resource and technological and product-reproduction (RTPR) basis of the motor transport. A promising and systematic concept of high-tech and resource-saving reproduction of motor transport services is formulated, and a mathematical model of the target function of strategic and technologically innovative management of motor transport is proposed. The object of the research is innovative motor transport technologies and processes, taking into account the influence of the energy resource mechanism of the material integrity of the system. The purpose of the work is the statement and ways of solving the scientific and practical problem of conceptual management of the development of the RTPR of the motor transport basis, as well as its processes and functions. The results of the article can be used for the implementation of system-synergetic and conceptual-innovative management on the motor transport and in other subsystems of the motor transport system. Predictive assumptions about the development of the research object - the implementation of a technologically innovative mechanism of energy-resource synergy in the motor transport and in other subsystems of the motor transport system, taking into account their structures and functions. KEY WORDS: CONCEPT, MOTOR TRANSPORT TECHNOLOGY, INNOVATIVE MANAGEMENT, MOTOR TRANSPORT, TRANSPORT FUNCTIONS, ENERGY EFFICIENCY, ENERGY RESOURCE SYNERGY.
FORMATION OF RISK MANAGEMENT SYSTEM IN THE LOGISTICS ACTIVITY OF THE ENTERPRISЕS
Authors:   National Transport University, Kyiv, Ukraine, L Volynets , I Khomenko ,   Polytechnic National University, Chernihiv, Ukraine, I Khalatsk ,   National Transport University, Kyiv, Ukraine, Y Bozhok ,   National Transport University, Kyiv, Ukraine, K Penkivska ,   National Transport University, Kyiv, Ukraine
Published: October 2021

The article analyzes the approaches to the formation of a risk management system in the logistics activities of enterprises. The main principles of risk management are systematized and it is proved that the proposed set of principles can form the basis of risk management process in logistics activities of enterprises and most adequately reflect its essence, and practical implementation of these principles can contribute to the formation of risk management system in logistics activities. To solve the main problems of risk management in the management system of logistics activities of enterprises, taking into account the need to apply the concept of risk management, which will take into account the interests of each link in the logistics chain, we have formed an algorithm for risk management in the logistics system.
FEATURES OF THE IMPLEMENTATION OF MONETARY POLICY IN MODERN CONDITIONS
Authors:   National Transport University, Kyiv, Ukraine, I Gorobinska , V Ulianitska ,   National Transport University, Kyiv, Ukraine
Published: October 2021

The article is devoted to the problem of forming an effective monetary policy in modern conditions. The relevance of the chosen topic is explained by the fact that identifying the main directions of improving monetary policy and developing tools to improve its effectiveness is one of the most important 39 tasks today, as insufficient effectiveness of proposed and implemented measures can lead to loss of purchasing power, rising inflation, deterioration activities of the banking sector and the threat of its crisis. The object of research is monetary policy. The purpose of the study is to develop measures to improve the effectiveness of monetary policy of Ukraine in modern conditions through the study of theoretical and practical aspects of the studied issues.
STATISTICAL PROVISION OF MARKETING RESEARCH OF THE CAR SERVICE MARKET
Authors:   National Transport University, Kyiv, Ukraine, M Khobta , V Porfirenko ,   National Transport University, Kyiv, Ukraine, V Sukmaniuk ,   National Transport University, Kyiv, Ukraine
Published: October 2021

The article offers methodological approaches and recommendations for creating an information database from various information sources for the organization of statistical provision in the implementation of marketing research of the car service market, in conditions of changing consumer behavior. The object of study is the relationship process between the subjects of marketing activities of the car service market. The purpose of study is a theoretical justification of methodological approaches and the development of practical recommendations for the creation and operation of statistical provision for marketing research of the car service market. Research methods - generalization, systematization, comparison, observation, analysis, synthesis, scientific abstraction. The collection of primary data involves organization and conduction of statistical observation, the selection of information sources and methods for marketing research is determined by the characteristics of the studied segment of the car service market. Creating an information base is the accumulation of information from various sources in several stages. The article provides the classification of information in marketing research from various sources. Formation of information about companies and customers, enough general economic information, computer databases that contain a list of service stations, their details, information about the types of services they provide to their customers, etc. From internal sources of information, namely the number of concluded agreements for the maintenance of corporate cars, information on the number of customers, the volume of services provided, the number of invoices, the structure of orders. Analyzing the classification of service stations in the car service market, we conclude that they differ significantly from each other, so it is necessary to organize a selective stratified statistical survey covering all groups of enterprises and customers depending on the share of each group, which will form a complete and reliable information base of marketing research data. Methodical approaches and practical recommendations will allow marketers to better organize statistical observation, to form an information base of marketing research of the car service market. KEY WORDS: STATISTICAL OBSERVATION, MARKETING RESEARCH, MARKETING INFORMATION, SELECTIVE OBSERVATION, CLASSIFICATION OF CAR SERVICE STATIONS, INFORMATION SOURCES.
Political Overconfidence Inhibits the Effectiveness of Inoculations Against Misperceptions
Authors: Anson Ian
Published: October 2021

In this study, I develop an experimental framework to examine whether political overconfidence leads Americans to defend political misperceptions. Politically overconfident Americans, who suffer from the “double bind” of ignorance described by the Dunning-Kruger Effect, are expected to resist the effects of corrective inoculations against misperceptions. In two survey experiments, I measure political overconfidence, and assess its effects on skepticism towards five common misperceptions. In one study, I randomly expose respondents to an inoculation message, and observationally assess the effects of political overconfidence on the inoculation’s effectiveness. In a second study, I experimentally manipulate overconfidence itself, by exposing a random subset of respondents to an objective assessment of their political knowledgeability before random exposure to an inoculation. Together, the results show that corrective inoculations can reduce support for misperceptions. However, among the politically overconfident, these treatments are ineffective.
МАГИЧЕСКИЙ АТРИБУТ: МЕЖДУ ЯЗЫЧЕСТВОМ И ИСЛАМОМ
Authors: Сулейманова М.Н. , Нигматуллина З.Ф.
Published: October 2021

Целью исследования является изучение башкирских амулетов «бетеү», небольшая коллекция которых хранится в фондах Национального музея Республики Башкортостан. В музейном собрании отложились несколько типов «бетеү», бытовавших на рубеже XIX–XX вв. Предметы отличаются друг от друга формой, материалом, техникой изготовления и имеют разное содержание. Амулетам придавались магико-охранительные и сакральные свойства. Согласно древним поверьям башкир, «бетеү» приносит хозяину здоровье, долголетие, удачу во всех делах и оберегает от сглаза и влияния зловредных духов (духов болезней, шайтана и др.). Самым распространенным видом были треугольной формы амулеты, с вложенной в него молитвой или, реже, предметом. Такие кожаные амулеты-футляры носились на шнурке на шее как обереги или подшивались к одежде с внутренней стороны. Аналогичные обережные амулеты бытовали у многих народов, в том числе у среднеазиатских. Башкирские «бетеү» как магический предмет имели широкое распространение в прошлом и все еще популярны в настоящее время среди населения, прежде всего, пожилого возраста. Поэтому они представляют собой важный этнографический источник для изучения духовной и материальной культуры башкирского народа.
The research aims to study the Bashkir amulets "beteu", a small collection of which is kept in the funds of the National Museum of the Republic of Bashkortostan. The collection possesses several types of "beteu", used at the turn of the 19th-20th centuries. Objects differ from each other in shape, material, manufacturing technique, and usage. Magical, protective and sacred properties were attributed to the amulets. The Bashkirs believed that "beteu" brought health, longevity, good luck, and protection from the harmful influence of otherworldly forces. Triangular amulets were the most common, with a prayer or, less often, an object embedded in it. Such leather amulets were worn on a cord around the neck or were sewn to clothes from the inside. Many Central Asian peoples used similar amulets. The Bashkir "beteu", a magical object of cult and ritual significance, combines the pre-Islamic beliefs and the Muslim religion. Therefore, they represent an important ethnographic source for studying the spiritual and material culture of the Bashkir people.
Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model
Authors: Mostafavi Sepideh , Balafkan Novin , Pettersen Ina Katrine Nitschke , Nido Gonzalo S. , Siller Richard , Tzoulis Charalampos , Sullivan Gareth J. , Bindoff Laurence A.
Published: October 2021

Given the considerable interest in using stem cells for modeling and treating disease, it is essential to understand what regulates self-renewal and differentiation. Remodeling of mitochondria and metabolism, with the shift from glycolysis to oxidative phosphorylation (OXPHOS), plays a fundamental role in maintaining pluripotency and stem cell fate. It has been suggested that the metabolic “switch” from glycolysis to OXPHOS is germ layer-specific as glycolysis remains active during early ectoderm commitment but is downregulated during the transition to mesoderm and endoderm lineages. How mitochondria adapt during these metabolic changes and whether mitochondria remodeling is tissue specific remain unclear. Here, we address the question of mitochondrial adaptation by examining the differentiation of human pluripotent stem cells to cardiac progenitors and further to differentiated mesodermal derivatives, including functional cardiomyocytes. In contrast to recent findings in neuronal differentiation, we found that mitochondrial content decreases continuously during mesoderm differentiation, despite increased mitochondrial activity and higher levels of ATP-linked respiration. Thus, our work highlights similarities in mitochondrial remodeling during the transition from pluripotent to multipotent state in ectodermal and mesodermal lineages, while at the same time demonstrating cell-lineage-specific adaptations upon further differentiation. Our results improve the understanding of how mitochondrial remodeling and the metabolism interact during mesoderm differentiation and show that it is erroneous to assume that increased OXPHOS activity during differentiation requires a simultaneous expansion of mitochondrial content.
Metabolic Profile in Neonatal Pig Hearts
Authors: Li Pengsheng , Li Fan , Tang Ling , Zhang Wenjing , Jin Yan , Gu Haiwei , Zhu Wuqiang
Published: October 2021

We evaluated the metabolic profile in pig hearts at postnatal day 1, 3, 7, and 28 (P1, P3, P7, and P28, respectively) using a targeted liquid chromatography tandem mass spectrometry assay. Our data showed that there is a clear separation of the detected metabolites in P1 vs. P28 hearts. Active anabolisms of nucleotide and proteins were observed in P1 hearts when cardiomyocytes retain high cell cycle activity. However, the active posttranslational protein modification, metabolic switch from glucose to fatty acids, and the reduced ratio of collagen to total protein were observed in P28 hearts when cardiomyocytes withdraw from cell cycle.
Retrospective Analysis of Fondaparinux and Low-Molecular-Weight Heparin in the Treatment of Women With Recurrent Spontaneous Abortion
Authors: Zhao Long , Bi Shuqin , Fu Jinhua , Qi Lijuan , Li Lin , Fu Yinghui
Published: October 2021

Background

To compare the clinical efficacy of fondaparinux and LMWH and provide clinical evidence for the effectiveness of fondaparinux in the treatment of recurrent spontaneous abortion caused by PTS.

Methods

A retrospective analysis was conducted for 120 patients diagnosed with a recurrent spontaneous abortion caused by PTS in Qingdao Jinhua Women’s Hospital from March 2019 to April 2020. The patients were divided into two groups: 68 cases in the control group, treated with LMWH, 52 cases in the observational group, treated with fondaparinux. The pregnancy outcomes and adverse reactions between the two groups of recurrent miscarriage patients were compared.

Results

No significant difference was detected in the general data between the two groups of patients before treatment (P>0.05). In the observational group, the R value was increased, and the α and MA values were decreased after three months of treatment compared to those before treatment (P<0.05). In the control group, the R value was increased, and the MA value was decreased after three months of treatment compared to those before treatment (P<0.05). After treatment, no significant difference was observed in the pregnancy outcome between the two groups (P>0.05). The total adverse reaction rate of the fondaparinux group was lower than that of the LMWH group (P<0.05).

Conclusions

In this study, no significant difference was detected in the pregnancy outcome between fondaparinux and LMWH in the treatment of recurrent spontaneous abortion caused by PTS, but fondaparinux had a low occurrence rate of adverse reactions and high safety.
A Novel H∞ Robust Control Strategy for Voltage Source Inverter in Microgrid
Authors: Shi Hongtao , zhang Jie , Zhou Jian , Li Yifan , Jiang Zhongnan
Published: October 2021

The voltage control performance of the voltage source inverter (VSI) in a microgrid may change under different load conditions. However, in the case of traditional control strategies, the robustness of VSI is insufficient. In response to the above problems, a novel robust control scheme for VSI in the microgrid based on H∞ hybrid sensitivity is proposed in this study. The grid-side interference during the VSI operation is taken as the variable, and the sensitivity function is designed to build a H∞ robust voltage controller for VSI. In addition, an adaptive virtual impedance group is designed to further improve the voltage control robustness under a variety of operation conditions. Finally, comparative simulation experiments are carried out to verify the anti-interference ability of the proposed control strategy under different working conditions.
Nature-Based Solutions for Urban Climate Change Adaptation and Wellbeing: Evidence and Opportunities From Kiribati, Samoa, and Vanuatu
Authors: Kiddle Gabriel L. , Bakineti Tokintekai , Latai-Niusulu Anita , Missack Willy , Pedersen Zari Maibritt , Kiddle Rebecca , Chanse Victoria , Blaschke Paul , Loubser David
Published: October 2021

Climate change and urbanisation in combination put great pressure on terrestrial and ocean ecosystems, vital for subsistence and wellbeing in both rural and urban areas of Pacific islands. Adaptation is urgently required. Nature-based solutions (NbS) offer great potential, with the region increasingly implementing NbS and linked approaches like ecosystem-based adaptation in response. This paper utilises three Pacific island nation case-studies, Kiribati, Samoa and Vanuatu, to review current NbS approaches to adapt and mitigate the converging resilience challenges of climate change and urbanisation. We look at associated government policies, current NbS experience, and offer insights into opportunities for future work with focus on urban areas. These three Pacific island case-studies showcase their rich cultural and biological diversity and, importantly, the role of traditional ecological knowledge in shaping localised, place-based, NbS for climate change adaptation and enhanced wellbeing. But gaps in knowledge, policy, and practice remain. There is great potential for a nature-based urban design agenda positioned within an urban ecosystems framework linked closely to Indigenous understandings of wellbeing.
Multi-Similarities Bilinear Matrix Factorization-Based Method for Predicting Human Microbe–Disease Associations
Authors: Yang Xiaoyu , Kuang Linai , Chen Zhiping , Wang Lei
Published: October 2021

Accumulating studies have shown that microbes are closely related to human diseases. In this paper, a novel method called MSBMFHMDA was designed to predict potential microbe–disease associations by adopting multi-similarities bilinear matrix factorization. In MSBMFHMDA, a microbe multiple similarities matrix was constructed first based on the Gaussian interaction profile kernel similarity and cosine similarity for microbes. Then, we use the Gaussian interaction profile kernel similarity, cosine similarity, and symptom similarity for diseases to compose the disease multiple similarities matrix. Finally, we integrate these two similarity matrices and the microbe-disease association matrix into our model to predict potential associations. The results indicate that our method can achieve reliable AUCs of 0.9186 and 0.9043 ± 0.0048 in the framework of leave-one-out cross validation (LOOCV) and fivefold cross validation, respectively. What is more, experimental results indicated that there are 10, 10, and 8 out of the top 10 related microbes for asthma, inflammatory bowel disease, and type 2 diabetes mellitus, respectively, which were confirmed by experiments and literatures. Therefore, our model has favorable performance in predicting potential microbe–disease associations.
Case Report: Combined Liver-Kidney Transplantation to Correct a Mutation in Complement Factor B in an Atypical Hemolytic Uremic Syndrome Patient
Authors: López-Trascasa Margarita , Alonso-Melgar Ángel , Melgosa-Hijosa Marta , Espinosa-Román Laura , Lledín-Barbancho María Dolores , García-Fernández Eugenia , Rodríguez de Córdoba Santiago , Sánchez-Corral Pilar
Published: October 2021

Pathogenic gain-of-function variants in complement Factor B were identified as causative of atypical Hemolytic Uremic syndrome (aHUS) in 2007. These mutations generate a reduction on the plasma levels of complement C3. A four-month-old boy was diagnosed with hypocomplementemic aHUS in May 2000, and he suffered seven recurrences during the following three years. He developed a severe hypertension which required 6 anti-hypertensive drugs and presented acrocyanosis and several confusional episodes. Plasma infusion or exchange, and immunosuppressive treatments did not improve the clinical evolution, and the patient developed end-stage renal disease at the age of 3 years. Hypertension and vascular symptoms persisted while he was on peritoneal dialysis or hemodialysis, as well as after bilateral nephrectomy. C3 levels remained low, while C4 levels were normal. In 2005, a heterozygous gain-of-function mutation in Factor B (K323E) was found. A combined liver and kidney transplantation (CLKT) was performed in March 2009, since there was not any therapy for complement inhibition in these patients. Kidney and liver functions normalized in the first two weeks, and the C3/C4 ratio immediately after transplantation, indicating that the C3 activation has been corrected. After remaining stable for 4 years, the patient suffered a B-cell non-Hodgkin lymphoma that was cured by chemotherapy and reduction of immunosuppressive drugs. Signs of liver rejection with cholangitis were observed a few months later, and a second liver graft was done 11 years after the CLKT. One year later, the patient maintains normal kidney and liver functions, also C3 and C4 levels are within the normal range. The 12-year follow-up of the patient reveals that, in spite of severe complications, CLKT was an acceptable therapeutic option for this aHUS patient.
Role of Gut Microbiome in COVID-19: An Insight Into Pathogenesis and Therapeutic Potential
Authors: Hussain Ikram , Cher Gabriel Liu Yuan , Abid Muhammad Abbas , Abid Muhammad Bilal
Published: October 2021

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut–lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a “leaky gut”. The intestinal permeability then allows access to bacterial products and toxins into the circulatory system and further exacerbates the systemic inflammatory response. In this review, we discuss the available data related to the role of the gut microbiome in the development and progression of COVID-19. We provide mechanistic insights into early data with a focus on immunological crosstalk and the microbiome’s potential as a biomarker and therapeutic target.
Sepsis of Patients Infected by SARS-CoV-2: Real-World Experience From the International HOPE-COVID-19-Registry and Validation of HOPE Sepsis Score
Authors: Abumayyaleh Mohammad , Nuñez-Gil Iván J. , El-Battrawy Ibrahim , Estrada Vicente , Becerra-Muñoz Víctor Manuel , Uribarri Aitor , Fernández-Rozas Inmaculada , Feltes Gisela , Arroyo-Espliguero Ramón , Trabattoni Daniela , López Pais Javier , Pepe Martino , Romero Rodolfo , Ortega-Armas María Elizabeth , Bianco Matteo , Astrua Thamar Capel , D'Ascenzo Fabrizio , Fabregat-Andres Oscar , Ballester Andrea , Marín Francisco , Buonsenso Danilo , Sanchez-Gimenez Raul , Weiß Christel , Fernandez Perez Cristina , Fernández-Ortiz Antonio , Macaya Carlos , Akin Ibrahim
Published: October 2021

Background: Patients with sepsis with a concomitant coronavirus (COVID-19) infection are related to a high morbidity and mortality rate. We investigated a large cohort of patients with sepsis with a concomitant COVID-19, and we developed a risk score for the estimation of sepsis risk in COVID-19.

Methods: We conducted a sub-analysis from the international Health Outcome Predictive Evaluation Registry for COVID-19 (HOPE-COVID-19-Registry, NCT04334291). Out of 5,837 patients with COVID-19, 624 patients were diagnosed with sepsis according to the Sepsis-3 International Consensus.

Results: In multivariable analysis, the following risk factors were identified as independent predictors for developing sepsis: current smoking, tachypnoea (>22 breath per minute), hemoptysis, peripheral oxygen saturation (SpO2) <92%, blood pressure (BP) (systolic BP <90 mmHg and diastolic BP <60 mmHg), Glasgow Coma Scale (GCS) <15, elevated procalcitonin (PCT), elevated troponin I (TnI), and elevated creatinine >1.5 mg/dl. By assigning odds ratio (OR) weighted points to these variables, the following three risk categories were defined to develop sepsis during admission: low-risk group (probability of sepsis 3.1–11.8%); intermediate-risk group (24.8–53.8%); and high-risk-group (58.3–100%). A score of 1 was assigned to current smoking, tachypnoea, decreased SpO2, decreased BP, decreased GCS, elevated PCT, TnI, and creatinine, whereas a score of 2 was assigned to hemoptysis.

Conclusions: The HOPE Sepsis Score including nine parameters is useful in identifying high-risk COVID-19 patients to develop sepsis. Sepsis in COVID-19 is associated with a high mortality rate.
Powered Respirators Are Effective, Sustainable, and Cost-Effective Personal Protective Equipment for SARS-CoV-2
Authors: Munro Alasdair , Prieto Jacqui , Mentzakis Emmanouil , Dibas Mohammed , Mahobia Nitin , Baker Peter , Herbert Sarah , Smith Trevor , Hine Matthew , Hall Joann , McClarren Angie , Davidson Mike , Brooks Julie , Fisher Jane , Griffiths David , Morgan Hywel , Giulietti Corrado , Faust Saul N. , Elkington Paul
Published: October 2021

Objectives: The provision of high-quality personal protective equipment (PPE) has been a critical challenge during the COVID-19 pandemic. We evaluated an alternative strategy, mass deployment of a powered air-purifying respirator (PeRSo), in a large university hospital.

Methods: We performed prospective user feedback via questionnaires sent to healthcare workers (HCWs) issued PeRSos, economic analysis, and evaluated the real-world impact.

Results: Where paired responses were available, PeRSo was preferred over droplet precautions for comfort, patient response, overall experience, and subjective feeling of safety. For all responses, more participants reported the overall experience being rated “Very good” more frequently for PeRSo. The primary limitation identified was impairment of hearing. Economic simulation exercises revealed that the adoption of PeRSo within ICU is associated with net cost savings in the majority of scenarios and savings increased progressively with greater ITU occupancy. In evaluation during the second UK wave, over 3,600 respirators were deployed, all requested by staff, which were associated with a low staff absence relative to most comparator hospitals.

Conclusions: Health services should consider a widespread implementation of powered reusable respirators as a safe and sustainable solution for the protection of HCWs as SARS-CoV-2 becomes an endemic viral illness.
Dual-Cell Patch-Clamp Recording Revealed a Mechanism for a Ribbon Synapse to Process Both Digital and Analog Inputs and Outputs
Authors: Pang Ji-Jie , Gao Fan , Wu Samuel M.
Published: October 2021

A chemical synapse is either an action potential (AP) synapse or a graded potential (GP) synapse but not both. This study investigated how signals passed the glutamatergic synapse between the rod photoreceptor and its postsynaptic hyperpolarizing bipolar cells (HBCs) and light responses of retinal neurons with dual-cell and single-cell patch-clamp recording techniques. The results showed that scotopic lights evoked GPs in rods, whose depolarizing Phase 3 associated with the light offset also evoked APs of a duration of 241.8 ms and a slope of 4.5 mV/ms. The depolarization speed of Phase 3 (Speed) was 0.0001–0.0111 mV/ms and 0.103–0.469 mV/ms for rods and cones, respectively. On pairs of recorded rods and HBCs, only the depolarizing limbs of square waves applied to rods evoked clear currents in HBCs which reversed at −6.1 mV, indicating cation currents. We further used stimuli that simulated the rod light response to stimulate rods and recorded the rod-evoked excitatory current (rdEPSC) in HBCs. The normalized amplitude (R/Rmax), delay, and rising slope of rdEPSCs were differentially exponentially correlated with the Speed (allp< 0.001). For the Speed < 0.1 mV/ms, R/Rmaxgrew while the delay and duration reduced slowly; for the Speed between 0.1 and 0.4 mV/ms, R/Rmaxgrew fast while the delay and duration dramatically decreased; for the Speed > 0.4 mV/ms, R/Rmaxreached the plateau, while the delay and duration approached the minimum, resembling digital signals. The rdEPSC peak was left-shifted and much faster than currents in rods. The scotopic-light-offset-associated major and minor cation currents in retinal ganglion cells (RGCs), the gigantic excitatory transient currents (GTECs) in HBCs, and APs and Phase 3 in rods showed comparable light-intensity-related locations. The data demonstrate that the rod-HBC synapse is a perfect synapse that can differentially decode and code analog and digital signals to process enormously varied rod and coupled-cone inputs.
Novel in vitro Experimental Approaches to Study Myelination and Remyelination in the Central Nervous System
Authors: Marangon Davide , Caporale Nicolò , Boccazzi Marta , Abbracchio Maria P. , Testa Giuseppe , Lecca Davide
Published: October 2021

Myelin is the lipidic insulating structure enwrapping axons and allowing fast saltatory nerve conduction. In the central nervous system, myelin sheath is the result of the complex packaging of multilamellar extensions of oligodendrocyte (OL) membranes. Before reaching myelinating capabilities, OLs undergo a very precise program of differentiation and maturation that starts from OL precursor cells (OPCs). In the last 20 years, the biology of OPCs and their behavior under pathological conditions have been studied through several experimental models. When co-cultured with neurons, OPCs undergo terminal maturation and produce myelin tracts around axons, allowing to investigate myelination in response to exogenous stimuli in a very simple in vitro system. On the other hand, in vivo models more closely reproducing some of the features of human pathophysiology enabled to assess the consequences of demyelination and the molecular mechanisms of remyelination, and they are often used to validate the effect of pharmacological agents. However, they are very complex, and not suitable for large scale drug discovery screening. Recent advances in cell reprogramming, biophysics and bioengineering have allowed impressive improvements in the methodological approaches to study brain physiology and myelination. Rat and mouse OPCs can be replaced by human OPCs obtained by induced pluripotent stem cells (iPSCs) derived from healthy or diseased individuals, thus offering unprecedented possibilities for personalized disease modeling and treatment. OPCs and neural cells can be also artificially assembled, using 3D-printed culture chambers and biomaterial scaffolds, which allow modeling cell-to-cell interactions in a highly controlled manner. Interestingly, scaffold stiffness can be adopted to reproduce the mechanosensory properties assumed by tissues in physiological or pathological conditions. Moreover, the recent development of iPSC-derived 3D brain cultures, called organoids, has made it possible to study key aspects of embryonic brain development, such as neuronal differentiation, maturation and network formation in temporal dynamics that are inaccessible to traditional in vitro cultures. Despite the huge potential of organoids, their application to myelination studies is still in its infancy. In this review, we shall summarize the novel most relevant experimental approaches and their implications for the identification of remyelinating agents for human diseases such as multiple sclerosis.
Practical Fundamentals of Clinical MEG Interpretation in Epilepsy
Authors: Laohathai Christopher , Ebersole John S. , Mosher John C. , Bagić Anto I. , Sumida Ai , Von Allmen Gretchen , Funke Michael E.
Published: October 2021

Magnetoencephalography (MEG) is a neurophysiologic test that offers a functional localization of epileptic sources in patients considered for epilepsy surgery. The understanding of clinical MEG concepts, and the interpretation of these clinical studies, are very involving processes that demand both clinical and procedural expertise. One of the major obstacles in acquiring necessary proficiency is the scarcity of fundamental clinical literature. To fill this knowledge gap, this review aims to explain the basic practical concepts of clinical MEG relevant to epilepsy with an emphasis on single equivalent dipole (sECD), which is one the most clinically validated and ubiquitously used source localization method, and illustrate and explain the regional topology and source dynamics relevant for clinical interpretation of MEG-EEG.
Transcranial Magnetic Stimulation Trains at 1 Hz Frequency of the Right Posterior Parietal Cortex Facilitate Recognition Memory
Authors: Mangano Giuseppa Renata , Oliveri Massimiliano , Smirni Daniela , Tarantino Vincenza , Turriziani Patrizia
Published: October 2021

Neuroimaging, neuropsychological, and brain stimulation studies have led to contrasting findings regarding the potential roles of the lateral parietal lobe in episodic memory. Studies using brain stimulation methods reported in the literature do not offer unequivocal findings on the interactions with stimulation location (left vs. right hemisphere) or timing of the stimulation (encoding vs. retrieval). To address these issues, active and sham 1 Hz repetitive transcranial magnetic stimulation (rTMS) trains of 600 stimuli were applied over the right or left posterior parietal cortex (PPC) before the encoding or before the retrieval phase of a recognition memory task of unknown faces in a group of 40 healthy subjects. Active rTMS over the right but not the left PPC significantly improved non-verbal recognition memory performance without any significant modulation of speed of response when applied before the retrieval phase. In contrast, rTMS over the right or the left PPC before the encoding phase did not modulate memory performance. Our results support the hypothesis that the PPC plays a role in episodic memory retrieval that appears to be dependent on both the hemispheric lateralization and the timing of the stimulation (encoding vs. retrieval).
Spatially Covarying Patterns of Gray Matter Volume and Concentration Highlight Distinct Regions in Schizophrenia
Authors: Rootes-Murdy Kelly , Zendehrouh Elaheh , Calhoun Vince D. , Turner Jessica A.
Published: October 2021

Introduction: Individuals with schizophrenia have consistent gray matter reduction throughout the cortex when compared to healthy individuals. However, the reduction patterns vary based on the quantity (concentration or volume) utilized by study. The objective of this study was to identify commonalities between gray matter concentration and gray matter volume effects in schizophrenia.

Methods: We performed both univariate and multivariate analyses of case/control effects on 145 gray matter images from 66 participants with schizophrenia and 79 healthy controls, and processed to compare the concentration and volume estimates.

Results: Diagnosis effects in the univariate analysis showed similar areas of volume and concentration reductions in the insula, occipitotemporal gyrus, temporopolar area, and fusiform gyrus. In the multivariate analysis, healthy controls had greater gray matter volume and concentration additionally in the superior temporal gyrus, prefrontal cortex, cerebellum, calcarine, and thalamus. In the univariate analyses there was moderate overlap between gray matter concentration and volume across the entire cortex (r = 0.56, p = 0.02). The multivariate analyses revealed only low overlap across most brain patterns, with the largest correlation (r = 0.37) found in the cerebellum and vermis.

Conclusions: Individuals with schizophrenia showed reduced gray matter volume and concentration in previously identified areas of the prefrontal cortex, cerebellum, and thalamus. However, there were only moderate correlations across the cortex when examining the different gray matter quantities. Although these two quantities are related, concentration and volume do not show identical results, and therefore, should not be used interchangeably in the literature.
Circular RNAs: The Novel Actors in Pathophysiology of Spinal Cord Injury
Authors: Sámano Cynthia , Mladinic Miranda , Mazzone Graciela L.
Published: October 2021

Spinal Cord Injury (SCI) can elicit a progressive loss of nerve cells promoting disability, morbidity, and even mortality. Despite different triggering mechanisms, a cascade of molecular events involving complex gene alterations and activation of the neuroimmune system influence either cell damage or repair. Effective therapies to avoid secondary mechanisms underlying SCI are still lacking. The recent progression in circular RNAs (circRNAs) research has drawn increasing attention and opened a new insight on SCI pathology. circRNAs differ from traditional linear RNAs and have emerged as the active elements to regulate gene expression as well as to facilitate the immune response involved in pathophysiology-related conditions. In this review, we focus on the impact and possible close relationship of circRNAs with pathophysiological mechanisms following SCI, where circRNAs could be the key transcriptional regulatory molecules to define neuronal death or survival. Advances in circRNAs research provide new insight on potential biomarkers and effective therapeutic targets for SCI patients.