bluuebunny/crossref_metadata_2025 huggingface dataset:
The Critical Role of Hippocampal Dopamine in the Pathogenesis of Hepatic Encephalopathy
Authors: CHEN B , YANG Y , LI S , ZHU X , QI Y , HONG F
Published: March 2021

The pathogenesis of hepatic encephalopathy (HE) has been generally linked to blood ammonia, gamma-aminobutyric acid and serotonin. However, the exact mechanism remains unclear. In the present study, we aimed to explore the role of hippocampal dopamine (DA) and its receptors in the pathogenesis of HE through the use of behavioral testing, western blotting, and immunofluorescence staining in normal rats, HE model rats and rats treated with the DA precursor-levodopa (L-DOPA). HE model rats manifested fibrotic livers and showed serious behavioral disorders. They also had significantly lower hippocampal DA content and increased expression of both D1 and D2 receptors relative to normal rats. After treatment with L-DOPA, the HE model rats showed normal behavior and expression of D1 returned to normal levels. Furthermore, pretreatment with the D1 antagonist SCH23390 blocked the therapeutic effect of L-DOPA on behavior in HE model rats. Taken together, these results clarify that the decrease in hippocampal DA plays a role in the pathogenesis of HE and that this effect is mediated by D1. These findings provide new evidence for the pathogenesis of HE.
Прочность композитов на основе модифицированного портландцемента, активированного в аппарате вихревого слоя
Authors: ИБРАГИМОВ Руслан Абдирашитович , КОРОЛЕВ Евгений Валерьевич
Published: March 2021

Строительные материалы c заданными эксплуатационными свойствами в настоящее время продолжают сохранять свою актуальность. Методы проектирования данных материалов основываются на управлении их структурообразованием. Один из способов формирования цементных композитов с параметрами структуры, обеспечивающими высокие эксплуатационные свойства, - введение первичных наноразмерных материалов. Для таких материалов характерны сложности при их диспергировании в среде-носителе, что особенно четко проявляется у лиофобных материалов. Часто применяют физико-химический метод диспергирования (введение поверхностно-активных веществ и ультразвуковая обработка), который ограниченно эффективен вследствие условий, связанных с обратимостью физической адсорбции поверхностно-активного вещества при повышении температуры. В данной работе представлены результаты исследования влияния на прочность бетона портландцемента, модифицированного углеродными нанотрубками и подвергнутого обработке в аппарате вихревого слоя. Обработка в указанном аппарате проводилась для диспергирования углеродных нанотрубок и физической активации поверхности частиц портландцемента. Установлено, что применение такого портландцемента совместно с пластификатором при дополнительном введении углеродных нанотрубок позволяет значительно повысить прочность при сжатии цементных композитов как в ранние сроки твердения, так и на 28-е сутки твердения по сравнению с контрольным составом.
Бетоны и технологии для строительства зданий и сооружений в Арктической зоне
Authors: ФАЛИКМАН Вячеслав Рувимович , СТЕПАНОВА Валентина Федоровна , ЧЕХНИЙ Галина Васильевна
Published: March 2021

В настоящее время в арктических и субарктических регионах проводятся мероприятия по возведению социальной инфраструктуры, аэродромов и обслуживающих их объектов, а также автономных жилых комплексов. Минстерство строительства и жилищно-коммунального хозйяства РФ инициировало разработку новых нормативных документов для строительства за полярным кругом, базой для которых станут проводимые научные исследования. В статье анализируются параметры, влияющие на срок службы бетонных и железобетонных конструкций в условиях Арктики, и приводятся примеры создания коррозионностойких бетонов и долговечных конструкций для неблагоприятных природных условий эксплуатации в суровых климатических условиях Крайнего Севера. Показано, что с целью обеспечения эффективности строительства в Арктической зоне необходима актуализация нормативных документов по полному жизненному циклу в части, связанной с проектированием, с требованиями к материалам, с технологией строительства и, наконец, с обследованием и ремонтом.
Математическое моделирование динамики процесса массопереноса при коррозии цементных бетонов
Authors: ДАВИДЮК Артем Алексеевич , РЫБНОВ Дмитрий Сергеевич , ГОГЛЕВ Илья Николаевич , СОКОЛОВ Константин Юрьевич , КУСТИКОВА Юлия Олеговна
Published: March 2021

Рассмотрены особенности протекания коррозии цементных бетонов: коррозии вымывания, биологической и кислотной, встречающейся на полевой стадии обследования различных бетонных и железобетонных конструкций (опоры мостов и эстакад, изгибаемые участки ребристых плит мостовых пролетов, вертикально сжатые стойки опорных зон площадки градирни, стенки водохозяйственных и гидротехнических сооружений). С целью оценки интенсивности протекания массопереноса при коррозии цементных бетонов и прогнозирования остаточного срока службы бетонных и железобетонных конструкций, предлагаются способы применения методов математического моделирования коррозионных процессов. Математические модели позволяют рассчитать концентрацию целевого компонента в зависимости от габаритов бетонных конструкций; определить концентрацию переносимого "свободного" гидроксида кальция в жидкой кислотно-солевой среде; вычислить среднее значение концентрации в произвольный момент времени. Физико-математическая модель процесса массопереноса при биокоррозии дает возможность рассчитывать динамику и кинетику переноса целевого компонента цементных бетонов независимо от вида биообрастания. Предложенные модели легли в основу рекомендаций по увеличению срока службы железобетонных конструкций без капитального ремонта и мониторингу развития коррозионных процессов.
Конструктивные решения защиты одноэтажных каркасных зданий от прогрессирующего обрушения
Authors: КЕЛАСЬЕВ Николай Геннадьевич , ТРЕКИН Николай Николаевич , КОДЫШ Эмиль Наумович , ЛЕОНТЬЕВ Евгений Владимирович , ТЕРЕХОВ Иван Александрович , ШМАКОВ Сергей Дмитриевич
Published: March 2021

Рассмотрены вопросы защиты одноэтажных производственных и общественных каркасных зданий от прогрессирующего обрушения. Приведены перспективные конструктивные решения, основанные на принципе включения их в работу только при возникновении запроектных вертикальных перемещений несущих конструкций здания. Применение данных конструктивных решений позволяет эффективно справиться с проблемой защиты от прогрессирующего обрушения при удалении крайних угловых колонн одноэтажных каркасных зданий, что весьма затруднительно при использовании рекомендованных в нормативах конструктивных решений. Особенно актуальны эти решения при реконструкции эксплуатируемых зданий, запроектированных и построенных до введения требований по защите от прогрессирующего обрушения. Они являются страховочными и включаются в работу только в критической ситуации, что дает возможность с относительно небольшими затратами выполнять требования нормативных документов. Представлены предложения по внесению изменений в действующие своды правил. Дальнейшие разработки позволят преодолеть сложности в проектировании защиты от прогрессирующего обрушения одноэтажных каркасных зданий, в том числе выполненных из сборных железобетонных конструкций.
Обследование светопрозрачных фасадных конструкций
Authors: АВДЕЕВ Кирилл Владимирович , ВАХРУШЕВ Константин Геннадиевич
Published: March 2021

Представлен анализ качества проектных решений, монтажа и особенностей эксплуатации светопрозрачных фасадных конструкций. Рассмотрены некоторые характерные дефекты и повреждения, выявленные при обследовании фасадов специалистами института "ЦНИИПромзданий". Приведены причины возникающих проблем на объектах при строительстве и эксплуатации, связанные в основном с разрушением или риском разрушения стекол, а также даны рекомендации по их устранению. Рекомендации, сформулированные по результатам работы, позволят повысить качество проектирования и монтажа, а также надежность и безопасность светопрозрачных фасадных конструкций. Выводы по результатам обследований будут полезны специалистам по строительному надзору при контроле качества возводимых конструкций и специалистам по эксплуатации при обслуживании фасадов.
How gamification can drive customer loyalty
Authors: Schmäh Prof. Dr. Marco , Leon Ritz Alexander
Published: March 2021

This paper intends to give an insight on how to develop a customer loyalty-focused gamification concept, that will trigger intrinsic motivation and hence strengthen customer loyalty, using the mobility industry as an example. The authors conducted explorative expert interviews to create a cross-industry process chart that guides the generic development of a customer loyalty-focused gamification concept.
The Function of Metapsychology – Study of an American Controversy, 1970s–1980s
Authors: Batsch Manuel
Published: March 2021

This article explores the controversies triggered by Freud's metapsychology, specifically the American critiques of the 1970s – Heinz Hartmann, Merton Gill and David Rapaport, Robert Waelder, and Lawrence Kubie for ego-psychology, leading into Roy Schafer, George Klein and again Merton Gill for hermeneutics, Emmanuel Peterfreund and Charles Brenner for positivism, before concluding with a summary of more inventive engagements with metapsychology including that of Joseph Sandler and André Green. The article argues that in the name of empirical or clinical evidence, the American critiques tried to reintroduce a subjectivity made of data into the heart of psychoanalytic theory and as a result, replaced the subject of the unconscious with a new figure of the subject not only transparent to itself, but also transparent to two main forms of discourse: the hermeneutic discourse, on the one hand, and the positivist discourse, on the other.
Communal Authority, Counsel and Resistance in the Reign of James I: A Conceptual Approach
Authors: Kilgallon Lynn
Published: March 2021

This article examines the relationship between counsel and resistance, as well as the interplay between royal and communal authority, in the kingdom of the Scots during the reign of James I. It does so through an analysis of the language and ideas used in political tracts and literary texts—particularly ‘The Dethe of the Kynge of Scotis’—and also in the records of parliaments and councils. The aim of this article is to suggest that counsel is usefully viewed not simply as a tool which contemporaries might deploy as a passive response to the exercise of royal (or quasi-regal) authority, but as a means by which medieval actors could proactively shape the governance they experienced in late medieval Scotland.
MAKING LEARNING MEDIA FOR GREENBOX EFFECT SIMULATOR TO IMPROVE UNDERSTANDING OF THE CONCEPT OF THE GREENHOUSE EFFECT
Authors: Ainy Noer Sarifah , Hadi Nestiyanto
Published: March 2021

The earth is experiencing global warming due to an increase in air temperature (greenhouse effect). This is due to the large number of greenhouse gases produced by human activities. In addition, it is also due to the reduced number of plants that absorb greenhouse gases, especially carbon dioxide. This condition causes the study of the greenhouse effect to become an object studied by students at school. Understanding the greenhouse effect is somewhat difficult if only understood in theory. Increasing understanding can be done by making practicum learning media. This study aims to create learning media for the Greenbox Effect Simulator to help understand the concept of the greenhouse effect. The research was conducted using control variables and independent variables (use of plants and without plants). The plants used are Caisim, Sri Gading and Anggrek. The presence of carbon dioxide (CO2) greenhouse gases can be detected by three things, namely changes in the color of the CO2 indicator, changes in temperature, and visibility of the box. The color of the CO2 indicator shows green and green yellow for Box B (with plants) which means the concentration of CO2 in normal conditions. Whereas Box C (without plants) gives a yellow color, which means that the concentration of CO2 is at high conditions. The presence of carbon dioxide gas from combustion will increase the temperature by 1.4 - 1.9 oC in Box C (without plants) and 0.7 - 1.5 oC in Box B (use of plants). The visibility of Box B shows a higher brightness level than Box C. The best plants that can absorb CO2 concentrations are orchids. The ability of orchids to absorb CO2 is assisted by their roots which also function to carry out photosynthesis. The existence of plants functions to absorb CO2 quite well when viewed from changes in temperature, color indicators and visibility.
Pelaksanaan Kegiatan Ekstrakurikuler dalam Penguatan Karakter Religius Siswa di Smp Islamic Centre Kota Tangerang
Authors: Oktafiani Adetri
Published: March 2021

Extracurricular activities have an important role in the process of strengthening the religious character of students. Students who have religious values will show good behavior towards Allah SWT, fellow humans, themselves and their surroundings. For the success of strengthening religious character, coaches of extracurricular activities are expected to be able to instill religious values. Therefore, in the implementation of extracurricular activities there is a strengthening of the religious character of students. In this study using a descriptive method by taking place at the Islamic Center Junior High School in Tangerang City. The informants in this study were the deputy principal, extracurricular coaches, and students of the Islamic Center Junior High School in Tangerang City. The data were collected by means of observation, interviews and documentation. The results of this study explain that the Implementation of Extracurricular Activities in Strengthening the Religious Character of Students at the Islamic Center Junior High School in Tangerang City 2020, namely the existence of a program of habituation of noble, spiritual and marawis morals. Extracurricular activities are carried out regularly and once a week. Strengthening the religious character of students at the Islamic Center Junior High School in Tangerang City is carried out by exemplary, learning, empowering and cultivating, praise and assessment.Â
Normal Variations in Blood Pressure in Ambulatory Blood Pressure Measurements
Authors: Mistik Selcuk , Goktas Kevser , Unalan Demet , Oguzhan Abdurrahman , Tokgöz Bulent
Published: March 2021

Aim: Hypertension is very common in primary care patients. The diagnosis of hypertension is made by office measurements and home blood pressure measurements. The aim of this study was to define the normal variation levels of blood pressure in individuals in primary care by using ambulatory blood pressure measurement.

Methods: This study was performed in primary care. Individuals who had no hypertension history were included in the study. Subjects were evaluated by using three office measurements, seven days home blood pressure measurements and 24 hours ambulatory blood pressure measurement. The ambulatory blood pressure gave us the variations in blood pressure values.

Results: The study started in January 2018 and ended in May 2018. Of the 47 subjects, 70.2% were women and 29.8% were men. The mean age was 41.63±12.00. The most common educational level was elementary school graduates. The most common occupation was housewives. Of the participants, 84.2% were married. At ambulatory blood pressure measurements, 34.0% of the subjects had mean systolic blood pressures 24 hours between 120-129 mmHg. Of the diastolic blood pressure 24 hours mean values, 15.3% had values between 80-89, where 51.0% were between the 71-79 mmHg groups. The mean value of 24 hours variation in systolic blood pressure was 15.75±18.59 (median=11.40, min=8.80, max=106.00). The 24 hours variation in the mean values of diastolic blood pressures was 12.12±10.90 (median=9.70, min=6.80, max=64.00).

Conclusion: The results of this study demonstrated that there were high levels of variations in normal blood pressures, which could show candidates for hypertension.

Keywords: ambulatory monitoring, blood pressure, variability, primary care
Microstructure and Mechanical Properties of Zinc Matrix Biodegradable Composites Reinforced by Graphene
Authors: Dai Qianfei , Peng Shanshan , Zhang Zongkui , Liu Yuan , Fan Mei , Zhao Fei
Published: March 2021

This work used spark plasma sintering (SPS) to prepare graphene nanosheets (GNS) reinforced zinc matrix composites. The influence of GNS on the microstructure and mechanical properties of zinc matrix composites was studied. The results show that the GNS/Zn composites prepared by SPS have a dense structure and good interface bonding, and GNS are uniformly distributed in the zinc matrix. Adding GNS can significantly improve the mechanical properties of the zinc matrix. When 0.7 wt% GNS are added, the comprehensive mechanical properties of the composite material are improved. The ultimate tensile strength is 254 MPa, and the Vickers hardness is 65 HV, which are 126 and 20.3% higher than those of pure zinc (112 MPa and 54 HV), respectively. The strengthening mechanisms of GNS/Zn composites are mainly load transfer of GNS and dislocation strengthening caused by coefficient of thermal expansion (CTE) mismatch. In addition, the biodegradability of GNS/Zn composites was evaluated by electrochemical measurement and immersion test. The results show that adding GNS to the zinc matrix will accelerate the degradation rate of the composite material. But the degradation rate can be controlled by the content of GNS. Its degradation rate is in the range of 69–301 μm/a, an ideal degradation rate as an orthopedic implant material.
In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications
Authors: Bai Xue , Wang Jiali , Mu Qingxin , Su Gaoxing
Published: March 2021

Understanding the basic interactions between engineered nanoparticles (ENPs) and biological systems is essential for evaluating ENPs’ safety and developing better nanomedicine. Profound interactions between ENPs and biomolecules such as proteins are inevitable to occur when ENPs are administered or exposed to biological systems, for example, through intravenous injection, oral, or respiration. As a key component of these interactions, protein corona (PC) is immediately formed surrounding the outlayer of ENPs. PC formation is crucial because it gives ENPs a new biological identity by altering not only the physiochemical properties, but also the biobehaviors of ENPs. In the past two decades, most investigations about PC formation were carried out with in vitro systems which could not represent the true events occurring within in vivo systems. Most recently, studies of in vivo PC formation were reported, and it was found that the protein compositions and structures were very different from those formed in vitro. Herein, we provide an in-time review of the recent investigations of this in vivo PC formation of ENPs. In this review, commonly used characterization methods and compositions of in vivo PC are summarized firstly. Next, we highlight the impacts of the in vivo PC formation on absorption, blood circulation, biodistribution, metabolism, and toxicity of administered ENPs. We also introduce the applications of modulating in vivo PC formation in nanomedicine. We further discuss the challenges and future perspectives.
Using the Major Components (Cellulose, Hemicellulose, and Lignin) of Phyllostachys praecox Bamboo Shoot as Dietary Fiber
Authors: Yang Jinlai , Wu Liangru , Yang Huimin , Pan Yanhong
Published: March 2021

Bamboo shoots are a renewable and abundant biomass containing cellulose, hemicellulose, and lignin. Although many studies have explored the applications of each of these components in the preparation of biochemicals and biopolymers, few studies have evaluated the utility of these components as a dietary fiber supplement. In this study, a powder consisting of the main components of bamboo shoots (cellulose, hemicellulose, and lignin) was prepared from fresh Phyllostachys praecox shoots and characterized by scanning electron microscopy, infrared spectroscopy, and X-ray diffraction. To evaluate the potential utility of these components as a dietary fiber supplement, we conducted an experiment in which this powder was supplemented in the diet of mice for 7 weeks. The experiment included three diet groups (n = 10/group): a low-fat control diet (LFC), high-fat diet (HFD), and high-fat diet with bamboo shoot powder (HFBSP). Compared with HFD mice, the body weights of LFC and HFBSP mice were lower, indicating that the addition of bamboo shoot powder could reduce the weight gain associated with the HFD. Bamboo shoot powder supplementation could also reduce the levels of triglycerides (TG), blood glucose (GLU), total cholesterol (CHOL), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) in HFD mice. The fat histology images indicated that obesity was alleviated in HFBSP mice, and the liver histology images indicated that the addition of bamboo shoot powder to the HFD could reduce the risk of fatty liver disease. The addition of bamboo shoot powder to the HFD might also improve the gut microbiota of mice. Thus, the major components of bamboo shoot powder (cellulose, hemicellulose, and lignin) could be used as beneficial natural additives in the food industry.
Dynamic Behavior in Transition Zones and Long-Term Railway Track Performance
Authors: Paixão André , Varandas José Nuno , Fortunato Eduardo
Published: March 2021

Transition zones between embankments and bridges or tunnels are examples of critical assets of the railway infrastructure. These locations often exhibit higher degradations rates, mostly due to the development of differential settlements, which amplify the dynamic train-track interaction, thus further accelerating the development of settlements and deteriorating track components and vehicles. Despite the technical and scientific interest in predicting the long-term behavior of transition zones, few studies have been able to develop a robust approach that could accurately simulate this complex structural response. To address this topic, this work presents a three-dimensional finite element (3D FEM) approach to simulate the long-term behavior of railway tracks at transition zones. The approach considers both plastic deformation of the ballast layer using a high-cycle strain accumulation model and the non-linearity of the dynamic vehicle-track interaction that results from the evolution of the deformed states of the track itself. The results shed some light into the behavior of transition zones and evidence the complex long-term response of this structures and its interdependency with the transient response of the train-track interaction. Aspects that are critical when assessing the performance of these systems are analyzed in detail, which might be of relevance for researchers and practitioners in the design, construction, and maintenance processes.
Progress and Achievements in Glycosylation of Flavonoids
Authors: Khodzhaieva Ruslana S. , Gladkov Eugene S. , Kyrychenko Alexander , Roshal Alexander D.
Published: March 2021

In recent years, the chemistry of flavonoid glycosylation has undergone significant developments. This mini-review is devoted to summarizing existing strategies and methods for glycosylation of natural and synthetic flavonoids. Herein we overviewed the reaction conditions of flavonoid glycosylation depending on the position of hydroxyl groups in a parent molecule, the degree of it conjugation with the π-system, the presence of steric factors, the formation of intramolecular hydrogen bonds, etc. Especial attention was given to the choice of the glycosyl donor moiety, which has a significant effect on the yield of the final glycosidated products. Finally, a general strategy for regioselective glycosylation of flavonoids containing several hydroxyl groups is outlined.
A Facile and Catalyst-Free Microwave-Promoted Multicomponent Reaction for the Synthesis of Functionalised 1,4-Dihydropyridines With Superb Selectivity and Yields
Authors: Kerru Nagaraju , Maddila Suresh , Jonnalagadda Sreekantha B.
Published: March 2021

We report a highly efficient green protocol for developing a novel library of 1,2,4-triazole-tagged 1,4-dihydropyridine analogs through the one-pot process from the four-component fusion of the 1H-1,2,4-triazol-3-amine with different chosen aldehydes, diethyl acetylenedicarboxylate, and active methylene compounds in a water medium under microwave irradiation and catalyst-free conditions. Excellent yields (94–97%) of the target products were achieved with high selectivity with a short reaction time (<12 min) at room temperature. The structures of the synthesized pyrimidine analogs were established by NMR and HRMS spectroscopic analysis. Simple workup, impressive yields, no column chromatography, green solvent, rapid reaction, and excellent functional group tolerance are the benefits of this protocol.
M. bovis BCG Moreau N-Terminal Loss Leads to a Less Stable Dodecin With Lower Flavin Binding Capacity
Authors: Schwarz Marcos Gustavo Araujo , Luzes Bianca Gallart Cinelli , Correa Paloma Rezende , Silva-Gonçalves Antônio José da , Machado Lucas de Almeida , Guimarães Ana Carolina Ramos , Mendonça-Lima Leila
Published: March 2021

Tuberculosis still remains a concerning health problem worldwide. Its etiologic agent, Mycobacterium tuberculosis, continues to be the focus of research to unravel new prophylactic and therapeutic strategies against this disease. The only vaccine in use against tuberculosis is based on the in vitro attenuated strain, M. bovis BCG. Dodecin is a dodecameric complex important for flavin homeostasis in Archea and Eubacteria, and the M. tuberculosis protein is described as thermo- and halostable. M. bovis BCG Moreau, the Brazilian vaccine strain, has a single nucleotide polymorphism in the dodecin start codon, leading to a predicted loss of seven amino acids at the protein N-terminal end. In this work we aimed to characterize the effect of this mutation in the BCG Moreau protein features. Our recombinant protein assays show that the predicted BCG homolog is less thermostable than M.tb’s but maintains its dodecamerization ability, although with a lower riboflavin-binding capacity. These data are corroborated by structural analysis after comparative modeling, showing that the predicted BCG dodecin complex has a lower interaction energy among its monomers and also a distinct electrostatic surface near the flavin binding pocket. However, western blotting assays with the native proteins were unable to detect significant differences between the BCG Moreau and M.tb orthologs, indicating that other factors may be modulating protein structure/function in the bacterial context.
Pulmonary Vascular Resistance Measurement Remains Keystone in Congenital Heart Disease Management
Authors: Tamimi Omar , Mohammed Mohammed H. A.
Published: March 2021

Pulmonary vascular resistance (PVR) plays a major role in congenital heart management and critical decision. The impact of pulmonary vascular disease in the early and late morbidity and mortality after cardiac surgery and interventional catheterization in congenital heart defect (CHD) highlights the importance of critical evaluation for PVR. Currently, PVR is evaluated with invasive cardiac catheterization for hemodynamic data collection, processing, and analysis. Despite the limitation of hemodynamic evaluation in the setting of CHD, accurate data analysis, and interpretation have significant impact on clinical outcome and procedure success. This article reviews the basic calculation of PVR in the setting of congenital heart disease with diagrammatic illustration for easy understanding of the hemodynamic.
The Roles and Pharmacological Effects of FGF21 in Preventing Aging-Associated Metabolic Diseases
Authors: Yan Junbin , Nie Yunmeng , Cao Jielu , Luo Minmin , Yan Maoxiang , Chen Zhiyun , He Beihui
Published: March 2021

With the continuous improvement of living standards but the lack of exercise, aging-associated metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) are becoming a lingering dark cloud over society. Studies have found that metabolic disorders are near related to glucose, lipid metabolism, and cellular aging. Fibroblast growth factor 21 (FGF21), a member of the FGFs family, efficiently regulates the homeostasis of metabolism and cellular aging. By activating autophagy genes and improving inflammation, FGF21 indirectly delays cellular aging and directly exerts anti-aging effects by regulating aging genes. FGF21 can also regulate glucose and lipid metabolism by controlling metabolism-related genes, such as adipose triglyceride lipase (ATGL) and acetyl-CoA carboxylase (ACC1). Because FGF21 can regulate metabolism and cellular aging simultaneously, FGF21 analogs and FGF21 receptor agonists are gradually being valued and could become a treatment approach for aging-associated metabolic diseases. However, the mechanism by which FGF21 achieves curative effects is still not known. This review aims to interpret the interactive influence between FGF21, aging, and metabolic diseases and delineate the pharmacology of FGF21, providing theoretical support for further research on FGF21.
Patient-Specific Sedation Management via Deep Reinforcement Learning
Authors: Eghbali Niloufar , Alhanai Tuka , Ghassemi Mohammad M.
Published: March 2021

Introduction: Developing reliable medication dosing guidelines is challenging because individual dose–response relationships are mitigated by both static (e. g., demographic) and dynamic factors (e.g., kidney function). In recent years, several data-driven medication dosing models have been proposed for sedatives, but these approaches have been limited in their ability to assess interindividual differences and compute individualized doses.

Objective: The primary objective of this study is to develop an individualized framework for sedative–hypnotics dosing.

Method: Using publicly available data (1,757 patients) from the MIMIC IV intensive care unit database, we developed a sedation management agent using deep reinforcement learning. More specifically, we modeled the sedative dosing problem as a Markov Decision Process and developed an RL agent based on a deep deterministic policy gradient approach with a prioritized experience replay buffer to find the optimal policy. We assessed our method's ability to jointly learn an optimal personalized policy for propofol and fentanyl, which are among commonly prescribed sedative–hypnotics for intensive care unit sedation. We compared our model's medication performance against the recorded behavior of clinicians on unseen data.

Results: Experimental results demonstrate that our proposed model would assist clinicians in making the right decision based on patients' evolving clinical phenotype. The RL agent was 8% better at managing sedation and 26% better at managing mean arterial compared to the clinicians' policy; a two-sample t-test validated that these performance improvements were statistically significant (p < 0.05).

Conclusion: The results validate that our model had better performance in maintaining control variables within their target range, thereby jointly maintaining patients' health conditions and managing their sedation.
Deciphering Reparative Processes in the Inflamed Dental Pulp
Authors: El karim Ikhlas A. , Cooper Paul R. , About Imad , Tomson Phillip L. , Lundy Fionnuala T. , Duncan Henry F.
Published: March 2021

Research over several decades has increased our understanding of the nature of reparative and regenerative processes in the dental pulp, at both the cellular and molecular level. However, advances in scientific knowledge have not translated into novel clinical treatment strategies for caries-induced pulpitis. This narrative review explores the evidence regarding the ability of inflamed pulp tissue to heal and how this knowledge may be used therapeutically. A literature search and evidence analysis covering basic, translational and clinical pulp biology research was performed. The review focuses on (1) the regenerative and defense capabilities of the pulp during caries-induced inflammation; (2) the potential of novel biomaterials to harness the reparative and regenerative functions of the inflamed pulp; and (3) future perspectives and opportunities for conservative management of the inflamed pulp. Current conservative management strategies for pulpitis are limited by a combination of unreliable diagnostic tools and an outdated understanding of pulpal pathophysiological responses. This approach leads to the often unnecessary removal of the entire pulp. Consequently, there is a need for better diagnostic approaches and a focus on minimally-invasive treatments utilizing biologically-based regenerative materials and technologies.
Crustal Configuration and Seismic Stability of the Eastern Indian Shield and Adjoining Regions: Insights for Incidents of Great Earthquakes in the Nepal-Bihar-Sikkim Himalaya
Authors: Singh Rashmi , Khan Prosanta Kumar
Published: March 2021

The Eastern Indian Shield (EIS) is comprised of the intracratonic (coal-bearing) Damodar Gondwana basin, rift-controlled extensional Lower Gangetic basin (LGB), and the downward flexed Indo-Gangetic basin (IGB). The present study involves the computations and mapping of the basement configuration, sediment thickness, Moho depth, and the residual isostatic gravity anomaly, based on 2-D gravity modeling. The sediment thickness in the area ranges between 0.0 and 6.5 km, and the Conrad discontinuity occurs at ∼17.0–20 km depth. The depth of the Moho varies between 36.0 and 41.5 km, with the maximum value beneath the Upper Gangetic basin (UGB), and the minimum of ∼36 km (uplifted Moho) in the southeastern part beneath the LGB. The maximum residual isostatic anomaly of +44 mGal in the southern part indicates the Singhbhum shear zone, LGB, and Rajmahal trap to be under-compensated, whereas the northern part recording the minimum residual isostatic anomaly of –87.0 mGal is over-compensated. Although the region experienced a few moderate-magnitude earthquakes in the past, small-magnitude earthquakes are sparsely distributed. The basement reactivation was possibly associated with a few events of magnitudes more than 4.0. Toward the south, in the Bay of Bengal (BOB), seismic activities of moderate size and shallow origin are confined between the aseismic 85 and 90°E ridges. The regions on the extreme north and south [along the Himalaya and the equatorial Indian Ocean (EIO)] are experienced moderate-to-great earthquakes over different times in the historical past, but the intervening EIS and the BOB have seismic stability. We propose that the two aseismic ridges are guiding the lithospheric stress fields, which are being further focused by the basement of the EIS, the BOB, and the N-S extended regional fault systems into the bending zone of the penetrating Indian lithosphere beneath the Himalaya. The minimum obliquity of the Indian plate and the transecting fault systems in the Foothills of the Himalaya channelize and enhance the stress field into the bending zone. The enhanced stress generates great earthquakes in the Nepal-Bihar-Sikkim Himalaya, and on being reflected back through the apparently stable EIS and BOB, the stress field creates deformation and great earthquakes in the EIO.
A New Relative Risk Index for Hospitals Exposed to Tsunami
Authors: Baiguera Marco , Rossetto Tiziana , Palomino Juan , Dias Priyan , Lopez-Querol Susana , Siriwardana Chandana , Hasalanka Hashan , Ioannou Ioanna , Robinson David
Published: March 2021

The failure of hospitals in recent tsunami have caused extensive social and economic losses. A simple but quantitative approach is required to assess the resilience of healthcare systems to tsunami, which relates not only to hospital building integrity, but also to maintaining hospital functionality. This paper proposes a new tsunami relative risk index (TRRI) that quantifies the impact of tsunami on critical units, (e.g. Intensive Care Unit, Maternity Ward, etc) in individual hospitals, as well as the impact on service provision across a network of hospitals. A survey form is specifically developed for collecting of field data on hospitals for the TRRI evaluation. In its current form TRRI is designed for hospital buildings of reinforced concrete construction, as these are the building types most commonly used worldwide for housing critical units. The TRRI is demonstrated through an application to three hospitals located along the southern coast of Sri Lanka. The TRRI is evaluated for three potential tsunami inundation events and is shown to be able to identify issues with both the building and functional aspects of hospital critical units. Three “what-if” intervention scenarios are presented and their effect on the TRRI is assessed. Through this exercise, it is shown that the TRRI can be used by decision makers to simply explore the effectiveness of individual and combined interventions in improving the tsunami resilience of healthcare provision across the hospital system.
Approbation of the Method for Examining the Performance of Seafloor Observatory Sensors Using Distant Earthquakes Records
Authors: Nosov Mikhail , Karpov Viacheslav , Sementsov Kirill , Kolesov Sergey , Matsumoto Hiroyuki , Kaneda Yoshiyuki
Published: March 2021

An algorithm is presented for testing the calibration accuracy of both z-accelerometers and pressure gauges (PG) installed in seafloor observatories. The test is based on the linear relationship between the vertical acceleration component of the seafloor movement and variations of the seafloor pressure, which is a direct consequence of Newton's 2-nd law and holds valid in the frequency range of “forced oscillations.” The operability of the algorithm is demonstrated using signals registered by 28 observatories of the DONET-2 system during 4 earthquakes of magnitude Mw ~ 8 that took place in 2018-2019 at epicentral distances from 55° up to 140°.
Serum Uric Acid Level Is Positively Associated With Higher Bone Mineral Density at Multiple Skeletal Sites Among Healthy Qataris
Authors: Ibrahim Wisam Nabeel , Younes Nadin , Shi Zumin , Abu-Madi Marawan Abdelhamid
Published: March 2021

Background

Oxidative stress has been implicated as a fundamental mechanism in the decline of bone mass. Although serum uric acid (SUA) has potent antioxidant properties, the findings of many epidemiological and experimental studies couldn’t draw a clear conclusion on the relation between SUA and bone health. We aim to investigate the association between SUA and bone mineral density (BMD) at different skeletal sites among healthy Qataris.

Methodology

A cross-sectional analysis including total-body and site-specific bone mineral density scores and other serological markers of 2981 healthy Qatari adults (36.4 ± 11.1 years) from the Qatar biobank database was conducted. The study participants were divided into quartiles based on the level of SUA, and the BMD was measured using dual-energy X-ray absorptiometry (DXA). Multiple regression analyses were applied to investigate the association between SUA and BMD adjusting for multiple confounding factors.

Results

High levels of SUA were significantly associated with the increased bone mineral density of the total body and at site-specific skeletal locations after adjusting for age and gender (p-value < 0.001). Further adjustment for body mass index (BMI), smoking, vitamin D, alkaline phosphatase, and estimated glomerular filtration rate (eGFR) levels attenuated the association but the association remained significant for individuals with high SUA levels (p-value ≤ 0.01).The association between SUA and BMD was not significant in non-obese, females, young adults, and smokers. However, no interaction was found between SUA and age, gender, BMI and smoking.

Conclusion

Higher SUA levels are associated with a high bone density among healthy Qatari adults. However, such observation demands further investigations to outline the underlying mechanisms.
The Role of Mondo Family Transcription Factors in Nutrient-Sensing and Obesity
Authors: Ke Huiyi , Luan Yu , Wu Siming , Zhu Yemin , Tong Xuemei
Published: March 2021

In the past several decades obesity has become one of the greatest health burdens worldwide. Diet high in fats and fructose is one of the main causes for the prevalence of metabolic disorders including obesity. Promoting brown or beige adipocyte development and activity is regarded as a potential treatment of obesity. Mondo family transcription factors including MondoA and carbohydrate response element binding protein (ChREBP) are critical for nutrient-sensing in multiple metabolic organs including the skeletal muscle, liver, adipose tissue and pancreas. Under normal nutrient conditions, MondoA and ChREBP contribute to maintaining metabolic homeostasis. When nutrient is overloaded, Mondo family transcription factors directly regulate glucose and lipid metabolism in brown and beige adipocytes or modulate the crosstalk between metabolic organs. In this review, we aim to provide an overview of recent advances in the understanding of MondoA and ChREBP in sensing nutrients and regulating obesity or related pathological conditions.
The Relationship Between Thyroid Function and Metabolic Syndrome and Its Components: A Cross-Sectional Study in a Chinese Population
Authors: He Jiaji , Lai Yaxin , Yang Jing , Yao Yongli , Li Yongze , Teng Weiping , Shan Zhongyan
Published: March 2021

Objective

The present study examined the relationship between thyroid function status and the prevalence of metabolic syndrome in a Chinese population.

Methods

Cross-sectional data were obtained from the Thyroid Disease, Iodine Nutrition and Diabetes Epidemiology (TIDE) Survey. A total of 62,408 subjects aged ≥18 years were enrolled. Differences in metabolic indicators and the prevalence of metabolic syndrome according to sex and thyroid function status were compared. Logistic regression was used to analyze the influence of thyroid function on metabolic syndrome and its components.

Results

The prevalence of metabolic syndrome was generally higher in men than women. Overt hyperthyroidism and subclinical hypothyroidism had a significant effect on metabolism in men. Body mass index (BMI), waist circumference, and triglycerides (TGs) were significantly lower in men in the overt hyperthyroidism group, and BMI, waist circumference, systolic blood pressure (SBP) and TGs were higher in men in the subclinical hypothyroidism group than men in the normal group. Overt and subclinical hypothyroidism had significant impacts on metabolic components in women. BMI, waist circumference, TGs, SBP and DBP in the subclinical and overt hypothyroidism groups were significantly higher than the euthyroid group in women. The relative risk of abdominal obesity and hypertriglyceridemia was increased in women with hypothyroidism. Thyroid dysfunction had different effects on metabolic syndrome and its components before and after menopause.

Conclusion

Thyroid function had important effects on the prevalence of metabolic syndrome. Women with hypothyroidism, especially post-menopausal women, had a higher risk of metabolic syndrome than men.
Metal Atom-Decorated Carbon Nanomaterials for Enhancing Li-S/Se Batteries Performances: A Mini Review
Authors: Gu Xingxing , Deng Lan , Ren Xiaolei
Published: March 2021

Lithium-sulfur (Li-S) and lithium-selenium (Li-Se) batteries are both facing the cathode issues of low Coulombic efficiency and unstable cycling stability due to the severe shuttle effect of lithium polysulfides or lithium polyselenides. Simultaneously inhibiting polysulfides/polyselenides dissolution in organic electrolytes and propelling them to conversion via introducing polar, catalytic materials has been proven as an effective strategy to enhance the durability of Li-S and Li-Se batteries. In this mini review, we systematically introduce various metal atom-decorated carbon nanomaterials to determine how to enhance the electrochemical performances of Li-S and Li-Se batteries by inhibiting the polysulfides/polyselenides shuttle phenomenon as well as catalyzing them toward quick redox conversions. We also briefly include the drawbacks and bottlenecks of this kind of material when used in Li-S and Li-Se batteries
iDNA-MT: Identification DNA Modification Sites in Multiple Species by Using Multi-Task Learning Based a Neural Network Tool
Authors: Yang Xiao , Ye Xiucai , Li Xuehong , Wei Lesong
Published: March 2021

Motivation

DNA N4-methylcytosine (4mC) and N6-methyladenine (6mA) are two important DNA modifications and play crucial roles in a variety of biological processes. Accurate identification of the modifications is essential to better understand their biological functions and mechanisms. However, existing methods to identify 4mA or 6mC sites are all single tasks, which demonstrates that they can identify only a certain modification in one species. Therefore, it is desirable to develop a novel computational method to identify the modification sites in multiple species simultaneously.

Results

In this study, we proposed a computational method, called iDNA-MT, to identify 4mC sites and 6mA sites in multiple species, respectively. The proposed iDNA-MT mainly employed multi-task learning coupled with the bidirectional gated recurrent units (BGRU) to capture the sharing information among different species directly from DNA primary sequences. Experimental comparative results on two benchmark datasets, containing different species respectively, show that either for identifying 4mA or for 6mC site in multiple species, the proposed iDNA-MT outperforms other state-of-the-art single-task methods. The promising results have demonstrated that iDNA-MT has great potential to be a powerful and practically useful tool to accurately identify DNA modifications.
Non-Genomic AhR-Signaling Modulates the Immune Response in Endotoxin-Activated Macrophages After Activation by the Environmental Stressor BaP
Authors: Großkopf Henning , Walter Katharina , Karkossa Isabel , von Bergen Martin , Schubert Kristin
Published: March 2021

Emerging studies revealed that the Aryl hydrocarbon receptor (AhR), a receptor sensing environmental contaminants, is executing an immunomodulatory function. However, it is an open question to which extent this is achieved by its role as a transcription factor or via non-genomic signaling. We utilized a multi-post-translational modification-omics approach to examine non-genomic AhR-signaling after activation with endogenous (FICZ) or exogenous (BaP) ligand in endotoxin-activated (LPS) monocyte-derived macrophages. While AhR activation affected abundances of few proteins, regulation of ubiquitination and phosphorylation were highly pronounced. Although the number and strength of effects depended on the applied AhR-ligand, both ligands increased ubiquitination of Rac1, which participates in PI3K/AKT-pathway-dependent macrophage activation, resulting in a pro-inflammatory phenotype. In contrast, co-treatment with ligand and LPS revealed a decreased AKT activity mediating an anti-inflammatory effect. Thus, our data show an immunomodulatory effect of AhR activation through a Rac1ubiquitination-dependent mechanism that attenuated AKT-signaling, resulting in a mitigated inflammatory response.