bluuebunny/crossref_metadata_2025 huggingface dataset:
Az első magyar köztársaság születése: Budapest 1918. november 16.
Authors: Vizi László Tamás
Published: February 2022

With the date of 16 November 1918, most people associate to the proclamation of the first Republic of Hungary at the Parliament, and certainly, the name of Mihály Károlyi comes to their minds. This is no coincidence, as that was undoubtedly the most massive event of the day. However, the relevant events in the sense of public law did not take place in the square in front of the Parlament, but inside its building. This relevant event was the last session and dissolution of the Parlament, that operated continously since 1910, and last session and closure of the Upper House, that resulted the end of the parliamentary procedure. On the same day, during the session of the Council of Ministers, the Government decided on the name of the country as well. The plenum defined the state form as People’s Republic. The Grand National Council, including the delegates of the county national councils, proclaimed the Republic during its first session in the Parlament’s House of Cups and adopted its first people's resolutions. At the same time declared that October 31 and November 16 would be national holidays.
Egy kérészéletű köztársaság: 1918. december 5-6.
Authors: Szávai Ferenc
Published: February 2022

A less known chapter of Hungarian historiography features the state-forming attempts taking place within the territory of the dualist state during 1918‒1919. These failed as they were unable to gain international recognition, were poorly prepared, or their independence efforts did not prevail among opposing interests. One of these attempts was the Heinzenland/Hoanznlaund Republic, existing for two days. This paper presents the very short history of the Republic of Heinzenland.
Development of Edupreneurship for Elementary School Students through Assignments at Home
Authors: Soetrisno Firdania Dewi , Khatimah Ihda A'yunil , Putra Andi Purnawan
Published: February 2022

This study aims to develop the attitudes, souls and abilities of elementary school students for entrepreneurship. Creative, innovative, independent, leadership, good at managing money, and having an unyielding spirit are some entrepreneurial attitudes that need to be instilled in children from an early age. This research uses a qualitative approach which is carried out by interviews, and documentation. The subjects of this study were second grade students of a Islamic Primate School in Banguntapan, Yogyakarta. The results of this study indicate that these entrepreneurial values become important points in the formation of life skills in children or students. In addition to education within the family, entrepreneurship education can be implemented in an integrated manner with learning activities at school through assignments at home.
Development of a New Teaching Model to Promote the Development of Second Graders' Metacognitive Monitoring
Authors: Yuehuan Ma , Zhou Ying
Published: February 2022

This paper is an empirical one."Learning to think" is the motivation system for students to "learn mathematics well", is a kind of inner stable cognitive psychological quality, and is the "engine" for the cultivation of innovative consciousness. Guiding students to learn to think plays an important role in mathematics teaching. However, students often do not understand the connection between mathematical knowledge and real life, and do not understand how to use mathematical knowledge to solve problems. In order to let students learn to think, the researchers designed a teaching model composed of "FROM-WHAT-WITH-HOW-CHANGE-HAVE" based on the concept of metacognitive monitoring. This is a new teaching method that uses a set of closely connected problems chains to guide students in solving problems and feel the charm of mathematical knowledge. At the same time, Thirty second grade students from a primary school in Yulin, Guangxi, were selected as the research object. The lesson "designing the best route to visit the zoo" was taken as an example to inspire second grade students to think and answer through the teaching experiment. Through experiments, students’ problem-solving and reflective abilities have been greatly improved. It shows that guiding students to think through real questions can improve students learning ability. In the process of mathematics learning, we must focus on real problems and guide students to think deeply.
CREATION OF NEW VARIETIES OF YELLOW ALFALFA (Medicago falcate L.) FOR STEPPE CONDITIONS OF THE CENTRAL CHERNOZEM REGION
Authors: Saprykin Sergey , Saprykina Natal'ya , Lyubtseva Olga
Published: February 2022

Yellow alfalfa (Medicago falcate L.) is important for feed production in the Central Chernozem region. It can be successfully cultivated in fodder, field and grassland crop rotations, as well as in hayfields and pastures. For the fullest realization of the potential of yellow alfalfa, it is necessary to create varieties adapted to the soil and climatic conditions of the region. The limiting factor of the effective economic use of yellow alfalfa in the Central Chernozem region of Russia is the insufficient number of zoned varieties. The zoned alfalfa varieties that exist today do not fully meet the requirements of modern feed production and the tasks of breeding new varieties with a complex of economically valuable signs and properties in conditions of insufficient moisture are becoming urgent. The created varieties should be drought-resistant, with a deep root system, capable of forming a high feed mass and a stable seed yield. Earlier, a highly productive variety of yellow alfalfa Pavlovskaya 7 was created at the Voronezh experimental station. The Pavlovskaya 7 variety is characterized by high resistance to fungal diseases and mycoplasmosis, drought resistance, long (up to 12 years) productive longevity. Breeding work is being carried out at the Voronezh experimental station to breed new varieties of yellow alfalfa. Currently, a new variety of yellow alfalfa has been created and is being prepared for transfer, characterized by increased feed and seed productivity, resistance to mycoplasmosis.
PREPARATION OF QUALITATIVE FERMENTED FEEDS FROM LEGUME GRASSES
Authors: Klimenko Vladimir , Malyarenko Svetlana
Published: February 2022

The current study presents the results on evaluation the preservative efficiency of domestic biological preparations, based on enzymes, at the ensiling and haylage preparation of high-protein leguminous grasses. High-yielding varieties of alfalfa, red clover and fodder galega (Galega orientalis Lam.), that were developed in Williams Research Center of Forage Production & Agroecology were used as plant raw material. Plants were harvested in the optimal vegetation phases. The effect of the new biological preparations on safety and quality of fermented feeds in terms of organoleptic and biochemical parameters, the effect on the digestibility of nutrients and their bioconversion into the valuable animal products were studied in the laboratory and scientific-production conditions. The effective methods of preparation the qualitative feeds with high protein and energy content of legume grasses, were suggested on the base the obtained results. Fermented feeds with complex of enzyme-bacterial preparations are suitable for highly productive dairy and beef cattle.
Development of Metal-Organic Framework-Based Dual Antibody Nanoparticles for the Highly Specific Capture and Gradual Release of Circulating Tumor Cells
Authors: Hu Mingchao , Li Cheng , Wang Zhili , Ding Pi , Pei Renjun , Wang Qiang , Xu Hua , Xing Chungen
Published: February 2022

Circulating tumor cells (CTCs) have been well-established as promising biomarkers that can be leveraged to gauge the prognosis of patients with cancers and to guide patient treatment efforts. Although the scarcity of CTCs within peripheral circulation and the associated phenotypic changes that they exhibit owing to the epithelial-mesenchymal transition (EMT) process make the reliable isolation of these cells very challenging. Recently, several studies have discussed platforms capable of mediating the efficient and sensitive isolation of CTCs, but these approaches are nonetheless subject to certain limitations that preclude their clinical application. For example, these platforms are poorly-suited to minimizing damage in the context of cellular capture and release or the in vitro culture of captured cells for subsequent molecular analyses, which would better enable clinicians to select appropriate precision treatments on an individualized basis. In this study, we report the layer-by-layer assembly approach to synthesize a novel composite nanomaterial consisting of modified zirconium-based metal-organic-frameworks (MOFs) on the surface of magnetic beads with dual antibody surface modifications capable of capturing CTCs without being hampered by the state of cellular EMT process. Our analyses indicated that these dual antibody-modified nanomaterials exhibited greater capture efficiency than that observed for single antibody. Importantly, captured cells can be gradually released following capture and undergo subsequent in vitro proliferation following water molecule-induced MOF structural collapse. This release mechanism, which does not require operator intervention, may be effective as a means of minimizing damage and preserving cellular viability such that cells can be more reliably utilized for downstream molecular analyses and associated treatment planning. To further confirm the potential clinical applicability of the developed nanomaterial, it was successfully utilized for capturing CTCs from peripheral blood samples collected from cases diagnosed with gastrointestinal tumors.
Strategies for High-Efficiency Mutation Using the CRISPR/Cas System
Authors: Feng Shuying , Wang Zilong , Li Aifang , Xie Xin , Liu Junjie , Li Shuxuan , Li Yalan , Wang Baiyan , Hu Lina , Yang Lianhe , Guo Tao
Published: February 2022

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems have revolutionized traditional gene-editing tools and are a significant tool for ameliorating gene defects. Characterized by high target specificity, extraordinary efficiency, and cost-effectiveness, CRISPR/Cas systems have displayed tremendous potential for genetic manipulation in almost any organism and cell type. Despite their numerous advantages, however, CRISPR/Cas systems have some inherent limitations, such as off-target effects, unsatisfactory efficiency of delivery, and unwanted adverse effects, thereby resulting in a desire to explore approaches to address these issues. Strategies for improving the efficiency of CRISPR/Cas-induced mutations, such as reducing off-target effects, improving the design and modification of sgRNA, optimizing the editing time and the temperature, choice of delivery system, and enrichment of sgRNA, are comprehensively described in this review. Additionally, several newly emerging approaches, including the use of Cas variants, anti-CRISPR proteins, and mutant enrichment, are discussed in detail. Furthermore, the authors provide a deep analysis of the current challenges in the utilization of CRISPR/Cas systems and the future applications of CRISPR/Cas systems in various scenarios. This review not only serves as a reference for improving the maturity of CRISPR/Cas systems but also supplies practical guidance for expanding the applicability of this technology.
Biogenesis and Breakdown of Lipid Droplets in Pathological Conditions
Authors: Fader Kaiser Claudio M. , Romano Patricia S. , Vanrell M. Cristina , Pocognoni Cristian A. , Jacob Julieta , Caruso Benjamín , Delgui Laura R.
Published: February 2022

Lipid droplets (LD) have long been considered as mere fat drops; however, LD have lately been revealed to be ubiquitous, dynamic and to be present in diverse organelles in which they have a wide range of key functions. Although incompletely understood, the biogenesis of eukaryotic LD initiates with the synthesis of neutral lipids (NL) by enzymes located in the endoplasmic reticulum (ER). The accumulation of NL leads to their segregation into nanometric nuclei which then grow into lenses between the ER leaflets as they are further filled with NL. The lipid composition and interfacial tensions of both ER and the lenses modulate their shape which, together with specific ER proteins, determine the proneness of LD to bud from the ER toward the cytoplasm. The most important function of LD is the buffering of energy. But far beyond this, LD are actively integrated into physiological processes, such as lipid metabolism, control of protein homeostasis, sequestration of toxic lipid metabolic intermediates, protection from stress, and proliferation of tumours. Besides, LD may serve as platforms for pathogen replication and defense. To accomplish these functions, from biogenesis to breakdown, eukaryotic LD have developed mechanisms to travel within the cytoplasm and to establish contact with other organelles. When nutrient deprivation occurs, LD undergo breakdown (lipolysis), which begins with the LD-associated members of the perilipins family PLIN2 and PLIN3 chaperone-mediated autophagy degradation (CMA), a specific type of autophagy that selectively degrades a subset of cytosolic proteins in lysosomes. Indeed, PLINs CMA degradation is a prerequisite for further true lipolysis, which occurs via cytosolic lipases or by lysosome luminal lipases when autophagosomes engulf portions of LD and target them to lysosomes. LD play a crucial role in several pathophysiological processes. Increased accumulation of LD in non-adipose cells is commonly observed in numerous infectious diseases caused by intracellular pathogens including viral, bacterial, and parasite infections, and is gradually recognized as a prominent characteristic in a variety of cancers. This review discusses current evidence related to the modulation of LD biogenesis and breakdown caused by intracellular pathogens and cancer.
H19 Promotes Osteoblastic Transition by Acting as ceRNA of miR-140-5p in Vascular Smooth Muscle Cells
Authors: Xu Feng , Zhong Jia-Yu , Guo Bei , Lin Xiao , Wu Feng , Li Fu-Xing-Zi , Shan Su-Kang , Zheng Ming-Hui , Wang Yi , Xu Qiu-Shuang , Lei Li-Min , Tan Chang-Ming , Liao Xiao-Bo , Yuan Ling-Qing
Published: February 2022

Arterial medial calcification is a common disease in patients with type 2 diabetes, end-stage renal disease and hypertension, resulting in high incidence and mortality of cardiovascular event. H19 has been demonstrated to be involved in cardiovascular diseases like aortic valve diseases. However, role of H19 in arterial medial calcification remains largely unknown. We identified that H19 was upregulated in ß-glycerophosphate (β-GP) induced vascular smooth muscle cells (VSMCs), a cellular calcification model in vitro. Overexpression of H19 potentiated while knockdown of H19 inhibited osteogenic differentiation of VSMCs, as demonstrated by changes of osteogenic genes Runx2 and ALP as well as ALP activity. Notably, H19 interacted with miR-140-5p directly, as demonstrated by luciferase report system and RIP analysis. Mechanistically, miR-140-5p attenuated osteoblastic differentiation of VSMCs by targeting Satb2 and overexpression of miR-140-5p blocked H19 induced elevation of Satb2 as well as the promotion of osteoblastic differentiation of VSMCs. Interestingly, over-expression of Satb2 induced phosphorylation of ERK1/2 and p38MAPK. In conclusion, H19 promotes VSMC calcification by acting as competing endogenous RNA of miR-140-5p and at least partially by activating Satb2-induced ERK1/2 and p38MAPK signaling.
Repressive Interactions Between Transcription Factors Separate Different Embryonic Ectodermal Domains
Authors: Klein Steven L. , Tavares Andre L. P. , Peterson Meredith , Sullivan Charles H. , Moody Sally A.
Published: February 2022

The embryonic ectoderm is composed of four domains: neural plate, neural crest, pre-placodal region (PPR) and epidermis. Their formation is initiated during early gastrulation by dorsal-ventral and anterior-posterior gradients of signaling factors that first divide the embryonic ectoderm into neural and non-neural domains. Next, the neural crest and PPR domains arise, either via differential competence of the neural and non-neural ectoderm (binary competence model) or via interactions between the neural and non-neural ectoderm tissues to produce an intermediate neural border zone (NB) (border state model) that subsequently separates into neural crest and PPR. Many previous gain- and loss-of-function experiments demonstrate that numerous TFs are expressed in initially overlapping zones that gradually resolve into patterns that by late neurula stages are characteristic of each of the four domains. Several of these studies suggested that this is accomplished by a combination of repressive TF interactions and competence to respond to local signals. In this study, we ectopically expressed TFs that at neural plate stages are characteristic of one domain in a different domain to test whether they act cell autonomously as repressors. We found that almost all tested TFs caused reduced expression of the other TFs. At gastrulation these effects were strictly within the lineage-labeled cells, indicating that the effects were cell autonomous, i.e., due to TF interactions within individual cells. Analysis of previously published single cell RNAseq datasets showed that at the end of gastrulation, and continuing to neural tube closure stages, many ectodermal cells express TFs characteristic of more than one neural plate stage domain, indicating that different TFs have the opportunity to interact within the same cell. At neurula stages repression was observed both in the lineage-labeled cells and in adjacent cells not bearing detectable lineage label, suggesting that cell-to-cell signaling has begun to contribute to the separation of the domains. Together, these observations directly demonstrate previous suggestions in the literature that the segregation of embryonic ectodermal domains initially involves cell autonomous, repressive TF interactions within an individual cell followed by the subsequent advent of non-cell autonomous signaling to neighbors.
Looking at the Pretty “Phase” of Membraneless Organelles: A View From Drosophila Glia
Authors: Arkov Alexey L.
Published: February 2022

Membraneless granules assemble in different cell types and cellular loci and are the focus of intense research due to their fundamental importance for cellular organization. These dynamic organelles are commonly assembled from RNA and protein components and exhibit soft matter characteristics of molecular condensates currently characterized with biophysical approaches and super-resolution microscopy imaging. In addition, research on the molecular mechanisms of the RNA–protein granules assembly provided insights into the formation of abnormal granules and molecular aggregates, which takes place during many neurodegenerative disorders including Parkinson’s diseases (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). While these disorders are associated with formation of abnormal granules, membraneless organelles are normally assembled in neurons and contribute to translational control and affect stability of neuronal RNAs. More recently, a new subtype of membraneless granules was identified in Drosophila glia (glial granules). Interestingly, glial granules were found to contain proteins which are the principal components of the membraneless granules in germ cells (germ granules), indicating some similarity in the functional assembly of these structures in glia and germline. This mini review highlights recent research on glial granules in the context of other membraneless organelles, including their assembly mechanisms and potential functions in the nervous system.
Role of Lysosomal Acidification Dysfunction in Mesenchymal Stem Cell Senescence
Authors: Zhang Weijun , Bai Jinwu , Hang Kai , Xu Jianxiang , Zhou Chengwei , Li Lijun , Wang Zhongxiang , Wang Yibo , Wang Kanbin , Xue Deting
Published: February 2022

Mesenchymal stem cell (MSC) transplantation has been widely used as a potential treatment for a variety of diseases. However, the contradiction between the low survival rate of transplanted cells and the beneficial therapeutic effects has affected its clinical use. Lysosomes as organelles at the center of cellular recycling and metabolic signaling, play essential roles in MSC homeostasis. In the first part of this review, we summarize the role of lysosomal acidification dysfunction in MSC senescence. In the second part, we summarize some of the potential strategies targeting lysosomal proteins to enhance the therapeutic effect of MSCs.
Cognitive Impairment in Heart Failure: Landscape, Challenges, and Future Directions
Authors: Yang Mengxi , Sun Di , Wang Yu , Yan Mengwen , Zheng Jingang , Ren Jingyi
Published: February 2022

Heart failure (HF) is a major global healthcare problem accounting for substantial deterioration of prognosis. As a complex clinical syndrome, HF often coexists with multi-comorbidities of which cognitive impairment (CI) is particularly important. CI is increasing in prevalence among patients with HF and is present in around 40%, even up to 60%, of elderly patients with HF. As a potent and independent prognostic factor, CI significantly increases the hospitalization and mortality and decreases quality of life in patients with HF. There has been a growing awareness of the complex bidirectional interaction between HF and CI as it shares a number of common pathophysiological pathways including reduced cerebral blood flow, inflammation, and neurohumoral activations. Research that focus on the precise mechanism for CI in HF is still ever insufficient. As the tremendous adverse consequences of CI in HF, effective early diagnosis of CI in HF and interventions for these patients may halt disease progression and improve prognosis. The current clinical guidelines in HF have begun to emphasize the importance of CI. However, nearly half of CI in HF is underdiagnosed, and few recommendations are available to guide clinicians about how to approach CI in patients with HF. This review aims to synthesize knowledge about the link between HF and cognitive dysfunction, issues pertaining to screening, diagnosis and management of CI in patients with HF, and emerging therapies for prevention. Based on data from current studies, critical gaps in knowledge of CI in HF are identified, and future research directions to guide the field forward are proposed.
HPTMT Parallel Operators for High Performance Data Science and Data Engineering
Authors: Abeykoon Vibhatha , Kamburugamuve Supun , Widanage Chathura , Perera Niranda , Uyar Ahmet , Kanewala Thejaka Amila , von Laszewski Gregor , Fox Geoffrey
Published: February 2022

Data-intensive applications are becoming commonplace in all science disciplines. They are comprised of a rich set of sub-domains such as data engineering, deep learning, and machine learning. These applications are built around efficient data abstractions and operators that suit the applications of different domains. Often lack of a clear definition of data structures and operators in the field has led to other implementations that do not work well together. The HPTMT architecture that we proposed recently, identifies a set of data structures, operators, and an execution model for creating rich data applications that links all aspects of data engineering and data science together efficiently. This paper elaborates and illustrates this architecture using an end-to-end application with deep learning and data engineering parts working together. Our analysis show that the proposed system architecture is better suited for high performance computing environments compared to the current big data processing systems. Furthermore our proposed system emphasizes the importance of efficient compact data structures such as Apache Arrow tabular data representation defined for high performance. Thus the system integration we proposed scales a sequential computation to a distributed computation retaining optimum performance along with highly usable application programming interface.
Survival Analysis of COPD Patients in a 13-Year Nationwide Cohort Study of the Brazilian National Health System
Authors: Gargano Ludmila Peres , Zuppo Isabella de Figueiredo , Nascimento Mariana Martins Gonzaga do , Augusto Valéria Maria , Godman Brian , Costa Juliana de Oliveira , Acúrcio Francisco Assis , Álvares-Teodoro Juliana , Guerra Augusto Afonso
Published: February 2022

Background

Chronic obstructive pulmonary disease (COPD) has an appreciable socioeconomical impact in low- and middle-income countries, but most epidemiological data originate from high-income countries. For this reason, it is especially important to understand survival and factors associated with survival in COPD patients in these countries.

Objective

To assess survival of COPD patients in Brazil, to identify risk factors associated with overall survival, including treatment options funded by the Brazilian National Health System (SUS).

Methodology

We built a retrospective cohort study of patients dispensed COPD treatment in SUS, from 2003 to 2015 using a National Database created from the record linkage of administrative databases. We further matched patients 1:1 based on sex, age and year of entry to assess the effect of the medicines on patient survival. We used the Kaplan-Meier method to estimate overall survival of patients, and Cox's model of proportional risks to assess risk factors.

Result

Thirty seven thousand and nine hundred and thirty eight patients were included. Patient's survival rates at 1 and 10 years were 97.6% (CI 95% 97.4–97.8) and 83.1% (CI 95% 81.9–84.3), respectively. The multivariate analysis showed that male patients, over 65 years old and underweight had an increased risk of death. Therapeutic regimens containing a bronchodilator in a free dose along with a fixed-dose combination of corticosteroid and bronchodilator seem to be a protective factor when compared to other regimens.

Conclusion

Our findings contribute to the knowledge of COPD patients' profile, survival rate and related risk factors, providing new evidence that supports the debate about pharmacological therapy and healthcare of these patients.
Integrated Analysis of Multiple Microarrays Based on Raw Data Identified Novel Gene Signatures in Recurrent Implantation Failure
Authors: Zeng Hong , Fu Yu , Shen Lang , Quan Song
Published: February 2022

Background

Recurrent implantation failure (RIF) is an intricate complication following IVF-ET, which refers to the situation that good-quality embryos repeatedly fail to implant following two or more IVF cycles. Intrinsic molecular mechanisms underlying RIF have not yet been fully elucidated. With enormous improvement in high-throughput technologies, researchers screened biomarkers for RIF using microarray. However, the findings of published studies are inconsistent. An integrated study on the endometrial molecular determinants of implantation will help to improve pregnancy outcomes.

Objective

To identify robust differentially expressed genes (DEGs) and hub genes in endometrium associated with RIF, and to investigate the diagnostic role of hub genes in RIF.

Methods

Raw data from five GEO microarrays regarding RIF were analyzed. Integrated genetic expression analyses were performed using the Robust Rank Aggregation method to identify robust DEGs. Enrichment analysis and protein-protein interaction (PPI) analysis were further performed with the robust DEGs. Cytohubba was used to screen hub genes based on the PPI network. GSE111974 was used to validate the expression and diagnostic role of hub genes in RIF.

Results

1532 Robust DEGs were identified by integrating four GEO datasets. Enrichment analysis showed that the robust DEGs were mainly enriched in processes associated with extracellular matrix remodeling, adhesion, coagulation, and immunity. A total of 18 hub genes (HMGCS1, SQLE, ESR1, LAMC1, HOXB4, PIP5K1B, GNG11, GPX3, PAX2, TF, ALDH6A1, IDH1, SALL1, EYA1, TAGLN, TPD52L1, ST6GALNAC1, NNMT) were identified. 10 of the 18 hub genes were significantly differentially expressed in RIF patients as validated by GSE111974. The 10 hub genes (SQLE, LAMC1, HOXB4, PIP5K1B, PAX2, ALDH6A1, SALL1, EYA1, TAGLN, ST6GALNAC1) were effective in predicting RIF with an accuracy rate of 85%, specificity rate of 100%, and sensitivity rate of 88.9%.

Conclusions

Our integrated analysis identified novel robust DEGs and hub genes in RIF. The hub genes were effective in predicting RIF and will contribute to the understanding of comprehensive molecular mechanisms in RIF pathogenesis.
Adaptive Balancing Control of Cell Voltage in the Charging/Discharging Mode for Battery Energy Storage Systems
Authors: Wang Yanfeng , Liu Di , Shen Yongpeng , Tang Yaohua , Chen Yanhui , Zhang Junmin
Published: February 2022

To improve the balancing time of battery energy storage systems with “cells decoupled and converters serial-connected,” a new cell voltage adaptive balancing control method in both charging and discharging modes is proposed in this study. The overall system architecture and basic operating principle of the active balancing system with “cells decoupled and converters serial-connected” are presented first. Then, by dynamically regulating the balancing acceleration coefficient of each cell according to the cell voltage deviation, the adaptive balancing control of cell voltage in charging and discharging modes is analyzed. An experimental prototype consisting of six smart cells is developed, and experiments in charging and discharging modes were carried out. The experiment results demonstrate that compared with the balancing process with a static acceleration coefficient, the proposed adaptive balancing control of cell voltage shows significant improvement in balancing speed and smaller cell voltage discrepancy.
The Burden of Neonatal Diseases Attributable to Ambient PM 2.5 in China From 1990 to 2019
Authors: Yuan Jia , Shi Lu , Li Hongbo , Zhou Jing , Zeng Lingxia , Cheng Yue , Han Bei
Published: February 2022

Background: Air pollution exposure is an environmental risk to public health. And the available data on relationships of air pollution and neonatal disease burden are scarce. This study assessed neonatal disease burden attributable to Particulate Matter 2.5 (PM 2.5) pollution in China.

Methods: This is a retrospective analysis with data from the GBD2019 database. Data of PM 2.5 pollution exposure levels and neonatal disease burden attributable to PM 2.5 in China from 1990 to 2019 were obtained from the Global Burden of Disease Study 2019 (GBD 2019); Data of PM2.5 concentration was collected from the Bulletin of the State of the Ecological Environment in China; Data of perinatal mortality was collected from the Chinese Maternal and Child Health Surveillance Network. Deaths, Disability-adjusted life years (DALYs), Year of life lost (YLLs), and Years lived with disability (YLDs) are primary indicators used to assess neonatal diseases burden. The correlation of PM2.5 pollution and neonatal death was analyzed. Average Annual Percentage Change (AAPC) and increment were used to assess exposure levels and disease burden trends.

Results: PM 2.5 pollution exposure level of newborns in China is much higher than global average, 32.08 per 100 people (95% UI: 26.57–38.06) in 2019 compared to 1990 (15.86 per 100 people, 95% UI: 6.83–30.88), with an increase of 102.27%. And it is statistically verified PM2.5 concentration was positively correlated with neonatal disease deaths (r = 0.9534, p = 0.0009) and DALYs (r = 0.9534, p = 0.0009). The overall disease burden of neonatal diseases attributed to PM 2.5 pollution in China has decreased from 1990 to 2019, with a decrement of 5738.34 deaths (decreased: 56.85%), 51.01 person/years (decreased: 56.84%) for DALYs, 51.23 person/years (decreased: 57.11%) for YLLs and an increase of 150.69 person/years (increased: 31.71%) for YLDs.

Conclusion: There exists positive correlation between environmental pollution and neonatal diseases in China. The number of neonatal disease deaths, DALYs, and YLLs due to PM 2.5 pollution showed a decreasing trend with the environmental pollution control. For the rising YLDs, there is a need to improve survival rates while focusing on prognosis of neonatal disease and reducing the burden of disease brought on by disability. Controlling environmental pollution is likely to help reduce neonatal disease burden, especially premature birth and neonatal encephalopathy.
The Major Transitions in Evolution—A Philosophy-of-Science Perspective
Authors: Okasha Samir
Published: February 2022

Over the last thirty years, the study of major evolutionary transitions has become a thriving research program within evolutionary biology. In addition to its obvious scientific interest, this research program raises interesting philosophical questions. These fall into two categories: conceptual and ontological. The former category includes questions about what exactly an evolutionary transition is, what form an evolutionary explanation of a transition should take, and whether a general theory that applies to all transitions is possible. The latter category includes questions about the status of the higher-level units to which evolutionary transitions give rise (e.g., organism, superorganism, or individual), and about the nature of the resulting hierarchical organization. Tackling these questions requires an integrative approach that draws on both biology and the philosophy of science.
Analysis of Upstream Regulators, Networks, and Pathways Associated With the Expression Patterns of Polycystic Ovary Syndrome Candidate Genes During Fetal Ovary Development
Authors: Azumah Rafiatu , Hummitzsch Katja , Hartanti Monica D. , St. John Justin C. , Anderson Richard A. , Rodgers Raymond J.
Published: February 2022

Polycystic Ovary Syndrome (PCOS) is a multifactorial syndrome with reproductive, endocrine, and metabolic symptoms, affecting about 10% women of reproductive age. Pathogenesis of the syndrome is poorly understood with genetic and fetal origins being the focus of the conundrum. Genetic predisposition of PCOS has been confirmed by candidate gene studies and Genome-Wide Association Studies (GWAS). Recently, the expression of PCOS candidate genes across gestation has been studied in human and bovine fetal ovaries. The current study sought to identify potential upstream regulators and mechanisms associated with PCOS candidate genes. Using RNA sequencing data of bovine fetal ovaries (62–276 days, n = 19), expression of PCOS candidate genes across gestation was analysed using Partek Flow. A supervised heatmap of the expression data of all 24,889 genes across gestation was generated. Most of the PCOS genes fell into one of four clusters according to their expression patterns. Some genes correlated negatively (early genes; C8H9orf3, TOX3, FBN3, GATA4, HMGA2, and DENND1A) and others positively (late genes; FDFT1, LHCGR, AMH, FSHR, ZBTB16, and PLGRKT) with gestational age. Pathways associated with PCOS candidate genes and genes co-expressed with them were determined using Ingenuity pathway analysis (IPA) software as well as DAVID Bioinformatics Resources for KEGG pathway analysis and Gene Ontology databases. Genes expressed in the early cluster were mainly involved in mitochondrial function and oxidative phosphorylation and their upstream regulators included PTEN, ESRRG/A and MYC. Genes in the late cluster were involved in stromal expansion, cholesterol biosynthesis and steroidogenesis and their upstream regulators included TGFB1/2/3, TNF, ERBB2/3, VEGF, INSIG1, POR, and IL25. These findings provide insight into ovarian development of relevance to the origins of PCOS, and suggest that multiple aetiological pathways might exist for the development of PCOS.
Using Image Recognition to Process Unbalanced Data in Genetic Diseases From Biobanks
Authors: Hsieh Ai-Ru , Li Yi-Mei Aimee
Published: February 2022

With precision medicine as the goal, the human biobank of each country should be analyzed to determine the complete research results related to genetic diseases. In addition, with the increase in medical imaging data, automatic image processing with image recognition has been widely studied and applied in biomedicine. However, case–control data imbalance often occurs in human biobanks, which is usually solved by the statistical method SAIGE. Due to the huge amount of genetic data in human biobanks, the direct use of the SAIGE method often faces the problem of insufficient computer memory to support calculations and excessive calculation time. The other method is to use sampling to adjust the data to balance the case–control ratio, which is called Synthetic Minority Oversampling Technique (SMOTE). Our study employed the Manhattan plot and genetic disease information from the Taiwan Biobank to adjust the imbalance in the case–control ratio by SMOTE, called “TW-SMOTE.” We further used a deep learning image recognition system to identify the TW-SMOTE. We found that TW-SMOTE can achieve the same results as that of SAIGE and the UK Biobank (UKB). The processing of the technical data can be equivalent to the use of data plots with a relatively large UKB sample size and achieve the same effect as that of SAIGE in addressing data imbalance.
Characterization of Two Heterogeneous Lethal Mouse-Adapted SARS-CoV-2 Variants Recapitulating Representative Aspects of Human COVID-19
Authors: Yan Feihu , Li Entao , Wang Tiecheng , Li Yuanguo , Liu Jun , Wang Weiqi , Qin Tian , Su Rina , Pei Hongyan , Wang Shen , Feng Na , Zhao Yongkun , Yang Songtao , Xia Xianzhu , Gao Yuwei
Published: February 2022

New emerging severe acute respiratory syndrome 2 (SARS-CoV-2) has caused a worldwide pandemic. Several animal models of coronavirus disease 2019 (COVID-19) have been developed and applied to antiviral research. In this study, two lethal mouse-adapted SARS-CoV-2 variants (BMA8 and C57MA14) with different virulence were generated from different hosts, which are characterized by high viral replication titers in the upper and lower respiratory tract, pulmonary pathology, cytokine storm, cellular tropism, lymphopenia, and neutrophilia. Two variants exhibit host genetics-related and age-dependent morbidity and mortality in mice, exquisitely reflecting the clinical manifestation of asymptomatic, moderate, and severe COVID-19 patients. Notably, both variants equally weaken the neutralization capacity of the serum derived from COVID-19 convalescent, but the C57MA14 variant showed a much higher virulence than the BMA8 variant in vitro. Q489H substitution in the receptor-binding domain (RBD) of BMA8 and C57MA14 variants results in the receptors of SARS-CoV-2 switching from human angiotensin-converting enzyme 2 (hACE2) to murine angiotensin-converting enzyme 2 (mACE2). Additionally, A22D and A36V mutation in E protein were first reported in our study, which potentially contributed to the virulence difference between the two variants. Of note, the protective efficacy of the novel bacterium-like particle (BLP) vaccine candidate was validated using the BMA8- or C57MA14-infected aged mouse model. The BMA8 variant- and C57MA14 variant-infected models provide a relatively inexpensive and accessible evaluation platform for assessing the efficacy of vaccines and novel therapeutic approaches. This will promote further research in the transmissibility and pathogenicity mechanisms of SARS-CoV-2.
An Assessment of Economic Viability of the Ascension Island Tuna Longline Fishery Management: Implications for Marine Protected Area Planning and Future Fisheries Management
Authors: Muench Angela , Mengo Elena , Weber Sam , Baum Diane , Richardson Andrew James , Thomas Hannah , Whomersley Paul
Published: February 2022

The designation of large scale marine protected areas (MPAs) has increased in recent years to address global issues such as biodiversity loss and the conservation of vulnerable marine habitats. While designing a large scale MPAs in the Exclusive Economic Zone (EEZ) of Ascension Island, the monitoring and enforcement costs were estimated for the two options under consideration: partial closure or full closure of the EEZ for the international commercial fleet. It was found that number of licenses to be sold to the international fleet to allow them access to the EEZ of Ascension Island would need to be increased to fund the monitoring and enforcement cost in case of a partial closure of the EEZ of Ascension Island. In this study, the future economic viability of the licensed big eye tuna fishery was addressed. The study explored economic drivers thought to be linked to license sales. It was shown that cost of licenses had not caused the observed decline in license sales but a shift in consumer demand toward lighter tuna species resulted in a decrease in Japanese imports for bigeye tuna (Thunnus obesus). This change in demand led to global changes in fishing effort and a drop in demand for licenses to fish within the Ascension Island EEZ. This study provided a valuable insight into the economic viability of the bigeye tuna fishery within the Ascension Island EEZ which informed the subsequent decision to close the bigeye tuna fishery as part of the designation of an Ascension Island highly protected large-scale MPA.
Pharmacokinetics of Esomeprazole in Critically Ill Patients
Authors: Xu Yanyan , Tian Xin , Wang Wei , Tian Weiqiang , Zhang Tao , Sun Jian , Zhou Qingyun , Shao Chuxiao
Published: February 2022

Background

Esomeprazole, a potent proton pump inhibitor (PPI), is widely used for the prevention of stress ulcers in intensive care unit (ICU) patients.

Objective

This study investigates the pharmacokinetics (PK) of esomeprazole in critically ill patients.

Methods

The study included eligible adult ICU patients who received endotracheal intubation assisted mechanical ventilation for more than 48 h and had at least an extra risk factor for stress ulcers. All enrolled patients received once-daily intravenous (IV) esomeprazole 40 mg. After the first dose of esomeprazole was administrated, serial blood samples were collected at 3, 5, 15, 30 min and 1, 2, 4, 6, 8, and 10 h. The total sample concentrations of esomeprazole were measured by UPLC-MS/MS. Esomeprazole PK parameters were analyzed using noncompartmental analysis.

Results

A total of 30 patients were evaluable. Mean age and body mass index (BMI) were 61.97 years and 23.14. PK sampling on the first dose resulted in the following median (IQR) parameters: AUC0−∞ 8.06 (6.65–9.47) mg·h/L; MRT0−∞ 4.70 (3.89–5.51) h; t1/2 3.29 (2.7–3.87) h; V 24.89 (22.09–27.69) L; CL 6.13 (5.01–7.26) L/h; and Cmax 2.56 (2.30–2.82) mg/L.

Conclusions

According to the label of esomeprazole, our study showed different esomeprazole PK parameters in ICU patients compared with healthy volunteers. Esomeprazole has unique pharmacokinetic parameters in critically ill patients.
MicroRNAs as Potential Biomarkers for the Diagnosis of Chronic Kidney Disease: A Systematic Review and Meta-Analysis
Authors: Li Jing , Ma Leilei , Yu Hangxing , Yao Yahong , Xu Zhiyuan , Lin Wei , Wang Lin , Wang Xuejun , Yang Hongtao
Published: February 2022

For Chronic Kidney Disease (CKD), the study of microRNA as a biomarker has become an exciting area, so we carried out a meta-analysis to investigate the potential diagnostic values of miRNAs in CKD. We searched Pubmed, Cochrane Library, Embase, and Web of science databases to identify relevant publications published from the establishment of the database to April 30, 2021. We included a total of 26 articles containing 56 studies. There were 4,098 patients with CKD and 2,450 patients without CKD. We found that the overall sensitivity and specificity of miRNAs in CKD diagnosis were 0.86 (95% CI: 0.83–0.89) and 0.79 (95% CI: 0.75–0.83), respectively. In addition, we plotted the summary receiver operator characteristic (SROC) curve to assess diagnostic accuracy, with the area under the curve (AUC) of 0.90 (95% CI: 0.87–0.92). Subgroup analysis showed that sensitivity, specificity, and AUC of miRNAs in plasma and serum were 0.84, 0.78, 0.88; and 0.79, 0.76, 0.83, respectively, while miRNAs in urine were 0.89 for sensitivity, 0.82 for specificity, and 0.92 for AUC. Moreover, we found that the panel of microRNAs (miRNAs) could improve the pooled sensitivity (0.88, 0.81, and 0.91 for sensitivity, specificity, and AUC, respectively). We believe that miRNAs have great potential to become an effective diagnostic biomarker for CKD. Panels of miRNA have higher accuracy than single miRNAs. Additionally, miRNAs in both blood and urine have significant accuracy in the diagnosis of CKD; nevertheless, urine is superior.
Research Hotspots and Trend Exploration on the Clinical Translational Outcome of Simulation-Based Medical Education: A 10-Year Scientific Bibliometric Analysis From 2011 to 2021
Authors: Yao Shun , Tang Yabin , Yi Chenyue , Xiao Yao
Published: February 2022

Background

In recent decades, an increasing number of studies have focused on the clinical translational effect of simulation-based medical education (SBME). However, few scientific bibliometric studies have analyzed the research hotspots and publication trends. This study aimed to investigate research hotspots and future direction in the clinical translational outcome of SBME via bibliometrics.

Method

Relevant publications on the clinical translational outcomes of SBME from 2011 to 2021 were identified and retrieved from the Web of Science Core Collection (WOSCC). Software including VOSviewer (1.6.17) and CiteSpace (5.8R3) and a platform (bibliometric.com) were employed to conduct bibliographic and visualized analysis on the literature.

Results

A total of 1,178 publications were enrolled. An increasing number of publications were observed in the past decades from 48 in 2011 to 175 in 2021. The United States accounted for the largest number of publications (488, 41.4%) and citations (10,432); the University of Toronto and Northwestern University were the leading institutions. Academic Medicine was the most productive journal concerning this field. McGaghie W C and Konge L were the most influential authors in this area. The hot topic of the translational outcome of SBME was divided into 3 stages, laboratory phase, individual skill improvement, and patient outcome involving both technical skills and non-technical skills. Translational research of comprehensive impact and collateral outcomes could be obtained in the future.

Conclusion

From the overall trend of 10 years of research, we can see that the research is roughly divided into three phases, from laboratory stage, individual skill improvement to the patient outcomes, and comprehensive impacts such as skill retention and collateral effect as cost-effectiveness is a major trend of future research. More objective evaluation measurement should be designed to assess the diverse impact and further meta-analysis and randomized controlled trials are needed to provide more clinical evidence of SBME as translational science.