bluuebunny/crossref_metadata_2025 huggingface dataset:
Обґрунтування бойового складу угруповання військ для відбиття агресії
Authors: Загорка О. , Бойко В. , Загорка І.
Published: June 2021

Найважливішим завданням, яке вирішується органами військового управління під час створення угруповання військ для відбиття агресії, є визначення його раціонального складу. У статті запропонована методика обґрунтування бойового складу угруповання військ, яка базується на використанні методу таксономії.

Угруповання військ розглядається як складна організаційно-технічна система, її основою є ударна підсистема, яка містить бойові сили і засоби родів військ видів Збройних Сил. Саме для визначення її складу призначена методика.

Визначення бойового складу ударної підсистеми здійснюється для можливих способів бойових дій військ противника і своїх військ. При цьому кожному способу бойових дій військ противника протиставляється декілька способів бойових дій наших військ. Для кожного способу бойових дій наших військ з використанням методу планування експериментів формуються варіанти бойового складу ударної підсистеми угруповання наших військ.

Раціональний варіант бойового складу ударної підсистеми визначається для кожного способу бойових дій угруповання наших військ з використанням методу таксономії за показниками, які характеризують ефективність його застосування і вартість озброєння. При розв’язанні задачі враховуються тільки варіанти бойового складу ударної підсистеми, при яких забезпечується ефективність застосування угруповання військ не нижче потрібної.

Удруге метод таксономії використовується для вибору найкращого (збалансованого) варіанта бойового складу із раціональних варіантів, які були визначені для кожного способу бойових дій угруповання військ. Двоетапне використання методу таксономії дозволяє найбільш обґрунтовано визначати бойовий склад угруповання військ з урахуванням можливих способів бойових дій військ противника.

Наведена методика може використовуватися органами військового управління під час визначення бойового складу угруповання військ для відбиття агресії.
BIM Dimensions and Application Areas for Enhancing Sustainability and Affordability of Affordable Housing: As a Key for Effective Housing Policies
Authors: Sertyesilisik Begum , Sertyesilisik Egemen , Çetin Hakan Taha , Ocakoglu Emre
Published: June 2021

Affordable housing plays a key role in well-being and sustainable development. The energy efficiency and sustainability performance of these houses support environmental sustainability and reduce their operational cost and energy consumption. Furthermore, enhanced energy efficiency is a significant factor in affordable houses in the fight against fuel poverty. This paper underlines the importance of sustainable affordable houses for reduced life cycle costs and enhanced welfare and well-being of its residents. Based on an in-depth literature review, considering the entire life cycle of affordable houses, this paper aims to investigate usage of all BIM dimensions and their application areas for enhancing sustainability and affordability of affordable housing as a key for effective housing policies. The integrated usage of Building Information Modelling (BIM) and energy simulation software has the potential to add value to the affordable houses as this integration supports energy savings and enhanced sustainability performance throughout the building's life-cycle. This paper highlights BIM’s usage for energy and facility management. Furthermore, this paper emphasises the importance of the policies for effective solutions to the housing problem and recommends holistic policies based on a systematic and interdisciplinary approach to the housing problem. This paper highlights the political economy of affordable housing policies and suggests affordable housing policies request usage of BIM throughout the entire life cycle of affordable houses.
Механізм стимулюючої функції міжбюджетного регулювання та стимулювання розвитку громад
Authors: Розмислов О.М. , Мартинов А.А. , Чернодубова Е.В.
Published: June 2021

У статті запропоновано методику реалізації механізму стимулюючої функції міжбюджетного регулювання та оцінки ефективності місцевих громад в залежності від цілей регулювання міжбюджетних відносин. При встановленні мети вирівнювання бюджетної забезпеченості регіонів із використанням дотацій фінансового вирівнювання визначається мінімальний рівень фінансування відповідних громад. При оцінці переданих на місцевий рівень делегованих повноважень – цільовим використанням переданих коштів та якістю реалізації завдань, на які вони були виділені були встановлені математичні залежності орієнтовані на забезпечення соціально-економічного зростання регіонів, а також першочергового і максимально повного фінансування за рахунок коштів державного та місцевих бюджетів пріоритетних для даного регіону напрямів розвитку.
DIFFERENTIAL CALCULUS: THE USE OF NEWTON’S METHODUS FLUXIONUM ET SERIERUM INFINITARUM IN AN EDUCATION CONTEXT
Authors: Bussotti Paolo
Published: June 2021

What is the possible use of history of mathematics for mathematics education? History of mathematics can play an important role in a didactical context, but a general theory of its use cannot be constructed. Rather a series of cases, in which the resort to history is useful to clarify mathematical concepts and procedures, can be shown. A significant example concerns differential calculus: Newton’s Methodus fluxionum et serierum infinitarum is a possible access-key to differential calculus. For, many concepts introduced by Newton ought be useful for the pupils/students (last or last but one year at the high school and first year at the university) to reach a more intuitive, geometrical and problem-oriented approach to calculus. The motivation to consider history of mathematics as an important didactical support is that the pupils/students often learn mathematics in a too formal manner, without understanding the real reasons for the introduction of several mathematical concepts. The problem is that the potential of such support is not exploited. The educational proposal is hence to show a concrete case to highlight what the teaching of mathematics based on history means. The conclusion is that a general theory, as differential calculus, should be considered by the pupils/students as a necessity, deriving from a specification, improvement and extension of the techniques used to solve significant problems posed and developed in the course of history. In this manner, mathematics appears as a human activity comparable with other activities and not as a merely formal exercise.
Key words: mathematics education, history of mathematics, Newton, fluxions, tangents, maxima and minima, problem solving approach to mathematics education.
Atividade antimicrobiana e antibiofilme da Ilex paraguariensis: Uma revisão de literatura
Authors: Hindi Julia Wolfart , Campos Gabrielle da Silva Flores de , Klafki Laura Barzotto , Marquezan Flávia Kolling , Brum Natália Franco , Marquezan Patricia Kolling
Published: June 2021

Nos últimos anos, o aumento da busca por alternativas medicinais e nutricionais no campo da saúde ocasionou a busca por plantas presentes no cotidiano da população. Consequentemente, diversas pesquisas almejavam avaliar o potencial e benefícios para a saúde. Portanto, o objetivo do estudo é realizar uma revisão de literatura sobre a potencial utilização medicinal e nutricional da planta Ilex paraguariensis. Foram realizadas pesquisas nas bases de dados PubMed, EMBASE, Biblioteca Virtual de Saúde (BVS), Cochrane Library, Web of Science, utilizando os descritores selecionados no MeSH, DeCs e Entree. As buscas foram realizadas no período de janeiro de 2020. O critério de inclusão utilizado englobava artigos dos últimos 20 anos encluindo revisões de literatura. Após as buscas foram selecionados 12 artigos para compor a revisão de literatura. A Ilex paraguariensis mostrou capacidade de atividade antimicrobiana e antiinflamatória. Os extratos da erva mate foram capazes de inibir os microrganismos: Salmonella enteritidis, Candida albicans, Proteus mirabilis, Pseudomas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus mutans, Listeria monocytogenes, Propionibacterium acnes, Enterobacteri cloacae, Bacillus cereus, Micrococcus flavus, Aspergillus fumigatus, Aspergillus versicolor, Aspergillus ochraceus, Aspergillus niger, Candida crusei, Penicillium funiculosum, Penicillium verrucosum var. ciclopium, Klebsiella pneumoniae, Enterobacter agglomerans, Enterobacter aerogeneses, Serratia marcesens, Proteus mirabilis. Porém, não houve consenso na literatura sobre atividade contra a Escherichia coli, Enterococcus faecalis e Acinetobacter baumannii. Assim, a erva mate apresenta um potencial antimicrobiano sob alguns microrganismos, mas ainda são necessários mais estudos para uma análise mais eficiente sobre a ação contra as bactérias e uma possível aplicação clínica.
Ação de capacitação de boas práticas de manejo e bem-estar animal aos profissionais do Turfe do Jockey Club de Pelotas
Authors: Scheffer Del Pino Taís , Da Rosa Curcio Bruna , Pivato Giovana , Aires da Silva Margarida , Castro da Silva Gabriela , Patten Ruth , Wayne Nogueira Carlos Eduardo
Published: June 2021

Este estudo traz a importância de ações educativas constantes aos profissionais do turfe do Jockey Club de Pelotas (JCP). O projeto de extensão “ClinEq - Grupo de Ensino, Pesquisa e Extensão em Medicina de Equino da Faculdade de Veterinária da UFPEL em parceria com o JCP realizou capacitação profissional com o objetivo de oferecer conhecimento e avaliar a percepção dos profissionais sobre boas-práticas de manejo com cavalos de corrida. Foram realizados seis encontros com exposição dos principais temas de manejo e três questionários referente a percepção dos treinadores em relação ao assunto abordado. Observou-se durante as capacitações que os profissionais demonstraram grande interesse nos conteúdos e aproveitaram todos os tópicos abordados, entendendo como um ganho na sua atuação profissional e melhorando seu entendimento sobre os conteúdos. Conseguindo durante o período que transcorreu a capacitação, colocar em prática algumas das sugestões apresentadas para melhorar as boas-práticas de manejo com os cavalos no JCP.
O sistema CEREC na confecção de prótese parcial fixa em cerâmica: Relato de caso clínico
Authors: Ahid Beatriz de Assis Rêgo Nogueira , Abreu-Pereira César Augusto , Ahid Vinicius Pires , Ferro Amanda Costa , Pereira Ana Luiza Gorayb , Casanovas Rosana Costa , Lima Darlon Martins , Ahid Fernando Jorge Mendes
Published: June 2021

As restaurações indiretas são comumentes fabricadas em laboratórios de prótese especializados requerendo mais etapas, pois estes laboratórios usualmente dependem de um técnico calibrado com experiência e habilidade, além de receberem vários trabalhos de diferentes dentistas. E como resposta à dependência de cirurgiões-dentistas em relação aos laboratórios de prótese, ocorreu o surgimento da tecnologia CAD/CAM (Computer-Aided Design/Computer-Aided Manufacturing) que vem transformando a maneira de realizar restaurações indiretas. O CAD/CAM é uma evolução da informática e da engenharia para as necessidades da odontologia e aumentou dramaticamente durante a última década, graças ao rápido desenvolvimento da tecnologia de computadores digitais, por meio de escaneadora intraoral e máquina fresadora, que podem ser executados vários sistemas como o CEREC. Assim, consegue-se otimizar as consultas, apresentando excelentes resultados estéticos e longevidade clínica. Com o sistema CEREC para dentistas, toda a etapa laboratorial pode ser desenvolvida pelo próprio dentista dentro do consultório odontológico. Este artigo tem como objetivo apresentar o sistema CEREC esclarecendo seu manuseio intuitivo por meio do relato de caso clínico.
Determination of BMI and Constitution of Females Living in Ecologically Unfavorable Conditions of the Aral Sea Region
Authors: Rozumbetov K. , Ibraimova A.
Published: June 2021

From the ontogenetic point of view, the adolescent period is considered an achievement of human biological development and a period that has accurate measurements of all morphofunctional indicators. The negative impact of environmental pollution is considered as one of the main factors of the phenotypic variability of the organism. The adaptation of the body to environmental factors contributes to the formation of the phenotype. This ensures optimal conditions for its vital activity. Somatotypes are considered as ways of adapting the body to the environment. The anthropometric survey was conducted on 84 females aged 20 years. This work is aimed at analyzing the main anthropometric indicators among females and identifying the features of physical development characteristic of the studied territory. According to the results of our study, the body weight deficit and asthenization of the body in females were revealed.
Back Pain, as One of the Problems of Medicine
Authors: Nurpolatova S. , Kosymbetova A. , Dzhumanazarova G.
Published: June 2021

Back pain has been an urgent problem for many decades. The article discusses the epidemiological aspects of risk factors, classification and treatment of back pain. In conclusion, the authors conclude that the timely implementation of a course of treatment at an adequate time and with the help of appropriate doses of drugs can ensure maximum efficacy and safety of treatment, prevent the chronization of the process and reduce the number of exacerbations.
Clinical Diagnostic and Therapeutic Characteristics of COVID-19 in Students of Kyrgyzstan
Authors: Esenalieva Zh. , Brimkulov N. , Sulaimanov Sh. , Muratova Zh. , Chernyshova E.
Published: June 2021

The study included 747 students. Out of 747 students 399 (53.4%) were women and 348 (46.6%) were men. According to the respondents, 22.6% (n=169) of them had a new coronavirus infection. Different symptoms of COVID-19 were observed in 72.58% of those interviewed. They were loss of taste (82.8%), fever (67.4%) and headache (67.4 %). Chills (47.3%), coughing (40.8%), pain in the throat (36.6%), shortness of breath (23.6%) and nausea (21.3%) were less frequent. 27.4% of respondents can assume asymptomatic course of the disease. A direct weak correlation between smoking and symptoms (cough, shortness of breath) of COVID-19 (r=0.39) has been identified. 59.8% (n=447) of respondents were diagnosed via PCR-test. At the same time, 62.2% (n=278) of the students had no COVID-19 confirmation. Antibodies to SARS-CoV-2 were determined in a total of 28.51% (n=213) of the respondents. Fibrinogen and D-dimer levels were determined in 9.4% and 7.1% of the students surveyed, respectively. Chest X-Rays were done in 22.6% (n=169) of respondents. Antibacterial and anti-inflammatory drugs (75.1%) were clearly prevalent among young students in the structure of therapeutic interventions for new coronavirus infection.
TOURISM AND ECONOMIC DEVELOPMENT: CONCEPT, EVOLUTION AND VALIDITY
Authors: Martin-Merino Mario
Published: June 2021

Questioning the importance of tourism is completely indisputable and, for this, it has been considered by several authors as one of the most important economic sectors in the world. According to the data provided by international institutions such as the World Tourism Organization (UNWTO), tourism is one of the fundamental bases for global socio-economic development, generating an estimated income that they can amount to approximately 10% of world´s GDP, fact that makes tourism the third most important global industry.
Current Biological Strategies to Enhance Surgical Treatment for Rotator Cuff Repair
Authors: Zhang Cheng , Wu Jun , Li Xiang , Wang Zejin , Lu Weijia William , Wong Tak-Man
Published: June 2021

Rotator cuff tear is one of the most common shoulder problems encountered by orthopedic surgeons. Due to the slow healing process and high retear rate, rotator cuff tear has distressed millions of people all around the world every year, especially for the elderly and active athletes. This disease significantly impairs patients’ motor ability and reduces their quality of life. Besides conservative treatment, open and arthroscopic surgery contributes a lot to accelerate the healing process of rotator cuff tear. Currently, there are many emerging novel treatment methods to promote rotator cuff repair. A variety of biological stimulus has been utilized in clinical practice. Among them, platelet-rich plasma, growth factors, stem cells, and exosomes are the most popular biologics in laboratory research and clinical trials. This review will focus on the biologics of bioaugmentation methods for rotator cuff repair and tendon healing, including platelet-rich plasma, growth factors, exosomes and stem cells, etc. Relevant studies are summarized in this review and future research perspectives are introduced.
RETRACTED: Ventricular Tachyarrhythmia Risk in Paediatric/Young vs. Adult Brugada Syndrome Patients: A Territory-Wide Study
Authors: Lee Sharen , Wong Wing Tak , Wong Ian Chi Kei , Mak Chloe , Mok Ngai Shing , Liu Tong , Tse Gary
Published: June 2021

Introduction: Brugada syndrome (BrS) is a cardiac ion channelopathy with a higher prevalence in Asia compared to the Western populations. The present study compared the differences in clinical and electrocardiographic (ECG) presentation between paediatric/young (≤25 years old) and adult (>25 years) BrS patients.

Method: This was a territory-wide retrospective cohort study of consecutive BrS patients presenting to public hospitals in Hong Kong. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF).

Results: The cohort consists of 550 consecutive patients (median age of initial presentation = 51 ± 23 years; female = 7.3%; follow-up period = 83 ± 80 months), divided into adult (n = 505, mean age of initial presentation = 52 ± 19 years; female = 6.7%; mean follow-up period = 83 ± 80 months) and paediatric/young subgroups (n = 45, mean age of initial presentation = 21 ± 5 years, female = 13.3%, mean follow-up period = 73 ± 83 months). The mean annual VT/VF incidence rate were 17 and 25 cases per 1,000 patient-year, respectively. Multivariate analysis showed that initial presentation of type 1 pattern (HR = 1.80, 95% CI = [1.02, 3.15], p = 0.041), initial asymptomatic presentation (HR = 0.26, 95% CI = [0.07, 0.94], p = 0.040) and increased P-wave axis (HR = 0.98, 95% CI = [0.96, 1.00], p = 0.036) were significant predictors of VT/VF for the adult subgroup. Only initial presentation of VT/VF was predictive (HR = 29.30, 95% CI = [1.75, 492.00], p = 0.019) in the paediatric/young subgroup.

Conclusion: Clinical and ECG presentation of BrS vary between the paediatric/young and adult population in BrS. Risk stratification and management strategies for younger patients should take into consideration and adopt an individualised approach.
Case Report: TNFα Antagonists Are an Effective Therapy in Cardiac Sarcoidosis
Authors: Stievenart Julien , Le Guenno Guillaume , Ruivard Marc , Rieu Virginie , André Marc , Grobost Vincent
Published: June 2021

Introduction:Cardiac sarcoidosis (CS) is a life-threatening disease in which clear recommendations are lacking. We report a case series of CS successfully treated by tumor necrosis factor (TNF)α antagonists.

Methods:We conducted a single-center retrospective study of our patients with CS treated by TNFα antagonists.

Results:Four cases (4/84, 4.7%) were found in our database. Mean age was 40 years (range 34–53 years), and all were Caucasian men. Mean follow-up was 54.75 months (range 25–115 months). All patients received corticosteroid therapy (CT) and immunosuppressive therapy (IT). TNFα antagonists (infliximab or adalimumab) were started after the first or second CS relapse under CT and IT. One patient experienced relapse under TNFα antagonists (isolated decreased left ventricular ejection) and responded to a shorter interval of TNFα antagonist infusion. CT was discontinued in three patients treated with TNFα antagonists without relapse or major cardiac events during follow-up. No serious adverse event occurred in our case series, possibly due to dose sparing and frequent arrest of CT.

Conclusion:TNFα antagonists were effective in refractory and/or relapsing CS treated by corticosteroids and/or immunosuppressive agents, without serious adverse events, and should be considered earlier in CS treatment scheme.
The Efficacy and Safety of Radiofrequency Ablation for Bilateral Papillary Thyroid Microcarcinoma
Authors: Yan Lin , Zhang Mingbo , Song Qing , Xiao Jing , Zhang Ying , Luo Yukun
Published: June 2021

Objective

To investigate the long-term clinical results of radiofrequency ablation (RFA) for bilateral papillary thyroid microcarcinoma (PTMC).

Materials and Methods

From October 2014 to February 2018, 47 patients (37 females, 10 males, mean age 43.39 ± 9.26 years) with 100 bilateral PTMC (mean volume 75.22 ± 73.87 mm3) treated by RFA were included in this retrospective study. Bilateral PTMC was defined as at least one tumor located in the contralateral lobe. Patients were followed up at 1, 3, 6, 12 months and every 6–12 months thereafter. Volume, volume reduction ratio (VRR) and local tumor recurrence were evaluated during the follow-up period.

Results

After a mean follow-up period of 47.77 ± 11.54 months, the mean volume of bilateral PTMC decreased from 75.22 ± 73.87 mm3 to 0.09 ± 0.44 mm3. The mean VRR was 99.94 ± 0.28% and the complete disappearance rate was 92.00%. During the follow-up, one patient (2.13%) developed lymph node metastasis and two patients (4.26%) had recurrent PTMC. All the recurrent lesions underwent additional RFA and two of them disappeared completely. No life-threatening or delayed complications occurred.

Conclusions

With sufficient preoperative evaluation, RFA might be a promising alternative for bilateral PTMC patients who were unsuitable for surgery or refused surgery.
Identification and Validation of an Immune-Related eRNA Prognostic Signature for Hepatocellular Carcinoma
Authors: Cai Shenglan , Hu Xingwang , Chen Ruochan , Zhang Yiya
Published: June 2021

Background

Enhancer RNAs (eRNAs) are intergenic long non-coding RNAs (lncRNAs) that participate in the progression of malignancies by targeting tumor-related genes and immune checkpoints. However, the potential role of eRNAs in hepatocellular carcinoma (HCC) is unclear. In this study, we aimed to construct an immune-related eRNA prognostic model that could be used to prospectively assess the prognosis of patients with HCC.

Methods

Gene expression profiles of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA). The eRNAs co-expressed from immune genes were identified as immune-related eRNAs. Cox regression analyses were applied in a training cohort to construct an immune-related eRNA signature (IReRS), that was subsequently used to analyze a testing cohort and combination of the two cohorts. Kaplan-Meier and receiver operating characteristic (ROC) curves were used to validate the predictive effect in the three cohorts. Gene Set Enrishment Analysis (GSEA) computation was used to identify an IReRS-related signaling pathway. A web-based cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) computation was used to evaluate the relationship between the IReRS and infiltrating immune cells.

Results

A total of sixty-four immune-related eRNAs (IReRNAs) was identified in HCC, and 14 IReRNAs were associated with overall survival (OS). Five IReRNAs were used for constructing an immune-related eRNA signature (IReRS), which was shown to correlate with poor survival and to be an independent prognostic biomarker for HCC. The GSEA results showed that the IReRS was correlated to cancer-related and immune-related pathways. Moreover, we found that IReRS was correlated to infiltrating immune cells, including CD8+ T cells and M0 macrophages. Finally, differential expressions of the five risk IReRNAs in tumor tissues vs. adjacent normal tissues and their prognostic values were verified, in which the AL445524.1 may function as an oncogene that affects prognosis partly by regulating CD4-CLTA4 related genes.

Conclusion

Our results suggest that the IReRS could serve as a biomarker for predicting prognosis in patients with HCC. Additionally, it may be correlated to the tumor immune microenvironment and could also be used as a biomarker in immunotherapy for HCC.
Electrically Reconfigurable Microwave Metasurfaces With Active Lumped Elements: A Mini Review
Authors: Shao Linda , Zhu Weiren
Published: June 2021

Metasurfaces, a kind of two-dimensional artificially engineered surfaces consist of subwavelength unit cells, have recently attracted tremendous attention, owing to their exotic abilities for tailoring electromagnetic responses. With active lump elements incorporated into the design of metasurfaces, dynamic reconfigurabilities enabled by external stimuli could be realized, offering opportunities for the dynamic manipulation of electromagnetic waves. In this mini review, we present a brief review on the recent progress of electrically reconfigurable metasurfaces at microwave frequencies. A brief discussion will also be given with our outlook on future development direction and possible challenges in this interesting field.
Development of a Multiplex PCR Assay for Genotyping the Fish Pathogen Piscirickettsia salmonis Through Comparative Genomics
Authors: Isla Adolfo , Martinez-Hernandez J. Eduardo , Levipan Héctor A. , Haussmann Denise , Figueroa Jaime , Rauch Maria Cecilia , Maracaja-Coutinho Vinicius , Yañez Alejandro
Published: June 2021

Piscirickettsia salmonis is a bacterial pathogen that severely impact the aquaculture in several countries as Canada, Scotland, Ireland, Norway, and Chile. It provokes Piscirickettsiosis outbreaks in the marine phase of salmonid farming, resulting in economic losses. The monophyletic genogroup LF-89 and a divergent genogroup EM-90 are responsible for the most severe Piscirickettsiosis outbreaks in Chile. Therefore, the development of methods for quick genotyping of P. salmonis genogroups in field samples is vital for veterinary diagnoses and understanding the population structure of this pathogen. The present study reports the development of a multiplex PCR for genotyping LF-89 and EM-90 genogroups based on comparative genomics of 73 fully sequenced P. salmonis genomes. The results revealed 2,322 sequences shared between 35 LF-89 genomes, 2,280 sequences in the core-genome of 38 EM-90 genomes, and 331 and 534 accessory coding sequences each genogroup, respectively. A total of 1,801 clusters of coding sequences were shared among all tested genomes of P. salmonis (LF-89 and EM-90), with 253 and 291 unique sequences for LF-89 and EM-90 genogroups, respectively. The Multiplex-1 prototype was chosen for reliable genotyping because of differences in annealing temperatures and respective reaction efficiencies. This method also identified the pathogen in field samples infected with LF-89 or EM-90 strains, which is not possible with other methods currently available. Finally, the genome-based multiplex PCR protocol presented in this study is a rapid and affordable alternative to classical sequencing of PCR products and analyzing the length of restriction fragment polymorphisms.
New Insights Into Microbiota Modulation-Based Nutritional Interventions for Neurodevelopmental Outcomes in Preterm Infants
Authors: Buffet-Bataillon Sylvie , Bellanger Amandine , Boudry Gaelle , Gangneux Jean-Pierre , Yverneau Mathilde , Beuchée Alain , Blat Sophie , Le Huërou-Luron Isabelle
Published: June 2021

Gut microbiota and the central nervous system have parallel developmental windows during pre and post-natal life. Increasing evidences suggest that intestinal dysbiosis in preterm infants predisposes the neonate to adverse neurological outcomes later in life. Understanding the link between gut microbiota colonization and brain development to tailor therapies aimed at optimizing initial colonization and microbiota development are promising strategies to warrant adequate brain development and enhance neurological outcomes in preterm infants. Breast-feeding has been associated with both adequate cognitive development and healthy microbiota in preterms. Infant formula are industrially produced substitutes for infant nutrition that do not completely recapitulate breast-feeding benefices and could be largely improved by the understanding of the role of breast milk components upon gut microbiota. In this review, we will first discuss the nutritional and bioactive component information on breast milk composition and its contribution to the assembly of the neonatal gut microbiota in preterms. We will then discuss the emerging pathways connecting the gut microbiota and brain development. Finally, we will discuss the promising microbiota modulation-based nutritional interventions (including probiotic and prebiotic supplementation of infant formula and maternal nutrition) for improving neurodevelopmental outcomes.
A Comprehensive Analysis of the Downregulation of miRNA-1827 and Its Prognostic Significance by Targeting SPTBN2 and BCL2L1 in Ovarian Cancer
Authors: Feng Penghui , Ge Zhitong , Guo Zaixin , Lin Lin , Yu Qi
Published: June 2021

Background: Previous studies demonstrated that miRNA-1827 could repress various cancers on proliferation, angiogenesis, and metastasis. However, little attention has been paid to its role in ovarian cancer as a novel biomarker or intervention target, especially its clinical significance and underlying regulatory network.

Methods: A meta-analysis of six microarrays was adopted here to determine the expression trend of miRNA-1827, and was further validated by gene expression profile data and cellular experiments. We explored the functional annotations through enrichment analysis for the differentially expressed genes targeted by miRNA-1827. Subsequently, we identified two hub genes, SPTBN2 and BCL2L1, based on interaction analysis using two online archive tools, miRWALK (it consolidates the resources of 12 miRNA-focused servers) and Gene Expression Profiling Interactive Analysis (GEPIA). Finally, we validated their characteristics and clinical significance in ovarian cancer.

Results: The comprehensive meta-analysis revealed that miRNA-1827 was markedly downregulated in clinical and cellular specimens. Transfection of the miRNA-1827 mimic could significantly inhibit cellular proliferation. Concerning its target genes, they were involved in diverse biological processes related to tumorigenesis, such as cell proliferation, migration, and the apoptosis signaling pathway. Moreover, interaction analysis proved that two hub genes, SPTBN2 and BCL2L1, were highly associated with poor prognosis in ovarian cancer.

Conclusion: These integrated bioinformatic analyses indicated that miRNA-1827 was dramatically downregulated in ovarian cancer as a tumor suppressor. The upregulation of its downstream modulators, SPTBN2 and BCL2L1, was associated with an unfavorable prognosis. Thus, the present study has identified miRNA-1827 as a potential intervention target for ovarian cancer based on our bioinformatic analysis processes.
Downregulation of CacyBP by CRISPR/dCas9-KRAB Prevents Bladder Cancer Progression
Authors: Zheng Hanxiong , Chen Chiheng
Published: June 2021

Bladder cancer (BCa) is a leading cause of cancer-related death in the world. CacyBP is initially described as a binding partner of calcyclin and has been shown to be involved in a wide range of cellular processes, including cell differentiation, proliferation, protein ubiquitination, cytoskeletal dynamics and tumorigenesis. In the present study, we found that CacyBP expression was significantly upregulated in BCa tissues compared with adjacent normal tissues. Moreover, its expression was negatively correlated with overall survival time. Secondly, CacyBP had higher expressions in BCa cell lines than normal urothelial cells which was consistent with the results of BCa tissues. Finally, knockdown of CacyBP by CRIPSR-dCas9-KRAB in T24 and 5,637 BCa cells inhibited cell proliferation and migration by CCK-8 assay and scratch assay, and promoted apoptosis by caspase-3/ELISA. These data elucidate that CacyBP is an important oncogene contributing to malignant behavior of BCa and provide a potentially molecular target for treatment of BCa.
Paroxysmal Movement Disorders
Authors: Harvey Susan , King Mary D. , Gorman Kathleen M.
Published: June 2021

Paroxysmal movement disorders (PxMDs) are a clinical and genetically heterogeneous group of movement disorders characterized by episodic involuntary movements (dystonia, dyskinesia, chorea and/or ataxia). Historically, PxMDs were classified clinically (triggers and characteristics of the movements) and this directed single-gene testing. With the advent of next-generation sequencing (NGS), how we classify and investigate PxMDs has been transformed. Next-generation sequencing has enabled new gene discovery (RHOBTB2, TBC1D24), expansion of phenotypes in known PxMDs genes and a better understanding of disease mechanisms. However, PxMDs exhibit phenotypic pleiotropy and genetic heterogeneity, making it challenging to predict genotype based on the clinical phenotype. For example, paroxysmal kinesigenic dyskinesia is most commonly associated with variants in PRRT2 but also variants identified in PNKD, SCN8A, and SCL2A1. There are no radiological or biochemical biomarkers to differentiate genetic causes. Even with NGS, diagnosis rates are variable, ranging from 11 to 51% depending on the cohort studied and technology employed. Thus, a large proportion of patients remain undiagnosed compared to other neurological disorders such as epilepsy, highlighting the need for further genomic research in PxMDs. Whole-genome sequencing, deep-sequencing, copy number variant analysis, detection of deep-intronic variants, mosaicism and repeat expansions, will improve diagnostic rates. Identifying the underlying genetic cause has a significant impact on patient care, modification of treatment, long-term prognostication and genetic counseling. This paper provides an update on the genetics of PxMDs, description of PxMDs classified according to causative gene rather than clinical phenotype, highlighting key clinical features and providing an algorithm for genetic testing of PxMDs.
Shared and Distinct Topologically Structural Connectivity Patterns in Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder
Authors: Qian Lu , Li Yun , Wang Yao , Wang Yue , Cheng Xin , Li Chunyan , Cui Xiwen , Jiao Gongkai , Ke Xiaoyan
Published: June 2021

Background

Previous neuroimaging studies have described shared and distinct neurobiological mechanisms between autism spectrum disorders (ASDs) and attention-deficit/hyperactivity disorder (ADHD). However, little is known about the similarities and differences in topologically structural connectivity patterns between the two disorders.

Methods

Diffusion tensor imaging (DTI) and deterministic tractography were used to construct the brain white matter (WM) structural networks of children and adolescents (age range, 6–16 years); 31 had ASD, 34 had ADHD, and 30 were age- and sex-matched typically developing (TD) individuals. Then, graph theoretical analysis was performed to investigate the alterations in the global and node-based properties of the WM structural networks in these groups. Next, measures of ASD traits [Social Responsiveness Scale (SRS)] and ADHD traits (Swanson, Nolan, and Pelham, version IV scale, SNAP-IV) were correlated with the alterations to determine the functional significance of such changes.

Results

First, there were no significant differences in the global network properties among the three groups; moreover, compared with that of the TD group, nodal degree (Ki) of the right amygdala (AMYG.R) and right parahippocampal gyrus (PHG.R) were found in both the ASD and ADHD groups. Also, the ASD and ADHD groups shared four additional hubs, including the left middle temporal gyrus (MTG.L), left superior temporal gyrus (STG.L), left postcentral gyrus (PoCG.L), and right middle frontal gyrus (MFG.R) compared with the TD group. Moreover, the ASD and ADHD groups exhibited no significant differences regarding regional connectivity characteristics. Second, the ADHD group showed significantly increased nodal betweenness centrality (Bi) of the left hippocampus (HIP.L) compared with the ASD group; also, compared with the ADHD group, the ASD group lacked the left anterior cingulate gyrus (ACG.L) as a hub. Last, decreased nodal efficiency (Enodal) of the AMYG.R, Ki of the AMYG.R, and Ki of the PHG.R were associated with higher SRS scores in the ASD group. Decreased Ki of the PHG.R was associated with higher SRS scores in the full sample, whereas decreased Bi of the PHG.R was associated with lower oppositional defiance subscale scores of the SNAP-IV in the ADHD group, and decreased Bi of the HIP.L was associated with lower inattention subscale scores of the SNAP-IV in the full sample.

Conclusion

From the perspective of the topological properties of brain WM structural networks, ADHD and ASD have both shared and distinct features. More interestingly, some shared and distinct topological properties of WM structures are related to the core symptoms of these disorders.
EGFR and PI3K Pathway Activities Might Guide Drug Repurposing in HPV-Negative Head and Neck Cancers
Authors: Mock Andreas , Plath Michaela , Moratin Julius , Tapken Maria Johanna , Jäger Dirk , Krauss Jürgen , Fröhling Stefan , Hess Jochen , Zaoui Karim
Published: June 2021

While genetic alterations in Epidermal growth factor receptor (EGFR) and PI3K are common in head and neck squamous cell carcinomas (HNSCC), their impact on oncogenic signaling and cancer drug sensitivities remains elusive. To determine their consequences on the transcriptional network, pathway activities of EGFR, PI3K, and 12 additional oncogenic pathways were inferred in 498 HNSCC samples of The Cancer Genome Atlas using PROGENy. More than half of HPV-negative HNSCC showed a pathway activation in EGFR or PI3K. An amplification in EGFR and a mutation in PI3KCA resulted in a significantly higher activity of the respective pathway (p = 0.017 and p = 0.007). Interestingly, both pathway activations could only be explained by genetic alterations in less than 25% of cases indicating additional molecular events involved in the downstream signaling. Suitable in vitro pathway models could be identified in a published drug screen of 45 HPV-negative HNSCC cell lines. An active EGFR pathway was predictive for the response to the PI3K inhibitor buparlisib (p = 6.36E-03) and an inactive EGFR and PI3K pathway was associated with efficacy of the B-cell lymphoma (BCL) inhibitor navitoclax (p = 9.26E-03). In addition, an inactive PI3K pathway correlated with a response to multiple Histone deacetylase inhibitor (HDAC) inhibitors. These findings require validation in preclinical models and clinical studies.
Pediatric Multisystem Inflammatory Syndrome in Children as a Challenging Problem for Pediatric Surgeons in the COVID 19 Pandemic—A Case Report
Authors: Jurkiewicz Beata , Szymanek-Szwed Magdalena , Hartmann Piotr , Samotyjek Joanna , Brędowska Eliza , Kaczorowska Joanna , Wajszczuk Ewa , Twardowska-Merecka Martyna , Cybulska Joanna
Published: June 2021

The first cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were identified at the end of 2019 and, in the next few months, coronavirus disease (COVID-19) spread throughout the world. Initially, it was believed that this disease mainly affected elderly individuals with comorbidities, in whom respiratory failure often occurs. It was believed that children fell ill from the infection more often, although the course of infection in the vast majority of pediatric cases has been asymptomatic or mildly symptomatic. In April and May 2020, the first report of a rapidly progressing disease, similar to Kawasaki syndrome, was found in children who had been infected with SARS-CoV-2. Shortly thereafter, children with symptoms of pediatric inflammatory multisystem syndrome (PIMS-ST [temporally associated with SARS-CoV-2 infection]) began presenting to pediatric hospitals around the world. The syndrome has a mortality rate of up to 2%. Symptoms of PIMS-TS include those that may suggest the need for surgical treatment (severe abdominal pain with the presence of peritoneal symptoms, ascites, high levels of inflammatory markers, intestinal inflammation, and appendages revealed on ultrasound examination). However, there are few reports addressing surgical cases associated with this condition. The authors present a case involving an 11-year-old boy who was admitted to hospital with severe abdominal pain and underwent surgery for symptoms of peritonitis and was diagnosed with PIMS in the post-operative period. Due to the large number of illnesses caused by SARS-CoV-2 infection in recent months, the diagnosis of PIMS-TS/MISC should be considered in the differential diagnosis of acute abdominal symptoms, especially in atypical courses and interviews indicating exposure to SARS-CoV-2.
Proteomic Analysis of Red Ginseng on Prolonging the Life Span of Male Drosophila melanogaster
Authors: Hou Wei , Pei Jin
Published: June 2021

Ginseng (Panax ginseng C. A. Mey.) is a traditional medicine that has been utilized for over 2000 years in Asia and shows varied pharmacological effects. Red ginseng (RG) is steamed and dried ginseng root and is considered to be more effective. Heating inactivates its catabolic enzymes and increases the activities of RG, which can improve the immune system, alleviate fatigue, and has anti-inflammatory effects and antioxidant activity. In addition, RG has a good anti-aging effect, but its mechanism is unclear. Senescence, a side-effect of normal developmental and metabolic processes, is a gradual decline in physiological integrity and function of the body. Senescence is usually associated with a variety of diseases, including neurodegenerative diseases and diabetes. Research on anti-aging and the prolongation of life span has always been a focus topic. In this study, we investigated the molecular mechanism of RG that results in prolonged the life span for male Drosophila melanogaster. Isobaric tag for relative and absolute quantitation (iTRAQ) was used to identify protein changes in an old male D. melanogaster treated with RG. The differential proteins were verified by qRT-PCR and western blotting. The results showed that 12.5 mg/ml RG prolonged its life span significantly. iTRAQ results showed that, compared to the control group, 32 upregulated proteins and 62 downregulated proteins displayed significantly differential expression in the RG group. In this study, we explored the pathways that RG may participate in that extend the life span of D. melanogaster, and the results showed that the PI3K/AKT/FoxO pathway was involved. In addition, 4E-BP increased and participated in the regulation of life span.
Screening for Anti-Inflammation Quality Markers of Lianhua Qingwen Capsule Based on Network Pharmacology, UPLC, and Biological Activity
Authors: Zhou Yongfeng , Niu Ming , Zhang Dingkun , Liu Zhenxing , Wu Qinghua , Chen Jiang , Zhang Haizhu , Zhang Ping , Pei Jin
Published: June 2021

Influenza is a common respiratory infectious disease. In China, Lianhua Qingwen capsule (LHQWC), a drug with significant clinical efficacy and few side effects, is commonly used to treat influenza. However, the composition of LHQWC is complicated, and currently used quality control methods cannot ensure its consistency. In this study, combined with its clinical efficacy, the targets of LHQWC were screened using network pharmacology. Then, anti-inflammation quality markers of LHQWC were screened and judged by combined chemical with biological evaluation. Cyclooxygenase-2 (COX-2) was identified as one of the main targets of the anti-inflammatory activity of LHQWC. The rate of inhibition of COX-2 by different batches of LHQWC was determined. Furthermore, seven components of LHQWC were identified. The potential quality markers were screened by spectral-effect relationship. As a result, chlorogenic acid, isochlorogenic acid B, and isochlorogenic acid C were identified and confirmed as anti-inflammatory quality markers of LHQWC. We hope that these findings provide a scientific basis for the accurate quality control of LHQWC and serve as a reference for the quality control of other drugs.
Gestational Folic Acid Administration Alleviated Maternal Postpartum Emotional and Cognitive Dysfunction in Mice
Authors: Zhang Qianyu , Huang Qianwen , Yao Li , Liu Wenjuan , Ruan Jianxing , Nong Yingqi , Chen Ye , Fan Lin , Wei Jinyan , Wang Songlu , Sun Li , Li Hao , Zhang Yan , Zhang Xiqian , Liu Fenghua
Published: June 2021

Gestational folic acid (FA) supplementation has been widely recognized for its benefits in preventing offspring defects, but its effect on postpartum females has not yet been adequately assessed. The occurrence of emotional and cognitive dysfunction is common in postpartum women, and its treatment remains limited. Considering the promising results of FA in various psychiatric disorders both in human and redents, we tested the effect of gestational FA administration on postpartum psychiatric behavioral phenotypes and the implicated brain-related mechanisms in a murine model. FA was administered orally in both the hormone-stimulated-pregnancy (HSP) model and pregnant mice at doses of 1 and 5 mg/kg. Postpartum behavioral results showed that the disorders of cognitive performance, depressive, and anxiety-related behaviors were all alleviated in the 5 mg/kg FA group. However, the general development of their offspring remained unaffected. Immunofluorescence and immunoblot results revealed that FA pretreatment significantly activated the maternal hippocampal BDNF-related pathway. Morphological studies have confirmed that FA promotes hippocampal neurogenesis. Moreover, synaptic plasticity and synaptic transmission are enhanced. All of these hippocampal changes play critical roles in rescuing neuronal function and behaviors. Thus, our data suggest that gestational FA administration has a therapeutic effect that improves cognition and reduces depression and anxiety in a murine postpartum model. This may be developed as a preventive and adjuvant therapeutic option for pregnant women.
Occlusion Robust Wheat Ear Counting Algorithm Based on Deep Learning
Authors: Wang Yiding , Qin Yuxin , Cui Jiali
Published: June 2021

Counting the number of wheat ears in images under natural light is an important way to evaluate the crop yield, thus, it is of great significance to modern intelligent agriculture. However, the distribution of wheat ears is dense, so the occlusion and overlap problem appears in almost every wheat image. It is difficult for traditional image processing methods to solve occlusion problem due to the deficiency of high-level semantic features, while existing deep learning based counting methods did not solve the occlusion efficiently. This article proposes an improved EfficientDet-D0 object detection model for wheat ear counting, and focuses on solving occlusion. First, the transfer learning method is employed in the pre-training of the model backbone network to extract the high-level semantic features of wheat ears. Secondly, an image augmentation method Random-Cutout is proposed, in which some rectangles are selected and erased according to the number and size of the wheat ears in the images to simulate occlusion in real wheat images. Finally, convolutional block attention module (CBAM) is adopted into the EfficientDet-D0 model after the backbone, which makes the model refine the features, pay more attention to the wheat ears and suppress other useless background information. Extensive experiments are done by feeding the features to detection layer, showing that the counting accuracy of the improved EfficientDet-D0 model reaches 94%, which is about 2% higher than the original model, and false detection rate is 5.8%, which is the lowest among comparative methods.