bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH KETELADANAN PIMPINAN TERHADAP DISIPLIN KERJA GURU SD KECAMATAN BONTOMARANNU KABUPATEN GOWA
Authors: Sahabuddin Saha
Published: May 2021

ABSTRAKDisiplin merupakan keadaan yang menyebabkan atau memberikan dorongan kepada seseorang untuk berbuat dan melakukan segala kegiatan sesuai dengan norma-norma atau aturan-aturan yang telah ditetapkan. Tujuan penelitian ini adalah untuk menganalisis dan mengetahui Pengaruh faktor keteladanan kepemimpinan terhadap disiplin kerja guru SD di Kecamatan Bontomarannu Kabupaten Gowa. Populasi dalam penelitian ini adalah seluruh guru dan kepala sekolah SD di Kecamatan Bontomarannu Kabupaten Gowa sebanyak 113 orang yang berstatus Pegawai Negeri Sipil (PNS) dengan jumlah sekolah sebanyak 18. Mengingat jumlah populasi yang cukup besar maka penentuan sampel yang diambil dalam penelitian ini sebanyak 50% sehingga jumlah sampel yang diambil sebanyak 47 orang guru dan kepala sekolah sebanyak 18 orang, dimana sampel diambil dari setiap sekolah secara Random Simple sampling.Adapun hasil penelitian ini adalah 1) kompensasi, keteladanan kepemimpinan dan ketegasan aturan secara bersama-sama mempengaruhi disiplin kerja guru SD di Kecamatan Bontomarannu Kabupaten Gowa hal ini didasarkan pada hasil uji F yang telah dilakukan terlihat bahwa nilai F hitung sebesar 47,352   dengan nilai signifikansi sebesar 0,000 pada tingkat signifikansi 95% (α = 0,05). Nilai signifikansi  sebesar 0,000 < 0,05. Dengan demikian untuk meningkatkan disiplin kerja guru SD di Kecamatan Bontomarannu Kabupaten Gowa perlu memperhatikan faktor kompensasi, keteladanan kepemimpinan dan ketegasan aturan; 2) Faktor kompensasi, keteladanan kepemimpinan dan ketegasan aturan secara sendiri-sendiri mempengaruhi disiplin kerja guru SD di Kecamatan Bontomarannu Kabupaten Gowa yaitu kompensasi berpengaruh positif dan signifikan sebesar 0,212, keteladanan pimpinan berpengaruh positif dan signifikan sebesar 0,342, ketegasan aturan berpengaruh positif dan signifikan sebesar 0,340 dan ketiganya berpengaruh secara signifikan terhadap disiplin kerja guru SD di Kecamatan Bontomarannu Kabupaten Gowa.Kata Kunci : Kompensasi, Ketaladanan, Ketegasan , disiplin
TEACHING MATERIAL DEVELOPMENT BASED CONSTRUCTIVISM APPROACH OF READING DESCRIPTIVE TEXT
Authors: Razak Abdul , Hermandra Hermandra , Elmustian Elmustian
Published: May 2021

This research method is used to produce a products i.e teaching material  of reading desceriptive text based constructivist approach. Data collection techniques used were questionnaires, and learning outcomes tests. The data analysis technique was carried out by analyzing the questionnaire which was seen from the results of the high and low percentage of the needs desired by students and the next teacher. Development of teaching materials follows the procedure: 1) preliminary study or need assessment; 2) preparation of prototype teaching material design; 3) draft product preparation; 4) draft product trials on a limited scale; 5)draft product revision; 6) testing the revised product on a large scale; 7) writing final product.  Development of teaching materials based constructivism by Needham’s 5 fase. The research instrument was in the form of a questionnaire addressed to the team of experts, users, and audience. The cloze test instrument is used to measure the readability of the reading text and the main description of teaching materials. The product trial is carried out in seventh grade of junior high school of Lingga and East Lingga district, Lingga regency,  Riau Island province which is not exposed the Covid-19.   The conclusion of this study found that the print instructional materials Curriculum 2013, which has been made, deserves to be used in learning activities.. This development resulted in a teaching material  product  which is believed to be able to contribute to the development of science in the field of education.
THE ROLE OF PARENTS IN ACCOMPANYING CHILDREN DURING CHILD LEARNING DURING COVID-19 PANDEMIC
Authors: HAPSARI RIRIK WORO
Published: May 2021

Covid-19 virus has an impact on various field, one which is in education field, so that the Indonesian Goverment made a policy of replacing face to face learning with distance learning or known as online learning. In online learning, parents have a double role as a parent and as a teacher for children in accompany childrend in online learning during Covid-19 pandemic. Lack of understanding of the importance of accompanying children to learn during online learning causes parents to pay less attention to their role in accompanying children during online learning. The aim of this reasearch is to know the role of parents to accompanying children in online learning during Covid-19 pandemic. The research use qualitative methods with case study research type. This research was conducted in Temulus Village, Mejobo District, Kudus Regency, with 5 parents and 5 children who attend 1 Temulus Elemantary School, who living around in environment researcher. Data collection techiques in this research was observation, interviews and documentation.  This research use descriptive qualitative data analysis with triangulation methods as a validity test. The step of data analysis is reduction, presentation of data, and conclusions. The result of the role of parents in online learning during th eCovid-19 pandemic is a.) the role  as caregivers and educators; b) the role as mentors; c) the role as motivators; d) the role as facilitators. Therefore, parents should provide time and attention in accompanying children to leaen during online learning.
PENINGKATAN KEMAMPUAN GURU DALAM PELAKSANAAN KEGIATAN BELAJAR DARI RUMAH DI MASA PANDEMI COVID-19 MELALUI MONITORING KEPALA SEKOLAH
Authors: Winarya Ahmad
Published: May 2021

Tujuan penelitian ini adalah meningkatkan kemampuan guru dalam pelaksanaan kegiatan belajar dari rumah di masa pandemi Covid-19 melalui monitoring kepala sekolah di SDN 1 Purwasari Kecamatan Cicurug Kabupaten Sukabumi. Subjek dalam penelitian ini adalah guru SDN 1 Purwasari Kecamatan Cicurug Kabupaten Sukabumi. Metode penelitian yang dilakukan merupakan penelitian tindakan sekolah dengan menggunakan 2 siklus tindakan. Hasil penelitian tindakan kelas menunjukkan bahwa pelaksanaan monitoring kepala sekolah efektif untuk meningkatkan kemampuan guru dalam pelaksanaan kegiatan belajar dari rumah di masa pandemi Covid-19.  Pada siklus I aktivitas guru dalam melaksanakan kegiatan pembelajaran tergolong baik dengan nilai sebesar 80,21, namun masih terdapat aspek yang perlu diperbaiki terutama pada penggunaan media dan alat peraga. Sementara itu, pada siklus II terjadi peningkatan aktivitas guru menjadi 92,36 dengan kategori sangat baik. Pelaksanaan monitoring kepala sekolah efektif dalam meningkatkan kemampuan guru dalam melaksanakan kegiatan belajar dari rumah di tengah pandemi Covid-19 sehingga mampu mengembangan proses pembelajaran yang efektif di SDN 1 Purwasari Kecamatan Cicurug Kabupaten Sukabumi.
UPAYA MENINGKATKAN KOMPETENSI GURU DALAM MEMBUAT MEDIA PEMBELAJARAN DARI LIMBAH ANORGANIK
Authors: Nurmaini Nurmaini
Published: May 2021

This research is motivated by the need for learning which demands that the teacher is not only proficient in teaching but also facilitates student learning activities in order to create student-centered learning. This study aims to improve teacher competence in making instructional media, in this case media from inorganic materials. This research was conducted at SDN 11 Bathin Solapan with 18 teachers as the subject. The instrument in this study was an observation sheet. The results showed that in the first cycle the competence of the teacher in making learning media was 67.13%, and the second cycle was 74.54% with good criteria. Based on the results of the study, it can be concluded that providing guidance can improve teacher competence in making learning media from inorganic materials.
Oromo’s religious conversion in Ethiopia: Historical perspective
Authors: DUİBE Negesso Jima
Published: May 2021

The Oromo are one of the indigenous peoples of Ethiopia who lived in the country for time immemorial. Nowadays, most of the Oromo are Christians (Orthodox, Protestant) and Muslim. Still, some Oromo adhere to their indigenous religion called Waqefanna. After the coming of Christianity and Islam, however, the Oromo abandoned Waqefanna and embraced either Christianity or Islam. The Oromo has undergone a major religious conversion over the past 150 years. While Oromo’s history has undergone a remarkable phase of study in recent years, it has remained quite impervious to the anthropological field. Specifically, issues related to Oromo’s religious changes have not been sufficiently studied, debated and historically reconstructed across many disciplines. The main purpose of this article is to document and overview the process of religious conversion in Oromo and how they were positioned in Ethiopian history until 1974. The current religious study, therefore, adds to the existing body of knowledge by presenting an outline of the Oromo religious conversion and its place before 1974. It discusses the Oromo religious conversion in Ethiopian history using oral and secondary sources. In fact, oral sources formed an integral part of the research due to insufficient written material on the previous history of Oromo until recently. The article shows that the religious conversion in Oromo took place as a means of resistance against the Ethiopian central government administration.
The Riemann Hypothesis
Authors: Vega Frank
Published: May 2021

Let's define $\delta(x) = (\sum_{{q\leq x}}{\frac{1}{q}}-\log \log x-B)$, where $B \approx 0.2614972128$ is the Meissel-Mertens constant. The Robin theorem states that $\delta(x)$ changes sign infinitely often. Let's also define $S(x) = \theta(x) - x$, where $\theta(x)$ is the Chebyshev function. A theorem due to Erhard Schmidt implies that $S(x)$ changes sign infinitely often. Using the Nicolas theorem, we prove that when the inequalities $\delta(p) \leq 0$ and $S(p) \geq 0$ are satisfied for a prime $p \geq 127$, then the Riemann Hypothesis should be false. However, we could restate the Mertens second theorem as $\lim_{{n\to \infty }} \delta(p_{n}) = 0$ where $p_{n}$ is the $n^{th}$ prime number. In addition, we could modify the well-known formula $\lim_{{n \to \infty }} \frac{\theta(p_{n})}{p_{n}} = 1$ as $\lim_{{n\to \infty }} S(p_{n}) = 0$. In this way, this work could mean a new step forward in the direction for finally solving the Riemann Hypothesis.
THE ANALYSIS OF SECONDARY SCHOOL STUDENTS' TRANSITION SITUATIONS IN MULTIPLE REPRESENTATIONS
Authors:   Department of Mathematics and Science Education, Kastamonu University, Turkey, Kurnaz Mehmet Altan , Bayri Nezihe Gökçen ,   Graduate School of Natural and Applied Science, Kastamonu University, Turkey
Published: May 2021

In this article, the relationships between students’ personal relationship to the concept of pressure and teaching conditions of this concept were investigated in terms of the Anthropological Theory of Didactics. To determine these complex relationships, first an institutional analysis was conducted, and in this same manner, the textbook has been analyzed to uncover the institutional eelationship to the concept of pressure, and second, an achievement test has been used to gather data to uncover personal relationship to concept of pressure. 348 8th-grade students who successfully completed the pressure topic in their science classes participated in this study. The gathered data were analyzed in a descriptive and qualitative way. The results of this study emphasize the relationship between the teaching conditions and the students’ understanding of pressure and support the need for multiple representations to teach effectively the pressure concept.
Enhancing Bhutanese Students’ Views of the Nature of Science in Matter and its Composition and Study of Gas Laws through an Explicit and Reflective Approach
Authors:   Darla Middle Secondary School, Chukha, Bhutan, Das Pabi Maya , Faikhamta Chatree ,   Department of Education, Faculty of Education, Kasetsart University, Bangkok, Thailand, Punsuvon Vittaya ,   Department of Chemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok, Thailand
Published: May 2021

This study investigated the development of Bhutanese students’ views of the nature of science (NOS) as they engaged in an explicit and reflective approach. Seven aspects of NOS were integrated into the chemistry content in two learning units titled “matter and its composition” and “study of gas laws” over a time span of 6 weeks in a 9th Grade class. This study employed mixed method approaches which included the use of a questionnaire, semi-structured interviews, classroom observations, and a review of students’ journals, and assignments. Data were analyzed for established patterns and themes. Students’ views of the NOS in pre-instruction and post-instruction were categorized as naïve, transitional, or informed. The results indicated that at the end of the intervention, students’ views of the NOS had improved. It was seen that NOS-specific pedagogical knowledge and subject knowledge played an important role in the teacher’s ability to enhance students’ views of the NOS.
What is the Purpose of Ethnobiology in Biology Teacher Training?
Authors:   Department of Education, State University of Feira de Santana, Brazil, Baptista Geilsa Costa Santos
Published: May 2021

This article aims to discuss the purpose of ethnobiology in biology teachers’ training based on conceptions of biology teachers before and after their participation in a training course for science teachers that involved ethnobiology. The research was developed in 2009 and involved semi-structured interviews with nine biology teachers of public schools in the state of Bahia (Northeastern Brazil). Analyzes were conducted inductively, using categories based on the teachers’ answers and carefully studying literature on science teaching. Results indicate that teachers expanded their conceptions about ethnobiology after their participation in the training course. They perceived this science as the study of complex relationships between human beings and other living beings. They also perceived the importance of exploring their students’ cultural knowledge to the intercultural dialog and having ethnobiology as a tool in this process. It is concluded that ethnobiology contributes to the biology teachers’ training guiding his/her practices and giving the opportunity to identify students’ cultural knowledge that can be used in an intercultural dialog with the biology taught in schools; hence, it is imperative to offer training courses for teachers as a starting point.
Joint Interpolation and Representation Learning for Irregularly Sampled Satellite-Derived Geophysical Fields
Authors: Fablet Ronan , Beauchamp Maxime , Drumetz Lucas , Rousseau François
Published: May 2021

Earth observation satellite missions provide invaluable global observations of geophysical processes in play in the atmosphere and the oceans. Due to sensor technologies (e.g., infrared satellite sensors), atmospheric conditions (e.g., clouds and heavy rains), and satellite orbits (e.g., polar-orbiting satellites), satellite-derived observations often involve irregular space–time sampling patterns and large missing data rates. Given the current development of learning-based schemes for earth observation, the question naturally arises whether one might learn some representation of the underlying processes as well as solve interpolation issues directly from these observation datasets. In this article, we address these issues and introduce an end-to-end neural network learning scheme, which relies on an energy-based formulation of the interpolation problem. This scheme investigates different learning-based priors for the underlying geophysical field of interest. The end-to-end learning procedure jointly solves the reconstruction of gap-free fields and the training of the considered priors. Through different case studies, including observing system simulation experiments for sea surface geophysical fields, we demonstrate the relevance of the proposed framework compared with optimal interpolation and other state-of-the-art data-driven schemes. These experiments also support the relevance of energy-based representations learned to characterize the underlying processes.
FGD5-AS1 Is a Hub lncRNA ceRNA in Hearts With Tetralogy of Fallot Which Regulates Congenital Heart Disease Genes Transcriptionally and Epigenetically
Authors: Zhang Xingyu , Gao Yunqian , Zhang Xiaoping , Zhang Xiaoqing , Xiang Ying , Fu Qihua , Wang Bo , Xu Zhuoming
Published: May 2021

Heart development requires robust gene regulation, and the related disruption could lead to congenital heart disease (CHD). To gain insights into the regulation of gene expression in CHD, we obtained the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in 22 heart tissue samples with tetralogy of Fallot (TOF) through strand-specific transcriptomic analysis. Using a causal inference framework based on the expression correlations and validated microRNA (miRNA)–lncRNA–mRNA evidences, we constructed the competing endogenous RNA (ceRNA)-mediated network driven by lncRNAs. Four lncRNAs (FGD5-AS1, lnc-GNB4-1, lnc-PDK3-1, and lnc-SAMD5-1) were identified as hub lncRNAs in the network. FGD5-AS1 was selected for further study since all its targets were CHD-related genes (NRAS, PTEN, and SMAD4). Both FGD5-AS1 and SMAD4 could bind with hsa-miR-421, which has been validated using dual-luciferase reporter assays. Knockdown of FGD5-AS1 not only significantly reduced PTEN and SMAD4 expression in HEK 293 and the fetal heart cell line (CCC-HEH-2) but also increased the transcription of its interacted miRNAs in a cell-specific way. Besides ceRNA mechanism, RNAseq and ATACseq results showed that FGD5-AS1 might play repression roles in heart development by transcriptionally regulating CHD-related genes. In conclusion, we identified a ceRNA network driven by lncRNAs in heart tissues of TOF patients. Furthermore, we proved that FGD5-AS1, one hub lncRNA in the TOF heart ceRNA network, regulates multiple genes transcriptionally and epigenetically.
Claudin h Is Essential for Hair Cell Morphogenesis and Auditory Function in Zebrafish
Authors: Gong Jie , Qian Peipei , Hu Yuebo , Guo Chao , Wei Guanyun , Wang Cheng , Cai Chengyun , Wang Haibo , Liu Dong
Published: May 2021

Hereditary hearing loss caused by defective hair cells is one of the most common congenital diseases, whose nosogenesis is still unclear because many of the causative genes remain unidentified. Claudins are one kind of transmembrane proteins that constitute the most important components of the tight junctions and paracellular barrier and play important roles in neurodevelopment. In this study, we investigated the function of claudin h in morphogenesis and auditory function of the hair cell in zebrafish. The results of in situ hybridization showed that claudin h was specifically localized in the otic vesicle and neuromasts in zebrafish embryos. The deficiency of claudin h caused significant reduction of otic vesicle size and loss of utricle otolith. Moreover, the startle response and vestibulo-ocular reflex experiments revealed that loss of claudin h led to serious hearing loss and vestibular dysfunction. Importantly, the confocal microscopy observation found that compared to the control zebrafish, the claudin h morphants and mutants displayed significantly reduced the number of cristae hair cells and shortened kinocilia. Besides, the deficiency of claudin h also caused the loss of hair cells in neuromasts which could be rescued by injecting claudin h mRNA into the mutant embryos at one cell stage. Furthermore, the immunohistochemistry experiments demonstrated remarkable apoptosis of hair cells in the neuromasts, which might contribute to the loss of hair cells number. Overall, these data indicated that claudin h is indispensable for the development of hair cells, vestibular function, and hearing ability of zebrafish.
Mental State Verb Production as a Measure of Perspective Taking in Narrations of Individuals With Down Syndrome
Authors: Neitzel Isabel , Penke Martina
Published: May 2021

Introduction: Perspective taking is an important ability to enrich narrations by empathizing with a real or fictional character. Mental state verbs (MSV) are a good indicator for this ability as they serve to reflect the mindset that the narrator attributes to a protagonist. Especially syntactic abilities have been argued to be relevant for MSV use. Investigating persons with Down Syndrome (DS) is likely to provide important insights into the relationship of MSV use and syntactic abilities: MSV are mostly used in complex sentence structures, which are a frequent difficulty for individuals with this syndrome. Indeed, previous investigations have found first evidence for impaired MSV production in individuals with DS, indicating a link to syntactic abilities and expressive vocabulary. Our aim was to provide evidence on MSV production and on the syntactic context of MSV production in individuals with DS and to target a possible connection to both cognitive and language abilities using specific language assessments. Typically-developing (pre-)school children were included as a comparison group to identify impaired respectively developmentally-adequate performance.

Method: 28 individuals with Down syndrome (aged 10; 0–20; 1 years) participated in a battery of cognitive, narrative and language measures. MSV-performance and syntactical context of MSV use were compared to data from 33 typically-developing children aged 3–9 years. We also analyzed the relationship between MSV production and language performance (vocabulary, syntax measures, mean length of utterance).

Results: The total number and types of MSV used were comparable for individuals with DS and TD. Moreover, a syntactic analysis indicated that individuals with DS and TD use MSV in the same syntactic contexts. Nevertheless, the syntactic difficulties of participants with DS are reflected in their frequent use of MSV in sentence-fragments. Correlations over the DS group yielded that syntactic abilities were not decisive for the richness and diversity of MSV in narrations.

Conclusion: Our findings suggest a comparable performance in MSV use in individuals with DS and school-aged TD children. The data indicate that MSV production is possible even with an impaired syntax suggesting unimpaired perspective taking abilities in individuals with DS.
StreptInCor, a Group A Streptococcal Adsorbed Vaccine: Evaluation of Repeated Intramuscular Dose Toxicity Testing in Rats
Authors: de Sá-Rocha Luiz Carlos , Demarchi Lea Maria Macruz Ferreira , Postol Edilberto , Sampaio Roney Orismar , de Alencar Raquel Elaine , Kalil Jorge , Guilherme Luiza
Published: May 2021

Streptococcus pyogenesinfections continue to be a worldwide public health problem, causing various diseases in humans, with rheumatic fever and rheumatic heart disease being the most harmful manifestations. Impetigo and post-streptococcal glomerulonephritis are also important sequelae of skin infections. We have developed a candidate vaccine epitope (StreptInCor) that presents promising results in diverse animal models. To assess whether the StreptInCor alum-adsorbed vaccine could induce undesirable effects, a certified independent company conducted a repeated intramuscular dose toxicity evaluation in Wistar rats, a choice model for toxicity studies. We did not observe significant alterations in clinical, hematological, biochemical, anatomical, or histopathological parameters due to vaccine administration, even when the animals received the highest dose. In conclusion, repeated intramuscular doses did not show signs of macroscopic or other significant changes in the clinical or histopathological parameters, indicating that StreptInCor can be considered a safe candidate vaccine.
Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice
Authors: Liu Xin-Hua , Graham Zachary A. , Harlow Lauren , Pan Jiangping , Azulai Daniella , Bauman William A. , Yarrow Joshua , Cardozo Christopher P.
Published: May 2021

Spinal cord injury (SCI) results in dysregulation of carbohydrate and lipid metabolism; the underlying cellular and physiological mechanisms remain unclear. Fibroblast growth factor 21 (FGF21) is a circulating protein primarily secreted by the liver that lowers blood glucose levels, corrects abnormal lipid profiles, and mitigates non-alcoholic fatty liver disease. FGF21 acts via activating FGF receptor 1 and ß-klotho in adipose tissue and stimulating release of adiponectin from adipose tissue which in turn signals in the liver and skeletal muscle. We examined FGF21/adiponectin signaling after spinal cord transection in mice fed a high fat diet (HFD) or a standard mouse chow. Tissues were collected at 84 days after spinal cord transection or a sham SCI surgery. SCI reduced serum FGF21 levels and hepatic FGF21 expression, as well as β-klotho and FGF receptor-1 (FGFR1) mRNA expression in adipose tissue. SCI also reduced serum levels and adipose tissue mRNA expression of adiponectin and leptin, two major adipokines. In addition, SCI suppressed hepatic type 2 adiponectin receptor (AdipoR2) mRNA expression and PPARα activation in the liver. Post-SCI mice fed a HFD had further suppression of serum FGF21 levels and hepatic FGF21 expression. Elevated serum free fatty acid (FFA) levels after HFD feeding were observed in post-SCI mice but not in sham-mice, suggesting defective FFA uptake after SCI. Moreover, after SCI several genes that are implicated in insulin’s action had reduced expression in tissues of interest. These findings suggest that downregulated FGF21/adiponectin signaling and impaired responsiveness of adipose tissues to FGF21 may, at least in part, contribute to the overall picture of metabolic dysfunction after SCI.
The Green Innovation Effect on Heavy-Polluting Enterprises Under the Environmental Protection Law
Authors: Ouyang Leqian , You Daming
Published: May 2021

One of the main purposes of the 2015 Environmental Protection Law (EPL) of the People's Republic of China is to boost the green innovation of the enterprises. Using heavy-polluting enterprises as examples, this paper uses the Difference-in-difference analysis (DDD) technique to analyze the influence of EPL on the green innovation of enterprises under fiscal decentralization and enterprise heterogeneity. Results show that EPL exerts a negative impact on the green innovation of heavy-polluting enterprises at the national level, as well as those in the central and western areas specifically. The only presence of positive motivation for green innovation is being found in the eastern area, although, the motivation seems to be insignificant. The negative impacts have been lasting in the long run, especially for the low-performance enterprises in the central areas. As for the targeted implementation of EPL in China, local governments should make the best use of financial power under fiscal decentralization. This balanced approach is designed to motivate enterprises in different regions with various performance levels to develop green innovation based on their different weaknesses and strengths.
Predicting the Key Genes Involved in Aortic Valve Calcification Through Integrated Bioinformatics Analysis
Authors: Wang Dinghui , Xiong Tianhua , Yu Wenlong , Liu Bin , Wang Jing , Xiao Kaihu , She Qiang
Published: May 2021

Background: Valvular heart disease is obtaining growing attention in the cardiovascular field and it is believed that calcific aortic valve disease (CAVD) is the most common valvular heart disease (VHD) in the world. CAVD does not have a fully effective treatment to delay its progression and the specific molecular mechanism of aortic valve calcification remains unclear.

Materials and Methods: We obtained the gene expression datasets GSE12644 and GSE51472 from the public comprehensive free database GEO. Then, a series of bioinformatics methods, such as GO and KEGG analysis, STING online tool, Cytoscape software, were used to identify differentially expressed genes in CAVD and healthy controls, construct a PPI network, and then identify key genes. In addition, immune infiltration analysis was used via CIBERSORT to observe the expression of various immune cells in CAVD.

Results: A total of 144 differential expression genes were identified in the CAVD samples in comparison with the control samples, including 49 up-regulated genes and 95 down-regulated genes. GO analysis of DEGs were most observably enriched in the immune response, signal transduction, inflammatory response, proteolysis, innate immune response, and apoptotic process. The KEGG analysis revealed that the enrichment of DEGs in CAVD were remarkably observed in the chemokine signaling pathway, cytokine-cytokine receptor interaction, and PI3K-Akt signaling pathway. Chemokines CXCL13, CCL19, CCL8, CXCL8, CXCL16, MMP9, CCL18, CXCL5, VCAM1, and PPBP were identified as the hub genes of CAVD. It was macrophages that accounted for the maximal proportion among these immune cells. The expression of macrophages M0, B cells memory, and Plasma cells were higher in the CAVD valves than in healthy valves, however, the expression of B cells naïve, NK cells activated, and macrophages M2 were lower.

Conclusion: We detected that chemokines CXCL13, CXCL8, CXCL16, and CXCL5, and CCL19, CCL8, and CCL18 are the most important markers of aortic valve disease. The regulatory macrophages M0, plasma cells, B cells memory, B cells naïve, NK cells activated, and macrophages M2 are probably related to the occurrence and the advancement of aortic valve stenosis. These identified chemokines and these immune cells may interact with a subtle adjustment relationship in the development of calcification in CAVD.
Case Report: Successful Response to Intravenous Immunoglobulin and Steroid Pulses in a Renal Transplant Recipient With Severe Covid-19 Disease and Associated Acute Allograft Failure
Authors: Rosa-Guerrero Pedro , Trujillo-Aguilera Antonio , Molina Juan , Navas Ana , López-Martín Cristina , Jurado Aurora , Rodríguez-Benot Alberto , Torres-De-Rueda Álvaro
Published: May 2021

The impact of Covid-19 pneumonia caused by SARS-CoV-2 on transplanted populations under chronic immunosuppression seems to be greater than in normal population. Clinical management of the disease, particularly in those patients worsening after a cytokine storm, with or without allograft impairment and using available therapeutic approaches in the absence of specific drugs to fight against the virus, involves a major challenge for physicians. We herein provide evidence of the usefulness of high-dose intravenous immunoglobulin (IVIG) combined with steroid pulses to successfully treat a case of Covid-19 pneumonia in a single-kidney transplanted patient with mechanical ventilation and hemodialysis requirements in the setting of a cytokine storm. A rapid decrease in the serum level of inflammatory cytokines, particularly IL-6, IL-8, TNF-α, MCP-1 and IL-10, as well as of acute-phase reactants such as ferritin, D-dimer and C-reactive protein was observed after the IVIG infusion and methylprednisolone bolus administration with a parallel clinical improvement and progressive allograft function recovery, allowing the patient’s final discharge 40 days after the treatment onset. The immunomodulatory effect of IVIG together with the anti-inflammatory and immunosuppressive potential of steroids could be an alternative strategy to treat severe cases of Covid-19 pneumonia associated with an uncontrolled inflammatory response in transplanted populations.
Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion
Authors: Ruedas-Torres Inés , Rodríguez-Gómez Irene M. , Sánchez-Carvajal José María , Guil-Luna Silvia , Larenas-Muñoz Fernanda , Pallarés Francisco J. , Carrasco Librado , Gómez-Laguna Jaime
Published: May 2021

Virulent porcine reproductive and respiratory syndrome virus (PRRSV) strains, such as the Lena strain, have demonstrated a higher thymus tropism than low virulent strains. Virulent PRRSV strains lead to severe thymus atrophy, which could be related to marked immune dysregulation. Impairment of T-cell functions through immune checkpoints has been postulated as a strategy executed by PRRSV to subvert the immune response, however, its role in the thymus, a primary lymphoid organ, has not been studied yet. Therefore, the goal of this study was to evaluate the expression of selected immune checkpoints (PD1/PDL1, CTLA4, TIM3, LAG3, CD200R1 and IDO1) in the thymus of piglets infected with two different PRRSV-1 strains. Thymus samples from piglets infected with the low virulent 3249 strain, the virulent Lena strain and mock-infected were collected at 1, 3, 6, 8 and 13 days post-infection (dpi) to analyze PRRSV viral load, relative quantification and immunohistochemical staining of immune checkpoints. PD1/PDL1, CTLA4, TIM3, LAG3 and IDO1 immune checkpoints were significantly up-regulated in the thymus of PRRSV infected piglets, especially in those infected with the virulent Lena strain from 6 dpi onwards. This up-regulation was associated with disease progression, high viral load and cell death. Co-expression of these molecules can affect T-cell development, maturation and selection, negatively regulating the host immune response against PRRSV.
Current Approaches to Desensitization in Solid Organ Transplantation
Authors: Schinstock Carrie , Tambur Anat , Stegall Mark
Published: May 2021

Major advancements in the development of HLA antibody detection techniques and our understanding of the outcomes of solid organ transplant in the context of HLA antibody have occurred since the relevance of sensitization was first recognized nearly 50 years ago. Additionally, kidney paired donation programs (KPD) have become widespread, deceased donor allocation policies have changed, and several new therapeutic options have become available with promise to reduce HLA antibody. In this overview we aim to provide thoughtful guidance about when desensitization in kidney transplantation should be considered taking into account the outcomes of HLA incompatible transplantation. Novel therapeutics, desensitization endpoints, and strategies for future study will also be discussed. While most of our understanding about desensitization comes from studying kidney transplant candidates and recipients, many of the concepts discussed can be easily applied to desensitization in all of solid organ transplantation.
Optimizing the Timeframe to Produce Polychaetes (Hediste diversicolor) Enriched With Essential Fatty Acids Under Different Combinations of Temperature and Salinity
Authors: Jerónimo Daniel , Lillebø Ana Isabel , Rey Felisa , Ii Henrique Koga , Domingues M. Rosário M. , Calado Ricardo
Published: May 2021

Polychaetes can be successfully employed to recover essential fatty acids (EFA) from wasted uneaten aquafeeds present in aquaculture effluents. The optimization of the timeframe required to produce premium ragworms (Hediste diversicolor) biomass rich in EFA is paramount to make available to the aquafeeds industry another alternative ingredient to fish meal and fish oil. The present study aimed to evaluate the potential enrichment of ragworms fatty acid (FA) profile when fed a commercial aquafeed during 10, 20, and 40 days (D10, D20, and D40) under different combinations of water temperature (20 and 25°C) and salinity (15, 20, and 25). Total FA incremented progressively overtime, with D40 polychaetes exhibiting average values ranging between 70 and 90 μg mg–1 DW. The average values of n-6 FA ranged between 13 and 17 μg mg–1 DW, while that of n-3 FA varied between 17 and 19 μg mg–1 DW at D40. No significant differences were found in the FA profile of H. diversicolor cultured under different combinations of temperature and salinity. The FA profile of cultured polychaetes exhibited between 28 and 31% dissimilarity from that of wild conspecifics and displayed a higher content of two essential n-3 FA: eicosapentaenoic (20:5 n-3, EPA) and docosahexaenoic acids (22:6 n-3, DHA) (values ranging between 9.6–11.2% and 4.3–5.0% of total FA, respectively). A higher similarity in FA profile was recorded between D40 polychaetes and aquafeed than with initially stocked or wild specimens. Palmitic (16:0), oleic (18:1 n-9), linoleic (18:2 n-6), eicosadienoic (20:2 n-6), EPA (20:5 n-3), and DHA (22:6 n-3) were the FA whose concentration exhibited the highest increment. Evidence of de novo FA biosynthesis was observed through the formation of some FA that were neither present in the initially stocked biomass, nor in the aquafeed supplied, such as 5,11-eicosadienoate (Δ5,1120:2), 7,13,16-docosatrienoate (Δ7,13,1622:3), dihomo-gamma-linolenic (20:3 n-6), eicosatrienoic (20:3 n-3) and eicosatetraenoic (20:4 n-3) acids. A plateau of total FA, n-6, and n-3 FA was not reached over the study period. Overall, the present study highlights the potential of H. diversicolor as an extractive species for integrated multi-trophic aquaculture (IMTA) applications.
Post-partum Coronavirus Disease 19 Like Pneumonia Before the COVID-19 Italian Pandemic Outbreak: A Case Report
Authors: Busnelli Andrea , Bulfoni Alessandro , Caprotti Andrea , Acerboni Stefano , Levi-Setti Paolo Emanuele
Published: May 2021

Here we present a case of severe post-partum pneumonia that we observed at the end of January 2020. Specimen of blood was cultured and revealed Klebsiella pneumoniae bacteremia. However, the course of infection was atypical and the recovery time particularly long. Subsequently emerged COVID-19 hallmarks suggested to re-evaluate the case. After a multidisciplinary consultation, we concluded that, considering the clinical and imaging characteristics, the most likely hypothesis was that the patient was affected by novel Coronavirus pneumonia. The present case supports the hypothesis that Coronavirus might have circulated in northern Italy for weeks before its official detection.
Metformin, the Rise of a New Medical Therapy for Endometriosis? A Systematic Review of the Literature
Authors: Stochino-Loi Emanuela , Major Attila L. , Gillon Tessa E. R. , Ayoubi Jean-Marc , Feki Anis , Bouquet de Joliniere Jean
Published: May 2021

Medical treatments for endometriosis aim to control pain symptoms and stop progression of endometriotic lesions. However, their adverse effects and their contraceptive effect in women who desire pregnancy, limit their long terms use. Although there is only one study investigating the effects of metformin on women with endometriosis, metformin seems to have a unique therapeutic potential. It may be a helpful anti-inflammatory and antiproliferative agent in the treatment of endometriosis. As such metformin may be more beneficial thanks to the lack of serious side effects.
Increased Incidence of Total Knee Replacement Surgery in Patients With Psoriasis: A Secondary Cohort Analysis of a Nationwide, Population-Based Health Claims Database
Authors: Lu Ming-Chi , Fan Kuo-Sheng , Hsu Chia-Wen , Koo Malcolm , Lai Ning-Sheng
Published: May 2021

Patients with rheumatic diseases, such as rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, have increased risk of receiving total knee replacement surgery or total hip replacement surgery. We speculated that psoriasis could also attack the joints of the knees and hips, leading to an increased risk of receiving total knee replacement surgery or total hip replacement surgery. The aim of this study was to investigate the risk of total knee replacement or total hip replacement surgery in patients with psoriasis using a nationwide, population-based health claims database in Taiwan. Using the Taiwan's National Health Insurance Research Database, we identified 10,819 patients with psoriasis between 2000 and 2012. A comparison cohort consisting of five patients without psoriasis for each patient with psoriasis was assembled, based on frequency matching for sex, 10-year age interval, and index year. Both groups were followed until a diagnosis of the study outcomes (total knee replacement or total hip replacement surgery) or the end of the follow-up period. Incidence rate ratios (IRRs) for the outcome variables were calculated using multiple Poisson regression models. Female patients with psoriasis exhibited a significantly higher incidence of receiving total knee replacement surgery [adjusted IRR = 1.44, p = 0.014)]. Analyses stratified by age groups showed that the risk of receiving total knee replacement surgery was significantly higher older (adjusted IRR = 1.31, p = 0.047) patients with psoriasis. There were no significant differences in the risk of receiving total hip replacement surgery in patients with psoriasis compared with controls, either with or without stratification by sex or age groups. In conclusion, patients with psoriasis were associated with an increased risk of receiving total knee. Clinicians should be vigilant in assessing the presence of arthritis in these patients, and initiate strategies to delay or prevent the need for joint replacement.
Three Ribosomal Operons of Escherichia coli Contain Genes Encoding Small RNAs That Interact With Hfq and CsrA in vitro
Authors: Stenum Thomas Søndergaard , Kongstad Mette , Holmqvist Erik , Kallipolitis Birgitte , Svenningsen Sine Lo , Sørensen Michael Askvad
Published: May 2021

Three out of the seven ribosomal RNA operons in Escherichia coli end in dual terminator structures. Between the two terminators of each operon is a short sequence that we report here to be an sRNA gene, transcribed as part of the ribosomal RNA primary transcript by read-through of the first terminator. The sRNA genes (rrA, rrB and rrF) from the three operons (rrnA, rrnB and rrnD) are more than 98% identical, and pull-down experiments show that their transcripts interact with Hfq and CsrA. Deletion of rrA, B, F, as well as overexpression of rrB, only modestly affect known CsrA-regulated phenotypes like biofilm formation, pgaA translation and glgC translation, and the role of the sRNAs in vivo may not yet be fully understood. Since RrA, B, F are short-lived and transcribed along with the ribosomal RNA components, their concentration reflect growth-rate regulation at the ribosomal RNA promoters and they could function to fine-tune other growth-phase-dependent processes in the cell. The primary and secondary structure of these small RNAs are conserved among species belonging to different genera of Enterobacteriales.
Enterovirus 71 Induces INF2 Cleavage via Activated Caspase-2 in Infected RD Cells
Authors: Wang Bei , Zhang Chongyang , Yu Congci , Zhu Yue , Tang Qing , Huang He , Zhao Zhendong
Published: May 2021

Enterovirus 71 (EV71) is the major causative pathogen of hand, foot, and mouth disease. The lack of understanding of the virus’s pathogenesis hinders the development of anti-virus drugs and the control of EV71 infection. Our previous studies have demonstrated that both mitochondria and endoplasmic reticulum (ER) were altered significantly in EV71 infected cells, but the mechanism is still unclear. In this study, we investigated the effects of EV71 infection on the expression of INF2, a key regulator factor in ER-Mitochondria communication and mitochondrial fission. We found that INF2 was cleaved in EV71 infected RD cells. The INF2 cleavage occurred at Aspartic 1,051 of INF2 and is mediated by activated caspases, predominantly by activated caspase-2. The subcellular localization of INF2 and caspase-2 was significantly altered in infected cells. We speculate that caspase-2-mediated INF2 cleavage is involved in forming viral replication organelles (ROs) and is a positive feedback regulatory mechanism of mitochondrial disorders caused by EV71 infection.
Cannabidiol Modulates Mitochondrial Redox and Dynamics in MCF7 Cancer Cells: A Study Using Fluorescence Lifetime Imaging Microscopy of NAD(P)H
Authors: Mould Rhys Richard , Botchway Stanley W. , Parkinson James R. C. , Thomas Elizabeth Louise , Guy Geoffrey W , Bell Jimmy D. , Nunn Alistair V. W.
Published: May 2021

The cannabinoid, cannabidiol (CBD), is part of the plant's natural defense system that when given to animals has many useful medicinal properties, including activity against cancer cells, modulation of the immune system, and efficacy in epilepsy. Although there is no consensus on its precise mode of action as it affects many cellular targets, CBD does appear to influence mitochondrial function. This would suggest that there is a cross-kingdom ability to modulate stress resistance systems that enhance homeostasis. As NAD(P)H autofluorescence can be used as both a metabolic sensor and mitochondrial imaging modality, we assessed the potential of this technique to study thein vitroeffects of CBD using 2-photon excitation and fluorescence lifetime imaging microscopy (2P-FLIM) of NAD(P)H against more traditional markers of mitochondrial morphology and cellular stress in MCF7 breast cancer cells. 2P-FLIM analysis revealed that the addition of CBD induced a dose-dependent decrease in bound NAD(P)H, with 20 µM treatments significantly decreased the contribution of bound NAD(P)H by 14.6% relative to the control (p< 0.001). CBD also increased mitochondrial concentrations of reactive oxygen species (ROS) (160 ± 53 vs. 97.6 ± 4.8%, 20 µM CBD vs. control, respectively,p< 0.001) and Ca2+(187 ± 78 vs. 105 ± 10%, 20 µM CBD vs. the control, respectively,p< 0.001); this was associated with a significantly decreased mitochondrial branch length and increased fission. These are all suggestive of mitochondrial stress. Our results support the use of NAD(P)H autofluorescence as an investigative tool and provide further evidence that CBD can modulate mitochondrial function and morphology in a dose-dependent manner, with clear evidence of it inducing oxidative stress at higher concentrations. This continues to support emerging data in the literature and may provide further insight into its overall mode of action, not only in cancer, but potentially its function in the plant and why it can act as a medicine.
Synthesis and Cytotoxic Activity of Novel Indole Derivatives and Their in silico Screening on Spike Glycoprotein of SARS-CoV-2
Authors: Gobinath Perumal , Packialakshmi Ponnusamy , Vijayakumar Kaliappillai , Abdellattif Magda H. , Shahbaaz Mohd , Idhayadhulla Akbar , Surendrakumar Radhakrishnan
Published: May 2021

This work investigated the interaction of indole with SARS-CoV-2. Indole is widely used as a medical material owing to its astounding biological activities. Indole and its derivatives belong to a significant category of heterocyclic compounds that have been used as a crucial component for several syntheses of medicine. A straightforward one-pot three-component synthesis of indole, coupled with Mannich base derivatives 1a–1j, was synthesized without a catalyst. The products were confirmed by IR, 1H-NMR, 13C-NMR, mass spectra, and elemental analysis. The indole derivatives were tested for cytotoxic activity, using three cancer cell lines and normal cell lines of Human embryonic kidney cell (HEK293), liver cell (LO2), and lung cell (MRC5) by MTT assay using doxorubicin as the standard drug. The result of cytotoxicity indole compound 1c (HepG2, LC50−0.9 μm, MCF−7, LC50−0.55 μm, HeLa, LC50−0.50 μm) was found to have high activity compared with other compounds used for the same purpose. The synthesized derivatives have revealed their safety by exhibiting significantly less cytotoxicity against the normal cell line (HEK-293), (LO2), and (MRC5) with IC50 > 100 μg/ml. Besides, we report an in silico study with spike glycoprotein (SARS-CoV-2-S). The selective molecules of compound 1c exhibited the highest docking score −2.808 (kcal/mol) compared to other compounds. This research work was successful in synthesizing a few compounds with potential as anticancer agents. Furthermore, we have tried to emphasize the anticipated role of indole scaffolds in designing and discovering the much-awaited anti-SARS CoV-2 therapy by exploring the research articles depicting indole moieties as targeting SARS CoV-2 coronavirus.