bluuebunny/crossref_metadata_2025 huggingface dataset:
MEB’in 2018-2019 Eğitim Öğretim Yılında LGS’ye Yönelik Yayınlamış Olduğu Türkçe Dersi Örnek Soruları ile 2019 LGS Türkçe Sorularının Karşılaştırılması
Authors: Ordu Hasan Hüseyin , Engin Ahmet Sencer , Topçuoğlu Ünal Fulya
Published: October 2021

2018 yılında uygulanmaya başlayan Liselere Geçiş Sistemi, ortaokul ders müfredatı ve TİMS-PİSA gibi sınavların soruları örnek alındığı, beceri temelli soruların yoğunlukta olduğu, mantık ve muhakeme yeteneğini ölçen bir sınavdır. Bu araştırmada, Millî Eğitim Bakanlığının 2018-2019 eğitim öğretim yılında LGS’ye yönelik yayınladığı örnek Türkçe sorularıyla, 2019 LGS Türkçe sorularının arasındaki ilişkinin belirlenmesi amaçlanmıştır. Araştırma nitel bir çalışmadır. Çalışma grubu 80 adet örnek soru ve 20 adet LGS Türkçe soruşu olmak üzere toplam 100 sorudan oluşmaktadır. Bu bağlamda 2018-2019 eğitim öğretim yılında yayınlanan örnek Türkçe soruları ve 2019 yılı LGS Türkçe soruları incelenerek; soru kazanımları, seçilen metinlerin türleri ve öğrenme/beceri alanları alt başlıklarında ele alınmıştır. Veriler belgesel kaynak tarama ile toplanmıştır. Verilerin analizinde içerik analizinden yararlanılmıştır. Araştırma sonucunda örnek sorular ile LGS sorularının kullanılan metin türleri uygunluğunun %100, kazanım uygunluğunun %93,3, öğrenme/beceri alanları uygunluğunun %100 olduğu sonucuna ulaşılmıştır.
Beyond the Trinity of Gender, Race and Class
Authors: Hanson Cindy , Fletcher Amber
Published: October 2021

Research exploring the gendered dimensions of adult learning has blossomed in the past two decades. Despite this trend, intersectional approaches in adult learning, research, and teaching remain limited primarily to the three categories of gender, race, and class. Intersectionality theory is more diverse than this and includes discussions of social structures, geographies, and histories that serve to build richer, more nuanced descriptions of how privilege and oppression are experienced. Because the purpose of intersectionality is to understand how social identities are constructed and to challenge the structures of power that oppress particular social groups, this approach is important for feminist and social justice educators. The Canadian authors of this manuscript posit that adult learning should move beyond intersectionality that focuses only on the trinity of gender + race + class in order to consider the nuances of inequality and the true complexities of representation and collective identities. By exploring literature in feminism, adult education, and intersectionality, they illustrate a gap at the core of adult education for social justice. Finally, they use two examples to illustrate how intersectionality works in practice.
Varieties of agencies during working life changes
Authors: Järvensivu Anu
Published: October 2021

The aim of this study is to shed light on the varieties of workers´ agencies in working life change situations, which is an under-researched topic in the literature of workplace learning and in working life studies. The research questions are what kinds of agencies there are to be found when workers encounter changes and how the different kinds of agencies are connected together. The understanding of agency is grounded on the subject-centered socio-cultural approach, whereas the methodological approach is based on applying life-course perspective on research material consisting of 48 working life narratives written by Finnish adults. The narratives are analyzed by abductive content analysis. The results reveal the dynamical and periodical processes between the different kinds of agencies during one´s working life narrative. The different forms of agency overlap and rotate. Suffering can be seen as a dynamic concept mediating transformative agencies, small agency and resistance.
The Study Of Law In The Theory Of Leadership John E. Maxwell As Well As Its Application Against The Leadership Of The Effective
Authors: Ranto Ranto
Published: October 2021

In the Legal Foundation That Vamp this, the cornerstone of which is the basis for true leadership it is the belief, not the belief in the sense of faith or religion, but rather a statement of the credibility of someone that can be trusted, or childbirth trust of those they lead.  So trust is the cornerstone of leadership. The Law Of True Leadership: Apply The Law Of-This Law Then People Will Become Your Followers.  While the confidence in his own awakened/formed mainly from the role of the character and integrity to be a key factor for the creation of trust in leadership.  That character is the basis of the defense is at the root of the realization of beliefs that sustain and maintain its leadership of the collapse.  While trust is the cornerstone of strong leadership.
Adapting the Scar-in-a-Jar to Skin Fibrosis and Screening Traditional and Contemporary Anti-Fibrotic Therapies
Authors: Coentro João Q. , May Ulrike , Prince Stuart , Zwaagstra John , Ritvos Olli , Järvinen Tero A.H. , Zeugolis Dimitrios I.
Published: October 2021

Skin fibrosis still constitutes an unmet clinical need. Although pharmacological strategies are at the forefront of scientific and technological research and innovation, their clinical translation is hindered by the poor predictive capacity of the currently available in vitro fibrosis models. Indeed, customarily utilised in vitro scarring models are conducted in a low extracellular matrix milieu, which constitutes an oxymoron for the in-hand pathophysiology. Herein, we coupled macromolecular crowding (enhances and accelerates extracellular matrix deposition) with transforming growth factor β1 (TGFβ1; induces trans-differentiation of fibroblasts to myofibroblasts) in human dermal fibroblast cultures to develop a skin fibrosis in vitro model and to screen a range of anti-fibrotic families (corticosteroids, inhibitors of histone deacetylases, inhibitors of collagen crosslinking, inhibitors of TGFβ1 and pleiotropic inhibitors of fibrotic activation). Data obtained demonstrated that macromolecular crowding combined with TGFβ1 significantly enhanced collagen deposition and myofibroblast transformation. Among the anti-fibrotic compounds assessed, trichostatin A (inhibitors of histone deacetylases); serelaxin and pirfenidone (pleiotropic inhibitors of fibrotic activation); and soluble TGFβ receptor trap (inhibitor of TGFβ signalling) resulted in the highest decrease of collagen type I deposition (even higher than triamcinolone acetonide, the gold standard in clinical practice). This study further advocates the potential of macromolecular crowding in the development of in vitro pathophysiology models.
Overexpression of Lifeact-GFP Disrupts F-Actin Organization in Cardiomyocytes and Impairs Cardiac Function
Authors: Xu Rui , Du Shaojun
Published: October 2021

Lifeact-GFP is a frequently used molecular probe to study F-actin structure and dynamic assembly in living cells. In this study, we generated transgenic zebrafish models expressing Lifeact-GFP specifically in cardiac muscles to investigate the effect of Lifeact-GFP on heart development and its application to study cardiomyopathy. The data showed that transgenic zebrafish with low to moderate levels of Lifeact-GFP expression could be used as a good model to study contractile dynamics of actin filaments in cardiac muscles in vivo. Using this model, we demonstrated that loss of Smyd1b, a lysine methyltransferase, disrupted F-actin filament organization in cardiomyocytes of zebrafish embryos. Our studies, however, also demonstrated that strong Lifeact-GFP expression in cardiomyocytes was detrimental to actin filament organization in cardiomyocytes that led to pericardial edema and early embryonic lethality of zebrafish embryos. Collectively, these data suggest that although Lifeact-GFP is a good probe for visualizing F-actin dynamics, transgenic models need to be carefully evaluated to avoid artifacts induced by Lifeact-GFP overexpression.
6-Phosphogluconolactonase Promotes Hepatocellular Carcinogenesis by Activating Pentose Phosphate Pathway
Authors: Li Changzheng , Chen Jie , Li Yishan , Wu Binghuo , Ye Zhitao , Tian Xiaobin , Wei Yan , Hao Zechen , Pan Yuan , Zhou Hongli , Yang Keyue , Fu Zhiqiang , Xu Jingbo , Lu Yanan
Published: October 2021

Hepatocellular carcinoma (HCC) has a poor prognosis due to the rapid disease progression and early metastasis. The metabolism program determines the proliferation and metastasis of HCC; however, the metabolic approach to treat HCC remains uncovered. Here, by analyzing the liver cell single-cell sequencing data from HCC patients and healthy individuals, we found that 6-phosphogluconolactonase (PGLS), a cytosolic enzyme in the oxidative phase of the pentose phosphate pathway (PPP), expressing cells are associated with undifferentiated HCC subtypes. The Cancer Genome Atlas database showed that high PGLS expression was correlated with the poor prognosis in HCC patients. Knockdown or pharmaceutical inhibition of PGLS impaired the proliferation, migration, and invasion capacities of HCC cell lines, Hep3b and Huh7. Mechanistically, PGLS inhibition repressed the PPP, resulting in increased reactive oxygen species level that decreased proliferation and metastasis and increased apoptosis in HCC cells. Overall, our study showed that PGLS is a potential therapeutic target for HCC treatment through impacting the metabolic program in HCC cells.
Towards Engineering an Orthogonal Protein Translation Initiation System
Authors: Lee Byeong Sung , Choi Woon Jong , Lee Sang Woo , Ko Byoung Joon , Yoo Tae Hyeon
Published: October 2021

In the last two decades, methods to incorporate non-canonical amino acids (ncAAs) into specific positions of a protein have advanced significantly; these methods have become general tools for engineering proteins. However, almost all these methods depend on the translation elongation process, and strategies leveraging the initiation process have rarely been reported. The incorporation of a ncAA specifically at the translation initiation site enables the installation of reactive groups for modification at the N-termini of proteins, which are attractive positions for introducing abiological groups with minimal structural perturbations. In this study, we attempted to engineer an orthogonal protein translation initiation system. Introduction of the identity elements of Escherichia coli initiator tRNA converted an engineered Methanococcus jannaschii tRNATyr into an initiator tRNA. The engineered tRNA enabled the site-specific incorporation of O-propargyl-l-tyrosine (OpgY) into the amber (TAG) codon at the translation initiation position but was inactive toward the elongational TAG codon. Misincorporation of Gln was detected, and the engineered system was demonstrated only with OpgY. We expect further engineering of the initiator tRNA for improved activity and specificity to generate an orthogonal translation initiation system.
Does Homeschooling Fit Students With School Attendance Problems? Exploring Teachers’ Experiences During COVID-19
Authors: Havik Trude , Ingul Jo Magne
Published: October 2021

Attending school on a regular basis and to complete school is usually seen as a precondition for academic, emotional, and social learning and development. However, some students struggle with school attendance problems (SAPs) caused by a myriad of reasons. Homeschooling is a topic of concern in long-term or problematic SAPs cases. Some scholars claim that school absenteeism might increase and be maintained during homeschooling, while others argue that homeschooling may reduce student’s anxiety associated with school attendance. Anyway, homeschooling is often an intervention for academic learning and/or as a part of gradual reintegration to school for SAP students. Moreover, homeschooling/home education/home tuition is not a new phenomenon and is an intervention for students with long-term sickness. When schools in many countries closed from the middle of March 2020 caused by the Covid-19-pandemic, all students were given homeschooling. This gave us the opportunity to investigate homeschooling more closely in a large sample. In the current study, teachers’ thoughts, and experiences of homeschooling for students with SAPs prior to the pandemic, are investigated. The main aim was to gain more insight and knowledge about homeschooling: does it work for SAP students? Practical implications of homeschooling for SAP students are discussed.
Instructionally Embedded Assessment: Theory of Action for an Innovative System
Authors: Clark Amy K. , Karvonen Meagan
Published: October 2021

Policy shifts in the United States are beginning to reduce the emphasis on using statewide assessment results primarily for accountability and teacher evaluation. Increasingly, there are calls for and interest in innovative and flexible assessments that shift the purposes of assessment and use of results toward instructional planning and student learning. Under the Innovative Assessment Demonstration Authority, some states are exploring options for replacing traditional large-scale summative assessments with innovative measures. However, many of these programs are still in early phases of planning and research and have not yet fully articulated how the innovative system achieves desired outcomes. This conceptual paper presents an argument in the form of a theory of action for a flexible and innovative assessment system already in operational use. The system replaces traditional summative assessments with large-scale through-year Instructionally Embedded assessments. We describe the components of the theory of action, detailing the theoretical model and supporting literature that illustrate how system design, delivery, and scoring contribute to the intended outcomes of teachers using assessment results to inform instruction and having higher expectations for student achievement, in addition to accountability uses. We share considerations for others developing innovative assessment systems to meet stakeholders’ needs.
miR-25 Regulates Gastric Cancer Cell Growth and Apoptosis by Targeting EGR2
Authors: Yang Liuqing , Li Lina , Chang Pan , Wei Ming , Chen Jianting , Zhu Chaofan , Jia Jing
Published: October 2021

Gastric cancer is one of the most common malignancies harmful to human health. The search for effective drugs or gene therapy has aroused the attention of scientists. So far, microRNAs, as small non-coding RNAs, have the potential to be therapeutic targets for cancer. Herein, we found a highly expressed miR-25 in gastric cancer cell. However, the function of miR-25 for gastric cancer cell growth and apoptosis was unknown. Functionally, we used RT-qPCR, western blot, CCK-8, and flow cytometry to detect gastric cancer cell growth and apoptosis. The results indicated that miR-25 promoted gastric cancer cell growth and inhibited their apoptosis. Mechanistically, we found that a gene EGR2 was a potential target gene of miR-25. Further dual-luciferase results supported this prediction. Moreover, knockdown of EGR2 promoted gastric cancer cell growth and inhibited their apoptosis by flow cytometry detection. Altogether, these findings revealed miR-25 as a regulator of gastric cancer cell growth and apoptosis through targeting EGR2.
Expression Profile and Potential Function of Circular RNAs in Peripheral Blood Mononuclear Cells in Male Patients With Primary Gout
Authors: Dai Fei , Zhang Quan-Bo , Tang Yi-Ping , He Yi-Xi , Yi Ting , Qing Yu-Feng
Published: October 2021

Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) with a single-stranded covalently closed-loop structure, and their abnormal expression may participate in the pathogenesis of various human diseases. Currently, knowledge of circRNAs in gout is limited. In this case-control study, human circRNA microarrays were used to identify differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with primary gout (n = 5) and healthy controls (HC; n = 3). Bioinformatics methods were used to analyze significantly different circRNAs (fold change >1.5, p < 0.05). In addition, four significantly differentially expressed circRNAs were selected for quantitative real-time polymerase chain reaction to detect expression levels in 90 gout patients and 60 HC. Subsequently, circRNA-miRNA-mRNA network was established to predict the function of circRNAs of interest. Microarray analysis indicated that 238 circRNAs were upregulated and 41 circRNAs were down-regulated in the gout group (fold change >1.5, p < 0.05). Bioinformatics analysis showed that differentially expressed circRNAs were involved in the pathogenesis of gout via various pathways. Moreover, the expression levels of hsa_circRNA_103657 and hsa_circRNA_000241 were significantly higher in the gout group than those in the HC group, and both correlated significantly with lipid metabolism parameters. Furthermore, the area under the curve of hsa_circRNA_103657 was 0.801 (95% confidence interval (CI): 0.730–0.871; p < 0.001). Our results provide novel insights into the pathogenesis of primary gout. Differentially expressed circRNAs were identified in the PBMCs of gout patients, and these differential circRNAs may play important roles in the development and progression of gout.
Trophic Plasticity of Bombay Duck (Harpadon nehereus) in the South-Central East China Sea Based on Stable Isotope Evidence
Authors: Song Pu-Qing , Zhang Hu-Shun , Zheng Xin-Qing , Li Yuan-Yuan , Lin Long-Shan , Li Yuan
Published: October 2021

High trophic plasticity is often invoked to explain the successful expansion of many aquatic species. Bombay duck (BD) outcompete other traditionally commercial fishes in the East China Sea (ECS) in recent years, displaying a continuous and sharp increase of catches, however, little is known whether the competition advantage of BD was related to its trophic plasticity. Using stable isotope analysis (SIA), we investigated the trophic ecology of BD in the south-central ECS in two periods. Significant differences in δ13C and δ15N values were found between sampling months and among body sizes. Modal (95% credibility limits) estimation showed that BD’s trophic position (TP) gradually increased from 3.56 (3.31–3.82) in G1 (120–150 mm for body size) to 4.09 (3.69–4.50) in G5 (241–270 mm) in November, and from 3.37 (2.92–3.88) in G2 (151–180 mm) to 3.66 (3.07–4.23) in G4 (211–240 mm) in April, respectively, suggesting obvious ontogenetic variation of δ15N and TP. More importantly, the TP of BD within the same body size showed wide amplitude, indicating BD possess high trophic plasticity, and can capture prey from low to high trophic levels. Further quantitative analysis based on the MixSIAR model showed that BD mainly fed on zooplankton and fish, but its feeding habit was characterized by the consumption of gradually reduced zooplankton and increased fish associated with increased body size. Interestingly, the fish’s contribution to BD showed obvious seasonal variation. It can be explained by varied food availability in ECS. Relatively low fish prey in April forced BD to adjust its diet, adding the ingestion of shrimps and cephalopods corresponding to temporal variations in food availability. The present study provides the evidence that high trophic plasticity exists in the feeding strategy of BD, which is reflected in the ability to adjust the feeding preference according to nutritional needs and food environmental changes; thus, it is competitively advantageous and may partly explain why BD is becoming the predominant species and displays an extensive distribution in the ECS.
Experimental Assessment of Vulnerability to Warming in Tropical Shallow-Water Marine Organisms
Authors: Yucharoen Mathinee , Sinutok Sutinee , Chotikarn Ponlachart , Buapet Pimchanok
Published: October 2021

Tropical shallow-water habitats represent the marine environments with the greatest biodiversity; however, these habitats are the most vulnerable to climate warming. Corals, seagrasses, and macroalgae play a crucial role in the structure, functions, and processes of the coastal ecosystems. Understanding their growth and physiological responses to elevated temperature and interspecific sensitivity is a necessary step to predict the fate of future coastal community. Six species representatives, including Pocillopora acuta, Porites lutea, Halophila ovalis, Thalassia hemprichii, Padina boryana, and Ulva intestinalis, collected from Phuket, Thailand, were subjected to stress manipulation for 5 days. Corals were tested at 27, 29.5, 32, and 34.5°C, while seagrasses and macroalgae were tested at 27, 32, 37, and 42°C. After the stress period, the species were allowed to recover for 5 days at 27°C for corals and 32°C for seagrasses and macroalgae. Non-destructive evaluation of photosynthetic parameters (Fv/Fm, Fv/F0, ϕPSII and rapid light curves) was carried out on days 0, 3, 5, 6, 8, and 10. Chlorophyll contents and growth rates were quantified at the end of stress, and recovery periods. An integrated biomarker response (IBR) approach was adopted to integrate the candidate responses (Fv/Fm, chlorophyll content, and growth rate) and quantify the overall temperature effects. Elevated temperatures were found to affect photosynthesis, chlorophyll content, and growth rates of all species. Lethal effects were detected at 34.5°C in corals, whereas adverse but recoverable effects were detected at 32°C. Seagrasses and macroalgae displayed a rapid decline in photosynthesis and lethal effects at 42°C. In some species, sublethal stress manifested as slower growth and lower chlorophyll content at 37°C, while photosynthesis remained unaffected. Among all, T. hemprichii displayed the highest thermotolerance. IBR provided evidence that elevated temperature affected the overall performance of all tested species, depending on temperature level. Our findings show a sensitivity that differs among important groups of tropical marine organisms inhabiting the same shallow-water environments and highlights the importance of integrating biomarkers across biological levels to assess their vulnerability to climate warming.
Fabrication and Nanomechanical Characterization of Thermoplastic Biocomposites Based on Chemically Treated Lignocellulosic Biomass for Surface Engineering Applications
Authors: Sulaiman Muhammad , Iqbal Tanveer , Yasin Saima , Mahmood Hamayoun , Shakeel Ahmad
Published: October 2021

Diverse applications of polymeric materials have prompted development of eco-friendly, efficient, and economical materials. These characteristics can be obtained by incorporating appropriate fillers in the polymeric matrix. The objective of this work is to investigate impact of aqueous glycerol (Gly) treated rice husk (RH) on surface mechanical properties of produced biocomposites. RH was treated with aqueous Gly (75 wt%) and compounded with low density polyethylene (LDPE) at different loadings (10, 20, and 30 wt%). The resulting mixture was thermally pressed in molds to fabricate biocomposites. Surface mechanical properties such as elastic modulus, hardness, creep rate, and plasticity of biocomposites reinforced with untreated and treated RH were investigated using nanoindenter. Experimental values depicted that hardness (H) and elastic modulus (Es) of treated biocomposites were higher than untreated ones. Treated biocomposites showed the noticeable improvement in elastic modulus by 24 and 37% compared to untreated biocomposites at 20 wt% loading and neat LDPE, respectively. Reductions in the creep rate by 20 and 14% were observed for untreated and treated biocomposites, respectively, in comparison to the neat LDPE. H/E ratio was increased by 23 and 18% for treated and untreated biocomposites, respectively, as compared to virgin LDPE. Furthermore, mechanical and structural properties of untreated and treated RH are reported based on nanoindentation response and Fourier transform infrared spectroscopy (FTIR) techniques The study indicated that aqueous glycerol pretreatment can partially strip off non-cellulosic constituents from lignocellulose matrix to generate cellulose-rich pulp for engineered composite applications.
The Spread of Plasmidic AmpC in a General Lebanese Hospital Over Nine Consecutive Years and the Relationship With Restricted Isolation Protocols
Authors: Fleifel Mohamad , Machmouchi Ahmad , Alameddine Omar , Hoyek Kim , Melki Dimitri , Hallab Elsa , Masri Khalil , Sidaoui Hiam R. , Stockman David , Daoud Ziad
Published: October 2021

Background: The dreaded bacterial infection by extended-spectrum β-lactamases (ESBL)-producers has always troubled the medical field whether on the public, scientific, or clinical levels. One of the lesser known β-lactamases, which is capable of hydrolyzing broad and extended-spectrum cephalosporins—i.e., cephamycins plus oxyimino-β-lactams—are the AmpC β-lactamases. This group, which has also been termed occasionally—and incorrectly—as ESBL Class C, confers resistance to β-lactamase inhibitors. The prevalence of plasmidic AmpC (pAmpC) strains is possibly still a matter of debate considering the unevenly matched data between phenotypically-detected and molecularly-detected pAmpC.

Aim: In the absence of any study in Lebanon addressing the AmpC, our intention was to determine the numbers and percentages of AmpC Enterobacteriaceae isolates, notably plasmid-mediated ones, across different wards at the Centre Hospitalier du Nord (CHN), Lebanon, and highlight the importance of infection control protocols.

Materials and Methods: Carriage and infection with pAmpC Enterobacteriaceae were retrospectively investigated between 2011 and 2015 and prospectively between 2016 and 2019 at the Centre Hospitalier du Nord Hospital, North Lebanon. The rise or decline in the numbers of such strains, in concordance with the allegedly intensive isolation of the patients, were analyzed.

Results: Intensive care unit (ICU) data shows an initial rise in infection isolates from 2012 to 2014 and in the carriage isolates from 2012 to 2013 with later notable overall decrease in the both isolates' numbers with the application of the isolation protocols at CHN from 2014 onwards. Floors 2, 3, and 4 seemed to house the bulk of the isolates as well.

Conclusion: Preventive measures, such as on-going surveillance of the hospital wards by specialized healthcare personnel and strict implementation of infection control practices, should be a top priority in any medical center in order to isolate such strains and try to put a limit for the development and the dissemination of any possible multidrug resistant strains.
Whole-Genome Sequencing, Phylogenetic and Genomic Analysis of Lactiplantibacillus pentosus L33, a Potential Probiotic Strain Isolated From Fermented Sausages
Authors: Stergiou Odysseas Sotirios , Tegopoulos Konstantinos , Kiousi Despoina Eugenia , Tsifintaris Margaritis , Papageorgiou Aristotelis C. , Tassou Chrysoula C. , Chorianopoulos Nikos , Kolovos Petros , Galanis Alex
Published: October 2021

Lactobacillus is a diverse genus that includes species of industrial and biomedical interest. Lactiplantibacillus pentosus, formerly known as Lactobacillus pentosus, is a recently reclassified species, that contains strains isolated from diverse environmental niches, ranging from fermented products to mammalian gut microbiota. Importantly, several L. pentosus strains present health-promoting properties, such as immunomodulatory and antiproliferative activities, and are regarded as potential probiotic strains. In this study, we present the draft genome sequence of the potential probiotic strain L. pentosus L33, originally isolated from fermented sausages. Comprehensive bioinformatic analysis and whole-genome annotation were performed to highlight the genetic loci involved in host-microbe interactions and the probiotic phenotype. Consequently, we found that this strain codes for bile salt hydrolases, adhesins and moonlighting proteins, and for Class IIb bacteriocin peptides lacking the GxxxG and GxxxG-like motifs, crucial for their inhibitory activity. Its adhesion ability was also validated in vitro, on human cancer cells. Furthermore, L. pentosus L33 contains an exopolysaccharide (EPS) biosynthesis cluster, and it does not carry transferable antibiotic resistance genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and CAZymes analyses showed that L. pentosus L33 possesses biosynthetic pathways for seven amino acids, while it can degrade a wide array of carbohydrates. In parallel, Clusters of Orthologous Groups (COGs) and KEGG profiles of L. pentosus L33 are similar to those of 26 L. pentosus strains, as well as of two well documented L. plantarum probiotic strains. Conclusively, L. pentosus L33 exhibits good probiotic potential, although further studies are needed to elucidate the extent of its biological properties.
Bromodomain Containing Protein 4 (BRD4) Regulates Expression of its Interacting Coactivators in the Innate Response to Respiratory Syncytial Virus
Authors: Xu Xiaofang , Mann Morgan , Qiao Dianhua , Li Yi , Zhou Jia , Brasier Allan R.
Published: October 2021

Bromodomain-containing protein 4 plays a central role in coordinating the complex epigenetic component of the innate immune response. Previous studies implicated BRD4 as a component of a chromatin-modifying complex that is dynamically recruited to a network of protective cytokines by binding activated transcription factors, polymerases, and histones to trigger their rapid expression via transcriptional elongation. Our previous study extended our understanding of the airway epithelial BRD4 interactome by identifying over 100 functionally important coactivators and transcription factors, whose association is induced by respiratory syncytial virus (RSV) infection. RSV is an etiological agent of recurrent respiratory tract infections associated with exacerbations of chronic obstructive pulmonary disease. Using a highly selective small-molecule BRD4 inhibitor (ZL0454) developed by us, we extend these findings to identify the gene regulatory network dependent on BRD4 bromodomain (BD) interactions. Human small airway epithelial cells were infected in the absence or presence of ZL0454, and gene expression profiling was performed. A highly reproducible dataset was obtained which indicated that BRD4 mediates both activation and repression of RSV-inducible gene regulatory networks controlling cytokine expression, interferon (IFN) production, and extracellular matrix remodeling. Index genes of functionally significant clusters were validated independently. We discover that BRD4 regulates the expression of its own gene during the innate immune response. Interestingly, BRD4 activates the expression of NFκB/RelA, a coactivator that binds to BRD4 in a BD-dependent manner. We extend this finding to show that BRD4 also regulates other components of its functional interactome, including the Mediator (Med) coactivator complex and the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin (SMARC) subunits. To provide further insight into mechanisms for BRD4 in RSV expression, we mapped 7,845 RSV-inducible Tn5 transposase peaks onto the BRD4-dependent gene bodies. These were located in promoters and introns of cytostructural and extracellular matrix (ECM) formation genes. These data indicate that BRD4 mediates the dynamic response of airway epithelial cells to RNA infection by modulating the expression of its coactivators, controlling the expression of host defense mechanisms and remodeling genes through changes in promoter accessibility.
Inhibitory Effects of Trifluoperazine on Peripheral Proinflammatory Cytokine Expression and Hypothalamic Microglia Activation in Obese Mice Induced by Chronic Feeding With High-Fat-Diet
Authors: Huang Hui-Ting , Chen Pei-Chun , Chen Po-See , Chiu Wen-Tai , Kuo Yu-Min , Tzeng Shun-Fen
Published: October 2021

Microglia and astrocytes are the glial cells of the central nervous system (CNS) to support neurodevelopment and neuronal function. Yet, their activation in association with CNS inflammation is involved in the initiation and progression of neurological disorders. Mild inflammation in the periphery and glial activation called as gliosis in the hypothalamic region, arcuate nucleus (ARC), are generally observed in obese individuals and animal models. Thus, reduction in peripheral and central inflammation is considered as a strategy to lessen the abnormality of obesity-associated metabolic indices. In this study, we reported that acute peripheral challenge by inflammagen lipopolysaccharide (LPS) upregulated the expression of hypothalamic dopamine type 2 receptor (D2R) mRNA, and chronic feeding by high-fat-diet (HFD) significantly caused increased levels of D2R in the ARC. The in vitro and in vivo studies indicated that an FDA-approved antipsychotic drug named trifluoperazine (TFP), a D2R inhibitor was able to suppress LPS-stimulated activation of microglia and effectively inhibited LPS-induced peripheral inflammation, as well as hypothalamic inflammation. Further findings showed daily peripheral administration intraperitoneally (i.p.) by TFP for 4 weeks was able to reduce the levels of plasma tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in accompany with lower levels of plasma glucose and insulin in obese mice receiving HFD for 16 weeks when compared those in obese mice without TFP treatment. In parallel, the activation of microglia and astrocytes in the ARC was also inhibited by peripheral administration by TFP. According to our results, TFP has the ability to suppress HFD-induced ARC gliosis and inflammation in the hypothalamus.
Deep Learning Radiomics to Predict Regional Lymph Node Staging for Hilar Cholangiocarcinoma
Authors: Wang Yubizhuo , Shao Jiayuan , Wang Pan , Chen Lintao , Ying Mingliang , Chai Siyuan , Ruan Shijian , Tian Wuwei , Cheng Yongna , Zhang Hongbin , Zhang Xiuming , Wang Xiangming , Ding Yong , Liang Wenjie , Wu Liming
Published: October 2021

Background

Our aim was to establish a deep learning radiomics method to preoperatively evaluate regional lymph node (LN) staging for hilar cholangiocarcinoma (HC) patients.

Methods and Materials

Of the 179 enrolled HC patients, 90 were pathologically diagnosed with lymph node metastasis. Quantitative radiomic features and deep learning features were extracted. An LN metastasis status classifier was developed through integrating support vector machine, high-performance deep learning radiomics signature, and three clinical characteristics. An LN metastasis stratification classifier (N1 vs. N2) was also proposed with subgroup analysis.

Results

The average areas under the receiver operating characteristic curve (AUCs) of the LN metastasis status classifier reached 0.866 in the training cohort and 0.870 in the external test cohorts. Meanwhile, the LN metastasis stratification classifier performed well in predicting the risk of LN metastasis, with an average AUC of 0.946.

Conclusions

Two classifiers derived from computed tomography images performed well in predicting LN staging in HC and will be reliable evaluation tools to improve decision-making.
Association of Stress, Glucocorticoid Receptor, and FK506 Binding Protein Gene Polymorphisms With Internalizing Disorders Among HIV-Infected Children and Adolescents From Kampala and Masaka Districts—Uganda
Authors: Owalla Tonny Jimmy , Ssebajjwe Wilber Joseph , Muhanguzi Dennis , Womersley Jacqueline Samantha , Kinyanda Eugene , Kalungi Allan
Published: October 2021

Children and adolescents living with human immunodeficiency virus (CA-HIV) suffer a considerable burden of internalizing disorders (IDs; depressive and anxiety disorders). Environmental and genetic factors have been reported to influence the vulnerability to IDs in western settings; however, their role among African populations remains inadequately explored. We investigated the individual and interactive effects of stress and single-nucleotide polymorphisms within the FK506 binding protein 5 (rs1360780) and glucocorticoid receptor (rs10482605) genes on ID status in a cohort of CA-HIV in Uganda. We genotyped rs10482605 (309 cases and 315 controls) and rs1360780 (350 cases and 335 controls) among CA-HIV with and without IDs using Kompetitive Allele-Specific PCR. Socio-demographic variables, as well as allele and genotype distributions, were compared between cases and controls using chi-square tests. Genotypes were assessed for Hardy–Weinberg equilibrium. Composite indices of recent and chronic stress classes were also generated. A hierarchical cluster analysis was used to generate cutoff points within each of the indices of recent and chronic stress. Logistic regression was used to assess the association between IDs and each of recent stress, chronic stress, and the investigated genotypes. The interaction effect of chronic/recent stress on the association between each of the polymorphisms and IDs was determined using a likelihood ratio test. We observed no significant association between IDs and rs1360780 and rs10482605 polymorphisms within the FKBP5 and glucocorticoid receptor genes, respectively (P > 0.050). Severe recent stress increased the vulnerability to IDs among CA-HIV (P = 0.001). We did not observe any gene–environment effect on vulnerability to IDs in this population. These findings support the currently held opinion that polymorphisms at single genetic loci only contribute a very small effect to the genetic vulnerability to IDs.
C-to-G Base Editing Enhances Oleic Acid Production by Generating Novel Alleles of FATTY ACID DESATURASE 2 in Plants
Authors: Park Mid-Eum , Yun Jae-Young , Kim Hyun Uk
Published: October 2021

The demand for vegetable oil, which is mainly used for dietary purposes and cooking, is steadily increasing worldwide. It is often desirable to reduce unsaturation levels of fatty acids in order to increase storage stability and reduce trans-fat generation during cooking. Functional disruption of FATTY ACID DESATURASE 2 (FAD2) prevents the conversion of monounsaturated oleic acid to polyunsaturated linoleic acid, thereby enhancing the production of the desirable oleic acid. However, FAD2 null alleles, due to growth defects under stress conditions, are impractical for agronomical purposes. Here, we aimed to attenuate FAD2 activity in planta while avoiding adverse growth effects by introducing amino-acid substitutions using CRISPR base editors. In Arabidopsis, we applied the adenine base editor (ABE) and cytosine base editor (CBE) to induce semi-random base substitutions within several selected FAD2 coding regions. Isolation of base-edited fad2 alleles with higher oleic acid revealed that the CBE application induced C-to-T and/or C-to-G base substitutions within the targeted sequences, resulting in an alteration of the FAD2 enzyme activities; for example, fad2-144 with multiple C-to-G base substitutions showed less growth defects but with a significant increase in oleic acids by 3-fold higher than wild type. Our “proof-of-concept” approach suggests that equivalent alleles may be generated in vegetable oil crops via precision genome editing for practical cultivation. Our targeted semi-random strategy may serve as a new complementary platform for planta engineering of useful agronomic traits.
Psychological Adaptive Mechanism Maturity, Age, and Depression Symptoms in Advanced-Stage Cancer Patients
Authors: Beresford Thomas , Teschke Patricia U. , Hipp Daniel , Ronan Patrick J.
Published: October 2021

Background: Previously, we reported that the maturity of Psychological Adaptive Mechanism (PAM; alternatively, ego defense mechanism) endorsement, but not depression symptom severity, predicted 5-year survival rates in adult cancer patients and that study controlled for age as a significant variable. In this investigation, we hypothesized that greater PAM maturity would correlate significantly with age and with fewer depression symptoms in a larger sample.

Methods: In this cross-section study, adult cancer outpatients (N=293) completed the Defense Style Questionnaire (DSQ), the Beck Depression Inventory (BDI), and provided additional clinical data. Spearman’s correlation and multiple regression modeling provided statistical tests of the study hypotheses.

Results: Contrary to our hypothesis, DSQ PAM maturity endorsement did not correlate significantly with increasing age. Greater PAM maturity ratio on the DSQ (p<0.0001) and current antidepressant use (p<0.05), however, both provided inverse associations with total BDI symptom frequency (p<0.01). Age was inversely associated with BDI mood (p<0.0001) and somatic scores (p<0.04). Items that worsened BDI symptom frequency included self-reported mood-altering anti-cancer medications and any psychiatric history. Cancer stage, time since diagnosis, and chemotherapy treatment did not correlate with DSQ or BDI scores. Multiple regression analysis found that the correlated items accounted for 17.2% of the variance in mood symptoms and 4.9% in somatic symptoms. Specifically, adaptive maturity and age associated with fewer depression symptoms, while cancer medications affecting mood, and a previous psychiatric history each predicted higher frequency of depression scores.

Conclusion: The results suggest that PAM maturity likely predicts fewer depression symptoms while younger age associates with more depression symptoms in this clinical sample. Centrally, acting cancer medications, such as glucocorticoids, and any history of psychiatric disorder correlated with increased depression symptom frequencies. In this cross-section study, antidepressant medications indicated higher frequencies of depressive symptoms, likely reflecting their use in persons previously diagnosed with depression. Further research should target factors that improve PAM maturity as a potential treatment target, especially in younger age groups.
Impact of Advertising Campaigns Among Online Gamblers: The Role Perceptions of Social Support and Personality Traits
Authors: Tessier Samantha , Romo Lucia , Zerhouni Oulmann
Published: October 2021

Background: Few studies on problematic gamblers have focused on how environment and personality interact in gambling behavior. The aim of this research is to investigate how social support, dimensions of personality, and advertising campaigns are associated with gambling among problematic or moderate-risk gamblers and recreational gamblers and associated with online gambling (i.e., sport and poker).

Methods: One hundred nine participants (45% problematic or moderate-risk gamblers) answered an online survey including social support, five factor models of personality, typology of gamblers, and several sociodemographic variables.

Results: We found that problematic and moderate-risk gamblers were significantly more sensitive to gambling advertisements compared to light players. Social support was significantly lower among online gamblers compared to offline gamblers, but no association was found between social support and type of gamblers. Problematic and moderate-risk gamblers presented lower levels of extraversion compared with recreational gamblers. Notably, when the onset of gambling is before 18 years old, participants had more chances to recall more gambling advertisements as adults.

Conclusion: We propose that future longitudinal research should focus on characteristics of online gamers particularly regarding social support to understand this low level of adequacy compared to offline gamblers.
AI Systems and Respect for Human Autonomy
Authors: Laitinen Arto , Sahlgren Otto
Published: October 2021

This study concerns the sociotechnical bases of human autonomy. Drawing on recent literature on AI ethics, philosophical literature on dimensions of autonomy, and on independent philosophical scrutiny, we first propose a multi-dimensional model of human autonomy and then discuss how AI systems can support or hinder human autonomy. What emerges is a philosophically motivated picture of autonomy and of the normative requirements personal autonomy poses in the context of algorithmic systems. Ranging from consent to data collection and processing, to computational tasks and interface design, to institutional and societal considerations, various aspects related to sociotechnical systems must be accounted for in order to get the full picture of potential effects of AI systems on human autonomy. It is clear how human agents can, for example, via coercion or manipulation, hinder each other’s autonomy, or how they can respect each other’s autonomy. AI systems can promote or hinder human autonomy, but can they literally respect or disrespect a person’s autonomy? We argue for a philosophical view according to which AI systems—while not moral agents or bearers of duties, and unable to literally respect or disrespect—are governed by so-called “ought-to-be norms.” This explains the normativity at stake with AI systems. The responsible people (designers, users, etc.) have duties and ought-to-do norms, which correspond to these ought-to-be norms.
Terrain-Perception-Free Quadrupedal Spinning Locomotion on Versatile Terrains: Modeling, Analysis, and Experimental Validation
Authors: Zhu Hongwu , Wang Dong , Boyd Nathan , Zhou Ziyi , Ruan Lecheng , Zhang Aidong , Ding Ning , Zhao Ye , Luo Jianwen
Published: October 2021

Dynamic quadrupedal locomotion over rough terrains reveals remarkable progress over the last few decades. Small-scale quadruped robots are adequately flexible and adaptable to traverse uneven terrains along the sagittal direction, such as slopes and stairs. To accomplish autonomous locomotion navigation in complex environments, spinning is a fundamental yet indispensable functionality for legged robots. However, spinning behaviors of quadruped robots on uneven terrain often exhibit position drifts. Motivated by this problem, this study presents an algorithmic method to enable accurate spinning motions over uneven terrain and constrain the spinning radius of the center of mass (CoM) to be bounded within a small range to minimize the drift risks. A modified spherical foot kinematics representation is proposed to improve the foot kinematic model and rolling dynamics of the quadruped during locomotion. A CoM planner is proposed to generate a stable spinning motion based on projected stability margins. Accurate motion tracking is accomplished with linear quadratic regulator (LQR) to bind the position drift during the spinning movement. Experiments are conducted on a small-scale quadruped robot and the effectiveness of the proposed method is verified on versatile terrains including flat ground, stairs, and slopes.
The Extent and Economic Significance of Cultivated Forage Crops in Developing Countries
Authors: Fuglie Keith , Peters Michael , Burkart Stefan
Published: October 2021

Forage grasses and legumes are the principal source of nutrition for most ruminant livestock in developing countries. Raising yields of forage crops can increase the availability and affordability of livestock products as well as reduce pressure on increasingly scarce land resources by enabling greater herd densities on existing pasture. However, the economic significance of cultivated forage crops in developing countries is not well-understood. We provide estimates of the present area and production value of cultivated forage crops as well as review evidence on the extent of adoption of CGIAR-derived improved varieties of cultivated forage species and their economic impact in developing countries. There are at least 159 million hectares under cultivated forage crops producing yield worth around $63 billion per year (at 2014-2016 prices). Latin America accounts for about 85% of this forage crop area. CGIAR forage breeding programs have developed and helped disseminate improved varieties of Brachiaria, Stylosanthes, Vigna unguiculata, and Calliandra spp., which by 2015 had been adopted on over 12 million hectares producing economic benefits of over $5.8 billion/year.