bluuebunny/crossref_metadata_2025 huggingface dataset:
EPC项目造价管理分析
Authors: 吕 雪芳 , 王 修俭 , 曾 德才
Published: May 2021

近年来，EPC工程总承包项目管理模式，因其具有优化资源配置、缩短工程建设周期、降低工程造价成本、降低发包方技术管理难度等的作用，得到了广泛的推广和应用。为确保总承包单位的合理或最优利润，降低项目建设成本，提高总承包单位的市场竞争力，做好工程造价管理尤为重要，本篇文章先对EPC项目管理模式下的造价管理特点进行了简单的介绍，然后对项目建设各个阶段的造价控制重点进行分析，以期从造价管理方面有利推进EPC项目的顺利开展。
造价过程中结算控制的实际实施的一些要点
Authors: 宋 潇
Published: May 2021

我国的经济发展中，建设项目发挥着积极作用，只有提高了工程管理水平，才能切实发挥工程价值，促进我国经济发展。造价结算控制作为工程造价管理的重要部分，对提高工程管理水平、确保工程建设质量有关键性的意义。文章分析了造价结算控制中存在的一些问题，提出了几点应对措施，以供借鉴。
建筑工程屋面刚性防水和柔性防水相结合的施工技术研究
Authors: 刁 明宝
Published: May 2021

在建筑工程项目的建设工程中，经常受到屋面渗漏问题的干扰，从而对整个建筑的质量造成直接的影响。对于屋面渗漏问题的防治技术，是一种综合性较强的施工技术，因此在文章的分析中，就基于当下建筑工程项目对于屋面开展的刚性与柔性防水技术进行结合的技术，进行详细的施工技术分析，以此为施工人员提供一定的参考。
建筑工程现场安全管理影响因素及对策分析
Authors: 罗 瑜 , 冯 振伟
Published: May 2021

在社会经济发展的过程中建筑行业起到了重要的作用，因此其建设质量及安全也得到更多的关注。从现代建筑企业发展情况来看，如果要想在激烈的市场竞争中脱颖而出应不断强化施工现场安全管理工作。假如在施工建设过程中没有认识到施工现场安全管理的重要性，无法及时发现安全隐患，也会给建筑工程施工进度带来影响，最终给建筑工程经济效益带来损失，阻碍建筑企业发展。因此相关管理人员应深刻的认识到施工现场安全管理的重要性，并通过有效的安全管理来了提高工程建设质量，同时在进行施工现场安全管理过程中应将管理责任落实到人，并做好防控工作及应急事件处理，不断对施工现场安全管理进行规范，从而为施工人员创建安全的施工环境。
浅谈水泥企业的节电措施
Authors: 姬 均 , 张 闪
Published: May 2021

众所周知，我国能源较为匮乏，在很多企业生产发展过程中，都会耗电耗能，其中水泥企业较为突出，由此有必要将节电节能落实到位，针对水泥企业的节电举措，文章主要从以下两大方面进行探讨，以期为有关人员提供参考。
概预算编制质量对工程造价的影响分析
Authors: 李 保华
Published: May 2021

近年来，我国加大了对外经济开放的力度，有效的促进了社会经济水平的显著提升，为各个行业的发展壮大带来了良好的机遇，有效的推动了建筑工程行业的持续稳定发展，在这种发展形势下大量的建筑工程施工企业应时而生，加剧了整个行业内部的竞争形势，建筑工程施工企业要想保证自身能够持续稳定发展，那么最为重要的就是需要从多个层面入手来不断提升企业的综合实力。在进行建筑工程项目建设工作的时候，加大力度对概预算编制质量加以保证，能够确保将施工材料的成本造价控制在既定规定的范围之内，促使工程项目能够获得良好的经济效益，从而为建筑工程施工企业的未来良好发展打下坚实的基础。就现如今实际情况来说，很多建筑工程施工企业对于概预算工作缺少基本的重视，从而引发了严重的成本超预算的情况发生。建筑工程施工企业应当针对现如今概预算编制中所存在的问题加以综合分析，利用有效的方式方法来提升概预算编制的质量，促进工程造价控制工作整体水平的提高，推动企业的稳定健康发展。
Testing the Prediction of Knowledge Sharing Behavior through the Lens of Organizational Culture and Organizational Citizenship Behavior
Authors: Ibrahim Siddig Balal , Ahmed Umair , Abdullahi Mohammed Sani
Published: May 2021

This research intended to focus on the impact of organizational culture on knowledge sharing by bank employees directly and indirectly through mediation by organizational citizenship behavior. For achieving the purpose, 402 employees from banks in the Kingdom of Bahrain through simple random sampling. Data were collected through questionnaires. A current study found a significant outcome of organizational culture on knowledge sharing and organizational citizenship behavior. Besides this current study also found significant results between organizational citizenship behavior and knowledge sharing. Along with significant direct results, current research also found the mediating effect by organizational citizenship behavior in relationships of organizational culture with knowledge sharing. The current study contributes notable theoretical implications under social exchange theory. In addition, the current study also provides practical learnings and recommendations for the future.
Using new insights in grazing management to buffer the impacts of climatic variability on pasture resilience
Authors: Stevens David , Matthew Cory , Tozer Katherine
Published: May 2021

Pasture is the main source of nutrition for the New Zealand ruminant livestock industry. Changing climatic conditions and relentless intensification are putting the ability of pastures to provide that nutrition under pressure. Recent understanding of the interactions between grazing management and the life cycle of roots, leaves and seedheads of pasture species creates further opportunities to increase pasture resilience. Root production is directly related to, though lagging, leaf production and turnover. Tiller production is modified by temperature and seedhead production. Matching grazing patterns to maximise the production of each of these features is generally impossible at the farm scale. However, matching some of these characteristics on some of the farm can be achievable, and have long-lasting benefits for pasture resilience. Therefore, grazing management practices such as deferred grazing in late spring, summer and autumn may be used both to provide a boost to root and tiller production, and to transfer feed from one grazing period to another. Changing our winter management practices away from intensive daily allocations towards 4-day shifting may also increase early spring production, while reducing summer grazing pressure in droughts will aid pasture productivity and persistence in the long term. These techniques have the potential to ensure that the future nutritional needs of grazing ruminants will continue to be met by grazed pasture.
Yield and botanical composition of four dryland pastures at Ashley Dene Research Farm over 8 years
Authors: Taylor Breanna , Mills Anna , Smith Malcolm , Lucas Richard , Moot Derrick
Published: May 2021

Dry matter yield and botanical composition of four grazed dryland pasture types were compared over 8 years in summer-dry conditions at Ashley Dene, Canterbury, New Zealand. The experiment was sown in March 2013 to evaluate cocksfoot (CF)- or meadow fescue/ryegrass hybrid (RG)-based pastures established with either subterranean (Sub) or subterranean and balansa (S+B) clovers. Plantain was included in all pasture types. Perennial ryegrass established poorly on the low soil moisture holding capacity Lismore soil and in Year 2 was re-broadcast into the RG pastures. Despite this, plantain was the main sown species in RG pastures beyond Year 3. Total spring yield was greatest in Year 5 at 6720 kg DM/ha and varied with spring rainfall. Cocksfoot-based pastures had 60% of sown species present in the spring of Year 8, compared with 28% in RG-based pastures. Balansa clover was only present up to Year 5 after a managed seeding event in the first spring. White clover did not persist in the dryland environment past Year 2. Sub clover yield depended on the time and amount of autumn rainfall but contributed up to 45% of the spring yield. Cocksfoot-sub clover pastures appear to be most resilient in this summer-dry environment with variable spring rainfall.
Rural Ritual, Gardened Faith: Ford Madox Ford's Memorial Plots
Authors: Walters Harriet
Published: May 2021

This article examines the importance of the working country garden to the memorial narratives of Ford Madox Ford. It begins with a study of Ford before the Great War; considering how his particular brand of Literary Impressionism was frequently used to make a case for memorializing the rural poor and their surrounding landscape from The Heart of the Country (1906) to The Fifth Queen saga (1906–08). Moving to Post-War Sussex and Kent, it examines Ford's continuing interest in the country garden and rural community, reading his gardening practices as attempted personal reconstruction through faith in landscape production. As Ford moves from small-holding to small-holding, and eventually away for good, it discusses how the narratives of his part-fictive biographies, including Thus to Revisit (1921) and It was the Nightingale (1934), repeatedly return to rural England to resituate the developments of Literary Impressionism – and Ford's most formative literary friendships – in and about the garden. The repetitions of garden work; of sowing, weeding, and digging over plots, proved essential to Ford's in-text ritualisations of rural life and literary innovation alike.
MODEL PROFESSIONAL DEVELOPMENT BERBASIS INTERNET UNTUK MENINGKATKAN TEAM LEARNING SEKOLAH
Authors: Wulandari Farida , Hendarman Hendarman
Published: May 2021

INTERNET BASED PROFESSIONAL DEVELOPMENT MODEL TO IMPROVE SCHOOL LEARNING TEAMThe tendency of the fact where the teachers do not need to learn or do not want to improve professional competence is a reflection of the opposite of team learning. Schools need to improve their performance to achieve maximum results. This study aimed to analyze an Internet-Based Professional Development model that can improve the ability of kindergarten teachers to carry out professional development independently and build team learning as well. Internet-Based Professional Development is an alternative effort in overcoming the improvement of kindergarten teachers' ability to organize Professional Development as well as team-learning. Limited trial research was conducted at Smartskul Preschool Kindergarten with 5 teachers. Extensive trials were carried out at TKI Al-Hamidiyah Depok with 25 teachers, and at TKIT Aliya Bogor with 13 teachers. The method of research used was research and model development (Research Professional Development / R D). Each trial carried out three times actions in limited trials and two actions in extensive trials at each school. In this study, the data analysis used was qualitative, quantitative, and formative. To measure the validity, this research used non-test and expert judgment. The Internet-Based Professional Development model consisted of input, process, and output. The input consisted of the Internet-Based Professional Development module, and kindergarten teachers and principals. The process consisted of planning, implementing monitoring, as well as evaluation reflection. The output of the Internet-Based Professional Development model was able to improve the ability of kindergarten teachers in organizing Internet-Based Professional Development as well as being able to build team learning.
IMPLEMENTASI MANAJEMEN BERBASIS SEKOLAH (STUDI DI SMP ISLAM AL-AZHAR 37 PEKANBARU)
Authors: Setyaningsih Rini , Suci Aisyah Nurhuda , Puspasari Feni Adriani
Published: May 2021

IMPLEMENTATION OF SCHOOL BASED MANAGEMENT (Studi at Al-Azhar 37 Middle School in Pekanbaru)School Based Management (SBM) is the alignment of resources which independently ran by schools where all stakeholder groups involved. SBM also provides a flexibility for schools to determine directions and policies that are relevant to the situation and environmental conditions. The purpose of this study was to determine the implementation of SBM in Islamic-Based Junior High Schools. This research was taken at Al-Azhar 37 Middle School in Pekanbaru. The research method that was qualitative research with a case study approach. The research subjects were the principal, student representatives, public relations representatives, administrative staff, and 2 teachers and 5 students. The research object was the implementation of school-based management it self. The data collection techniques used observation, interviews and documentation. As the results of this study, the authors found that several school policies were related to student management, school relationship management with the community, curriculum management, personal management, special service management, facilities and infrastructure management, school budget management. One of the policies that related to student management was providing the online registration of prospective new students as well as giving prospective students the terms and conditions It was continually completed by the requirements to do an interview, taking test of Math, English, Recitation and memorization test juz 30.
PENINGKATAN EFEKTIVITAS KERJA GURU MELALUI PENGUATAN KOMPETENSI PEDAGOGIK DAN IKLIM ORGANISASI
Authors: Maretha Sherly , Hidayat Nandang , Hidayat Rais
Published: May 2021

IMPROVING TEACHER WORK EFFECTIVENESS THROUGH PEDAGOGIC COMPETENCY STRENGTHENING AND ORGANIZATIONAL CLIMATE AT PRIVATE JUNIOR HIGH SCHOOLS IN CIBINONG, KABUPATEN BOGOR This study aimed to determine empirically the enhancement of teacher work effectiveness. The sampling in the study was 146 teachers who were determined by using proportional technique. The method used was the correlation method.  Hypothetical testing was carried out by using parametric statistical analysis in the form of simple and multiple linear regression analysis, where a significance level of α = 0.05. The research came up with three conclusions. Firstly, there was a positive and significant relationship between pedagogical competence and teacher work effectiveness where a random sampling correlation coefficient of ry1= 0.75.  Secondly, there was a positive and significant relationship between organizational climate and teacher work effectiveness where its correlation coefficient of ry2 = 0.56. Thirdly, there was a positive and significant relationship between pedagogic competence and organizational climate together with teacher work effectiveness where its correlation coefficient of ry.12 = 0.79. It could be concluded that teacher work effectiveness might be enhanced by strengthening the pedagogic competence and organizational climate.
Teratogenic Effects of Durian Fruit (Durio Zibethinus Murr) on White Mice Fetus (Mus musculus L)
Authors: Rusdi Mesa Sukmadani , Efendi M. Rifqi , Hilma Hafizhatul
Published: May 2021

Durian (Durio zibethinus L.) is one of the most consumed and liked fruit in Indonesia, but there was no evidence about the safety of consuming durian during pregnancy. This study was determine the level of safety of durian fruit consumption during pregnancy by conducted teratogenicity test of durian fruit (Durio zibethinus Linn) on fetuses of white mice (Mus musculus L). Teratogenicity test was conducted in vivo, by step: preparation of experimental animal, observation during administration, laparotomy, fixation and observation of morphological defects. Data were analyzed using Analysis of Variance (ANOVA). If the results were significant (P < 0.05), the analysis was continued using Duncan Multiple Range Test. Administration durian during pregnancy did not affects the bodyweight of the mice (P > 0,05), but significantly influences the number of fetuses (P < 0,05) and its body weight (P < 0,05). Consumption of durian during pregnancy is safe in 32,5 mg / KgBW, but it has the potential teratogenic in 65 mg / KgBW and 97,5 mg/KgBW groups. Teratogen effects that were found in several fetuses were underweight, dead, hemorrhage, maternal death and there were resorption sites.
Evaluasi Pengelolaan Obat di Instalasi Farmasi Rumah Sakit Bhayangkara Kota Kendari Tahun 2019
Authors: Sabarudin Sabarudin , Ihsan Sunandar , Arfan Arfan , Hasmi Waode Indri Sasmita , Anwar Irvan , Hukmah Nurul
Published: May 2021

Pengelolaan obat yang kurang baik di rumah sakit dapat memberikan dampak yang kurang baik dari segi ekonomi, sosial maupun kesehatan. Penelitian ini bertujuan untuk mengevaluasi pengelolaan obat di Rumah Sakit Bhayangkara Kota Kendari Tahun 2019. Penelitian ini bersifat deskriptif non eksperimental dengan pengambilan data secara retrospektif dan concurent yang disertai wawancara mendalam. Instrumen penelitian menggunakan lembar observasi dan panduan wawancara. Hasil penelitian menunjukkan bahwa kesesuaian item obat dengan Formularium Nasional sebesar 88.14%, kesesuaian item obat dengan Formularium Rumah Sakit sebesar 100%, persentase jumlah item obat yang direncanakan dengan yang diadakan mencapai 100%, frekuensi kurang lengkapnya surat SP/kontrak sebesar 0%, frekuensi pengadaan tiap item obat pertahun sebanyak 6 kali, frekuensi tertundanya pembayaran sebesar 0%, ketepatan data jumlah obat dengan kenyataan pakai obat sebesar 100%, sistem penataan gudang menggunakan sistem FEFO, persentase obat kadaluwarsa atau rusak sebesar 0%, persentase stok mati sebesar 0%, persentase peresepan nama generik mencapai 87.06% dan rata-rata kecepatan pelayanan resep non racikan 3,8 menit dan resep racikan 4,6 menit. Pengelolaan obat di Instalasi Farmasi Rumah Sakit Bhayangkara Kota Kendari Tahun 2019 sudah efisien, namun persentase kesesuaian item obat yang tersedia dengan formularium nasional belum memenuhi dan frekuensi pengadaan obat dalam setahun masih cukup rendah
Formulasi dan Evaluasi Fisik Sediaan Hand Body Lotion Ekstrak Etanol Daun Miana (Pleactranthus scutellarioides (L.) R. Br.)
Authors: Rasydy La Ode Akbar , Zaky Mohammad , Surtiana Rika
Published: May 2021

Daun miana (Pleactranthus scutellarioides (L.) R. Br.) merupakan tanaman yang memiliki varietas yang sangat banyak dan beragam macam senyawa, 2-methylthiophene, (Z)-3-heptadecen-5-yne, dotriacontane yang dapat digunakan sebagai antioksidan alami untuk antipenuaan. Penelitian ini bertujuan memformulasikan ekstrak daun miana menjadi lotion dan uji evuluasi sehingga memiliki stabilitas yang baik. Penelitian dilakukan secara eksperimental yang diawali dengan mengekstraksi daun miana dengan metode maserasi. Ekstrak kemudian diformulasikan dalam sediaan lotion yang dibuat dengan konsentrasi ekstrak 0,5% (F1), 1% (F2) dan 1,5% (F3). Hasil penelitian menunjukan bahwa ekstrak daun miana dapat diformulasikan dalam bentuk sediaan lotion. Hasil lotion dari ekstrak daun miana dievaluasi selama 3 minggu meliputi uji organoleptis, uji pH, uji omogenitas, uji daya sebar, uji viskositas, uji berat jenis, uji daya lekat dan uji hedonik. Lotion dengan konsentrasi ekstrak 0,5% pada F1 merupakan sediaan yang paling baik dengan karakteristik bentuk agak kental, warna coklat muda, wangi lemon, homogen, memiliki pH 5,9-5,5 dan daya sebar 5,2–5,9 cm, viskositas 2903-3103 Cps, berat jenis 0,966, daya lekat 4,27-4,56 detik serta tes hedonik menunjukkan responden menyukai warna menarik, bau harum, dan tekstur lembut dari lotion
Penetapan Kadar Fenolik dan Flavonoid Ekstrak dan Fraksi Daun Ghoenu (Abelmoschus manihot L.) serta Uji Antiradikal Secara In Vitro
Authors: Yamin Yamin
Published: May 2021

Ghoenu (Abelmoschus manihot L) merupakan tanaman tropis dari family Malvaceae yang dimasyakat selain digunakan sebagai sayuran juga digunakan sebagai bahan pengobatan tradisional. Secara empiris, rebusan daun ghoenu (A. manihot L) digunakan sebagai penurun kolesterol, analgetik, obat sakit ginjal, maag. Ghoenu mengandung metabolit sekunder antara lain flavonoid, asam amino, nukleosida, polisakarida, asam organik, steroid, minyak volatil. Tujuan penelitian ini adalah untuk mentukan kadar fenolik dan flavonoid ekstrak dan fraksi daun Ghoenu (Abelmoschus manihot L) serta uji antioksidan secara in vitro menggunakan DPPH (1-1-diphenyl-2-picrahidrazyl). Daun ghoenu diekstraksi dengan menggunakan metode maserasi. Pengukuran kandungan fenolik total ditentukan dengan menggunakan metode Folin-Ciocalteau, kadar flavonoid ditentukan dengan menggunakan metode kolorimeter kompleks aluminium klorida, serta aktivitas antiradikal ditentukan dengan menggunakan metode DPPH. Fraksi etil asetat menunjukkan kadar fenolik dan flavonoid yang lebih tinggi dibandingkan ekstrak metanol, fraksi n-heksana dan fraksi air dengan kadar berturut-turut sebesar 28,476 g EAG/100 g sampel, 26,098 g EAG/100 g sampel, 15,905 g EAG/100 g sampel, 7,397 g EAG/100 g sampel untuk fenolik dan 49,812 g EK/100 g sampel, 44,198 g EK/100 g sampel, 41,898 g EK/100 g sampel dan 24,042 g EK/100 g sampel. Fraksi etil asetat menunjukkan aktivitas antioksidan yang sangat kuat dengan nilai IC50 sebesar 7,42 µg/mL.
Droplet-Based Microfluidic High Throughput Screening of Corynebacterium glutamicum for Efficient Heterologous Protein Production and Secretion
Authors: Balasubramanian Suvasini , Chen Jun , Wigneswaran Vinoth , Bang-Berthelsen Claus Heiner , Jensen Peter Ruhdal
Published: May 2021

With emerging interests in heterologous production of proteins such as antibodies, growth factors, nanobodies, high-quality protein food ingredients, etc. the demand for efficient production hosts increases. Corynebacterium glutamicum is an attractive industrial host with great secretion capacity to produce therapeutics. It lacks extracellular protease and endotoxin activities and easily achieves high cell density. Therefore, this study focuses on improving protein production and secretion in C. glutamicum with the use of droplet-based microfluidic (DBM) high throughput screening. A library of C. glutamicum secreting β-glucosidase was generated using chemical mutagenesis coupled with DBM screening of 200,000 mutants in just 20 min. Among 100 recovered mutants, 16 mutants exhibited enhanced enzyme secretion capacity, 13 of which had unique mutation profiles. Whole-genome analysis showed that approximately 50–150 SNVs had occurred on the chromosome per mutant. Functional enrichment analysis of genes with non-synonymous mutations showed overrepresentation of genes involved in protein synthesis and secretion relevant biological processes, such as DNA and ribosome RNA synthesis, protein secretion and energy turnover. Two mutants JCMT1 and JCMT8 exhibited the highest secretion with a six and a fivefold increase in the β-glucosidase activity in the supernatant, respectively, relative to the reference strain JC0190. After plasmid curing, a new plasmid with the gene encoding α-amylase was cloned into these two mutants. The new strains SB024 and SB025 also exhibited a five and a sixfold increase in α-amylase activity in the supernatant, respectively, relative to the reference strain SB023. The results demonstrate how DBM screening can serve as a powerful development tool to improve cell factories for the production and secretion of heterologous proteins.
Unchaining Collective Intelligence for Science, Research, and Technology Development by Blockchain-Boosted Community Participation
Authors: Ducrée Jens , Etzrodt Martin , Bartling Sönke , Walshe Ray , Harrington Tomás , Wittek Neslihan , Posth Sebastian , Wittek Kevin , Ionita Andrei , Prinz Wolfgang , Kogias Dimitrios , Paixão Tiago , Peterfi Iosif , Lawton James
Published: May 2021

Since its launch just over a decade ago by the cryptocurrency Bitcoin, the distributed ledger technology (DLT) blockchain has followed a breathtaking trajectory into manifold application spaces. This study aper analyses how key factors underpinning the success of this ground-breaking “Internet of value” technology, such as staking of collateral (“skin in the game”), competitive crowdsourcing, crowdfunding, and prediction markets, can be applied to substantially innovate the legacy organization of science, research, and technology development (RTD). Here, we elaborate a highly integrative, community-based strategy where a token-based crypto-economy supports finding best possible consensus, trust, and truth by adding unconventional elements known from reputation systems, betting, secondary markets, and social networking. These tokens support the holder’s formalized reputation and are used in liquid-democracy style governance and arbitration within projects or community-driven initiatives. This participatory research model serves as a solid basis for comprehensively leveraging collective intelligence by effectively incentivizing contributions from the crowd, such as intellectual property work, validation, assessment, infrastructure, education, assessment, governance, publication, and promotion of projects. On the analogy of its current blockbusters like peer-to-peer structured decentralized finance (“DeFi”), blockchain technology can seminally enhance the efficiency of science and RTD initiatives, even permitting to fully stage operations as a chiefless decentralized autonomous organization (DAOs).
Relationship Embeddedness in Construction Project Teams: The Effect of Social Behaviors on Relational Behaviors
Authors: Kereri James Ogechi , Friedland Carol , Harper Christofer , Nahmens Isabelina
Published: May 2021

Relational and social behaviors of construction project team members explain relationship embeddedness. The literature review revealed three social behaviors (i.e., past experience, benevolence, and integrity) and seven relational behaviors (i.e., harmonization of conflict, propriety of means, restraint of power, reliance and expectation, contractual solidarity, flexibility, and reciprocity) commonly exhibited by construction project team members. Through a binomial logistic regression, research findings revealed that past experience was a significant (p < 0.01) predictor for five of the seven relational behaviors while benevolence and integrity were each significant (p < 0.01) predictors for three of the seven relational behaviors. Overall, out of the seven relational behaviors, only propriety of means is predicted by all the three social behaviors. Through internal validation, the prediction models performed well based on both positive predictive values and negative predictive values. From a relationship management standpoint, this research introduces relational and social behaviors of team members as triggers of relationship embeddedness. The results contribute to understanding the effect of social behaviors on the relational behaviors found in construction project teams where eleven statistically significant models that predict relational behaviors using the social behaviors were validated. The implication of this is that construction industry practitioners can use these prediction models to predict relationship interdependencies of team members.
Modeling the Th17 and Tregs Paradigm: Implications for Cancer Immunotherapy
Authors: Corral-Jara Karla F. , Rosas da Silva Gonçalo , Fierro Nora A. , Soumelis Vassili
Published: May 2021

CD4 + T cell differentiation is governed by gene regulatory and metabolic networks, with both networks being highly interconnected and able to adapt to external stimuli. Th17 and Tregs differentiation networks play a critical role in cancer, and their balance is affected by the tumor microenvironment (TME). Factors from the TME mediate recruitment and expansion of Th17 cells, but these cells can act with pro or anti-tumor immunity. Tregs cells are also involved in tumor development and progression by inhibiting antitumor immunity and promoting immunoevasion. Due to the complexity of the underlying molecular pathways, the modeling of biological systems has emerged as a promising solution for better understanding both CD4 + T cell differentiation and cancer cell behavior. In this review, we present a context-dependent vision of CD4 + T cell transcriptomic and metabolic network adaptability. We then discuss CD4 + T cell knowledge-based models to extract the regulatory elements of Th17 and Tregs differentiation in multiple CD4 + T cell levels. We highlight the importance of complementing these models with data from omics technologies such as transcriptomics and metabolomics, in order to better delineate existing Th17 and Tregs bifurcation mechanisms. We were able to recompilate promising regulatory components and mechanisms of Th17 and Tregs differentiation under normal conditions, which we then connected with biological evidence in the context of the TME to better understand CD4 + T cell behavior in cancer. From the integration of mechanistic models with omics data, the transcriptomic and metabolomic reprograming of Th17 and Tregs cells can be predicted in new models with potential clinical applications, with special relevance to cancer immunotherapy.
The Impact of Nutritional Supplementation on Sweat Metabolomic Content: A Proof-of-Concept Study
Authors: Harshman Sean W. , Browder Andrew B. , Davidson Christina N. , Pitsch Rhonda L. , Strayer Kraig E. , Schaeublin Nicole M. , Phelps Mandy S. , O'Connor Maegan L. , Mackowski Nicholas S. , Barrett Kristyn N. , Eckerle Jason J. , Strang Adam J. , Martin Jennifer A.
Published: May 2021

Sweat is emerging as a prominent biosource for real-time human performance monitoring applications. Although promising, sources of variability must be identified to truly utilize sweat for biomarker applications. In this proof-of-concept study, a targeted metabolomics method was applied to sweat collected from the forearms of participants in a 12-week exercise program who ingested either low or high nutritional supplementation twice daily. The data establish the use of dried powder mass as a method for metabolomic data normalization from sweat samples. Additionally, the results support the hypothesis that ingestion of regular nutritional supplementation semi-quantitatively impact the sweat metabolome. For example, a receiver operating characteristic (ROC) curve of relative normalized metabolite quantities show an area under the curve of 0.82 suggesting the sweat metabolome can moderately predict if an individual is taking nutritional supplementation. Finally, a significant correlation between physical performance and the sweat metabolome are established. For instance, the data illustrate that by utilizing multiple linear regression modeling approaches, sweat metabolite quantities can predict VO2 max (p = 0.0346), peak lower body Windage (p = 0.0112), and abdominal circumference (p = 0.0425). The results illustrate the need to account for dietary nutrition in biomarker discovery applications involving sweat as a biosource.
Cardiac Magnetic Resonance Imaging Right Ventricular Longitudinal Strain Predicts Mortality in Patients Undergoing TAVI
Authors: Schmid Johannes , Kamml Claus , Zweiker David , Hatz Dominik , Schmidt Albrecht , Reiter Ursula , Toth Gabor G. , Fuchsjäger Michael , Zirlik Andreas , Binder Josepha S. , Rainer Peter P.
Published: May 2021

Background: Right ventricular (RV) function predicts survival in numerous cardiac conditions, including left heart disease. The reference standard for non-invasive assessment of RV function is cardiac magnetic resonance imaging (CMR). The aim of this study was to investigate the association between pre-procedural CMR-derived RV functional parameters and mortality in patients undergoing transcatheter aortic valve implantation (TAVI).

Methods: Patients scheduled for TAVI were recruited to undergo pre-procedural CMR. Volumetric function and global longitudinal and circumferential strain (GLS and GCS) of the RV and left ventricle (LV) were measured. The association with the primary endpoint (1-year all-cause mortality) was analyzed with Cox regression.

Results: Of 133 patients undergoing CMR, 113 patients were included in the analysis. Mean age was 81.8 ± 5.8 years, and 65% were female. Median follow-up was 3.9 [IQR 2.3–4.7] years. All-cause and cardiovascular mortality was 14 and 12% at 1 year, and 28 and 20% at 3 years, respectively. One-year all-cause mortality was significantly predicted by RV GLS [HR = 1.109 (95% CI: 1.023–1.203); p = 0.012], RV ejection fraction [HR = 0.956 (95% CI: 0.929–0.985); p = 0.003], RV end-diastolic volume index [HR = 1.009 (95% CI: 1.001–1.018); p = 0.025], and RV end-systolic volume index [HR = 1.010 (95% CI: 1.003–1.017); p = 0.005]. In receiver operating characteristic (ROC) analysis for 1-year all-cause mortality, the area under the curve was 0.705 (RV GLS) and 0.673 (RV EF). Associations decreased in strength at longer follow-up. None of the LV parameters was associated with mortality.

Conclusions: RV function predicts intermediate-term mortality in TAVI patients while LV parameters were not associated with outcomes. Inclusion of easily obtainable RV GLS may improve future risk scores.
Scalable Declarative HEP Analysis Workflows for Containerised Compute Clouds
Authors: Šimko Tibor , Heinrich Lukas Alexander , Lange Clemens , Lintuluoto Adelina Eleonora , MacDonell Danika Marina , Mečionis Audrius , Rodríguez Rodríguez Diego , Shandilya Parth , Vidal García Marco
Published: May 2021

We describe a novel approach for experimental High-Energy Physics (HEP) data analyses that is centred around the declarative rather than imperative paradigm when describing analysis computational tasks. The analysis process can be structured in the form of a Directed Acyclic Graph (DAG), where each graph vertex represents a unit of computation with its inputs and outputs, and the graph edges describe the interconnection of various computational steps. We have developed REANA, a platform for reproducible data analyses, that supports several such DAG workflow specifications. The REANA platform parses the analysis workflow and dispatches its computational steps to various supported computing backends (Kubernetes, HTCondor, Slurm). The focus on declarative rather than imperative programming enables researchers to concentrate on the problem domain at hand without having to think about implementation details such as scalable job orchestration. The declarative programming approach is further exemplified by a multi-level job cascading paradigm that was implemented in the Yadage workflow specification language. We present two recent LHC particle physics analyses, ATLAS searches for dark matter and CMS jet energy correction pipelines, where the declarative approach was successfully applied. We argue that the declarative approach to data analyses, combined with recent advancements in container technology, facilitates the portability of computational data analyses to various compute backends, enhancing the reproducibility and the knowledge preservation behind particle physics data analyses.
Changes in Student Motivation and Teacher Decision Making When Implementing a Formative Assessment Practice
Authors: Näsström Gunilla , Andersson Catarina , Granberg Carina , Palm Torulf , Palmberg Björn
Published: May 2021

Motivation is a prerequisite for students’ learning, and formative assessment has been suggested as a possible way of supporting students’ motivation. However, there is a lack of empirical evidence corroborating the hypothesis of large effects from formative assessment interventions on students’ autonomous forms of motivation and motivation in terms of behavioral engagement in learning activities. In addition, formative assessment practices that do have an impact on students’ motivation may put additional requirements on teachers than more traditional teaching practices. Such requirements include decisions teachers need to make in classroom practice. The requirements on teachers’ decision-making in formative assessment practices that have a positive impact on students’ autonomous forms of motivation and behavioral engagement have not been investigated. This study describes one teacher’s formative assessment practice during a sociology course in upper secondary school, and it identifies the requirements for the teacher’s decision-making. The teacher had participated in a professional development program about formative assessment just prior to this study. This study also investigated changes in the students’ motivation when the teacher implemented the formative assessment practice. The teacher’s practice was examined through observations, weekly teacher logs, the teacher’s teaching descriptions, and an interview with the teacher. Data on changes in the students’ type of motivation and engagement were collected in the teacher’s class and in five comparison classes through a questionnaire administered in the beginning and the end of the course. The students responded to the questionnaire items by choosing the extent to which they agreed with the statements on a scale from 1–7. The teacher’s formative assessment practice focused on collecting information about the students’ knowledge and skills and then using this information to make decisions about subsequent instruction. Several types of decisions, and the knowledge and skills required to make them that exceed those required in more traditional teaching practices, were identified. The students’ in the intervention teacher’s class increased their controlled and autonomous forms of motivation as well as their engagement in learning activities more than the students in the comparison classes.
Effects of the Thyroid Endocrine System on Gonadal Sex Ratios and Sex-Related Gene Expression in the Pufferfish Takifugu rubripes
Authors: Yuan Zhen , Shen Xufang , Yan Hongwei , Jiang Jieming , Liu Binwei , Zhang Lei , Wu Yumeng , Liu Ying , Liu Qi
Published: May 2021

To examine the effect and mechanism of thyroid hormone on gonadal sex differentiation, Takifugu rubripes larvae were treated with goitrogen (methimazole, MET, 1000 μg/g), and thyroxine (T4, 2nM) from 25 to 80 days after hatching (dah). Gonadal histology and sex ratios of fish were then determined at 80 dah. MET treatment induced masculinization, but T4 treatment did not induce feminization in T. rubripes larvae. Transcriptomic analysis of gonads at 80 dah was then conducted. Among the large number of differentially expressed genes between the groups, the expression of foxl2, cyp19a1a, and dmrt1 was altered. The expression of foxl2, cyp19a1a, dmrt1 and gsdf at 25, 40, 55 days after treatment (dat) was further analyzed by qPCR. MET treatment suppressed the expression of foxl2 and cyp19a1a, and induced the expression of dmrt1 in genetic females (p < 0.05). Additionally, T4 treatment induced an increase in the expression of cyp19a1a in genetic XY gonads only at 25 dat. However, the increase in cyp19a1a expression did not continue to 40 and 55 dat. This may explain why feminization of larvae was not found in the T4-treated group. Thus, the present study provides the first evidence that MET treatment causes masculinization in teleost fish. The effects of MET-induced masculinization in T. rubripes may act primarily via suppression of the expression of foxl2 and cyp19a1a, and stimulation of the expression of dmrt1. Moreover, the effects of higher concentrations of T4 or different concentrations of T3, on sex differentiation require further testing.
CTRP1 Aggravates Cardiac Dysfunction Post Myocardial Infarction by Modulating TLR4 in Macrophages
Authors: Gu Yang , Hu Xiao , Ge Pei-Bing , Chen Yu , Wu Shen , Zhang Xi-Wen
Published: May 2021

CTRP1 (C1q/TNF-α [tumour necrosis factor-α]-related protein 1), an adiponectin paralog, is associated with diabetes and adverse events in cardiovascular disease. However, its effect on cardiac function post myocardial infarction (MI) is unclear. Our study aimed to explore the role of CTRP1 in cardiac function post MI. CTRP1 global knockout mice were subjected to left anterior descending ligation to establish the MI model. C57BL6J mice were also administered recombinant CTRP1 protein (200 μg/kg) 7 days post MI. As a result, mice with CTRP1 deficiency exhibited an increased survival rate, a reduced infarct area, improved cardiac function and decreased inflammation and oxidative stress levels at 4 weeks post MI compared with those of mice receiving the CRTP1 injection, whose conditions deteriorated. However, cardiomyocytes with either CTRP1 silencing or CTRP1 treatment showed few differences in inflammation and oxidative stress levels compared with those of the control under hypoxic conditions. The activation of macrophages isolated from CTRP1-deficient mice was decreased in response to interferon-γ, while CTRP1 enhanced the activation of macrophages in response to interferon-γ. Macrophage scavengers and clodronate liposomes antagonized the effects of CTRP1 injection in mice. We also found that CTRP1 regulated macrophage activation via adiponectin receptor 1, which binds to TLR4 on the macrophage membrane. TLR4 knockout also antagonized the effects of the CTRP1 protein on mice with MI. Taken together, these data indicate that CTRP1 supresses cardiac function post MI via TLR4 on macrophages. Targeting CTRP1 may become a promising therapeutic approach to cardiac dysfunction post MI.
Pyruvate Kinase M2 Contributes to TLR-Mediated Inflammation and Autoimmunity by Promoting Pyk2 Activation
Authors: Zhang Xin , Yang Yonghong , Jing Lina , Zhai Weiwei , Zhang Hui , Ma Qun , Li Chunxia , Yan Fenglian , Cheng Dalei , Zhang Junfeng , Ning Zhaochen , Shi Hui , Wang Changying , Zhao Mingsheng , Dai Jun , Li Zhihua , Ming Jiankuo , Yu Meimei , Wang Haiyan , Cheng Hongyan , Xiong Huabao , Dong Guanjun
Published: May 2021

Toll-like receptors (TLRs) play critical roles in regulating the abnormal activation of the immune cells resulting in the pathogenesis of inflammation and autoimmune diseases. Pyruvate kinase M2 (PKM2), which governs the last step of glycolysis, is involved in multiple cellular processes and pathological conditions. However, little is known about the involvement of PKM2 in regulating TLR-mediated inflammation and autoimmunity. Herein, we investigated the role of PKM2 in the activation of the TLR pathways and the pathogenesis of inflammation and autoimmune diseases. The activation of TLR4, TLR7 and TLR9 pathways was found to induce the up-regulation of PKM2 expression in macrophages, dendritic cells (DCs) and B cells. The over-expression of PKM2 promotes the activation of TLR4, TLR7 and TLR9 pathways while interference with the PKM2 expression or the addition of the PKM2 inhibitor (PKM-IN) markedly inhibited the activation of TLR4, TLR7 and TLR9 pathways. Mechanistically, PKM2 augmented the activation of TLR4, TLR7 and TLR9 pathways by promoting the activation of the proline-rich tyrosine kinase 2 (Pyk2). Intriguingly, the PKM2 inhibitor PKM2-IN significantly protected the mice from the endotoxic shock mediated by the TLR4-agonist LPS. Additionally, it alleviated the progression in the TLR7-agonist imiquimod-mediated lupus mice and spontaneous lupus MRL/lpr mice. Moreover, PKM2 expression was highly elevated in the monocytes, DCs and B cells from systemic lupus erythematous (SLE) patients compared with those from the healthy donors. Besides, the PKM2 expression level was positively correlated with the degree of activation of these immune cells. In summary, PKM2 contributed to TLR-mediated inflammation and autoimmunity and can be a valuable target to control inflammation and autoimmunity.
Intravenous Dexmedetomidine Administration Prior Anesthesia Induction With Propofol at 4°C Attenuates Propofol Injection Pain: A Double-Blind, Randomized, Placebo-Controlled Trial
Authors: Lu Yayun , Gu Yaping , Liu Lihua , Tang Xuefeng , Xia Qing , Xu Zhiyue
Published: May 2021

Background: Propofol injection pain, despite various interventions, still occurs during the anesthesia induction and causes intense discomfort and anxiety in patients. This study aimed to explore the effect of intravenous dexmedetomidine on propofol injection pain prior to anesthesia induction with propofol at 4°C.

Methods: A total of 251 patients (American Society of Anesthesiologists I–II) who underwent oral and maxillofacial surgery were randomly assigned to a combination group (n = 63), lidocaine group (n = 62), dexmedetomidine group (n = 63), and placebo-control group (n = 63); they received 0.5 ug/kg dexmedetomidine prior to anesthesia induction with propofol at 4°C, 40 mg lidocaine, 0.5 ug/kg dexmedetomidine prior to anesthesia induction, and normal saline, respectively. Incidence of pain, pain intensity, and reaction to the pain stimulus were evaluated by using verbal categorial scoring (VCS), a numerical rating scale (NRS), and the Surgical Pleth Index (SPI), respectively. In addition, hemodynamic parameters such as heart rate (HR) and mean arterial pressure (MAP) were also measured. The VCS and NRS were evaluated at 5 s after propofol injection. In addition, SPI, HR, and MAP were evaluated at three time points (before anesthesia induction and 5 and 30 s after propofol injection).

Results: The incidence of pain in the combination group (51%) was significantly lower than that in the lidocaine group (71%), dexmedetomidine group (67%), or placebo-control group (94%) (p < 0.001). VCS and NRS scores in the combination group were also lower compared with the other three groups (p < 0.001), with no statistically significant differences between the lidocaine group and dexmedetomidine group (p > 0.05). The SPI of the combination group decreased significantly in comparison with the other three groups at 5 s after propofol injection (F = 96.23, p < 0.001) and 30 s after propofol injection (F = 4.46, p = 0.005). Further comparisons between HR and MAP revealed no significant differences across the groups (p > 0.05).

Conclusion: Because of the sedative nature of dexmedetomidine and analgesic effect of low temperature, this study showed that intravenous dexmedetomidine prior to anesthesia induction with propofol at 4°C is highly effective in attenuating the incidence and severity of pain during injection compared with lidocaine (40 mg), dexmedetomidine 0.5 ug/kg) and placebo. This approach was not associated with any anesthesia complications.

Clinical Trial Registration:ClinicalTrials.gov, identifier: ChiCTR-2000034663
Review of Current COVID-19 Diagnostics and Opportunities for Further Development
Authors: Mardian Yan , Kosasih Herman , Karyana Muhammad , Neal Aaron , Lau Chuen-Yen
Published: May 2021

Diagnostic testing plays a critical role in addressing the coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Rapid and accurate diagnostic tests are imperative for identifying and managing infected individuals, contact tracing, epidemiologic characterization, and public health decision making. Laboratory testing may be performed based on symptomatic presentation or for screening of asymptomatic people. Confirmation of SARS-CoV-2 infection is typically by nucleic acid amplification tests (NAAT), which requires specialized equipment and training and may be particularly challenging in resource-limited settings. NAAT may give false-negative results due to timing of sample collection relative to infection, improper sampling of respiratory specimens, inadequate preservation of samples, and technical limitations; false-positives may occur due to technical errors, particularly contamination during the manual real-time polymerase chain reaction (RT-PCR) process. Thus, clinical presentation, contact history and contemporary phyloepidemiology must be considered when interpreting results. Several sample-to-answer platforms, including high-throughput systems and Point of Care (PoC) assays, have been developed to increase testing capacity and decrease technical errors. Alternatives to RT-PCR assay, such as other RNA detection methods and antigen tests may be appropriate for certain situations, such as resource-limited settings. While sequencing is important to monitor on-going evolution of the SARS-CoV-2 genome, antibody assays are useful for epidemiologic purposes. The ever-expanding assortment of tests, with varying clinical utility, performance requirements, and limitations, merits comparative evaluation. We herein provide a comprehensive review of currently available COVID-19 diagnostics, exploring their pros and cons as well as appropriate indications. Strategies to further optimize safety, speed, and ease of SARS-CoV-2 testing without compromising accuracy are suggested. Access to scalable diagnostic tools and continued technologic advances, including machine learning and smartphone integration, will facilitate control of the current pandemic as well as preparedness for the next one.
Successful Treatment of Relapsed/Refractory Extramedullary Multiple Myeloma With Anti-BCMA CAR-T Cell Therapy Followed by Haploidentical Hematopoietic Stem Cell Transplantation: A Case Report and a Review of the Contemporary Literature
Authors: Qian Ying , Qian Zijun , Zhao Xiujie , Pan Wenjue , Wei Xinzheng , Meng Huimin , Yang Lin , Xiao Haowen
Published: May 2021

Extramedullary multiple myeloma (EMM) is an aggressive sub-entity of multiple myeloma (MM). Despite an excellent improvement in survival for most patients with MM over recent decades, the overall survival (OS) of patients with EMM was usually not longer than 3 years. Standard treatment for patients with EMM has not been established, and their management is particularly challenging. We presented a heavily pretreated young patient with relapsed EMM and refractoriness to a proteasome inhibitor (PI; bortezomib), a next-generation PI (ixazomib), immunomodulatory drugs (IMiDs; lenalidomide), autologous hematopoietic stem cell transplantation (ASCT), and monoclonal antibody (directed against CD38: daratumumab) and indicated that myeloablative haploidentical hematopoietic stem cell transplantation (haploidentical-HSCT) as a salvage treatment of relapse after a chimeric antigen receptor (CAR)-T cell therapy that targeted B-cell maturation antigen (BCMA) (NCT04650724) is feasible. Taken together of the contemporary literature, the promising results on the effect of anti-BCMA CAR-T cell therapy and allogeneic HSCT might present a proof-of-principle for patients with EMM, and therefore, patients with the disease need to be included in future studies.