bluuebunny/crossref_metadata_2025 huggingface dataset:
Gamal Leaves (Gliricidia sepium) as Hydroponic Nutrition for Lettuce (Lactucasativa L.)
Authors: Indarto  , Qoniah U , Ulmillah A , Fatimatuzzahra  , Maretta G , Sugiharta I
Published: March 2020

Cultivating with a hydroponic system is an alternative with increasingly limited agricultural land. Gamal leaves contain nutrients that are suitable to be used as hydroponic nutrients for lettuce (Lactuca sativa L.). This article will explain the effect of Gamal leaves nutrition on the growth and productivity of lettuce using the hydroponic method. The method used in this study was a Completely Randomized Design (CRD) consisting of 5 treatments namely P1 = (negative control) only water, P2 = 20% Gamal leaf nutrition, P3 = 30% Gamal leaf nutrition, P4 = leaf nutrition 40% Gamal and P5 = (positive control) AB-Mix nutrition. The parameters observed consisted of plant height, number of leaves, leaf width and gross weight. Analysis with One Way ANOVA assisted by SPSS 17 and LSD advanced test. The results on the parameters observed and analyzed carried out had a real effect on all parameters. Gamal leaf nutrition treatment on plant height P4 and P2 were not significantly different from P2, the number of leaves and leaf width of P2, P3 and P4 were not significantly different, whereas the wet weight P4 had the highest value which is significantly different from other treatments.
How Is the Students’ Concept Mastery in Terms of Gender Differences? The Effectiveness of Probing Prompting Learning Model
Authors: Amalia Ricadesta , Trisnaningsih  , Anwar C , Thahir A , Lutfiana N , Susilowati N E , Wekke I S , Saregar A
Published: March 2020

The relationship between gender and educational outcomes is still very interesting to talk about. This study aims to test the effectiveness of the probing prompting learning model on the physics concept mastery, the effect of gender on the physics concept mastery and examine the interaction between the application of the probing prompting learning model and discovery learning in terms of gender on the students’ physics concept mastery. The research method used is quasi-experiment with a post-test only control group design. The research sample consisted of two classes chosen by purposive sampling technique; class VIII A as the experimental class and class VIII B as the control class. Data collection techniques used were test to obtain the data of concept mastery. The hypothetical test used was two-way ANOVA. The conclusions from the results of this study are: (1) The probing prompting learning model is more effective than the discovery learning model on students’ physics concept mastery, (2) gender affects the students’ physics concept mastery, and (3) there is no interaction between the application of the probing prompting learning model and discovery learning in terms of gender toward the students’ physics concept mastery.
Reconstruction of Teaching Materials with Socio-Scientific Issues Context on Source of Energy Content
Authors: Saefullah A , Guntara Y , Nulhakim L
Published: March 2020

One innovation that can be done to improve the quality of science learning is through the development of teaching materials. In this study teaching material was developed through a reconstruction process, where regard to educational goals, carefully described, and related to the context in real life. One of the science contents that is very close to the context in real life is a source of energy. Source of energy content can be used in science learning as a controversial Socio-Scientific Issues (SSI). This study used a modified R&D in two mains steps, research and initial information collection, as well as planning and development of products that adopt model of educational reconstruction (MER). Teaching material with SSI context on source of energy content that had been developed has several characteristics including, designed based on SSI learning, each description in theme is packaged by context, consisting of a cover page, introduction structure, end section, and additional reading lists. The teaching materials are validated and given an evaluation by experts to determine the feasibility of the teaching materials. In addition, students collected responses to determine the level of understanding and expectations of students towards teaching material that had been produced.
Community Participation in Flood Disaster Mitigation Oriented on The Preparedness: A Literature Review
Authors: Nugraheni I L , Suyatna A
Published: March 2020

The purpose of this paper is to examine community participation in mitigating flood preparedness. The method used in the form of meta-analysis from the literature study of various journal articles in 2011-2019 with the topic of flood disaster mitigation in Indonesia includes Sumatra, Java, Sulawesi, Kalimantan, taken from the international journal Disaster risk reduction, Sumatra Journal of disaster, geography and geography education Jamba: Journal of disaster risk studies, nature science, and from international seminars. The lack of articles in Indonesia that discusses public participation in English language flooding disasters such as articles from other countries, causes this research has never been done. The review results show that of the 9 articles used, it turns out that community participation in dealing with floods in several regions in Indonesia is included in the active category. Forms of participation include participation in the form of money, labor contributions, inter-community education, supervision of infrastructure development and the addition of green open space.
The Making of E-Portfolios for Performance Assessment in Chemical Practicum
Authors: Hakim R Ismail , Irwansyah F S , Farida Ida
Published: March 2020

This research aims to create a media that can facilitate the assessment of chemical practicum following the development of information technology. Through the Design-Based Research method, an e-portfolio has been made for performance evaluation on chemical practicum that can assess the work of student practicum in the form of documents, photos, and videos online.E-portfolios can be used to assess aspects of planning, implementation, and reporting on digital-based chemical labs. The validation results show that the product is declared valid by the acquisition of an average value of 0.85. The results of a limited trial conducted on chemistry education students indicate that the product is declared suitable for use with an average percentage value of 86.87%.
The Scientific Argumentation Profile of Earthquake Mitigation of Non-Science Undergraduate Student in Universitas Negeri Surabaya
Authors: Deta Utama Alan , Fadillah Rizki Nur , Ria Agustina Putri Zulaiha , Prakoso Irvan , Nurlailiyah Alfi , Saregar Antomi , Misbah  , Lestari Nurita Apridiana
Published: March 2020

Arguments are one of the important purposes in the modern era of learning because it is the basic step to promote student’s critical thinking process and science literature. This research aims to describe and analyse scientific argumentation profile of earthquake of non-science undergraduate student in Universitas Negeri Surabaya. This research uses a qualitative descriptive with the subject of research is 37 first-year non-science students from Universitas Negeri Surabaya. The subject asked to choose the right answer and write their reasons or arguments that support their answer. The results showed that the subject’s ability in providing scientific argument is at the level of providing claims with the support of well warrant.
Identification of Students’ Metacognitive Levels in Physics Learning Viewed from the Problem-Solving Ability
Authors: Yuberti  , Kartika I , Viyanti  , Wulandari H , Anillah
Published: March 2020

This study aimed to look at the level of physics problem-solving ability achieved by students and identify the level of metacognition based on the ability to solve physics problems at each level. The research method used was a mixed method with a sequential explanatory strategy. The populations in this study were all eleventh-grade science students of Kebumen Islamic High School, Tanggamus District. The sampling technique used was a balanced sample with a participant selection model. The instruments used in this study were the physics tests, interviews, and documentation. The data analysis process included two stages of analysis, namely quantitative data analysis and qualitative data analysis. The results of this study indicated that 12.12% of students belong to the high problem-solving group, 66.67% of students belong to the moderate problem-solving group, and 21.21% of students belong to the low problem-solving group. The high problem-solving group had a high level of metacognition, namely Semi-reflective use with a percentage of 10% and Strategic use with a percentage of 10%. The moderate problem-solving group had Semi-strategic use level with a percentage of 40% and Aware use with a percentage of 20%. The low problem-solving group had the lowest metacognition level, namely Tacit use with a percentage of 20% of the total sample taken. so, the levels of metacognition ability of students in learning physics identified in this study were: tacit use, aware use, semi strategic use, strategic use, and semi-reflective use.
Improving Students’ Science Process Skills and Critical Thinking Skills in Physics Learning through FERA Learning Model with SAVIR Approach
Authors: Diani Rahma , Latifah Sri , Jamaluddin Wan , Pramesti Ardya , Susilowati Nur Endah , Diansah Irani
Published: March 2020

This study aimed to determine the effectiveness of FERA learning model (Focus, Explore, Reflect and Apply) with SAVIR approach in improving students’ science process skills and critical thinking skills in physics learning. The method used in this research was Quasi-Experiment with non-equivalent control group design. The subject of this research was students in one of the senior high schools in Lampung District. MANOVA test (Multivariate of Variance) in SPSS 20 was used as a hypothesis test. The analysis result showed that there were differences in science process skills and critical thinking skills between the experimental class and the control class. The effectiveness of FERA learning model with SAVIR approach in improving students’ science process skills and critical thinking skills in physics learning was tested by Effect Size test. The results showed that FERA learning model with SAVIR approach was more effective in improving students’ science process skills and critical thinking skills than using discovery learning model.
Remote Control Caras Physics Teaching Aids by Utilizing Recycled Wastes
Authors: Dermawan Oki , Ayu Sovia Mas , Junaidah  , Meisuri  , Defriyanto  , Indriyani Rosa
Published: March 2020

This study aimed to determine the feasibility of a simple remote control car by utilizing recycled waste and to know the responses of students regarding the developed remote control car. This study used a research and development (R&D) method proposed by Borg & Gall adapted from Sugiyono’s development model. The data of this study were obtained from the teacher’s questionnaire and students’ responses, material expert validation, and media expert validation. The type of data generated is qualitative data that was analyzed based on the assessment criteria to determine the product’s quality. The score obtained from the material expert is 80.59%, the score obtained from the media expert is 92.92%, the score from the teachers of three schools is 88.33%, and the score from the students in all schools is 82.50%. Based on the assessment of the material experts, the media experts, and the teachers, it can be concluded that the remote control car as physics teaching aids using recycled wastes suitable to be used as teaching aids.
Identifying K-10 Students’ Learning Difficulties on Learning Kepler’s Law using Worksheet: Is It Worth?
Authors: Setyadin A H , Suryana T G S , Utari S , Efendi R , Liliawati W , Utama J A
Published: March 2020

This study set out to identify K-10 students’ learning difficult when they learn about Kepler’s Law. The research method utilized in this study was the single-intrinsic case study. The subject of this study was 19 students of one of a private school in Cianjur, Indonesia that consist of 12 females and 7 males from people with a background were mostly merchant. Students’ worksheet was used to identify students’ learning obstacles. Through the qualitative analysis of student answers to student worksheets, it can be found that students’ learning difficulties when learning Kepler Laws in the form: 1) understand the physical meaning of First Kepler’s law, 2) identify and discover the relationship of physical quantities that work planets when interacting with the sun, 3) perform mathematical operations to derivate the Kepler’s third law equation and apply it in some cases. Through this analysis, we can identify K-10 grade students’ learning difficulties when learning Kepler’s Laws.
Developing an Android-Based Test on Colligative Properties of Solution
Authors: Sari S , Nuralam R , Subarkah C Z
Published: March 2020

Android-based tests in chemistry are still limited and few in development. This research has been carried out to describe the result of developing an Android-based test on the colligative properties of the solution. The method used in this research was descriptive qualitative. The product/application was created using the Android Studio application (in the.apk format) and can be used on smartphones. Moreover, its details are described, including every visual appearance. The application is interesting, easy to use, can be accessed offline and visualizes animated videos so that it can be used to measure student’s ability to explain the colligative properties.
Design of Computer-Based Testing for Higher-order Thinking Skills on Static Fluid Material
Authors: Pratiwi Diah Eka , Suyatna Agus , Viyanti V
Published: March 2020

The purpose of this study is to develop a Computer Based Test (CBT) design model that is suitable for stimulating students’ higher-order thinking skills (HOTS) on static fluid material. The development of CBT-HOTS is used as a practice (drill) which is expected to be able to familiarize students in working on computer-based questions. The design of this study is guided by the ADDIE instructional development model with 5 stages of development, namely: the analysis phase, the initial product design stage, the development stage, the product implementation stage, and the product evaluation stage (evaluation). This article only reported up to the design analysis and design stages. Data collection used was a questionnaire collected from 12 high school physics teachers in Lampung Province. The data analysis used was descriptive qualitative analysis. The results of this study were the design of the CBT model that is suitable for stimulating students’ HOTS according to the needs in the field. The designs that were developed include the design of the illustration problems, the design of the quiz settings, the design of the questioning settings, and the design of the stimulus for several types of questions namely fill in the blank, matching, and sequence.
The Effect Size Test of Talking Stick Learning Model on Students’ critical thinking skills
Authors: Ifrianti Syofnidah , Shawmi Ayu Nur , Asiah Nur , Asyhari Ardian , Putri Livia , Komikesari Happy
Published: March 2020

The backgrounds of this study are students can increase concentration when learning through talking stick, students have a low category in critical thinking skills, and students become passive because learning is only focused on the teacher. This study aimed to determine the effectiveness of the Talking Stick learning model on the critical thinking skills of the tenth-grade students of SMA N Trimurjo 1. This research was quasi-experimental. The population of this study was all tenth-grade students of SMA N 1 Trimurjo. The sampling technique used was purposive. The samples of this study were 2 classes, they were class X.Mipa1 as the experimental class and class X.Mipa2 as the Control class. The instrument used in this study was students’ critical thinking skills test in the form of essay questions applied in the pretest and posttest. The hypothetical test used was the t-test with a significance level of 0.05%. Previously, the prerequisite tests were done to verify the normality and homogeneity of the tests. Based on the results of the hypothetical test, the result shows that tobserved>tcritical is equal to 1.86 > 1.67. The effectiveness of the Talking Stick model can be determined by the effect size test with the obtained value of 0.3 in the medium category. It can be concluded that Ha is accepted. It means that the Talking Stick learning model is effective for students’ critical thinking skills.
Identification of Phytoplankton That Causes Harmful Algae Blooms (Habs) in The Hurun Bay Water
Authors: Pawhestri S W , Nurdevita R , Saputri D A , Winandari O P
Published: March 2020

This study aimed to determine the abundance of phytoplankton and determine the type of phytoplankton that has the potential to cause Harmful Algae Blooms (HABs) in the waters of the Hurun Bay, and analyze the water quality in the Hurun Bay with physical, chemical and biological parameters. The results of this study are expected to be a source of information regarding the diversity of phytoplankton and water quality in Hurun Bay so that HABs can be prevented. Phytoplankton sampling was carried out in February 2018 at three observation stations (floating net cages, floating fish cage and docks) with sampling using the plankton net. The results of this study detected 9 genus of potentially dangerous phytoplankton (HABs) namely Chaetoceros (46,097 cells/L), Bacteriastrum (1,011 cells/L), Nitzschia (1,295 cells/L), Pseudo-nitzschia (598 cells/L), Pyrodinium (1,011 cells/L) 624 cells/L), Alexandrium (431 cells/L), Prorocentrum (836 cells/L) Skeletonema (615 cells/L), and Protoperidinium (640 cells/L). Based on the results of the correlation analysis it was concluded that the parameters that have a strong relationship and affect the abundance of phytoplankton (HABs and Non-HABs) are pH (p <0.01) with the strength of a strong and positive relationship.
Thinking Aloud Pair Problem Solving (TAPPS) Method: The Effect of Understanding Physics Concepts and Communication in High Schools in Indonesia
Authors: Rofiqah Siti Anisatur , Widayanti  , Rozaqi Ahmad
Published: March 2020

The purpose of this research is to improve the understanding of scientific concepts and communication of high school students in Indonesia. The method used in this research is quasi experiment method with the pre-test and post-test. Subjects of the research were obtained from random cluster sampling with 60 students. The experimental class was given treatment of the Thinking Aloud Pair Problem Solving method and the control class was given the treatment of the discussion method. The results of this study indicate an increase between the pre-test and post-test understanding of concepts and scientific communication both in the experimental class and the control class. However, the experimental class experienced more significant escalation with an effect size value of 0.3 in the medium category. The further research need to be applied the use of Thinking Aloud Pair Problem Solving method in more than one class to see the consistency of Thinking Aloud Pair Problem Solving method in improving students’ understanding of concepts and scientific communication.
Spirit of Mathematics Critical Thinking Skills (CTS)
Authors: Syafril S , Aini N R , Netriwati  , Pahrudin A , Yaumas N E , Engkizar
Published: March 2020

The mathematical critical-thinking skill is a process of thinking systematically to develop logical and critical thinking on mathematical problems, which characterize and demand to learn in the 21st century. This conceptual paper aims to analyze the spirit of critical thinking skill, and various approaches that can be applied in mathematics learning. Based on the analysis of several theories and research findings from various countries in the world, it can be concluded that the mathematical critical-thinking skill is very important for students, too; (i) help rational thinking in making decisions to express an idea, (ii) dare to make conclusions with alternative logical thinking, and (iii) able to examine and disregard various complex problems in learning Mathematics. Indeed, mathematics learning does not occur, if the learning process has not demonstrated the spirit of developing mathematical critical thinking skills.
Implementation of STEM Approach Based on Project-based Learning to Improve Creative Thinking Skills of High School Students in Physics
Authors: Widyasmah M , Abdurrahman  , Herlina K
Published: March 2020

Indonesia continues to improve the quality of education, especially in science learning. Science learning in Indonesia is not oriented yet towards improving 21st-century skills. Therefore, to develop science learning, it is necessary to improve the process thinking skills to release the potential that students have about creative thinking solutions that can be used to apply the STEM (Science, Technology, Engineering, and Mathematics) learning approach. Based on the results of preliminary research, the researchers focused this research on the implementation of the STEM approach which is oriented towards project-based learning to enhance student’s creative thinking. This research was conducted to find out the improvement of students’ creative thinking skills by applying a STEM approach oriented to project-based learning on Pascal’s law material. This research was conducted at SMAN 1 Blambangan Umpu in the first semester of the 2019/2020 academic year. The results of the study represent that the application of the STEM learning approach to pascal’s law has increased the creative thinking skills at a significant level of 0,000 and there are differences in the increase in students’ creative thinking skills before and after the application of the STEM learning approach.
Advance Organizer Model in Physics Learning: Effect Size Test on Learning Activities and Students’ Conceptual understanding
Authors: Thahir Andi , Diani Rahma , Permana Deby
Published: March 2020

This study aims to determine the effectiveness of the Advance Organizer learning model on learning activities and students’ conceptual understanding in learning physics. The research method used is a quasi-experimental design with a non-equivalent control group design. The population of this research was the tenth-grade nursing major students of SMK N 7 Bandar Lampung. The sampling technique used was purposive sampling. The instruments employed in this research were the non-test observation questionnaire to measure the students’ activity and test in the form of a Three-Tier Diagnostic test to measure students’ conceptual understanding. Data obtained were analyzed using the multivariate test (MANOVA). The Advance Organizer learning model is more effective in increasing learning activities and students’ conceptual understanding. It is indicated by the value of the effect size of learning activities which is 0.718 and the effect size of the conceptual understanding which is 0.392 in the medium category. Based on the results of the MANOVA test, the significance value of learning activities and conceptual understanding is less than 0.05 (sig <0.05), so it can be concluded that there is an influence of Advance Organizer learning model toward the learning activities and students’ conceptual understanding in physics learning.
Origin of the mid-temperature transition in vinylidenefluoride-based ferro-, pyro- and piezoelectric homo-, co- and ter-polymers
Authors: Venkatesan Thulasinath Raman , Gerhard Reimund
Published: March 2020

The existence of an intermediate transition between the glass and the Curie/melting temperatures in Poly(vinylidene fluoride) (PVDF) and some of its co- and ter-polymers has been reported by several authors. In spite (or because?) of various different explanations in the literature, the origins of the transition are still not clear. Here, we try to understand the extra transition in more detail and study it with thermal and dielectric methods on PVDF, on its co-polymers with trifluoroethylene (P(VDF-TrFE)) and tetrafluoroethylene (P(VDF-TFE)), and on its ter-polymer with trifluoroethylene and chlorofluoroethylene (P(VDF-TrFE-CFE). Based on interpretations from the literature and our experimental studies, we propose the new hypothesis that the intermediate transition should have several interrelated origins. Especially since the relevant range is not far above room temperature, better understanding and control of their properties may also have practical implications for the use of the respective polymer materials in devices.
Modeling Missing Cases and Transmission Links in Networks of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa
Authors: Nelson Kristin N , Gandhi Neel R , Mathema Barun , Lopman Benjamin A , Brust James C M , Auld Sara C , Ismail Nazir , Omar Shaheed Vally , Brown Tyler S , Allana Salim , Campbell Angie , Moodley Pravi , Mlisana Koleka , Shah N Sarita , Jenness Samuel M
Published: March 2020

Patterns of transmission of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases worldwide in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa, diagnosed in 2011–2014. We tested scenarios in which cases were missing at random, missing differentially by clinical characteristics, or missing differentially by transmission (i.e., cases with many links were under- or oversampled). Under the assumption that cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases, and models provided evidence for super-spreading. To our knowledge, this is the first analysis to have assessed support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving super-spreading.
Motives and Fiduciary Loyalty
Authors: Galoob* Stephen R , Leib* Ethan J
Published: March 2020

How, if at all, do motives matter to loyalty? We have argued that loyalty (and the duty of loyalty in fiduciary law) has a cognitive dimension. This kind of “cognitivist” account invites the counterargument that, because most commercial fiduciary relationships involve financial considerations, purity of motive cannot be central to loyalty in the fiduciary context. We contend that this counterargument depends on a flawed understanding of the significance of motive to loyalty. We defend a view of the importance of motivation to loyalty that we call the compatibility account. On this view, A acts loyally toward B only if A’s motives are compatible with A’s robustly assigning non-derivative significance to the interests of B. We show that the compatibility account describes the motivational structure of fiduciary loyalty and of loyalty as such. This account provides a realistic picture of motivation and helps respond to two broader criticisms of cognitivism: first, that attributing significance to motivation is paradoxical; second, that attributing significance to motive would make fiduciary law impossible to administer. We also show that the compatibility account can help explain features of ineffective assistance of counsel jurisprudence under the Sixth Amendment to the U.S. Constitution, which draws on the lawyer’s duty of loyalty toward the client.
Nodal is required to maintain the uterine environment in an anti-inflammatory state during pregnancy†
Authors: Ayash Taghreed A , Starr Lisa M , Dufort Daniel
Published: March 2020

Preterm birth remains the major cause of perinatal mortality and morbidity worldwide, affecting up to 12% of pregnancies and accounting for ~75% of neonatal deaths. However, the mechanisms and causes that underlie it are still largely unknown. One of the major causes of preterm birth is infection or inflammation within the maternal–fetal interface. Our lab has previously shown that a uterine specific deletion of Nodal results in mutant females delivering 2 days prior to term demonstrating an important role for this factor in the maintenance of pregnancy. Here, we have addressed the function of Nodal in the uterus during pregnancy. We demonstrate that Nodal heterozygous mice have an increase in basal levels of pro-inflammatory cytokines IL-1β, IL-6, IL-12p, TNF-α, and IFN-γ as well as an increase in the number of macrophages in response to the inflammatory agent, lipopolysaccharide (LPS). Using bone marrow-derived macrophages, we demonstrated that pretreatment with recombinant Nodal reduces pro-inflammatory gene expression when these cells are challenged with LPS. Our results demonstrate that Nodal is required to maintain the uterine environment in an anti-inflammatory state by preventing proinflammatory cytokine expression.
Rise of the rabbit model for implantation research. A commemoration of the scientific work of Bent G. Boving (1920–2019)
Authors: Denker Hans-Werner
Published: March 2020

Bent G. Boving, a remarkable pioneer of research on mechanistic aspects of embryo implantation and specifically of using the rabbit model for this purpose, passed away peacefully on 15 November 2019, not long before he would have been able to celebrate his 100th birthday on 23 February 2020. His work has been very stimulating for other researchers, in part possibly because it elicited controversial discussions. This article attempts to give an overview of his scientific contributions, which still harbor some treasures, including potentially stimulating ideas for future research on implantation.
Demystifying a class of multiply robust estimators
Authors: Li Wei , Gu Yuwen , Liu Lan
Published: March 2020

For estimating the population mean of a response variable subject to ignorable missingness, a new class of methods, called multiply robust procedures, has been proposed. The advantage of multiply robust procedures over the traditional doubly robust methods is that they permit the use of multiple candidate models for both the propensity score and the outcome regression, and they are consistent if any one of the multiple models is correctly specified, a property termed multiple robustness. This paper shows that, somewhat surprisingly, multiply robust estimators are special cases of doubly robust estimators, where the final propensity score and outcome regression models are certain combinations of the candidate models. To further improve model specifications in the doubly robust estimators, we adapt a model mixing procedure as an alternative method for combining multiple candidate models. We show that multiple robustness and asymptotic normality can also be achieved by our mixing-based doubly robust estimator. Moreover, our estimator and its theoretical properties are not confined to parametric models. Numerical examples demonstrate that the proposed estimator is comparable to and can even outperform existing multiply robust estimators.
Molecular data reveal hidden diversity in the central Andean speciesWeberbauera spathulifolia(Thelypodieae: Brassicaceae)
Authors: Salariato Diego L , Trinidad Huber , Cano Asunción , Zuloaga Fernando O , Al-Shehbaz Ihsan A
Published: March 2020

Weberbauera (Brassicaceae, tribe Thelypodieae) comprises 18 species distributed along the central Andes of Argentina, Bolivia, Chile and Peru. Of these species, W. spathulifolia has the largest geographical range in the genus, extending c. 3000 km along the Andean highlands from La Rioja Province in Argentina to Ancash Department in Peru. This species also shows the greatest morphological variation in the genus. However, whether this geographical and morphological variation represents one or more lineages remains unclear. In this study, we analyse W. spathulifolia across its entire distribution range using molecular, morphological and ecological data. Because there is no phylogenetic analysis for the genus, we generated a comprehensive molecular sampling using nuclear (ITS) and plastid (trnL-F and trnH-psbA) sequences for other Weberbauera spp. and representatives of South American Thelypodieae. Results support the presence of two different lineages within W. spathulifolia, one in the northern part of the species range and the other distributed across its southern and central range. In addition to the morphological differences and the allopatric distribution, these lineages also differ in their climatic niches. Therefore, we propose here to retain the northern lineage under W. spathulifolia and to treat the southern-central lineage under W. orophila, comb. nov. Phylogenetic placement of Weberbauera spp. among the South American Thelypodieae is also analysed and discussed. Results of this study contribute to understanding the biodiversity and evolution of the Andean Brassicaceae.
Arginine is a disease modifier for polyQ disease models that stabilizes polyQ protein conformation
Authors: Minakawa Eiko N , Popiel Helena Akiko , Tada Masayoshi , Takahashi Toshiaki , Yamane Hiroshi , Saitoh Yuji , Takahashi Yasuo , Ozawa Daisaku , Takeda Akiko , Takeuchi Toshihide , Okamoto Yuma , Yamamoto Kazuhiro , Suzuki Mari , Fujita Hiromi , Ito Chiyomi , Yagihara Hiroko , Saito Yuko , Watase Kei , Adachi Hiroaki , Katsuno Masahisa , Mochizuki Hideki , Shiraki Kentaro , Sobue Gen , Toda Tatsushi , Wada Keiji , Onodera Osamu , Nagai Yoshitaka
Published: March 2020

The polyglutamine (polyQ) diseases are a group of inherited neurodegenerative diseases that include Huntington’s disease, various spinocerebellar ataxias, spinal and bulbar muscular atrophy, and dentatorubral pallidoluysian atrophy. They are caused by the abnormal expansion of a CAG repeat coding for the polyQ stretch in the causative gene of each disease. The expanded polyQ stretches trigger abnormal β-sheet conformational transition and oligomerization followed by aggregation of the polyQ proteins in the affected neurons, leading to neuronal toxicity and neurodegeneration. Disease-modifying therapies that attenuate both symptoms and molecular pathogenesis of polyQ diseases remain an unmet clinical need. Here we identified arginine, a chemical chaperone that facilitates proper protein folding, as a novel compound that targets the upstream processes of polyQ protein aggregation by stabilizing the polyQ protein conformation. We first screened representative chemical chaperones using an in vitro polyQ aggregation assay, and identified arginine as a potent polyQ aggregation inhibitor. Our in vitro and cellular assays revealed that arginine exerts its anti-aggregation property by inhibiting the toxic β-sheet conformational transition and oligomerization of polyQ proteins before the formation of insoluble aggregates. Arginine exhibited therapeutic effects on neurological symptoms and protein aggregation pathology in Caenorhabditis elegans, Drosophila, and two different mouse models of polyQ diseases. Arginine was also effective in a polyQ mouse model when administered after symptom onset. As arginine has been safely used for urea cycle defects and for mitochondrial myopathy, encephalopathy, lactic acid and stroke syndrome patients, and efficiently crosses the blood–brain barrier, a drug-repositioning approach for arginine would enable prompt clinical application as a promising disease-modifier drug for the polyQ diseases.
Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury
Authors: Wang Xingxing , Zhou Tianna , Maynard George D , Terse Pramod S , Cafferty William B , Kocsis Jeffery D , Strittmatter Stephen M
Published: March 2020

After CNS trauma such as spinal cord injury, the ability of surviving neural elements to sprout axons, reorganize neural networks and support recovery of function is severely restricted, contributing to chronic neurological deficits. Among limitations on neural recovery are myelin-associated inhibitors functioning as ligands for neuronal Nogo receptor 1 (NgR1). A soluble decoy (NgR1-Fc, AXER-204) blocks these ligands and provides a means to promote recovery of function in multiple preclinical rodent models of spinal cord injury. However, the safety and efficacy of this reagent in non-human primate spinal cord injury and its toxicological profile have not been described. Here, we provide evidence that chronic intrathecal and intravenous administration of NgR1-Fc to cynomolgus monkey and to rat are without evident toxicity at doses of 20 mg and greater every other day (≥2.0 mg/kg/day), and far greater than the projected human dose. Adult female African green monkeys underwent right C5/6 lateral hemisection with evidence of persistent disuse of the right forelimb during feeding and right hindlimb during locomotion. At 1 month post-injury, the animals were randomized to treatment with vehicle (n = 6) or 0.10–0.17 mg/kg/day of NgR1-Fc (n = 8) delivered via intrathecal lumbar catheter and osmotic minipump for 4 months. One animal was removed from the study because of surgical complications of the catheter, but no treatment-related adverse events were noted in either group. Animal behaviour was evaluated at 6–7 months post-injury, i.e. 1–2 months after treatment cessation. The use of the impaired forelimb during spontaneous feeding and the impaired hindlimb during locomotion were both significantly greater in the treatment group. Tissue collected at 7–12 months post-injury showed no significant differences in lesion size, fibrotic scar, gliosis or neuroinflammation between groups. Serotoninergic raphespinal fibres below the lesion showed no deficit, with equal density on the lesioned and intact side below the level of the injury in both groups. Corticospinal axons traced from biotin-dextran-amine injections in the left motor cortex were equally labelled across groups and reduced caudal to the injury. The NgR1-Fc group tissue exhibited a significant 2–3-fold increased corticospinal axon density in the cervical cord below the level of the injury relative to the vehicle group. The data show that NgR1-Fc does not have preclinical toxicological issues in healthy animals or safety concerns in spinal cord injury animals. Thus, it presents as a potential therapeutic for spinal cord injury with evidence for behavioural improvement and growth of injured pathways in non-human primate spinal cord injury.
Masking the Detection of Taste Stimuli in Rats: NaCl and Sucrose
Authors: Blonde Ginger D , Spector Alan C
Published: March 2020

While psychophysical and neurophysiological assessments of taste sensitivity to single chemical compounds have revealed some fundamental properties of gustatory processing, taste stimuli are rarely ingested in isolation. Arguably, the gustatory system was adapted to identify and report the presence of numerous chemicals ingested concurrently. To begin systematically exploring the detectability of a target stimulus in a background in rodents, we used a gustometer to train rats in a 2-response operant task to detect either NaCl (n = 8) or sucrose (n = 8) dissolved in water, and then tested the sensitivity of rats to the trained NaCl stimulus dissolved in a sucrose masker (0.3, 0.6, or 1.0 M, tested consecutively) versus sucrose, or the trained sucrose stimulus dissolved in a NaCl masker (0.04, 0.2, or 0.4 M) versus NaCl. Detection thresholds (EC50 values) were determined for the target stimulus dissolved in each concentration of the masker. Except for 0.04 M NaCl, all masker concentrations tested increased the target stimulus EC50. Target stimulus detectability decreased systematically as masker concentrations increased. The shift in liminal sensitivity for either target was similar when the threshold for the masker was considered. At least for these prototypical stimuli, it appears that the attenuating impact of a masker on the detection of a target stimulus depends on sensitivity to the masking stimulus. Further study will be required to generalize these results and extend them to more complex maskers, and to discern neural circuits involved in the detection of specific taste signals in the context of noisy backgrounds.
Epidemiology of Escherichia coli Bacteremia: A Systematic Literature Review
Authors: Bonten Marc , Johnson James R , van den Biggelaar Anita H J , Georgalis Leonidas , Geurtsen Jeroen , de Palacios Patricia Ibarra , Gravenstein Stefan , Verstraeten Thomas , Hermans Peter , Poolman Jan T
Published: March 2020

Background

Escherichia coli is the most common cause of bacteremia in high-income countries. To enable the development and implementation of effective prevention strategies, a better understanding of the current epidemiology of invasive E. coli infections is needed.

Methods

A systematic review of literature published between 1 January 2007 and 31 March 2018 on the burden and epidemiology of E. coli bacteremia in populations that include adults in high-income countries was conducted. Meta-analysis was performed for descriptive purposes.

Results

During the studied time interval, the estimated incidence rate of E. coli bacteremia was 48 per 100 000 person-years, but this increased considerably with age: rates per 100 000 person-years were >100 in 55-to-75-year-olds and >300 in 75-to-85-year-olds. Overall, E. coli accounted for 27% of documented bacteremia episodes: 18% if hospital acquired, 32% if community-onset healthcare associated, and 33% if community acquired. The estimated case fatality rate was 12%. Approximately 44% of episodes were community acquired, 27% community-onset healthcare associated, and 27% hospital acquired. Urinary tract infection (UTI) was the primary source for 53% of episodes.

Conclusions

This systematic review confirms the substantial burden of E. coli bacteremia in older adults and justifies the implementation of community-level programs to prevent E. coli bacteremia and ideally UTI in this age group.
Gavi Support for Typhoid Conjugate Vaccines: Moving From Global Investments to Country Introduction
Authors: Soble Adam , Patel Zeenat , Sosler Stephen , Hampton Lee , Johnson Hope
Published: March 2020

Nine years elapsed between Gavi’s investment decision to support typhoid conjugate vaccines (TCVs) in 2008 and Gavi support becoming available for countries to introduce TCV. The protracted path toward Gavi support for TCV highlights the challenges of vaccine development for lower-income countries and the importance of Gavi engagement as early as possible in product development processes to support the alignment of manufacturing, global policy, and program implementation. Early engagement would provide inputs to inform strategic vaccine investment decisions that transition more efficiently toward country implementation. Several countries have been approved for Gavi support to introduce TCV in 2019–2020. The paucity of generalizable typhoid epidemiological data in early introducing countries has reinforced the need for continued evidence generation regarding typhoid epidemiology and TCV impact. This has led to the development of guidance and tools to support country decision making for TCV introduction based on enhanced understanding of local typhoid burden and risk.
Typhoid Conjugate Vaccines and Enteric Fever Control: Where to Next?
Authors: Steele A Duncan , Carey Megan E , Kumar Supriya , MacLennan Calman A , Ma Lyou-Fu , Diaz Zoey , Zaidi Anita K M
Published: March 2020

After the unprecedented success and acceleration of the global agenda towards typhoid fever control with a strong World Health Organization recommendation and the approval of funding from Gavi, the Vaccine Alliance (Gavi), for the use of a new typhoid conjugate vaccine (TCV), we should turn our minds to the challenges that remain ahead. Despite the evidence showing the safety and clinical efficacy of TCV in endemic populations in developing countries, we should remain vigilant and explore hurdles for the full public health impact of TCV, including vaccine supply for the potential global demand, immunization strategies to optimize the effectiveness and long-term protection provided by the vaccines, potential use of TCV in outbreak settings, and scenarios for addressing chronic carriers. Finally, challenges face endemic countries with poor surveillance systems concerning awareness of the need for TCV and the extent of the issue across their populations, and how to target immunization strategies appropriately.
The Late Arrival of Coronavirus Disease 2019 (COVID-19) in Africa: Mitigating Pan-continental Spread
Authors: Nachega Jean , Seydi Moussa , Zumla Alimuddin
Published: March 2020

The novel coronavirus disease 2019 (COVID-19) has rapidly spread to all 7 continents. Due to yet unknown reasons, the African continent has remained relatively unaffected. We discuss the importance of mitigating pan-continental spread in light of the fragile healthcare systems.
In vitro elimination of anti-infective drugs by the Seraph® 100 Microbind® affinity blood filter
Authors: Schmidt Julius J , Eden Gabriele , Seffer Malin-Theres , Winkler Manuela , Kielstein Jan T
Published: March 2020

Background

In August 2019, the European Union licensed the first ever haemoperfusion device aimed to reduce pathogens in the blood. The core of the adsorber consists of ultra-high molecular weight polyethylene beads with endpoint-attached heparin. These beads utilize pathogen inherent adhesion mechanisms to reduce pathogen load. So far, it is unknown whether the device has an effect on anti-infective drug concentrations. The aim of this study was to investigate the in vitro adsorption of multiple anti-infective drugs from human plasma.

Methods

In this in vitro study, 18 anti-infective drugs were administered to human donor plasma and pumped through the heparin-coated pathogen adsorber (Seraph® 100 Microbind®Affinity Blood Filter; ExThera Medical Corp., Martinez, CA, USA) at a plasma flow rate of 250 mL/min for 60 min. Pre- and post-adsorber plasma samples were quantified after 5, 15, 30 and 60 min.

Results

We found a reduction ratio (RR) in anti-infective plasma levels between −1% and 62%. This decrease occurred mainly in the first 5 min of the experiment (RR0–5 −4 to 62%). Mean plasma clearance rates ranged between –11.93 mL/min (fluconazole) and 4.86 mL/min (clindamycin). The highest RRs were measured for aminoglycosides (tobramycin 62% and gentamycin 59%).

Conclusions

The elimination of anti-infective drugs by the Seraph is neglectable in all but 2 of 18 of the investigated substances. Aminoglycosides may be adsorbed by the device during their first pass.