bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECTIVENESS OF IMPLEMENTING INQUIRY ACTIVITIES INTO THE TEACHING PROCESS IN THE PHASE OF REVISING AND DEEPENING THE LEARNING CONTENT
Authors:   Pavol Jozef Šafárik University in Košice, Slovak Republic, Sotáková Ivana , Ganajová Mária ,   Pavol Jozef Šafárik University in Košice, Slovak Republic, Babinčáková Mária ,   Pavol Jozef Šafárik University in Košice, Slovak Republic
Published: September 2021

The aim of research was to verify the effectiveness of implementing the inquiry-based teaching (IBT) into the teaching process of chemistry in secondary school in the phase of revising and deepening the previous-year learning content. The results of the research confirmed a significant difference on the level of knowledge and skills between the experimental group students (N=143) where the IBT was implemented and the control group students (N=149) where traditional teaching methods were implied. Keywords: changes in chemical reactions, inquiry-based teaching, learning content, secondary school students.
PILOTING MULTIDISCIPLINARY FIELDWORK PROJECT “FOREST”
Authors:   University of Latvia, Riga, Latvia, Bertule Dace , Burgmanis Girts ,   University of Latvia, Riga, Latvia, Namsone Dace ,   University of Latvia, Riga, Latvia
Published: September 2021

In Latvia, a new curriculum is introduced to provide the opportunity to acquire skills in multidisciplinary context. To achieve that, schools need to implement projects. In this paper, one example of a multidisciplinary project where fieldwork is involved is described. The aim of the research was to create support materials for teachers and students based on practice to experience multidisciplinary fieldwork to develop competencies. In the end, thirteen different support materials for teachers and students were piloted. Keywords: multidisciplinary fieldwork, fieldwork project, school practice.
HIGHER ORDER THINKING TASK AND QUESTION APPLICATION IN THE WORLD COGNITION LESSONS IN PRIMARY FORMS
Authors:   Vytautas Magnus University, Lithuania  Vilnius University, Lithuania, Venskuvienė Nadia
Published: September 2021

Recently, one has become concerned about the quality of natural science and social education basics of the primary school students. Particular attention is devoted to the higher-order thinking ability education. In the qualitative research, it was analysed what higher order thinking questions and tasks primary school teachers apply in the world cognition lessons. Research data were gathered using a lesson observation method. The gathered data were analysed making a technical picture. Research results showed that primary school teachers proportionally applied lower and higher-order thinking questions and tasks. Keywords: world cognition lessons, higher order thinking abilities, primary education.
EXAMINING THE PSYCHOMETRIC PROPERTIES OF A MALAYSIAN RELEVANCE OF SCIENCE EDUCATION (MROSE) QUESTIONNAIRE USING PARTIAL LEAST SQUARES STRUCTURAL EQUATION MODELING (PLS-SEM)
Authors:   University Malaysia Sabah, Malaysia, Fah Lay Yoon , Thoe Ng Khar ,   SEAMEO RECSAM, Malaysia, Hoon Khoo Chwee ,   Teacher Education Institute Kent Campus, Malaysia, Hwui Chan Sane ,   Kian Kok Middle School, Malaysia
Published: September 2021

This research is aimed to validate an instrument, the Malaysian version of ROSE or MROSE to gauge Malaysian secondary students’ interests, attitudes, values, and priorities in S&T-related issues. Partial Least Squares-Structural Equation Modeling approach was used to evaluate the validity and reliability of the instrument. The internal consistency reliability (composite reliability and Cronbach’s Alpha coefficient), convergent validity (Average Variance Extracted), and discriminant validity (cross loadings, Fornell-Larcker criterion, and Heterotrait-Monotrait ratio) for each individual item of the instrument were being assessed. Keywords: affective factor, PLS-SEM, science and technology, relevance of science education (ROSE).
METACOGNITIVE MODEL FOR DEVELOPING SCIENCE, TECHNOLOGY AND ENGINEERING FUNCTIONAL LITERACY
Authors:   University of Maribor, Slovenia, Kordigel Aberšek Metka , Cencel Zvonka ,   Primary School Vransko-Tabor, Slovenia, Aberšek Boris ,   University of Maribor, Slovenia, Flogie Andrej ,   University of Maribor, Slovenia
Published: September 2021

Technology and engineering functional literacy should be intentionally developed in the school system – like any other competence, it does not develop spontaneously. For this purpose, a didactic model, the Metacognitive model for developing technology and engineering literacy (McM_T&E), was developed, implemented and evaluated. The results of evaluation show that focusing on technology and engineering literacy in Technology and Engineering classes using the McM_T&E model increases students' technology and engineering functional literacy. Keywords: functional literacy, metacognitive model, science functional literacy, technology and engineering functional literacy.
Psicosis en el embarazo y posparto, manejo actual. Revision bibliografica
Authors: Salazar Flores Diana Estefania , Salazar Flores Juan Carlos , Salazar Robalino Paul Roberto , Suquilanda Toapanta Johanna Estefanía
Published: September 2021

Introducción. La enfermedad mental en un desafío para la medicina, ya que el médico debe confiar en lo que le dice el paciente ya que no hay signos visibles para llegar a un diagnóstico. Es necesario la mejor opción terapéutica para tratar la patología psiquiátrica en torno a la gestación sin con ello perjudicar ni el desarrollo de la misma ni la salud propia de la mujer. De igual manera es poder tener directrices de manejo para las mujeres que desarrollan psicosis en el periodo puerperal  en aras de mantener una adecuada calidad de vida tanto para la madre como para el neonato y sus familias; no se ha establecido un protocolo adecuado de manejo y más aún personalizado para aquellas pacientes gestantes y puérperas que declinan en su estado mental conllevando a establecer una patología psiquiátrica que sin un seguimiento adecuado desencadena en un grave problema de salud. El objetivo principal es reconocer con prontitud los diferentes trastornos de psicosis durante el embarazo y posparto poder dar su tratamiento adecuado, ya que en nuestro medio es muy tomado a la ligera por los profesionales no psiquiátricos e iniciar así una concientización a los médicos generales de la problemática actual de ámbito no orgánico, sino mental de los pacientes. La metodología del presente trabajo investigativo se realiza en torno a revisiones bibliográfica en la literatura médica sobre la repercusión psiquiátrica que se presenta en determinados gestantes así como en madres en periodo puerperal inmediato, mediato y tardío. Resultados. Síndrome de estrés postraumático muestra una prevalencia de 1 %,  aparece entre las 24 y 48 horas después de un parto dificultoso. Depresión del puerperio hay una prevalencia de 50-70 % o incluso 80 % de los nacimientos al tercer día del posparto, pero no suele superar la semana. Depresión posparto entre 10-15 % de las mujeres en los 2- 3 primeros meses luego del parto. Psicosis posparto se presenta en alrededor de 1-2 por cada 1 000 nacimientos, aunque otros autores determinan 3 por cada 1 000.
Numerical Algorithm for Solving General Linear Elliptic Quaternionic Matrix Equations
Authors: EREN Kemal , KÖSAL Hidayet Hüda
Published: September 2021

In this study, we develop a general method to solve the general linear elliptic quaternionic matrix equations by means of real representation of elliptic quaternion matrices. A pseudocode for our approach that provides the solution of the linear elliptic quaternionic matrix equations is expressed. Moreover, we apply this method to the well-known Slyvester matrix equations and Kalman Yakubovich matrix equations over the elliptic quaternion algebra.
Preliminary archaeological studies (surveys) on the project of the bypass road around Berezhany town
Authors: Osaulchuk Oleh , Ilchyshyn Zoya
Published: September 2021

The article offers results of preliminary archaeological investigations, conducted by Scientific Research Center «Rescue Archaeological Service» (Institute of Archaeology, National Academy of Sciences of Ukraine) in 2007 and 2017, prior to the construction project of the bypass road around Berezhany town in Ternopil region. It provides information concerning the newly discovered archeological sites as well as the elaboration of the obtainable data on formerly revealed sites in the surroundings of villages Lisnyky, Lapshyn, Hayok and Hlynovychi.
According to archival and bibliographic data, archaeological surveys were previously conducted in 2006 by the expeditions of Mykhailo Filipchuk and Mykola Bandrivsky nearby villages Lapshyn and Hynovychi. However, the summaries of these surveys are insufficiently published and besides presenting the incoherent results, which cause some confusion in the number of sites.
In 2007, expedition of Rescue Archaeological Service has re-examined the multi-layered settlement Hynovychi I, collecting the items from the Late Paleolithic to the Early Iron Age. Subsequent rescue archeological excavations were carried out in 2008 by the expedition led by Bohdan Salo.
Ancient Rus settlement Hlynovychi III was discovered adjacent to the previous site.
Around the village Lapshyn, additional archeological sites were discovered, namely Lapshyn III, IV, V, and VI, which behold several phases of the region’s inhabitants starting from the Paleolithic and until the Age of Principalities. Materials of Vysotsko and Chernyakhiv cultures are predominant on these sites.
Four groups of barrows were located on the forested hills near village Lisnyky, named therefore Lisnyky I, II, III, and IV. They contain a total of 20 barrows, which could be dated to the Bronze Age.
Altogether, the explorations of 2007 and 2017 has newly discovered or identified ten archaeological sites, including settlements and burrow necropolises. Seven previously known settlement were localized due to the updated information. As a result, the archeological map of the region was significantly supplemented, with the names and numbers of archaeological sites well-coordinated.
Some of the ancient settlements and the barrow groups are located along the route of future bypass road, thus making it necessary to conduct preventive archaeological excavations. The results of intended studies will definitely clarify cultural and chronological identity of these sites.
Key words: archeological surveys, preventive archeological studies, assessments of the impact on the archeological heritage, bypass road around Berezhany town, settlement, barrow group, Paleolithic, Bronze Age, Early Iron Age, Late Antiquity, Vysotsko culture, Chernyakhiv culture, Age of Principalities.
Nitrate levels in drinking water and their impact on the risk of developing gynecological diseases and adverse pregnancy outcomes
Authors: Pergialiotis Vasilios , Loutradis Dimitrios
Published: September 2021

Nitrate is a nitrogen oxoanion formed by loss of a proton from nitric acid. It is an important source of nitrogen which is essential for protein formation. Regular levels of nitrate in the environment do not exceed 2-5 mg/L. Fertilizers, herbicides and pesticides increase, however, the amount of nitrate in drinking water. In 2011 the World Health Organization (WHO) has issued a revised document on nitrate and nitrite levels in drinking water to help establish a common guideline that will help countries. To date, the majority of guidelines on drinking water quality that is directly related to nitrate levels are based in its toxic effect in infants and neonates (primarily the occurrence of methemoglobinemia) and suggest as an arbitrary cut-off the existence of less than 10 mg/L as a measure of safety. Exposure to nitrate levels has been linked to adverse neurodevelopmental effects, fetal malformations and several forms of cancer. However, the associations remain scarce in several fields as the majority of available data is retrieved from articles that investigate the impact of nitrosatable drugs, rather than environmental exposure. In Greece, seven vulnerable regions have been recently identified, following the country`s referral to the Court of Justice by Commission. The aim of the present article is to summarize current evidence and provide recommendations for clinical practice and future research in the field.
High levels of ca125 in a patient with large uterine fibroid.
Authors: Zacharis Konstantinos , Dafopoulos Konstantinos
Published: September 2021

Uterine leiomyomas, also known as uterine fibroids, are the most common benign tumors of the female genital tract and affect 60 to 80% of women at their reproductive age. Although elevated tumor markers may be measured in benign gynaecological diseases, the association of uterine fibroids with increased levels of serum cancer antigen 125 (CA125) has not been proven to date. In the present case report we present a rare case of a 21-year-old Caucasian woman attended to our outpatient department with hypermenorrhea and pelvic discomfort that was treated for an enlarged intra-abdominal mass with an abnormally high CA-12 (777.3 U/mL).
Developing Halal Village Tourism Through Asset Community In Setanggor, Lombok Tengah
Authors: Mahardika Fajar , Indrawati Indrawati
Published: September 2021

Overcoming poverty problem constitutes a part of da’wah bil hal. Moreover, it is a main problem experienced by Moslems in Indonesia. To overcome the problem, the governor of Nusa Tenggara Barat TGB. Muhammad Zainul Majdi pionered Halal Tourist Village through his Governor rule no. 51/2016. The term of Halal Tourist Village constituted a Governor’s attempt in packaging tourism, so that foreign tourists would like to come. Through the rule, Ida Wahyuni Sahabudin, a community development activist, took an innitiative to promote Setanggor Village as one of destinations of Halal Tourist Village. He improved various local assets into attractive tourist spots. This study described the roles of community assets in developing community of Halal Tourist Village of Setanggor. This study used library research method and a concept approach of community assets. The result of this study indicated that that those various assets came with different roles and all of them were integrated in the tourism of Setanggor Village to overcome the poverty problem there.
Abu Ishaq Al-Syathibi and His Perspective on Maslahat
Authors: Ikhsan Muhammad , Iskandar Azwar
Published: September 2021

This study aims to find out: (i) the position of Abu Ishaq al-Syathibi as a fiqh scholar al-maqāṣid; and (ii) the concept of maslahat in the perspective of Abu Isha al-Syathibi.  This research is qualitative descriptive research with library research techniques through historical and sociological approach. The results found that al-Syathibi's ability as a reformer in the realm of uṣūl al-fiqh was very clear in his role in performing new formulations of the theory of al-maqāṣid and managed to open the views of the scholars afterwards to further examine this issue. Al-Shatibi's view of maslahat cannot be separated from his view of al-maqāṣid, especially when he divides the al-maqāṣid into two major parts: those relating to maqāṣid al-syarī'ah and those relating to maqāṣid al-mukallafīn.
Economic Peace Revisited: Coercion and Democracy
Authors: Walentek Dawid
Published: September 2021

Scholars have argued whether democratic peace also holds in the realm of economic sanctions — whether there is an economic peace. Substantial amounts of evidence have been gathered both for and against economic peace and findings have been extremely sensitive to changes in research design. This article provides a new insight, with the use of the updated TIES data set and improved methodology, into the topic of economic peace. It find that democracies are more likely to issue economic sanctions and that there is no economic peace. In fact, democracies are more likely to sanction one another. The article indicate that lack of economic peace is consistent with the public choice approach to economic sanctions. It also argue that the exercise of power among democracies has been rechannelled to economic coercion.
Reputation or Interaction: What Drives Cooperation on Economic Sanctions?
Authors: Walentek Dawid
Published: September 2021

This article studies cooperation on multilateral economic sanctions. Despite low effectiveness and sanction-busting, multilateral economic sanctions are a popular tool of foreign policy. We explore an instrumental approach to sanctions and develop a game theory framework where sender states face a collective action problem when coordinating multilateral coercion. We indicate that cooperation can be achieved through repeated interactions and reputation. We test empirically the two mechanisms with the TIES data on economic sanctions and adherence to past sanction regimes and the Correlates of War data on membership in International Organisations. Our results indicate that reputation is a strong predictor of cooperation on multilateral economic coercion. The effect of repeated interaction appears conditional on reputation; states with poor reputation mediate its effect through repeated interaction.
Network Pharmacology and Experimental Validation Reveal the Effects of Chidamide Combined With Aspirin on Acute Myeloid Leukemia-Myelodysplastic Syndrome Cells Through PI3K/AKT Pathway
Authors: Liang Simin , Zhou Xiaojia , Cai Duo , Rodrigues-Lima Fernando , Chi Jianxiang , Wang Li
Published: September 2021

Chidamide (CDM), a novel histone deacetylase inhibitor, is currently used for patients with peripheral T-cell lymphoma. Aspirin (ASA), an anti-inflammatory drug, has been shown to exert anticancer activity. Herein, we investigated the effect of CDM combined with ASA on myelodysplastic syndromes-derived acute myeloid leukemia (AML-MDS) cells and explored the underlying mechanism. The putative targets of CDM and ASA were predicted by network pharmacology approach. GO functional and KEGG pathway enrichment analyses were performed by DAVID. Furthermore, experimental validation was conducted by Cell Counting Kit-8 assay, Flow cytometry and Western blotting. Network pharmacology analysis revealed 36 AML-MDS-related overlapping genes that were targets of CDM and ASA, while 10 hub genes were identified by the plug-in cytoHubba in Cytoscape. Pathway enrichment analysis indicated CDM and ASA significantly affected PI3K/AKT signaling pathway. Functional experiments demonstrated that the combination of CDM and ASA had a remarkable synergistic anti-proliferative effect by blocking the cell cycle in G0/G1 phase and inducing apoptosis. Mechanistically, the combination treatment significantly down-regulated the phosphorylation levels of PI3K and AKT. In addition, insulin-like growth factor 1 (IGF-1), an activator of PI3K/AKT pathway, reversed the effects of the combination treatment. Our findings suggested that CDM combined with ASA exerted a synergetic inhibitory effect on cell growth by inactivating PI3K/AKT pathway, which might pave the way for effective treatments of AML-MDS.
Metabolic Contributions of Wnt Signaling: More Than Controlling Flight
Authors: Abou Azar Frederic , Lim Gareth E.
Published: September 2021

The canonical Wnt signaling pathway is ubiquitous throughout the body and influences a diverse array of physiological processes. Following the initial discovery of the Wnt signaling pathway during wing development in Drosophila melanogaster, it is now widely appreciated that active Wnt signaling in mammals is necessary for the development and growth of various tissues involved in whole-body metabolism, such as brain, liver, pancreas, muscle, and adipose. Moreover, elegant gain- and loss-of-function studies have dissected the tissue-specific roles of various downstream effector molecules in the regulation of energy homeostasis. This review attempts to highlight and summarize the contributions of the Wnt signaling pathway and its downstream effectors on whole-body metabolism and their influence on the development of metabolic diseases, such as diabetes and obesity. A better understanding of the Wnt signaling pathway in these tissues may aid in guiding the development of future therapeutics to treat metabolic diseases.
Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation
Authors: Tokuhiro Takuto , Ishikawa Akane , Sato Haruka , Takita Shunya , Yoshikawa Ayuri , Anzai Ryoko , Sato Shinichi , Aoyagi Ryohei , Arita Makoto , Shibuya Takumi , Aratani Yasuaki , Shimizu Shigeomi , Tanaka Masato , Yotsumoto Satoshi
Published: September 2021

Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin DNA and contents of granules, such as myeloperoxidase (MPO) and neutrophil elastase (NE). NETs are usually released from neutrophils undergoing NETosis, a neutrophil-specific cell death mode characterized by the collapse and disappearance of cell membranes and nuclear envelopes. It is well known that production of reactive oxygen species (ROS) triggers NETosis and NET formation. However, details of intracellular signaling downstream of ROS production during NETosis and NET formation remains uncertain. Here, we demonstrated that the peroxidation of phospholipids plays a critical role in NETosis and NET formation induced by phorbol 12-myristate13-acetate (PMA) or immune complex in vitro and by lipopolysaccharide (LPS) in vivo. This phospholipid peroxidation is mediated by the enzymatic activity of MPO. On the other hand, NE, which was previously reported to be released from granules to cytosol by MPO during NET formation, is not required for either the peroxidation of phospholipids or the execution of NETosis, but contributes to chromatin decondensation and nuclear swelling independently of MPO-mediated oxidized phospholipids. Analysis of isolated nuclei clearly demonstrated that oxidized phospholipids and NE differently yet synergistically execute chromatin decondensation and nuclear swelling, and the subsequent release of nuclear contents. These findings indicate the dual roles of MPO in NETosis and NET formation, and provide new insight into the molecular mechanism of these phenomena.
Multi-Omics Analysis of the Anti-tumor Synergistic Mechanism and Potential Application of Immune Checkpoint Blockade Combined With Lenvatinib
Authors: Lu Yuting , Jin Jiangtao , Du Qi , Hu Min , Wei Yuhan , Wang Miao , Li Hongzhong , Li Qin
Published: September 2021

The combination of immune-checkpoint blockade (ICB) and lenvatinib has demonstrated robust clinical effects that are superior to those of monotherapies, but the synergistic anti-tumor mechanisms remain unclear. Exploring the synergistic molecular mechanisms and early identifying potential application have key importance for clinical therapeutics. We firstly systematically reviewed published data of ICB in combination with lenvatinib for the treatment of cancer by meta-analysis. A subsequent bioinformatics analysis explored the mechanism of combined ICB and lenvatinib therapy in 33 cancer types. Transcriptomic analysis was conducted by RNA-seq, and genomic analysis was performed on gene mutations and copy-number alteration data. Tumor-related pathways and tumor immune micro-environment (TIME) were also investigated. The meta-analysis showed a 38.0% objective response rate (ORR) and 79% disease control rate (DCR) for ICB combined with lenvatinib. Multi-omics analysis revealed that ICB and lenvatinib target genes were highly expressed and showed driving alterations in six specific malignancies. Pathway-enrichment analysis found target genes were implicated in tumor development, angiogenesis, and immunoregulatory associated pathways. This study verified the potential synergistic mechanisms of ICB combined with lenvatinib at transcriptomics, genomics, protein, and cellular levels and recognized nine tumor types had ≥ 2 positive treatment-related molecular characteristics, which might benefit particularly from this combined strategy. The findings would help to provide clinical insights and theoretical basis for optimizing of targeted therapy-immunotherapy combinations, and for guiding individualized precision-medicine approaches for cancer treatment.
Advanced Corrosion Protection of Additive Manufactured Light Metals by Creating Ceramic SurfaceThrough CERANOD® Plasma Electrolytical Oxidation Process
Authors: Jantimapornkij Patcharawee , Zerrer Jörg , Buling Anna
Published: September 2021

Lightweight structures produced by additive manufacturing (AM) technology such as the selective laser melting (SLM) process enable the fabrication of 3D structures with a high degree of freedom. A printed component can be tailored to have specific properties and render possible applications for industries such as the aerospace and automotive industries. Here, AlSi10Mg is one of the alloys that is currently used for SLM processes. Although the research with the aim improving the strength of AM aluminum alloy components is rapidly progressing, corrosion protection is scarcely addressed in this field. Plasma electrolytic oxidation (PEO) is an advanced electrolytical process for surface treatment of light metals such as aluminum, magnesium, and titanium. This process produces an oxide ceramic-like layer, which is extremely hard but also ductile, and significantly improves the corrosion and wear behavior. The aim of this study is to understand the corrosion behavior of 3D-printed AlSi10Mg alloy and to improve its corrosion resistance. For this reason, the properties of CERANOD®—PEO coating on an AlSi10Mg alloy produced by SLM were investigated on different AM surfaces, i.e., as-built, polished and stress relieved specimens. The corrosion performance of these surfaces was analyzed using electrochemical impedance spectroscopy (EIS), potentiodynamic polarization, and long-term immersion tests. Moreover, the microstructure and morphology of the resulting coatings were characterized by SEM/EDS, taking into account the corrosive attacks. The results exhibited a high amount of localized corrosion in the case of the uncoated specimens, while the PEO process conducted on the aluminum AM surfaces led to enclosed homogeneous coatings by protecting the material’s pores, which are typically observed in AM process. Thereby, high corrosion protection could be achieved using PEO surfaces, suggesting that this technology is a promising candidate for unleashing the full potential of 3D light metal printing.
Hollow Dodecahedra Graphene Oxide- Cuprous Oxide Nanocomposites With Effective Photocatalytic and Bactericidal Activity
Authors: Shan Zezhi , Yang Yanrong , Shi Haoran , Zhu Jiali , Tan Xiao , Luan Yi , Jiang Zhenqi , Wang Ping , Qin Jieling
Published: September 2021

In this study, a kind of graphene oxide-cuprous oxide (GO-Cu2O) nanocomposites was fabricated with different morphologies to serve as a photocatalytic material for the degradation of organic/inorganic dyes under visible light and the bactericidal effect against pathogenic bacteria. The GO-Cu2O was prepared with solid cube and hollow dodecahedra morphologies through in-situ synthesis, and characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Raman, Ultraviolet and visible spectrophotometry (UV/vis), and Fourier transform infrared spectroscopy. In comparison with cubic GO-Cu2O, the absorption and degradation efficiency of the GO-Cu2O dodecahedra (GCD) composite in Methyl orange (MO), Rhodamine B (RhB), and phenol was higher owning to the more active sites for the simultaneous dye and light absorption of hollow structure. The antibacterial effect of the GO-Cu2O dodecahedra was examined by the flat colony counting method with an excellent bactericidal effect against pathogenic bacteria. The possible mechanism for the preparation of GCD possessing the enhancement of the visible-light photocatalytic and antibacterial efficiencies were also investigated.
Exploring Narratives on Negative Emissions Technologies in the Post-Paris Era
Authors: Otto Danny , Thoni Terese , Wittstock Felix , Beck Silke
Published: September 2021

The 2015 Paris Agreement specified that the goal of international climate policy is to strengthen the global response to climate change by restricting the average global warming this century to “well below” 2°C above pre-industrial levels and to pursue efforts to limit it to 1.5°C. In this context, “Negative Emissions Technologies” (NETs)—technologies that remove additional greenhouse gases (GHGs) from the atmosphere—are receiving greater political attention. They are introduced as a backstop method for achieving temperature targets. A focal point in the discussions on NETs are the emission and mitigation pathways assessed by the Intergovernmental Panel on Climate Change (IPCC). Drawing on perspectives from Science & Technology Studies (STS) and discourse analysis, the paper explores the emergence of narratives about NETs and reconstructs how the treatment of NETs within IPCC assessments became politicized terrain of configuration for essentially conflicting interests concerning long-term developments in the post-Paris regime. NETs are—critics claim—not the silver bullet solution to finally fix the climate, they are a Trojan horse; serving to delay decarbonization efforts by offering apparent climate solutions that allow GHGs emissions to continue and foster misplaced hope in future GHG removal technologies. In order to explore the emerging controversies, we conduct a literature review to identify NETs narratives in the scientific literature. Based on this, we reevaluate expert interviews to reconstruct narratives emerging from German environmental non-governmental organizations (eNGOs). We find a spectrum of narratives on NETs in the literature review and the eNGO interviews. The most prominent stories within this spectrum frame NETs either as a moral hazard or as a matter of necessity to achieve temperature targets.
Secreted Frizzled-Related Protein 5 Protects Against Cardiac Rupture and Improves Cardiac Function Through Inhibiting Mitochondrial Dysfunction
Authors: Huang Xin , Yan Yan , Zheng Wen , Ma Youcai , Wang Xiao , Gong Wei , Nie Shaoping
Published: September 2021

Background: Secreted frizzled-related protein 5 (Sfrp5) has been suggested to be a protective regulatory protein in coronary heart disease. However, the role of Sfrp5 in regulating ischemic injury and its consequences is not known. The aim of our study was to explore the effects of Sfrp5 on hearts after myocardial infarction (MI) and to investigate the underlying mechanisms.

Methods and Results: We found that Sfrp5 was downregulated over time in the heart tissue of MI mice. To further elucidate the role of Sfrp5 during MI, we established a cardiac overexpression of an Sfrp5 mouse model using the cardiotropic adeno-associated virus serotype 9 (AAV9). Overexpression of Sfrp5 significantly reduced infarct size as demonstrated by a decrease in mortality owing to cardiac rupture. Moreover, cardiac overexpression of Sfrp5 increased left ventricular function and mitochondrial biogenesis, decreased cardiomyocyte apoptosis, suppressed inflammation reaction, inhibited oxidative stress, and ameliorated cardiac remodeling as demonstrated by left ventricular ejection fraction, mitochondrial morphology, heart weight, NADH oxidase activity levels, and myocardial fibrosis at 2 weeks post-MI. At the molecular level, overexpression of Sfrp5 significantly increased the expression of p-AMPKThr172 protein with higher expression of mitochondrial fusion protein (MFN1 and MFN2) and lower expression of mitochondrial fission protein (p-Drp1Ser616/Mid49/MFF/Fis-1). In isolated neonatal rat cardiac myocytes, Sfrp5 treatment attenuated hypoxia-induced mitochondrial dysfunction. Inhibition of AMPK activity with compound C abrogated this benefit.

Conclusions: Sfrp5 overexpression inhibits ischemic injury, reduces risk of cardiac rupture, ameliorates post-MI remodeling, and decreases the progression to heart failure via disrupting mitochondrial dysfunction and partly through normalizing the AMPK activity.
Transcription Factor-7-Like-2 (TCF7L2) in Atherosclerosis: A Potential Biomarker and Therapeutic Target
Authors: Li Junyi , Zhou Li , Ouyang Xinping , He Pingping
Published: September 2021

Transcription factor-7-like-2 (TCF7L2), a vital member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) family, plays an important role in normal human physiological and pathological processes. TCF7L2 exhibits multiple anti-atherosclerotic effects through the activation of specific molecular mechanisms, including regulation of metabolic homeostasis, macrophage polarization, and neointimal hyperplasia. A single-nucleotide substitution of TCF7L2, rs7903146, is a genetic high-risk factor for type 2 diabetes and indicates susceptibility to cardiovascular disease as a link between metabolic disorders and atherosclerosis. In this review, we summarize the anti-atherosclerosis effect and novel mechanisms underlying the function of TCF7L2 to elucidate its potential as an anti-atherosclerosis biomarker and provide a novel therapeutic target for cardiovascular diseases.
5 Year Outcomes of Patients With Aortic Structural Valve Deterioration Treated With Transcatheter Valve in Valve – A Single Center Prospective Registry
Authors: Schamroth Pravda Nili , Kornowski Ran , Levi Amos , Witberg Guy , Landes Uri , Perl Leor , Shapira Yaron , Orvin Katia , Mishaev Raffael , Talmor Barkan Yeela , Hamdan Ashraf , Sharoni Ram , Vaknin Assa Hana , Codner Pablo
Published: September 2021

The Valve-in-Valve (ViV) technique is an established alternative for the treatment of structural bioprosthetic valve deterioration (SVD). Data describing the intermediate term follow up of patients treated with this approach is scarce. We report on our intermediate-term outcomes of patients with SVD in the Aortic position treated with ViV. Included were patients with symptomatic SVD in the aortic position valve who were treated by Valve in valve transcatheter aortic valve implantation (ViV-TAVI) during the years 2010-2019 in our center. Three main outcomes were examined during the follow up period: NYHA functional class, ViV-TAVI hemodynamic per echocardiography, and mortality. Our cohort consisted of 85 patients (mean age 78.8 ± 8.9 years). The indications for aortic ViV were: SVD isolated aortic stenosis in 37.6%, SVD isolated aortic regurgitation in 42.2% and combined valve pathology in 20.0%. Self-expandable and balloon-expandable devices were used in 73 (85.9%) and 12 (14.1%), respectively. Average follow up was 3.7 ± 2.4 years. 95 and 91% of patients were in NYHA functional class I/II at 1 and 5 year follow up respectively. At one year, the mean trans-aortic valve pressure was 15 ± 9 mmHg and rates of ≥ moderate aortic regurgitation were 3.7%. Mortality at one year was 8.6% (95% CI 2.3–14.4) and 31% (95% CI 16.5–42.5) at 5 years. ViV in the aortic position offers an effective and durable treatment option for patient with SVD, with low rates of all-cause mortality, excellent hemodynamic and improved functional capacity at intermediate follow up.
Diagnosis and Management of Central Congenital Hypothyroidism
Authors: Lauffer Peter , Zwaveling-Soonawala Nitash , Naafs Jolanda C. , Boelen Anita , van Trotsenburg A. S. Paul
Published: September 2021

Central congenital hypothyroidism (CH) is defined as thyroid hormone (TH) deficiency at birth due to insufficient stimulation by the pituitary of the thyroid gland. The incidence of central CH is currently estimated at around 1:13,000. Central CH may occur in isolation, but in the majority of cases (60%) it is part of combined pituitary hormone deficiencies (CPHD). In recent years several novel genetic causes of isolated central CH have been discovered (IGSF1,TBL1X,IRS4), and up to 90% of isolated central CH cases can be genetically explained. For CPHD the etiology usually remains unknown, although pituitary stalk interruption syndrome does seem to be the most common anatomic pituitary malformation associated with CPHD. Recent studies have shown that central CH is a more severe condition than previously thought, and that early detection and treatment leads to good neurodevelopmental outcome. However, in the neonatal period the clinical diagnosis is often missed despite hospital admission because of feeding problems, hypoglycemia and prolonged jaundice. This review provides an update on the etiology and prognosis of central CH, and a practical approach to diagnosis and management of this intriguing condition.
Imaging-Based Body Fat Distribution in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
Authors: Zhu Shiqin , Li Zeyan , Hu Cuiping , Sun Fengxuan , Wang Chunling , Yuan Haitao , Li Yan
Published: September 2021

Background

Women with polycystic ovary syndrome (PCOS) are generally considered to be central obese and at higher risks of metabolic disturbances. Imaging methods are the golden standards for detecting body fat distribution. However, evidence based on magnetic resonance imaging (MRI) and computed tomography (CT) is conflicting. This study systematically reviewed the imaging-based body fat distribution in PCOS patients and quantitatively evaluated the difference in body fat distribution between PCOS and BMI-matched controls.

Methods

PUBMED, EMBASE, and Web of Science were searched up to December 2019, and studies quantitatively compared body fat distribution by MRI, CT, ultrasound, or X-ray absorptiometry (DXA) between women with PCOS and their BMI-matched controls were included. Two researchers independently reviewed the articles, extract data and evaluated the study quality based on Newcastle-Ottawa Scale (NOS).

Results

47 studies were included in systematic review and 39 were eligible for meta-analysis. Compared to BMI-matched controls, higher accumulations of visceral fat (SMD 0.41; 95%CI: 0.23-0.59), abdominal subcutaneous fat (SMD 0.31; 95%CI: 0.20-0.41), total body fat (SMD 0.19; 95% CI: 0.06-0.32), trunk fat (SMD 0.47; 95% CI: 0.17-0.77), and android fat (SMD 0. 36; 95% CI: 0.06-0.66) were identified in PCOS group. However, no significant difference was identified in all the above outcomes in subgroups only including studies using golden standards MRI or CT to evaluate body fat distribution (SMD 0.19; 95%CI: -0.04-0.41 for visceral fat; SMD 0.15; 95%CI: -0.01-0.31 for abdominal subcutaneous fat). Moreover, meta-regression and subgroup analyses showed that young and non-obese patients were more likely to accumulate android fat.

Conclusions

PCOS women seem to have abdominal fat accumulation when compared with BMI-matched controls. However, MRI- and CT- assessed fat distribution was similar between PCOS and controls, suggesting central obesity may be independent of PCOS. These findings will help us reappraise the relationship between PCOS and abnormal fat deposition and develop specialized lifestyle interventions for PCOS patients.

Systematic Review Registration

PROSPERO, identifier CRD42018102983.
Effects of Coolants of Double Layer Transpiration Cooling System in the Leading Edge of a Hypersonic Vehicle
Authors: Luo Shibin , Miao Zhichao , Liu Jian , Song Jiawen , Xi Wenxiong , Liu Chaoyang
Published: September 2021

As a promising and efficient active cooling method, double layer transpiration cooling is introduced into the design of the cooling system in the leading edge of a hypersonic vehicle. The physical model is built combined with hypersonic transpiration cooling, film cooling, heat conduction, porous media heat conduction and convection heat transfer. In addition, effects of different kinds of coolants are considered to reveal cooling mechanisms in different operation conditions. A comprehensive turbulence model validation and mesh independence study are provided. Flow characteristics caused by flow impingement, separation, transition and interaction with the cooling flows are displayed and analyzed in the work. When different kinds of coolants supplied at the same mass flow rate, the coolants with low densities, i.e., H2and He, have the lowest peak temperature compared with the coolants with large densities, i.e., N2and CO2. The coolants with low densities have a large ejecting velocity which provides large kinetic energy to penetrate deeply in the porous media. In addition, when the ejecting velocity is large enough, a recirculation is formed in front of the leading edge and pushes the high temperature region located in stagnation region away from the leading edge. However, when the coolants are ejected at the same velocity, the coolants with large densities exhibit better cooling performance.
Night Capture of Roosting Cave Birds by Neanderthals: An Actualistic Approach
Authors: Blanco Guillermo , Sánchez-Marco Antonio , Negro Juan José
Published: September 2021

Evidence is accumulating on the regular and systematic Neanderthal exploitation of birds. However, the motivations, mechanisms, and circumstances underlying this behavior remains little explored despite their potential implications on Neanderthal ecology and capabilities. Fossil remains of choughs (Pyrrhocorax, Corvidae) are among the most abundant in cave sites with Mousterian technology. We reviewed the evidence showing that Neanderthals processed choughs for food, and confirmed that it occurred frequently over a widespread spatial and temporal scale. This lead us to propose the hypothesis that the cave-like refuge is the keystone resource connecting Neanderthals and choughs captured at night in rocky shelters eventually used by both species. By adopting an actualistic approach, we documented the patterns of refuge use and population dynamics of communally roosting choughs, the strategies and technology currently used to capture them, and their behavioral response against experimental human predators at night. Actualistic experiments showed that large numbers of choughs can be captured without highly sophisticated tools at night regularly and periodically, due to their occupation year-round during long-term periods of the same nocturnal shelters, the constant turnover of individuals, and their high site tenacity at these roost-sites even after recurrent disturbance and predation. Captures even with bare hands are further facilitated because choughs tend to flee confused into the cavity in darkness when dazzled and cornered by human (experimental) predators. Given the extreme difficulty of daylight chough capturing in open country, nocturnal hunting with the help of fire in the roosting caves and consumption in situ are proposed as the most plausible explanations for the strong association of choughs and Neanderthals in fossil assemblages. Night hunting of birds has implications for the social, anatomical, technological, and cognitive capacities of Neanderthals.
A Modeling and Machine Learning Pipeline to Rationally Design Treatments to Restore Neuroendocrine Disorders in Heterogeneous Individuals
Authors: Zhang Tongli
Published: September 2021

Heterogeneity among individual patients presents a fundamental challenge to effective treatment, since a treatment protocol working for a portion of the population often fails in others. We hypothesize that a computational pipeline integrating mathematical modeling and machine learning could be used to address this fundamental challenge and facilitate the optimization of individualized treatment protocols. We tested our hypothesis with the neuroendocrine systems controlled by the hypothalamic–pituitary–adrenal (HPA) axis. With a synergistic combination of mathematical modeling and machine learning (ML), this integrated computational pipeline could indeed efficiently reveal optimal treatment targets that significantly contribute to the effective treatment of heterogeneous individuals. What is more, the integrated pipeline also suggested quantitative information on how these key targets should be perturbed. Based on such ML revealed hints, mathematical modeling could be used to rationally design novel protocols and test their performances. We believe that this integrated computational pipeline, properly applied in combination with other computational, experimental and clinical research tools, can be used to design novel and improved treatment against a broad range of complex diseases.
Simultaneous Identification of Both MFSD8 and RDH12 Pathogenic Variants in a Chinese Family Affected With Retinitis Pigmentosa
Authors: Wang Yihui , Teng Yanling , Liang Desheng , Li Zhuo , Wu Lingqian
Published: September 2021

Retinitis pigmentosa (RP) is characterized by tremendous genetic and phenotypic heterogeneity. Here, we investigate the pathogeny of RP in a family to provide evidence for genetic and reproductive counseling for families. Although this pregnant woman of 8+3 weeks presented with RP, her first baby was born with RP, epilepsy, and cerebellar atrophy. The research identified a compound heterozygous mutation (c.998+3_998+6del/deletion) in the MFSD8 gene of the first born, explaining the cause of the proband’s disease, which cannot explain the mother’s. Then, a homozygous mutation c.343+1G > A in RDH12 of the mother was found. RT-PCR is employed to find that there is a skipping of exon 10 in MFSD8 and a 15-nucleotide retention of intron5 in RDH12. The coexistence of two independent instances of RP caused by distinct genes in one pedigree is demonstrated. Based on the diagnosis, a prenatal diagnosis performed on the fetus found that the fetus’s MFSD8 is affected by the same mutation as the proband. The research underscoring the complexity of RP and the need for the combination of extensive molecular genetic testing and clinical characterization in addition expands the spectrum of MFSD8 mutations. Finally, it is expected that the family members would be prevented from reproducing children with the similar disease.
Effect of Basal Metabolic Rate on Cancer: A Mendelian Randomization Study
Authors: Ng Jack C. M. , Schooling C. Mary
Published: September 2021

Background: Basal metabolic rate is associated with cancer, but these observations are open to confounding. Limited evidence from Mendelian randomization studies exists, with inconclusive results. Moreover, whether basal metabolic rate has a similar role in cancer for men and women independent of insulin-like growth factor 1 increasing cancer risk has not been investigated.

Methods: We conducted a two-sample Mendelian randomization study using summary data from the UK Biobank to estimate the causal effect of basal metabolic rate on cancer. Overall and sex-specific analysis and multiple sensitivity analyses were performed including multivariable Mendelian randomization to control for insulin-like growth factor 1.

Results: We obtained 782 genetic variants strongly (p-value < 5 × 10–8) and independently (r2 < 0.01) predicting basal metabolic rate. Genetically predicted higher basal metabolic rate was associated with an increase in cancer risk overall (odds ratio, 1.06; 95% confidence interval, 1.02–1.10) with similar estimates by sex (odds ratio for men, 1.07; 95% confidence interval, 1.002–1.14; odds ratio for women, 1.06; 95% confidence interval, 0.995–1.12). Sensitivity analyses including adjustment for insulin-like growth factor 1 showed directionally consistent results.

Conclusion: Higher basal metabolic rate might increase cancer risk. Basal metabolic rate as a potential modifiable target of cancer prevention warrants further study.