bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGGUNAAN MEDIA PLASTISIN SEBAGAI ALTERNATIF PENGGANTI MOLYMOD UNTUK MENINGKATKAN HASIL BELAJAR PSIKOMOTORIK SISWA PADA POKOK BAHASAN STRUKTUR SENYAWA ALKANA, ALKENA DAN ALKUNA
Authors: Indiatiningsih Indiatiningsih
Published: December 2020

This research aims to describe the use of plasticine learning media to improve psychomotor learning outcomes of students on the subject matter of the structure of alkenes and alkunes 11th class MIPA 3 in SMAN 8. The structure of alkanes and alkunes, which is one of the abstract Chemical topis, so that this topics is not understood by many students. This requires the teacher’s creativity to be able to explain concrretely. So that the teacher must use a variety of interesting media, to solve this problem the teacher tries to teach the stucture of alkenes and alkunes using plasticine media. The use of plasticine media is expected to overcome problems in the field. This research is ClassroomAction Research. The instruments used ware observation sheets, reports on the practice of making stucture of alkanes, alkenes and alkunes. Data reduction, in general, all indicators of skills increase, especially indicators of cooperation and responsibility has increased significantly. Cycle II in this research obtain 98 for the highest score and 80 for the lowest score which is the use of plasticine in learning the structure of hydrocarbon compounds, especially alkene, is quite effective because this material is quite flexible compared to the use of molymod which is done in the first cycle which takes a long time to install, besides that plasticine is quite cheap and easy to obtain.
PENINGKATAN HASIL BELAJAR BIOLOGI MELALUI METODE PEMBELAJARAN MIND MAPPING MATERI JARINGAN DAN ORGAN HEWAN PADA SISWA KELAS XI-IPA 1
Authors: Yuarifka Imelda Santi
Published: December 2020

The purpose of this study was to apply the Mind mapping method to increase the creativity of students' learning outcomes in Class XI Science 1 at MAN Malang 02 Kota Batu. This type of research used is Classroom Action Research is a form of study that is descriptive in nature, to improve the rational stability and actions taken and improve the conditions under which learning practices are carried out. The research procedure was carried out in two cycles with stages of planning, implementation and reflection. The data obtained in the form of observational data and the results of the first cycle test will be compared with cycle II. The results of observations of student actions during learning increased by 20.7% of the actions of students in cycle 1 of 70.7% to 91.4%. The results of the mind mapping assessment in cycle 1 did not meet the mind mapping criteria with the acquisition of scores below the KKM and experienced an increase in cycle II, all mind mapping met the criteria with a value reaching KKM of 80. For the evaluation test results there was an increase of 76.4%, in the cycle I many students who completed KKM only 5 students with a percentage of 14.7% of 34 students who did not complete KKM with a percentage of 85.29%, while in cycle II there was an increase namely there were 31 students who completed KKM with a percentage of 91.1% and 3 students who are incomplete with a percentage of 8.82%.
Processo f chemical disifection of health products: review of the standard operating procedure and socialization with the nursing team
Authors: Reginaldo Daiane Signorini , Silva Katryn Corrêa da , Graube Sandra Leontina , Lucca Jane Conceição Perin , Meneghete Maria Cristina , Rodrigues Francisco Carlos Pinto , Bittencourt Vivian Lemes Lobo
Published: December 2020

Objective: to review and socialize Standard Operating Procedure (SOP) on the process of disinfecting health products (PPS). Method: An experience report study of an intervention performed in a hospital in the Northwest region of the State of Rio Grande do Sul, in the second semester of 2018, with the participation of the nursing team of the Material and Sterilization Center (CME) and the nurse responsible for the Hospital Infection Control Service (SCIH). The activities took place after contact with the nurse responsible for the unit, who passed on the SOP to be reviewed, there was also the elaboration of a mural on high-level disinfection. Results: five nursing professionals and five academic students who interned at the location participated in the action. It was noticed that two important actions of the PPS disinfection process were not described in the CME POPs, which are: hand hygiene and the use of personal protective equipment (PPE). The team interacted through the exchange of ideas, a principle of permanent health education. Final considerations: The nurse must act as an educator seeking constant updating of his team and solutions for his practice. Finally, the execution of the project made it possible to review the SOPs and discuss with the unit's team and, in addition, it also showed the need for further studies in this area.
Análise dos princípios bioéticos que permeiam a Política Nacional de Enfrentamento à Violência Contra as Mulheres
Authors: Macedo Daiane Schultz , Mattos Maria das Graças de Almeida , Santos Paulo Ueslei de Jesus , Yarid Sérgio Donha , Casotti Cezar Augusto , Santos Charles Souza
Published: December 2020

A violência contra a mulher tem estimulado, ao longo dos anos, muitas mobilizações sociais e o problema inclui diferentes expressões de violência, como: doméstica, sexual, física, psicológica, patrimonial, moral, institucional, dentre outras, o que exige de toda sociedade civil organizada e do governo ações efetivas para o seu combate. Diante disso, o trabalho teve como objetivo analisar os princípios bioéticos que permeiam a Política Nacional de Enfrentamento da Violência Contra Mulheres (PNEVCM). Trata-se de uma pesquisa documental, exploratória e qualitativa. A coleta de dados foi realizada com base no documento estrutural da PNEVCM, disponível no portal da Secretaria Nacional de Políticas para Mulheres (SNPM). Para organização e tratamento dos dados utilizou-se a análise de conteúdo de Bardin. Os dados foram alocados por meio dos seguintes tópicos: aspectos conceituais de enfrentamento a violência; princípios, diretrizes e objetivos da PNEVCM e ações e prioridades da política em questão. Diante do estudo realizado verificou-se que a Política Nacional de Enfrentamento à Violência Contra as Mulheres (PNEVCM) aborda, mesmo que implicitamente, os princípios bioéticos da beneficência, não maleficência e justiça ou equidade, trazendo explicitamente o princípio da autonomia.
Kényelmiélelmiszer-fogyasztási szokások és -fogyasztói csoportok
Authors: Plasek Brigitta , Nagy Evelin , Temesi Ágoston
Published: December 2020

A folyton fejlődő, globalizálódó világban a társadalmunk mai életvitelének és fogyasztási szokásainak egyre gyorsabb változását figyelhetjük meg. Napjainkban a társadalom széles rétegének életvitele egy egyre növekvő igényt formál olyan élelmiszerek iránt, amik azonnal fogyaszthatók vagy nagyon kis energia vagy idő befektetésével elkészíthetők. Erre az élelmiszeripar már ma is rengeteg lehetőséget kínál és a kényelmi élelmiszerek széles termékskálával találkozhatunk a boltok polcain. Élelmiszergyártók előrejelzései szerint a kényelmi élelmiszerek kategóriájának fontossága tovább fog nőni az elkövetkezendő években. Kutatásunkban a kevés hazai forrásra való tekintettel, arra kerestük a választ, hogy mi jellemző a kényelmiélelmiszer-fogyasztásra hazánkban, valamint milyen fogyasztói csoportokat különböztethetünk meg. Fogyasztói megkérdezéses módszerrel, valószínűségi mintavétellel 500 fő megkérdezése valósult meg. Varianciaanalízis segítségével vizsgáltuk a különböző demográfiai csoportok és az attitűdállítások közötti szignifikáns különbségeket (p < 0,05). Eredményeink alapján elmondható, hogy a kényelmi élelmiszerek, konyhakész termékek fogyasztása inkább a férfiakra, és a fiatalabb korosztályokra jellemzők. Azok a korosztályok, akikre kevésbé jellemző a kényelmi élelmiszerek fogyasztása (50–59, 60–75), gyakrabban főznek hétvégente legalább egy óra hosszan, míg azok a korosztályok, akik több kényelmi élelmiszert fogyasztanak (18–29, 30–39) ritkábban töltenek ennyi időt a konyhában. Továbbá, inkább a középfokú végzettséggel rendelkezők esetében jellemző a kényelmi élelmiszerek választása, míg az alacsonyabb végzettségű, ill. felsőfokú tanulmányokkal rendelkezőkre ez kevésbé jellemző.Klaszteranalízis segítségével négy fogyasztói csoportot különítettünk el, a kényelmi élelmiszerekkel szemben közömbösek, a kényelmi élelmiszer keresők, a kényelmi élelmiszer kerülők és a főzéskerülők csoportjait.
Értékrendalapú élelmiszer-fogyasztói magatartásra vonatkozó minták a Z generáció körében
Authors: Garai-Fodor Mónika
Published: December 2020

A téma aktualitását és elméleti bázisát kettő pillér adja: az értékrend-alapú fogyasztói magatartásra vonatkozó elméletek és a generációs marketing. Az fogyasztói magatartásra vonatkozó elméletek közül vizsgálatom fókuszában az értékrendalapú elméletek állnak, melyek közös vonása, hogy a fogyasztó termék- és szolgáltatásválasztásának indítékai és az értékrendszer között összefüggést feltételeznek. Ez az alapkoncepció inspirált arra, hogy az értékrend és a fogyasztói magatartás összefüggéseit saját primer vizsgálat keretében generációspecifikusan elemezzem a Z generáció élelmiszer-fogyasztói szokásainak, azon belül is az egészséges táplálkozás iránti attitűdjének vizsgálata révén. A téma másik pillére a generációs marketing, mely a különböző generációk közötti eltérések végső eredőjeként szintén az értékrendet nevezi meg. Tekintettel arra, hogy a Z generáció a közeljövő potenciális fizetőképes keresletet teremtő fogyasztói bázisa lesz, megítélésem szerint érdemes és hasznos a generáció sajátos élelmiszer-fogyasztói preferenciájának, döntéseinek megismerése. Primer vizsgálatom során a Z generáció tagjaira fókuszáló kvalitatív és kvantitatív adatfelvétel keretében elemeztem e generáció értékrendjét, élelmiszer-fogyasztói magatartását és az egészségről,  egészséges táplálkozásról alkotott véleményét. Kvalitatív kutatás keretében húsz mini fókuszcsoportos interjút bonyolítottam le félig strukturált interjúvázlat segítségével. A kvantitatív kutatás keretében pedig sztenderdizált kérdőíves megkérdezést folytattam le, melynek eredményeként több mint 500 értékelhető kérdőívet elemeztem ki. Mindkét kutatás során szűrőfeltétel volt, hogy az alanyok életkor szerint a Z generáció köréből kerüljenek ki. Az eredmények alapján megállapítható, hogy a jövő nemzedéke milyen értékorientációval rendelkezik, és mennyire tartja fontosnak egészséget, mit tesz annak megóvása érdekében. Ezen felül a kutatás eredményei segítségével kirajzolódnak a Z generáció körében releváns élelmiszer-fogyasztói magatartásra vonatkozó minták, melyek segítségül szolgálthatnak az egészséges táplálkozás célcsoportjainak definiálásához és a Z generációra irányuló egészségnevelő kampányokhoz.
The partisan unit under the command of captain R. Rajs (Bury) activity on the territory of Białystok region in 1944–1946 in the politics of memory of the Republic of Poland
Authors: Kozik Lioubov A.
Published: December 2020

The polish politics of memory concerning the activities of the unit under the command of captain R. Rajs (Bury) in Białystok region in 1944–1946 is considered in the article. The aim of the study is to analyse public practices, places of memory and their role in forming and reflecting the collective memory about R. Rajs’s unit (whose representatives are referred to as «cursed soldiers»). The analysis of public practices, memorable days and places of memory in Poland revealed a confrontation between two narratives. The first one is the nationalist and anti-communist narrative. It is transmitted by the state through the Institute of National Remembrance, museum institutions, as well as by right-wing political parties, movement, public organisations and the media close to them. According to them, R. Rajs is a hero who fought in the interests of the Polish state. Another narrative is presented by Belarusian national minority, their public organisations and mass media. They try to preserve the memory of the 1946 tragedy in the society and define the activities of the R. Rajs’s unit as crimes. The author emphasises that the judicial investigation completed in 2005 by the Institute of National Remembrance came to the conclusion that R. Rajs actions had signs of genocide. The author notes that the polish historical politics departs in some sense from humanistic, universal values. It focuses on the nationalist vision of history and actually ignores the interests of the Belarusians of Białystok region.
Linear semidefinite programming problems: regularisation and strong dual formulations
Authors: Kostyukova Olga I. , Tchemisova Tatiana V.
Published: December 2020

Regularisation consists in reducing a given optimisation problem to an equivalent form where certain regularity conditions, which guarantee the strong duality, are fulfilled. In this paper, for linear problems of semidefinite programming (SDP), we propose a regularisation procedure which is based on the concept of an immobile index set and its properties. This procedure is described in the form of a finite algorithm which converts any linear semidefinite problem to a form that satisfies the Slater condition. Using the properties of the immobile indices and the described regularization procedure, we obtained new dual SDP problems in implicit and explicit forms. It is proven that for the constructed dual problems and the original problem the strong duality property holds true.
Hidden Markov model for malicious hosts detection in a computer network
Authors: Bubnov Yakov V. , Ivanov Nick N.
Published: December 2020

The problem of malicious host detection in a computer network is reviewed. Activity of computer network hosts is tracking by a noisy detector. The paper suggests method for detection malicious hosts using activity timeseries classification. The approach is based on hidden Markov chain model that analyses timeseries and consecutive search of the most probable final state of the model. Efficiency of the approach is based on assumption that advanced persisted threats are localised in time, therefore malicious hosts in a computer network can be detected by virtue of activity comparison with reliable safe hosts.
Neuroimaging does not support the representational nature of the earliest human engravings: comment on Mellet et al.(2019)
Authors: Hodgson Derek
Published: December 2020

This paper provides a commentary on an article by Mellet et al (2019), which points out a number of inaccuracies and misinterpretations of neuroscientific data regarding the significance of the earliest engravings in the archaeological record.
Cognitive and computational building blocks for more human-like language in machines
Authors: Tenenbaum Joshua B.
Published: December 2020

Humans learn language building on more basic conceptual and computational resources that we can already see precursors of in infancy. These include capacities for causal reasoning, symbolic rule formation, rapid abstraction, and common sense representations of events in terms of objects, agents and their interactions. I will talk about steps towards capturing these abilities in engineering terms, using tools from hierarchical Bayesian models, probabilistic programs, program induction, and neuro-symbolic architectures. I will show examples of how these tools have been applied in both cognitive science and AI contexts, and point to ways they might be useful in building more human-like language, learning and reasoning in machines.
Reflections on Implementation of the Framework Medium-Term Fiscal in Indonesia
Authors: Setiawan Lisno , Simanulang Adventus Parulian , Prasojo Wasis
Published: December 2020

To implement state financial reform under the Law no. 17 of 2003, the government applies professional principles in budgeting, especially medium-term budgeting. It has become best practices of The Organization for Economic Co-operation and Development (OECD) countries, which aim to synchronize development targets and fiscal balance. This study evaluates the implementation of the basic macroeconomic and fiscal framework in the medium term in aggregate (Medium Term Fiscal Framework—MTFF) which is the basis for medium-term budgeting. The components of the MTFF include basic macroeconomic assumptions, the budget realization, and fiscal sustainability. This study uses a comparative method, both structure comparisons and target-realization deviations. The structure comparison refers to the definition of the OECD, while the target and fiscal realization use a data comparison of the RPJMN/RKP, KEM PPKF, APBN, and LKPP. The result exhibits the economic growth and poverty rate on average have the highest deviation for macro assumptions assessment. On the fiscal side, the deviation of the budget deficit is decreasing steadily. To improve accuracy, it is necessary to increase coordination and harmonization in the mid-term policy making.
The Need for Provision of Social Assistance to Kiai Pondok Pesantren in the Covid-19 Pandemic
Authors: Effendi Edy , Suyono Suyono , Hidayat Amin
Published: December 2020

The Covid-19 pandemic has had a serious impact in almost all fields, including Islamic boarding schools and their owners, kiai. The government has helped Islamic boarding schools as institutions, but not to kiai personally. This study aims to provide answers to whether or not it is necessary to provide social assistance to kiai personally, so that it can be used as input to stakeholders. This study uses the Regulatory Impact Assessment (RIA) method, analyzing the aspects of the benefits and costs of providing social assistance to kiai and how these two things touch based on the perceptions of expert opinion. Data processing was carried out based on the results of a questionnaire conducted using the Analytical Hierarchy Process (AHP) model which was distributed to expert respondents. The results of the study indicate that it is necessary to provide social assistance to kiai personally.
Effects of Artificial Staining and Bleaching Protocols on the Surface Roughness, Color, and Whiteness Changes of an Aged Nanofilled Composite
Authors: dos Santos Muniz Mota Geyse Maria , Kury Matheus , Pereira da Silva Braga Tenório Cecília , Lucisano Botelho do Amaral Flávia , Turssi Cecília Pedroso , Cavalli Vanessa
Published: December 2020

This study evaluated the surface roughness and color alteration of an aged nanofilled composite exposed to different staining solutions and bleaching agents. Ninety nanofilled composite (Filtek Z350XT, 3M/Oral Care) specimens were submitted to 5,000 thermal cycles and immersed in (n = 30): red wine, coffee, and artificial saliva at 37°C for 48 h. Groups were subdivided according to the bleaching protocol (n = 10) with 20% carbamide peroxide, 38% hydrogen peroxide, or without bleaching - control. Mean surface roughness values (Ra - μm) and color parameters (L*, a*, b*) were measured at baseline (T0), after thermal cycling aging and staining (TS), and after bleaching (TB). Color (ΔE00) and whiteness index (ΔWID) changes were determined after aging and staining (Ts-T0) and after bleaching (TB-TS). The adopted perceptibility and acceptability thresholds of the nanofilled composite were 0.81 and 1.71 ΔE00 units and 0.61 and 2.90 ΔWID units, respectively. Ra was analyzed using mixed models for repeated measurements and L* by the Tukey-Kramer test. The a* and b* values were evaluated by generalized linear models for repeated measures. ΔE00 was tested using two-way ANOVA and Tukey tests, and ΔWID by Kruskal-Wallis and Dunn tests (α = 5%). Ra of all groups decreased after aging and staining (TS, p < 0.05), but increased after bleaching only for groups stained with red wine (TB). Aging and staining decreased the luminosity of the composites, but L* increased after bleaching (p < 0.05). Aging and staining increased a* and b* values, but after bleaching, b* values decreased (p < 0.05). After bleaching, ΔE00 and ΔWID were greater in stained groups at both time intervals, regardless of the bleaching protocol. Stained resin composites exhibited perceptible but unacceptable color (ΔE00 > 1.71) and whiteness (ΔWID > 2.90) changes, regardless of the bleaching treatment performed. Therefore, red wine affected the surface roughness of the aged nanofilled resin submitted to bleaching. Bleaching was unable to reverse the color changes promoted by red wine and coffee on the aged nanofilled composite.
Buffer Solution Reduces Acidic Toothpaste Abrasivity Measured in Standardized Tests
Authors: Zehnder Matthias , Masoch Luca , Gubler Andrea , Mohn Dirk , Attin Thomas , Wegehaupt Florian J.
Published: December 2020

It has been speculated that the diluent used to test toothpaste abrasivity in standard tests may have an impact on their results, especially in the context of acidic toothpastes. This study tested whether an acidic toothpaste is indeed more abrasive than a neutral counterpart of otherwise identical composition, and whether this increased abrasivity is prevented by a buffered solution simulating saliva. Two experimental toothpastes of identical composition yet different pH (7.0 vs. 5.0) were prepared using standard ingredients. Subsequently, they were tested in standard absolute dentin abrasion and relative dentin abrasivity (RDA) experiments. To prepare slurries for these tests, deionized water as recommended by the International Organization for Standardization (ISO 11609:2017) was used, or a buffer solution containing bicarbonate and phosphate. The pH in these slurries was assessed and compared to the pH obtained in oral slurries of healthy individuals. Results showed that a significant (one-way ANOVA, p < 0.05) increase in mean absolute dentin abrasion and RDA values by 35 and 14%, respectively, was obtained when water was used as the diluent in conjunction with the acidic toothpaste as compared to the buffer solution. This was not the case with the neutral toothpaste. This result was explained by the finding that the buffer solution neutralized the pH in experimental slurries of the acidic toothpaste, while deionized water was unable to elevate the pH of the acidic toothpaste. That toothpaste was also neutralized in oral slurries. It was concluded that indeed the current ISO standard may result in a systematic overestimation of acidic toothpaste abrasivity.
Groundwater Anomaly Related to CCS-CO2 Injection and the 2018 Hokkaido Eastern Iburi Earthquake in Japan
Authors: Sano Yuji , Kagoshima Takanori , Takahata Naoto , Shirai Kotaro , Park Jin-Oh , Snyder Glen T. , Shibata Tomo , Yamamoto Junji , Nishio Yoshiro , Chen Ai-Ti , Xu Sheng , Zhao Dapeng , Pinti Daniele L.
Published: December 2020

Carbon capture and storage (CCS) is considered a key technology for reducing CO2emissions into the atmosphere. Nonetheless, there are concerns that if injected CO2migrates in the crust, it may trigger slip of pre-existing faults. In order to test if this is the case, covariations of carbon, hydrogen, and oxygen isotopes of groundwater measured from Uenae well, southern Hokkaido, Japan are reported. This well is located 13 km away from the injection point of the Tomakomai CCS project and 21 km from the epicenter of September 6th, 2018 Hokkaido Eastern Iburi earthquake (M 6.7). Carbon isotope composition was constant from June 2015 to February 2018, and decreased significantly from April 2018 to November 2019, while total dissolved inorganic carbon (TDIC) content showed a corresponding increase. A decrease in radiocarbon andδ13C values suggests aquifer contamination by anthropogenic carbon, which could possibly be attributable to CCS-injected CO2. If such is the case, the CO2enriched fluid may have initially migrated through permeable channels, blocking the fluid flow from the source region, increasing pore pressure in the focal region and triggering the natural earthquake where the brittle crust is already critically stressed.
Examining the Efficacy of E-Service-Learning
Authors: Figuccio Michael J.
Published: December 2020

E-service-learning is a pedagogical technique in which instruction and/or service occur online. Students in a distance learning section of Atypical Development created a Google Site with resources for individuals with developmental disabilities. Additionally, students met with youths with developmental disabilities biweekly via Blackboard Collaborate Ultra sessions. At the end of the semester, students completed a questionnaire assessing their e-service-learning experience and wrote reflection papers. Students reported that the e-service-learning experience was related to course content, increased their understanding of individuals with disabilities, increased student engagement, helped them relate the subject matter to everyday life, positively impacted their future academic and career choices, and overall had a positive experience. Students in a traditional face-to-face section of Atypical Development who completed an in-person service-learning project did not significantly differ on any of the aforementioned questionnaire measures. Interestingly, students in the distance learning section reported in their reflection papers that the e-service-learning experience reduced their levels of anxiety. Course evaluations were also examined for both sections. Students in the e-service-learning section reported greater satisfaction than the in-person service-learning course. Specifically, e-service-learning students reported: the instructor attempted to make the course relevant to students; the assignments helped me learn the subject matter; I enjoyed the class greater than students in the in-person service-learning course. These results indicate that e-service-learning is an efficacious pedagogical practice in distance learning courses.
Activation of Melanocortin Receptors as a Potential Strategy to Reduce Local and Systemic Reactions Induced by Respiratory Viruses
Authors: Lonati Caterina , Gatti Stefano , Catania Anna
Published: December 2020

The clinical hallmarks of infections caused by critical respiratory viruses consist of pneumonia, which can progress to acute lung injury (ALI), and systemic manifestations including hypercoagulopathy, vascular dysfunction, and endotheliitis. The disease outcome largely depends on the immune response produced by the host. The bio-molecular mechanisms underlying certain dire consequences of the infection partly arise from an aberrant production of inflammatory molecules, an event denoted as “cytokine storm”. Therefore, in addition to antiviral therapies, molecules able to prevent the injury caused by cytokine excess are under investigation. In this perspective, taking advantage of melanocortin peptides and their receptors, components of an endogenous modulatory system that exerts marked anti-inflammatory and immunomodulatory influences, could be an effective therapeutic strategy to control disease evolution. Exploiting the melanocortin system using natural or synthetic ligands can form a realistic basis to counteract certain deleterious effects of respiratory virus infections. The central and peripheral protective actions exerted following melanocortin receptor activation could allow dampening the harmful events that trigger the cytokine storm and endothelial dysfunction while sustaining the beneficial signals required to elicit repair mechanisms. The long standing evidence for melanocortin safety encourages this approach.
Betulinic Acid Inhibits Endometriosis Through Suppression of Estrogen Receptor β Signaling Pathway
Authors: Xiang Dongfang , Zhao Min , Cai Xiaofan , Wang Yongxia , Zhang Lei , Yao Helen , Liu Min , Yang Huan , Xu Mingtao , Li Huilin , Peng Huijuan , Wang Min , Liang Xuefang , Li Ling , Yao Paul
Published: December 2020

Endometriosis is an inflammatory gynecological disorder characterized by endometrial tissue growth located outside of the uterine cavity in addition to chronic pelvic pain and infertility. In this study, we aim to develop a potential therapeutic treatment based on the pathogenesis and mechanism of Endometriosis. Our preliminary data showed that the expression of estrogen receptor β (ERβ) was significantly increased, while ERα was significantly decreased, in endometriotic cells compared to normal endometrial cells. Further investigation showed that betulinic acid (BA) treatment suppressed ERβ expression through epigenetic modification on the ERβ promoter, while had no effect on ERα expression. In addition, BA treatment suppresses ERβ target genes, including superoxide dismutase 2 (SOD2), nuclear respiratory factor-1 (NRF1), cyclooxygenase 2 (COX2), and matrix metalloproteinase-1 (MMP1), subsequently increasing oxidative stress, triggering mitochondrial dysfunction, decreasing elevated proinflammatory cytokines, and eventually suppressing endometriotic cell proliferation, mimicking the effect of ERβ knockdown. On the other hand, gain of ERβ by lentivirus infection in normal endometrial cells resulted in increased cell proliferation and proinflammatory cytokine release, while BA treatment diminished this effect through ERβ suppression with subsequent oxidative stress and apoptosis. Our results indicate that ERβ may be a major driving force for the development of endometriosis, while BA inhibits Endometriosis through specific suppression of the ERβ signaling pathway. This study provides a novel therapeutic strategy for endometriosis treatment through BA-mediated ERβ suppression.
The Genotype-Phenotype Association of Von Hipple Lindau Disease Based on Mutation Locations: A Retrospective Study of 577 Cases in a Chinese Population
Authors: Qiu Jianhui , Zhang Kenan , Ma Kaifang , Zhou Jingcheng , Gong Yanqing , Cai Lin , Gong Kan
Published: December 2020

Purpose

Von Hippel-Lindau (VHL) disease is a hereditary kidney cancer syndrome, with which patients are more likely to get affected by renal cell carcinoma (RCC), pancreatic cyst or tumor (PCT), central nervous system hemangioblastoma (CHB), retinal angiomas (RA), and pheochromocytoma (PHEO). Mutations of VHL gene located in 3p25 may impair the function of the VHL protein and lead to the disease. It’s unclear why obvious phenotype varieties exist among VHL patients. Here we aimed to ascertain whether the mutation types and locations affect the phenotype.

Methods

We enrolled 577 Chinese VHL patients from 211 families and divided them into three groups and six subgroups according to their mutation types and locations. Cox survival analysis and Kaplan-Meier analysis were used to compare intergroup age-related tumor risks.

Results

Patients with nonsense or frameshift mutations that were located before residues 117 of VHL protein (NoF1 subgroup) hold lower age-related risks of VHL associated tumors (HR = 0.638, 95%CI 0.461–0.883, p = 0.007), CHB (HR = 0.596, 95%CI 0.409–0.868, p = 0.007) or PCT (HR = 0.595, 95%CI 0.368–0.961, p = 0.034) than patients whose mutations were located after residues 117 (NoF2 subgroup). Patients in NoF1 subgroup still had lower age-related risks of CHB (HR = 0.652, 95%CI 0.476–0.893, p = 0.008) and PCT (HR = 0.605, 95%CI 0.398–0.918, p = 0.018) compared with those in combined NoF2 subgroup and other truncating mutation patients. NoF1 subgroup correspondingly had a longer estimated median lifespan (64 vs. 55 year, p = 0.037) than NoF2 subgroup. Among patients with missense mutations of VHL, only a small minority (23 of 286 missense mutations carriers) carried mutations involving neither HIF-α binding region nor elongin C binding region, who were grouped in MO subgroup. MO subgroup seemed to have a higher age-related risk of PHEO. In the whole cohort (n = 577), PHEO was an independent protective factor for CHB (p = 0.001) and survival (p = 0.005). RA and CHB failed to predict the age-related risk of each other.

Conclusion

The mutation types and locations of VHL gene are associated with phenotypes. Genetic counselors could predict phenotypes more accurately based on more detailed genotype-phenotype correlations. Further genotype-phenotype studies should focus on the prediction of tumor recurrence, progression, and metastasis. The deep molecular mechanism of genotype-phenotype correlation is worth further exploring.
Machine Learning Based Computational Gene Selection Models: A Survey, Performance Evaluation, Open Issues, and Future Research Directions
Authors: Mahendran Nivedhitha , Durai Raj Vincent P. M. , Srinivasan Kathiravan , Chang Chuan-Yu
Published: December 2020

Gene Expression is the process of determining the physical characteristics of living beings by generating the necessary proteins. Gene Expression takes place in two steps, translation and transcription. It is the flow of information from DNA to RNA with enzymes’ help, and the end product is proteins and other biochemical molecules. Many technologies can capture Gene Expression from the DNA or RNA. One such technique is Microarray DNA. Other than being expensive, the main issue with Microarray DNA is that it generates high-dimensional data with minimal sample size. The issue in handling such a heavyweight dataset is that the learning model will be over-fitted. This problem should be addressed by reducing the dimension of the data source to a considerable amount. In recent years, Machine Learning has gained popularity in the field of genomic studies. In the literature, many Machine Learning-based Gene Selection approaches have been discussed, which were proposed to improve dimensionality reduction precision. This paper does an extensive review of the various works done on Machine Learning-based gene selection in recent years, along with its performance analysis. The study categorizes various feature selection algorithms under Supervised, Unsupervised, and Semi-supervised learning. The works done in recent years to reduce the features for diagnosing tumors are discussed in detail. Furthermore, the performance of several discussed methods in the literature is analyzed. This study also lists out and briefly discusses the open issues in handling the high-dimension and less sample size data.
State of the Field in Multi-Omics Research: From Computational Needs to Data Mining and Sharing
Authors: Krassowski Michal , Das Vivek , Sahu Sangram K. , Misra Biswapriya B.
Published: December 2020

Multi-omics, variously called integrated omics, pan-omics, and trans-omics, aims to combine two or more omics data sets to aid in data analysis, visualization and interpretation to determine the mechanism of a biological process. Multi-omics efforts have taken center stage in biomedical research leading to the development of new insights into biological events and processes. However, the mushrooming of a myriad of tools, datasets, and approaches tends to inundate the literature and overwhelm researchers new to the field. The aims of this review are to provide an overview of the current state of the field, inform on available reliable resources, discuss the application of statistics and machine/deep learning in multi-omics analyses, discuss findable, accessible, interoperable, reusable (FAIR) research, and point to best practices in benchmarking. Thus, we provide guidance to interested users of the domain by addressing challenges of the underlying biology, giving an overview of the available toolset, addressing common pitfalls, and acknowledging current methods’ limitations. We conclude with practical advice and recommendations on software engineering and reproducibility practices to share a comprehensive awareness with new researchers in multi-omics for end-to-end workflow.
Dietary Lysine Regulates Body Growth Performance via the Nutrient-Sensing Signaling Pathways in Largemouth Bass (Micropterus salmoides)
Authors: Wang Wenqiang , Xu Yujue , Chi Shuyan , Yang Peng , Mai Kangsen , Song Fei
Published: December 2020

Lysine is known to be a functional nutrient from yeast to human beings. However, the mechanisms for lysine to regulate body growth and metabolism in fish species are far from fully illuminated. In order to elucidate the molecular effects of lysine on growth performance and metabolism, largemouth bass (Micropterus salmoides), which is extremely sensitive to protein composition, was chosen as the experimental model. Juvenile largemouth bass (4.16 ± 0.02g) were fed with the lysine control diet (LC diet), the lysine supplementation diet (LS diet), and the low lysine diet (LL diet) for 8 weeks. The results showed that the LS diet group significantly increased fish growth, feed efficiency, and nutrient retention compared with those of the LL diet group in largemouth bass. Moreover, compared to the LL diet, lysine supplementation also elevated the plasma total protein, total EAA, total AA, and some individual AA concentrations. Mechanistically, lysine supplementation had a significant effect to decrease the mRNA expression levels of peptide and AA transporters induced by lysine restriction. Lysine supplementation also had an important impact on regulating the target of rapamycin (TOR) signaling pathway. More importantly, the key regulators in the amino acid response (AAR) signaling pathway were also down-regulated by lysine supplementation. Our results provide a clear elucidation of how dietary lysine affected growth performance, physiological and biochemical responses, and signaling responses and represent a sound foundation for using lysine to improve the nutrient utilization of poultry by-product meal in largemouth bass.
Metabolomics and Marine Biotechnology: Coupling Metabolite Profiling and Organism Biology for the Discovery of New Compounds
Authors: Reverter Miriam , Rohde Sven , Parchemin Christelle , Tapissier-Bontemps Nathalie , Schupp Peter J.
Published: December 2020

The high diversity of marine natural products represents promising opportunities for drug discovery, an important area in marine biotechnology. Within this context, high-throughput techniques such as metabolomics are extremely useful in unveiling unexplored chemical diversity at much faster rates than classical bioassay-guided approaches. Metabolomics approaches enable studying large sets of metabolites, even if they are produced at low concentrations. Although, metabolite identification remains the main metabolomics bottleneck, bioinformatic tools such as molecular networks can lead to the annotation of unknown metabolites and discovery of new compounds. A metabolomic approach in drug discovery has two major advantages: it enables analyses of multiple samples, allowing fast dereplication of already known compounds and provides a unique opportunity to relate metabolite profiles to organisms’ biology. Understanding the ecological and biological factors behind a certain metabolite production can be extremely useful in enhancing compound yields, optimizing compound extraction or in selecting bioactive compounds. Metazoan-associated microbiota are often responsible for metabolite synthesis, however, classical approaches only allow studying metabolites produced from cultivatable microbiota, which often differ from the compounds produced within the host. Therefore, coupling holobiome metabolomics with microbiome analysis can bring new insights to the role of microbiota in compound production. The ultimate potential of metabolomics is its coupling with other “omics” (i.e., transcriptomics and metagenomics). Although, such approaches are still challenging, especially in non-model species where genomes have not been annotated, this innovative approach is extremely valuable in elucidating gene clusters associated with biosynthetic pathways and will certainly become increasingly important in marine drug discovery.
Investigation on Metal Adornments From Ancient Eastern Europe
Authors: Ghervase Luminița , Dinu Monica , Borș Corina , Angheluță Laurenţiu-Marian , Rădvan Roxana , Cortea Ioana-Maria
Published: December 2020

This study focuses on the investigation of certain bronze adornment objects from the First Iron Age (the so-called middle Hallstatt period), dating to the ninth–eighth c. BC. These objects are part of a bronze and iron hoard (labeled Cx 116) discovered in the present Romanian territory, at Tărtăria–Podu Tărtăriei vest archaeological site, in Alba County. Along with a second hoard of bronze and iron objects, this represents a unique discovery for the present Romanian territory, namely, for the inner Carpathian area and the Lower and Middle Danube Basin, where no such votive discovery had been made by archaeological excavations. The objects, approximately 450 bronze and iron objects—weapons, tools, adornments, and harnesses—were found in the two hoards, in the Southern ditch, which outlines the archaeological site. Digital radiography has been used to assess the physical state of the objects and to identify potential specific craftsmanship details. It showed a fairly good preservation status, with incipient corrosion processes located in the core of some of the objects and some specific traces of the crafting process and subsequent mechanical defects were highlighted. The relatively good state of preservation of the objects can result from the fact that they had been protected from the humid environment by the ceramic vessel they were placed in. XRF and LIBS were used to identify the materials and to stratigraphically evaluate the objects. XRF scanned the surface of the objects, revealing elements related to both the raw material—a copper alloy with tin and lead, together with trace elements related to the specific mining location of the ores, and the depositional environment of the objects–such as iron. LIBS allowed a more in-depth stratigraphic analysis, which indicated a higher copper ratio—compared to iron—as the kinetic series advance, fact that sustains the idea that the major iron input was coming from the depositional environment. Both XRF and LIBS results were consistent with high elemental variability, probably due to the nature of the original material and the influence of the deposition soil conditions.
ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal–Oral Routes
Authors: Zhong Mei , Lin Bingpeng , Pathak Janak L. , Gao Hongbin , Young Andrew J. , Wang Xinhong , Liu Chang , Wu Kaibin , Liu Mingxiao , Chen Jian-ming , Huang Jiangyong , Lee Learn-Han , Qi Cui-ling , Ge Linhu , Wang Lijing
Published: December 2020

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear.

Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level.

Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results.

Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal–oral routes.
Artificially Edited Alleles of the Eukaryotic Translation Initiation Factor 4E1 Gene Differentially Reduce Susceptibility to Cucumber Mosaic Virus and Potato Virus Y in Tomato
Authors: Atarashi Hiroki , Jayasinghe Wikum Harshana , Kwon Joon , Kim Hangil , Taninaka Yosuke , Igarashi Manabu , Ito Kotaro , Yamada Tetsuya , Masuta Chikara , Nakahara Kenji S.
Published: December 2020

Eukaryotic translation initiation factors, including eIF4E, are susceptibility factors for viral infection in host plants. Mutation and double-stranded RNA-mediated silencing of tomato eIF4E genes can confer resistance to viruses, particularly members of the Potyvirus genus. Here, we artificially mutated the eIF4E1 gene on chromosome 3 of a commercial cultivar of tomato (Solanum lycopersicum L.) by using CRISPR/Cas9. We obtained three alleles, comprising two deletions of three and nine nucleotides (3DEL and 9DEL) and a single nucleotide insertion (1INS), near regions that encode amino acid residues important for binding to the mRNA 5' cap structure and to eIF4G. Plants homozygous for these alleles were termed 3DEL, 9DEL, and 1INS plants, respectively. In accordance with previous studies, inoculation tests with potato virus Y (PVY; type member of the genus Potyvirus) yielded a significant reduction in susceptibility to the N strain (PVYN), but not to the ordinary strain (PVYO), in 1INS plants. 9DEL among three artificial alleles had a deleterious effect on infection by cucumber mosaic virus (CMV, type member of the genus Cucumovirus). When CMV was mechanically inoculated into tomato plants and viral coat accumulation was measured in the non-inoculated upper leaves, the level of viral coat protein was significantly lower in the 9DEL plants than in the parental cultivar. Tissue blotting of microperforated inoculated leaves of the 9DEL plants revealed significantly fewer infection foci compared with those of the parental cultivar, suggesting that 9DEL negatively affects the initial steps of infection with CMV in a mechanically inoculated leaf. In laboratory tests, viral aphid transmission from an infected susceptible plant to 9DEL plants was reduced compared with the parental control. Although many pathogen resistance genes have been discovered in tomato and its wild relatives, no CMV resistance genes have been used in practice. RNA silencing of eIF4E expression has previously been reported to not affect susceptibility to CMV in tomato. Our findings suggest that artificial gene editing can introduce additional resistance to that achieved with mutagenesis breeding, and that edited eIF4E alleles confer an alternative way to manage CMV in tomato fields.