bluuebunny/crossref_metadata_2025 huggingface dataset:
THE CONCEPTUAL STRUCTURE OF CHEMICAL EQUILIBRIUM IN UPPER-SECONDARY SCHOOL STUDENTS: EVIDENCE FROM FACTOR ANALYSIS
Authors: Mai Yuhua , Qian Yangyi , Li Linshen , Lan Haihang
Published: January 2021

This research aimed to explore the conceptual structure of chemical equilibrium in upper-secondary school students using factor analysis. Research on chemistry education has shown that chemical equilibrium is an important but difficult-to-understand topic. Exploring the conceptual structure of chemical equilibrium among students will help chemistry researchers and educators to conduct more targeted teaching practices. Based on a survey of chemistry research and teaching practice experts, a high-quality concept pool composed of 24 relevant concepts was developed. Next, a survey involving a total of over 700 twelfth-grade students from five upper-secondary schools was conducted, and a factor analysis was utilized to determine the conceptual structure. The results showed that a three-factor model and a five-factor model with 15 relevant concepts were all accepted as the conceptual structure for students. The new form of conceptual structure in this research helps understand the features and categories in students’ latent organization of concepts. Also, it may be revealed that factor analysis can be utilized as an approach to exploring students’ conceptual structure. Keywords: chemical equilibrium, chemistry education, conceptual structure, factor analysis
A novel combination regimen of BET and FLT3 inhibition for FLT3-ITD acute myeloid leukemia
Authors: Lee Lauren , Hizukuri Yoshiyuki , Severson Paul , Powell Benjamin , Zhang Chao , Ma Yan , Narahara Maiko , Sumi Hiroyuki , Hernandez Daniela , Rajkhowa Trivikram , Bollag Gideon , Levis Mark
Published: January 2021

Acute myeloid leukemia patients with FLT3-ITD mutations have a high risk of relapse and death. FLT3 tyrosine kinase inhibitors improve overall survival, but their efficacy is limited and most patients who relapse will ultimately die of the disease. Even with potent FLT3 inhibition, the disease persists within the bone marrow microenvironment, mainly due to bone marrow stroma activating parallel signaling pathways that maintain pro-survival factors. BET inhibitors suppress pro-survival factors such as MYC and BCL2, but these drugs thus far have shown only limited single-agent clinical potential. We demonstrate here, using pre-clinical and clinical correlative studies, that the novel 4-azaindole derivative, PLX51107, has BET-inhibitory activity in vitro and in vivo. The combination of BET and FLT3 inhibition induces a synergistic antileukemic effect in a murine xenograft model of FLT3-ITD AML, and against primary FLT3-ITD AML cells co-cultured with bone marrow stroma. Using suppression of MYC as a surrogate for BET inhibition, we demonstrate BET inhibition in human patients. The short plasma half-life of PLX51107 results in intermittent target inhibition to enable tolerability while overcoming the protective effect of the microenvironment. Mechanistically, the synergistic cytotoxicity is associated with suppression of key survival genes such as MYC. These data provide the scientific rationale for a clinical trial of a BET plus FLT3 inhibitor for the treatment of relapsed/refractory FLT3-ITD AML. A clinical trial of PLX51107 as monotherapy in patients with different malignancies is underway and will be reported separately.
Vulnerabilidades de adolescentes às infecções sexualmente transmissíveis: Uma revisão integrativa
Authors: Souza Antônio Tiago da Silva , Freitas Francisco Ricardo Nascimento , Silva Mercylha Francisca Gomes , Sousa Maria da Consolação Pitanga de , Pereira Marianne dos Santos , Nascimento Silmaria Bandeira do , Barros Daniela França de , Freitas Débora Joyce Nascimento , Fortes Júnior Edmar José , Alves Marisa Carla Silveira , Santos Naira Denise de Sousa , Almeida Roberto Carvalho Pinto de , Oliveira Daniel Mayco de Melo , Silva Ancelmo Jorge Soares da , Pedrosa José Ivo dos Santos
Published: January 2021

A adolescência é um período de crescimento heterogéneo que marca a passagem da infância à vida adulta, estando associada ao desenvolvimento do comportamento sexual, que pode levar ao aumento do risco de infeções sexualmente transmissíveis, devido às relações sexuais desprotegidas. O obtivo do presente estudo é analisar a produção científica sobre as vulnerabilidades de adolescentes às infecções sexualmente transmissíveis. A pesquisa baseou-se nos métodos de uma revisão integrativa da literatura, a qual possibilita a incorporação de evidências, foi realizado uma seleção de estudos nas bases de dados da saúde como: Lilacs, Scielo e Scopus. Os critérios de inclusão foram: artigos científicos, publicados entre os anos de 2013 a 2020. O período de coleta ocorreu em junho de 2020. A pesquisa mostrou que os adolescentes se encontram em um processo de vulnerabilidade individual por utilizar os métodos de prevenção às IST de forma irregular, como o preservativo, associada à falta de informação sobre questões relacionadas à sexualidade na adolescência como: corpo; sexo; gênero; prevenção as IST. Foi relatado sobre a importância da família para orientar os adolescentes sobre sexualidade e saúde, como também do enfermeiro por ser um profissional que atuam em ações educativas em saúde nos serviços de saúde. Há uma necessidade de ampliar e fortalecer as ações de prevenção entre os adolescentes dentro das escolas, como proposto pelo Programa Saúde na Escola, envolvendo alunos, docentes, família e comunidade em geral. Fortalecer as ações educativas em saúde construindo estratégias que tenham um alcance aos adolescentes, a fim de reduzir as infecções neste grupo.
Antimicrobial activity of Spondias mombin L. aqueous and hydroethanolic extracts on Enterococcus faecalis and Pseudomonas aeruginosa - an in vitro study
Authors: Lima Ingrid Priscila Américo de , Alves Rivanaldo Adriano Holanda , Mayer Juliana de Sousa Lima , Costa Maria Regina Macêdo , Mendonça Angélica Kercya Pereira de , Lima Emanuelle Louyde Ferreira de , Langassner Silvana Maria Zucolotto , Dametto Fábio Roberto , Lima Kenio Costa de , Lins Ruthinéia Diógenes Alves Uchoa
Published: January 2021

Objective: To chemically characterize Spondias mombin L. extracts and to evaluate the in vitro antimicrobial activity of these extracts on Enterococcus faecalis and Pseudomonas aeruginosa. Material and methods: Both extracts were submitted to phytochemical prospecting and thin layer chromatography (TLC) analysis prior to determination of Minimum Inhibitory Concentration (MIC), Minimum Inhibitory Adhesion Concentration (MIAC) and Bactericidal Kinetics (BK). The Student’s t-test was used to compare MIC results at the 5% significance level. The chemical characterization, MIAC and BK data were analyzed descriptively. Results: Phenolic compounds, flavonoids, tannins and saponins were detected in the extracts. The hydroethanolic extracts in different concentrations showed statistically superior inhibitory bacterial growth activity (p <0.05) compared to the control against the two investigated microorganisms, whereas the aqueous extracts (also in different concentrations) was statistically superior (p <0.05) to the control only against Pseudomonas aeruginosa. The anti-adherent effect of both extracts was superior to that of the control for P. aeruginosa, and similar to that for E. faecalis. In their crude and diluted concentrations, aqueous and hydroethanolic extracts showed bactericidal action within the first two to four hours of contact with the bacteria. Conclusion: Spondias mombin L. extracts in different concentrations showed superior antimicrobial activity than 0.12% chlorhexidine digluconate against the microorganisms with this activity associated to the chemical characterization of these extracts.
“Yo, dude! This chick is whack”: English exclamations in romantic films
Authors: A Herlianto
Published: January 2021

This research investigates the forms and functions of English exclamations. By applaying qualitative and quantitative research methods, this research takes romantic films as the subjects. The result showed that in those films the exclamations functioned in the most frequent intensities are to show wonder, anger, surprise and pleasure. While the most frequent forms used are declarative, interjection + declarative, interjection, directive, and interrogative, respectively. These indicate that romantic films tend to express exclamations by declarative rather than other forms in which the context plays an important role for determining what is an expression as exclamation or not rather than the form itself.Keywords: form; function; exclamation
The effectiveness of google classroom in teaching English during Covid-19 at SMA N 1 M. Payed
Authors: Isda Irma Dewi , Imran Imran , Purwati Purwati , Rahmiati Rahmiati
Published: January 2021

This research aimed to find out Google Classroom effectiveness, which was used to enhance students’ speaking skill. This research used a quasi-experimental with a pre-experimental research design. The subject of this study is the eleventh grade of senior high school at SMA N 1 M. Payed. It involved 25 students as a sample of this study. In the process of data collection, the researcher used a pre-test and post-test. The researcher analyzed the data using Wilcoxon Ranks Test to test the hypothesis. This study found the value of significance (2-tailed) was lower than the significance level (0.000 < 0.05), then the Ha was accepted. It means there was a significant value on students’ achievement of the speaking skill by using Google Classroom. Finding obtained of pretest 71,20 and posttest 78,16. In conclusion, the mean pretest and posttest scores differ significantly, or there is an effect of using google classroom enhancing students speaking skill at SMA N 1 Manyak Payed. However, it can be concluded that Google Classroom significantly affects students’ speaking skill and helps them finish and collect the assignment without any bound by time and space.Keywords: google classroom; teaching English; Covid-19
The elimination of anticipated written errors from L1 interference through flipped classrooms
Authors: Prapawadee Napacha
Published: January 2021

Several studies have been conducted on written errors discovered in an EFL classroom, and the findings are similar, and that common errors have been discovered in Thai students’ written work, so these studies conclude that the main cause of errors is L1 interference.  In addition, other related studies reveal that flipped classrooms can support students’ learning process.  It is due to the fact that these days, EFL students still have problems with some grammatical aspects due to their mother tongue, and the class time provided is limited.  Therefore, to ascertain that the flipped classroom can help eliminate the anticipated grammatical problems repeatedly in class; the study looks to develop online lessons on LMS to encourage the students to learn at their own pace and to engage students with class activities.  The online lessons and class activities are currently being implemented, and 25 freshmen participate in this study.  The questionnaire will be completed at the end of the semester to discover their attitudes towards the flipped classroom covering online lessons and class activities.  Also, a pre-test and post-test on simple sentences are used to investigate the students’ learning outcomes via the flipped classroom.  The findings from the pre- and post-tests confirm the results of the former studies that the students produce the anticipated errors such as articles, capitalization, punctuation, nouns, and subject-verb agreement.  Also, synchronous and asynchronous learning can help eliminate those mentioned errors and the students have positive attitudes towards the flipped classroom.Keywords: written errors; L1 interference; flipped classroom
Emotional Correctness
Authors: Flanagan Owen
Published: January 2021

First, I offer an analytic summary of the 10 main theses in Stephen Asma and Rami Gabriel’s (2019) The Emotional Mind. Second, I raise an objection about Asma and Gabriel’s assumption that the emotions have phenomenal sameness in individual psychology, across species and cultures. Third, I focus and develop a critique of Asma and Gabriel’s objections to evaluating emotions in terms of “correctness,” “aptness,” or “fittingness.” I argue that analyzing correctness is an essential task of normative inquiry in psychology, psychiatry, and moral philosophy, and it is perfectly intellectually respectable and compatible with most genealogies of the emotions.
The Emotional Mind and The Moral Mind
Authors: Seok Bongrae
Published: January 2021

In The Emotional Mind, Asma and Gabriel (2019) develop their grand vision of affect. Their goal is to demonstrate the foundational and pervasive nature of emotion in the mind, culture and society through the embodied, embedded, and enactive process of evolution. The book discusses how affective adaptation supports or leads diverse facets of human psychology and society. In this paper, however, I raise three critical questions about Asma and Gabriel’s approach to emotion: (1) whether emotion is a natural kind, (2) whether internalized self-critical emotions came to exist through the adaptive and interactive process of decoupling, and (3) whether the variance and integrity of the tripartite layers of the mind can be maintained.
Polar bear Ursus maritimus use of the western Hudson Bay flaw lead
Authors: Henderson EM , Derocher AE , Lunn NJ , Montpetit B , Merrill EH , Richardson ES
Published: January 2021

Flaw leads (FLs) and polynyas are recurrent areas of open water within sea ice that provide habitat for a diversity of Arctic species. The western Hudson Bay FL is a major, predictable habitat feature; however, its importance to polar bears Ursus maritimus has not been examined. We mapped the FL using synthetic aperture radar (resolution 62.3 × 121 m) from December to May, 2009-2018, and assessed FL use by 73 adult female polar bears tracked using satellite telemetry. Maximum FL width varied from 4 km in March to 145 km in May. Bears were closest to the FL in May, which coincided with their hyperphagic period and the seal pupping season. Only 31.5% (n = 23) of the bears used the FL, and they travelled faster, with lower turning angles along the FL (16° turns at 101° and -69° relative to the FL), suggesting the feature acted as a corridor that could increase prey encounters. Bears were closer to and crossed sections of the FL that were 68% narrower than those not crossed, indicating that a wider FL deters crossing. Abundant prey likely attracts some bears to the FL, but most bears avoid the FL between hunts, likely to conserve energy on consolidated ice or to reduce intraspecific interactions. Increases in open water resulting from climate warming might make the FL more challenging for bears to cross, but could make it more attractive if open-water prey densities increase.
Quality of Newly Formed Cartilaginous Tissue in Defects of Articular
Surface after Transplantation of Mesenchymal Stem Cells in a
Composite Scaffold Based on Collagen I with Chitosan Micro- and
Nanofibres
Authors: Nečas A , Plánka L , Srnec R , Crha M , Hlučilová J , Klíma J , Starý D , Křen L , Amler E , Vojtová L , Jančář J , Gál P
Published: January 2021

The aim of this study was to evaluate macroscopically,
histologically and immunohistochemically the quality of newly
formed tissue in iatrogenic defects of articular cartilage of the
femur condyle in miniature pigs treated with the clinically used
method of microfractures in comparison with the transplantation
of a combination of a composite scaffold with allogeneic
mesenchymal stem cells (MSCs) or the composite scaffold alone.
The newly formed cartilaginous tissue filling the defects of
articular cartilage after transplantation of the scaffold with MSCs
(Group A) had in 60 % of cases a macroscopically smooth
surface. In all lesions after the transplantation of the scaffold
alone (Group B) or after the method of microfractures (Group C),
erosions/fissures or osteophytes were found on the surface. The
results of histological and immunohistochemical examination
using the modified scoring system according to O’Driscoll were as
follows: 14.7±3.82 points after transplantations of the scaffold
with MSCs (Group A); 5.3±2.88 points after transplantations of
the scaffold alone (Group B); and 5.2±0.64 points after treatment
with microfractures (Group C). The O’Driscoll score in animals of
Group A was significantly higher than in animals of Group B or
Group C (p<0.0005 both). No significant difference was found in
the O’Driscoll score between Groups B and C. The treatment of
iatrogenic lesions of the articular cartilage surface on the
condyles of femur in miniature pigs using transplantation of MSCs
in the composite scaffold led to the filling of defects by a tissue
of the appearance of hyaline cartilage. Lesions treated by
implantation of the scaffold alone or by the method of
microfractures were filled with fibrous cartilage with worse
macroscopic, histological and immunohistochemial indicators.
Modulation of Type I Iodothyronine 5’-Deiodinase Activity in white
Adipose Tissue by Nutrition: Possible Involvement of Leptin
Authors: Macek Jílková Z , Pavelka S , Flachs P , Hensler M , Kůs V , Kopecký J
Published: January 2021

Adipose tissue is an important target for thyroid hormones (TH).
However, the metabolism of TH in white adipose tissue is poorly
characterized. Our objective was to describe possible changes in
activities of TH-metabolizing enzymes in white adipose tissue,
and the role of TH metabolism in the tissue during obesogenic
treatment, caloric restriction and in response to leptin in mice.
Activity of type I iodothyronine 5’-deiodinase (D1) in white fat
was stimulated by a high-fat diet, which also increased plasma
leptin levels, while brown adipose tissue D1 activity did not
change. Caloric restriction decreased the activity of D1 in white
fat (but not in the liver), reduced leptin levels, and increased the
expression of stearoyl CoA desaturase 1 (SCD-1), a marker and
mediator of the effect of leptin on tissue metabolism. Leptin
injections increased D1 activity and down-regulated SCD-1 in
white fat. Our results demonstrate changes in D1 activity in white
adipose tissue under the conditions of changing adiposity, and a
stimulatory effect of leptin on D1 activity in the tissue. These
results suggest a functional role for D1 in white adipose tissue,
with D1 possibly being involved in the control of adipose tissue
metabolism and/or accumulation of the tissue.
Central Autonomic Regulation Assessed by Pupillary Light Reflex is Impaired in Children With Attention Deficit Hyperactivity Disorder
Authors: HAMRAKOVA A , ONDREJKA I , SEKANINOVA N , BONA OLEXOVA L , VISNOVCOVA Z , CESNEKOVA D , HRTANEK I , OPPA M , HUTKA P , TONHAJZEROVA Ingrid
Published: January 2021

It is assumed that the Attention Deficit Hyperactivity Disorder is associated with the central autonomic dysregulation, however, the studies are rare. Analysis of pupillary light reflex represents a non-invasive tool to provide information related to the central autonomic regulation; thus, we aimed to evaluate potential disturbances in the central autonomic integrity using pupillary light reflex examination in Attention Deficit Hyperactivity Disorder. We have examined 20 children with Attention Deficit Hyperactivity Disorder (10 boys, 13.0±2.3 years) and 20 age/gender-matched healthy subjects. Pupillary light reflex was examined at rest for both eyes using Pupillometer PLR-2000 (NeurOptics, USA). Evaluated parameters were: diameter of the pupil before the application of light stimulus and after illumination at the peak of the constriction, the percentual change of the pupil diameter during constriction, average constriction velocity, maximum constriction velocity and average dilation velocity. We found significantly lower percentual change of the pupil diameter during constriction for both eyes in Attention Deficit Hyperactivity Disorder group compared to controls (right eye: -25.81±1.23 % vs. -30.32±1.31 %, p<0.05, left eye: -25.44±1.65 % vs. -30.35±0.98 %, p˂0.05). The average constriction velocity and maximum constriction velocity were significantly shortened in left eye in Attention Deficit Hyperactivity Disorder group compared to controls (p˂0.05). Our findings revealed altered pupillary light reflex indicating abnormal centrally-mediated autonomic regulation characterized by parasympathetic underactivity associated with relative sympathetic predominance in children suffering from Attention Deficit Hyperactivity Disorder.
YOĞUN BAKIM ÜNİTELERİNDEN İZOLE EDİLEN PSEUDOMONAS AERUGİNOSA SUŞLARININ ANTİBİYOTİKLERE DUYARLILIKLARI
Authors: ERDOĞAN Mehmet Mustafa , ACUN DELEN Leman , ERDOĞAN Esra
Published: January 2021

Pseudomonas aeruginosa suşları özellikle yoğun bakım ünitelerinde yatan hasta örneklerinden sıklıkla izole edilmektedir. Bu suşlar morbidite ve mortaliteyi artırıp, antibiyotik direnci nedeniyle zor tedavi edilen enfeksiyonlara yol açmaktadır. Bu çalışmanın amacı, Malatya Eğitim ve Araştırma Hastanesi’nin yoğun bakım hastalarından izole edilen P. aeruginosa izolatlarının çeşitli antibiyotiklere direncinin belirlenmesidir. Çalışmaya Temmuz 2016–Temmuz 2019 tarihleri arasında Malatya Eğitim ve Araştırma Hastanesi’nin yoğun bakım ünitelerinde izlenmiş olan hastaların çeşitli klinik örneklerinden izole edilen P. aeruginosa suşları dâhil edilmiştir. Suşların identifikasyonu ve in-vitro antibiyotik duyarlılıkları Vitek 2 otomatize sistemi (bioMérieux, France) ile belirlenmiştir. Çalışmaya dâhil edilen 468 P. aeruginosa suşunun % 51,7'si solunum yolu örneklerinden izole edilirken bunu % 31,2 ile idrar ve %9 ile abse ve yara örnekleri izlemiştir. P. aeruginosa suşları için en etkili antibiyotikler kolistin ve norfloksasin olarak belirlenirken, çalışılan antibiyotikler arasında en düşük duyarlılık aztreonam için tespit edilmiştir. Duyarlılık oranları amikasine %76,5, aztreonama %8,1, gentamisine %74,4, imipeneme %62,2, kolistine %97,1, levofloksasine %57,5, meropeneme %61,4, netilmisine %57,4, norfloksasine %89,9, piperasilin/tazobaktama %48,7, piperasiline %35,7, sefepime %57,7, seftazidime %62,7, siprofloksasine %66, tobramisine ise %80,9 olarak saptanmıştır. Özellikle yoğun bakım ünitelerinde yatan kritik hastalarda, etkin ve doğru enfeksiyon kontrol stratejileri geliştirebilmek, morbidite ve mortaliteyi azaltabilmek için enfeksiyon etkenlerinin dağılımının ve duyarlılıklarının bilinmesi önemlidir.
IDENTIFIKASI BORAKS PADA PENTOL BAKSO YANG DI KELURAHAN AIR HITAM DENGAN PEREAKSI KULIT BUAH NAGA MERAH (Hylocereus polyhizus)
Authors: Lestari Dwi , Dewi Mutia , Ningsih Suci Cahya , Hidayati Hidayati
Published: January 2021

Borax is often misused to preserve various foods such as wet noodles, meatballs, rice cake, rhombus and so on. Red dragon fruit skin contains secondary metabolites, namely anthocyanin, anthocyanin is the most important and widespread dye in the skin of red dragon fruit, but the use of red dragon fruit peels has not been studied much naturally. The purpose of this study was to identify borax on the meatball sold in the Air Hitam district with the red dragon fruit skin reagent (Hylocereus polyhizus). This research is experimental with data collection techniques by accidental sampling. In this study used several samples of meatball pentol purchased at the meatball merchant located in Air Hitam Village by using dragon fruit peel and AgNO3 reagent as a comparison indicator. This research includes plant determination, sample collection, sample preparation, spike making, dragon fruit skin extract reagents and qualitative sample testing. Data analysis using descriptive analysis method. The results of the identification of borax on 5 meatball samples using color reagents from the extract (essence) of the red dragon fruit peel and AgNO3 reagent as a comparative indicator showed that all samples of the meatball obtained Negative results
Emergence of Log-Normal Type Distributions in Avalanche Processes in Living Systems: A Network Model
Authors: Polizzi Stefano , Arneodo Alain , Pérez-Reche Francisco-José , Argoul Françoise
Published: January 2021

Actin is the major cytoskeletal protein of mammal cells that forms microfilaments organized into higher-order structures by a dynamic assembly-disassembly mechanism with cross-linkers. These networks provide the cells with mechanical support, and allow cells to change their shape, migrate, divide and develop a mechanical communication with their environment. The quick adaptation of these networks upon stretch or compression is important for cell survival in real situations. Using atomic force microscopy to poke living cells with sharp tips, we revealed that they respond to a local and quick shear through a cascade of random and abrupt ruptures of their cytoskeleton, suggesting that they behave as a quasi-rigid random network of intertwined filaments. Surprisingly, the distribution of the strength and the size of these rupture events did not follow power-law statistics but log-normal statistics, suggesting that the mechanics of living cells would not fit into self-organized critical systems. We propose a random Gilbert network to model a cell cytoskeleton, identifying the network nodes as the actin filaments, and its links as the actin cross-linkers. We study mainly two versions of avalanches. First, we do not include the fractional visco-elasticity of living cells, assuming that the ruptures are instantaneous, and we observe three avalanche regimes, 1) a regime where avalanches are rapidly interrupted, and their size follows a distribution decaying faster than a power-law; 2) an explosive regime with avalanches of large size where the whole network is damaged and 3) an intermediate regime where the avalanche distribution goes from a power-law, at the critical point, to a distribution containing both 1) and (ii). Then, we introduce a time varying breaking probability, to include the fractional visco-elasticity of living cells, and recover an approximated log-normal distribution of avalanche sizes, similar to those observed in experiments. Our simulations show that the log-normal statistics requires two simple ingredients: a random network without characteristic length scale, and a breaking rule capturing the broadly observed visco-elasticity of living cells. This work paves the way for future applications to large populations of non-linear individual elements (brain, heart, epidemics, … ) where similar log-normal statistics have also been observed.
Controlled Release Utilizing Initiated Chemical Vapor Deposited (iCVD) of Polymeric Nanolayers
Authors: Gleason Karen K.
Published: January 2021

This review will focus on the controlled release of pharmaceuticals and other organic molecules utilizing polymeric nanolayers grown by initiated chemical vapor deposited (iCVD). The iCVD layers are able conform to the geometry of the underlying substrate, facilitating release from one- and two-dimensional nanostructures with high surface area. The reactors for iCVD film growth can be customized for specific substrate geometries and scaled to large overall dimensions. The absence of surface tension in vapor deposition processes allows the synthesis of pinhole-free layers, even for iCVD layers <10 nm thick. Such ultrathin layers also provide rapid transport of the drug across the polymeric layer. The mild conditions of the iCVD process avoid damage to the drug which is being encapsulated. Smart release is enabled by iCVD hydrogels which are responsive to pH, temperature, or light. Biodegradable iCVD layers have also be demonstrated for drug release.
Mitochondrial Dynamics in the Drosophila Ovary Regulates Germ Stem Cell Number, Cell Fate, and Female Fertility
Authors: Garcez Marcia , Branco-Santos Joana , Gracio Patricia C. , Homem Catarina C. F.
Published: January 2021

The fate and proliferative capacity of stem cells have been shown to strongly depend on their metabolic state. Mitochondria are the powerhouses of the cell being responsible for energy productionviaoxidative phosphorylation (OxPhos) as well as for several other metabolic pathways. Mitochondrial activity strongly depends on their structural organization, with their size and shape being regulated by mitochondrial fusion and fission, a process known as mitochondrial dynamics. However, the significance of mitochondrial dynamics in the regulation of stem cell metabolism and fate remains elusive. Here, we characterize the role of mitochondria morphology in female germ stem cells (GSCs) and in their more differentiated lineage. Mitochondria are particularly important in the female GSC lineage. Not only do they provide these cells with their energy requirements to generate the oocyte but they are also the only mitochondria pool to be inherited by the offspring. We show that the undifferentiated GSCs predominantly have fissed mitochondria, whereas more differentiated germ cells have more fused mitochondria. By reducing the levels of mitochondrial dynamics regulators, we show that both fused and fissed mitochondria are required for the maintenance of a stable GSC pool. Surprisingly, we found that disrupting mitochondrial dynamics in the germline also strongly affects nurse cells morphology, impairing egg chamber development and female fertility. Interestingly, reducing the levels of key enzymes in the Tricarboxylic Acid Cycle (TCA), known to cause OxPhos reduction, also affects GSC number. This defect in GSC self-renewal capacity indicates that at least basal levels of TCA/OxPhos are required in GSCs. Our findings show that mitochondrial dynamics is essential for female GSC maintenance and female fertility, and that mitochondria fusion and fission events are dynamically regulated during GSC differentiation, possibly to modulate their metabolic profile.
Circular RNA_PDHX Promotes the Proliferation and Invasion of Prostate Cancer by Sponging MiR-378a-3p
Authors: Mao Yuanshen , Li Wenfeng , Hua Bao , Gu Xin , Pan Weixin , Chen Qi , Xu Bin , Lu Chao , Wang Zhong
Published: January 2021

The dysregulation of circular RNAs (circRNAs) is implicated in the pathogenesis of prostate cancer (PCa). However, the underlying mechanisms by which hsa_circ_0003768 (circPDHX) contributes to PCa remain elusive. The differentially expressed circRNAs between PCa and normal tissues were identified by Gene Expression Omnibus dataset. The association of circPDHX and miR-378a-3p expression with the clinicopathological parameters and prognosis in patients with PCa was analyzed by fluorescence in situ hybridization and The Cancer Genome Atlas dataset. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays as well as a xenograft tumor model were used to assess the role of circPDHX in PCa cells. circPDHX-specific binding with miR-378a-3p was validated by bioinformatic analysis, luciferase gene reporter, and RNA immunoprecipitation assays. As a result, we found that increased expression of circPDHX was associated with Gleason score (P = 0.001) and pathogenic T stage (P = 0.01) and acted as an independent prognostic factor of poor survival (P = 0.036) in patients with PCa. Knockdown of circPDHX inhibited cell proliferation and invasion in vitro and in vivo, but ectopic expression of circPDHX reversed these effects. Furthermore, circPDHX could sponge miR-378a-3p to promote cell proliferation, but miR-378a-3p counteracted circPDHX-induced cell proliferation and insulin-like growth factor 1 receptor (IGF1R) expression in PCa cells. In conclusion, our findings demonstrated that circPDHX facilitated the proliferation and invasion of PCa cells by sponging miR-378a-3p.
PRSS1 Upregulation Predicts Platinum Resistance in Ovarian Cancer Patients
Authors: Xing Linan , Tian Songyu , Mi Wanqi , Zhang Yongjian , Zhang Yunyan , Zhang Yuxi , Xu Fengye , Zhang Chunlong , Lou Ge
Published: January 2021

Ovarian cancer is the most frequent cause of death among gynecologic malignancies. A total of 80% of patients who have completed platinum-based chemotherapy suffer from relapse and develop resistance within 2 years. In the present study, we obtained patients' complete platinum (cisplatin and carboplatin) medication information from The Cancer Genome Atlas database and then divided them into two categories: resistance and sensitivity. Difference analysis was performed to screen differentially expressed genes (DEgenes) related to platinum response. Subsequently, we annotated DEgenes into the protein–protein interaction network as seed nodes and analyzed them by random walk. Finally, second-ranking protease serine 1 gene (PRSS1) was selected as a candidate gene for verification analysis. PRSS1's expression pattern was continuously studied in Oncomine and cBio Cancer Genomic Portal databases, revealing the key roles of PRSS1 in ovarian cancer formation. Hereafter, we conducted in-depth explorations on PRSS1's platinum response to ovarian cancer through tissue and cytological experiments. Quantitative real-time polymerase chain reaction and Western blot assay results indicated that PRSS1 expression levels in platinum-resistant samples (tissue/cell) were significantly higher than in samples sensitive to platinum. By cell transfection assay, we observed that knockdown of PRSS1 reduced the resistance of ovarian cancer cells to cisplatin. Meanwhile, overexpression of PRSS1 increased the resistance to cisplatin. In conclusion, we identified a novel risk gene PRSS1 related to ovarian cancer platinum response and confirmed its key roles using multiple levels of low-throughput experiments, revealing a new treatment strategy based on a novel target factor for overcoming cisplatin resistance in ovarian cancer.
Non-neuronal Role of Acetylcholinesterase in Bone Development and Degeneration
Authors: Luo Xiaohe , Lauwers Marianne , Layer Paul G. , Wen Chunyi
Published: January 2021

Acetylcholinesterase (AChE), an enzyme catalyzing the degradation of acetylcholine, plays an important suppressive role in the cholinergic regulation by terminating the action of acetylcholine. The expression of acetylcholinesterase and other cholinergic components is not restricted to only brain and nerve tissues but can also be found in non-neuronal tissues like the immune system and bone tissue. Primary identification of these components has been achieved. However, the information about their specific functions and underlying molecular mechanisms in bone remains scattered. Here, the physiological process of bone development, homeostasis, and degeneration are introduced. Next, the cholinergic system and its expression in bone tissue is documented. Among them, special attention goes to AChE, as the structure of this enzyme suggests diverse binding affinities, enabled by a peripheral site and a catalytic site. The peripheral site supports the non-enzymatic function of AChE in non-neuronal systems. Based on recent studies, the non-neuronal roles of acetylcholinesterase, both enzymatically and non-enzymatically, in bone development, homeostasis and degeneration are summarized briefly together with potential mechanisms to support these functions. We conclude that AChE may be a potential therapeutic target for bone diseases like osteoporosis.
Subtle Roles of Down Syndrome Cell Adhesion Molecules in Embryonic Forebrain Development and Neuronal Migration
Authors: Mitsogiannis Manuela D. , Pancho Anna , Aerts Tania , Sachse Sonja M. , Vanlaer Ria , Noterdaeme Lut , Schmucker Dietmar , Seuntjens Eve
Published: January 2021

Down Syndrome (DS) Cell Adhesion Molecules (DSCAMs) are transmembrane proteins of the immunoglobulin superfamily. Human DSCAM is located within the DS critical region of chromosome 21 (duplicated in Down Syndrome patients), and mutations or copy-number variations of this gene have also been associated to Fragile X syndrome, intellectual disability, autism, and bipolar disorder. The DSCAM paralogue DSCAM-like 1 (DSCAML1) maps to chromosome 11q23, implicated in the development of Jacobsen and Tourette syndromes. Additionally, a spontaneous mouse DSCAM deletion leads to motor coordination defects and seizures. Previous research has revealed roles for DSCAMs in several neurodevelopmental processes, including synaptogenesis, dendritic self-avoidance, cell sorting, axon growth and branching. However, their functions in embryonic mammalian forebrain development have yet to be completely elucidated. In this study, we revealed highly dynamic spatiotemporal patterns ofDscamandDscaml1expression in definite cortical layers of the embryonic mouse brain, as well as in structures and ganglionic eminence-derived neural populations within the embryonic subpallium. However, an in-depth histological analysis of cortical development, ventral forebrain morphogenesis, cortical interneuron migration, and cortical-subcortical connectivity formation processes in Dscam and Dscaml1 knockout mice (Dscamdel17andDscaml1GT) at several embryonic stages indicated that constitutive loss ofDscamandDscaml1does not affect these developmental events in a significant manner. Given that severalDscam- andDscaml1-linked neurodevelopmental disorders are associated to chromosomal region duplication events, we furthermore sought to examine the neurodevelopmental effects ofDscamandDscaml1gain of function (GOF).In vitro, ex vivo, andin vivoGOF negatively impacted neural migration processes important to cortical development, and affected the morphology of maturing neurons. Overall, these findings contribute to existing knowledge on the molecular etiology of human neurodevelopmental disorders by elucidating how dosage variations of genes encoding adhesive cues can disrupt cell-cell or cell-environment interactions crucial for neuronal migration.
An Evidence for a Novel Antiviral Mechanism: Modulating Effects of Arg-Glc Maillard Reaction Products on the Phase Transition of Multilamellar Vesicles
Authors: Ke Lijing , Luo Sihao , Rao Pingfan , Bradshaw Jeremy P. , Sa'adedin Farid , Rappolt Michael , Zhou Jianwu
Published: January 2021

Maillard reaction products (MRPs) of protein, amino acids, and reducing sugars from many foods and aqueous extracts of herbs are found to have various bioactivities, including antiviral effects. A hypothesis was proposed that their antiviral activity is due to the interaction with the cellular membrane. Aiming to estimate the possible actions of MRPs on phospholipid bilayers, the Arg-Glc MRPs were prepared by boiling the pre-mixed solution of arginine and glucose for 60 min at 100°C and then examined at a series of concentrations for their effects on the phase transition of MeDOPE multilamellar vesicles (MLVs), for the first time, by using differential scanning calorimetry (DSC) and temperature-resolved small-angle X-ray scattering (SAXS). Arg-Glc MRPs inhibited the lamellar gel–liquid crystal (Lβ-Lα), lamellar liquid crystal–cubic (Lα-QII), and lamellar liquid crystal–inverted hexagonal (Lα-HII) phase transitions at low concentration (molar ratio of lipid vs. MRPs was 100:1 or 100:2), but promoted all three transitions at medium concentration (100:5). At high concentration (10:1), the MRPs exhibited inhibitory effect again. The fusion peptide from simian immunodeficiency virus (SIV) induces membrane fusion by promoting the formation of a non-lamellar phase, e.g., cubic (QII) phase, and inhibiting the transition to HII. Arg-Glc MRPs, at low concentration, stabilized the lamellar structure of SIV peptide containing lipid bilayers, but facilitated the formation of non-lamellar phases at medium concentration (100:5). The concentration-dependent activity of MRPs upon lipid phase transition indiciates a potential role in modulating some membrane-related biological events, e.g., viral membrane fusion.
A Non-coding HES1 Variant Predisposes Children to Congenital Heart Disease in Chinese Population
Authors: Song Yangliu , Chen Weicheng , Huang Zitong , Tian Guixiang , Li Mengru , Zhao Zhengshan , Feng Zhiyu , Wu Feizhen , Qian Maoxiang , Ma Xiaojing , Sheng Wei , Huang Guoying
Published: January 2021

Background: As a key component in the NOTCH signaling pathway, HES1 plays an important role in vertebrate heart development. Variants in the HES1 coding sequence are known to be associated with congenital heart disease (CHD). However, little is known about HES1 non-coding sequence variants and their association with the risk of developing CHD.

Method and Results: We initially analyzed the non-coding sequence of the HES1 gene in 12 unrelated CHD families by direct sequencing and identified a previously unreported promoter region variant (NM_005524.4: c.−1279−1278 insAC, rs148941464) in the HES1 gene in four CHD families. The homozygous variant in patients was inherited from carrier parents with normal phenotypes, indicating a likely recessive genetic model. Given that the HES1 gene is predicted to be likely to exhibit haploinsufficiency (%HI: 11.44), we hypothesized that the HES1 homozygous variant is a genetic risk factor underlying CHD. We then carried out sequencing of this HES1 variant in 629 sporadic non-syndromic CHD cases and 696 healthy controls and performed association analysis. Interestingly, we observed a significant association of the homozygous HES1 promoter variant with CHD (18.92% of cases vs. 9.91% of controls; OR: 2.291, 95% CI: 1.637-3.207, p = 9.72 × 10−7). No significant association with CHD was observed for the HES1 promoter heterozygous variant (p > 0.05). However, association analysis tests of the HES1 homozygous variant with each subtype of CHD revealed that this homozygous variant was strongly associated with transposition of the great arteries (TGA) (OR: 3.726, 95% CI: 1.745-7.956, p = 0.0003). Moreover, the prevalence of HES1 homozygous variants in CHD patients with TGA (27.66%) was significantly higher than that in patients with other CHD subtypes or controls. Similar results were observed in a replication group of TGA (n = 64). Functional studies demonstrated that the homozygous variant in the HES1 promoter can disrupt its ability to bind RXRA, an inhibitory transcription factor, which results in abnormally high expression of the HES1 gene, indicating that this variant harbors gain-of-function effects.

Conclusions: Our findings reveal that the non-coding homozygous variant in the HES1 promoter has a gain-of-function effect and is associated with an increased risk of CHD development, especially the severe TGA subtype.
A Review of Stochastic Programming Methods for Optimization of Process Systems Under Uncertainty
Authors: Li Can , Grossmann Ignacio E.
Published: January 2021

Uncertainties are widespread in the optimization of process systems, such as uncertainties in process technologies, prices, and customer demands. In this paper, we review the basic concepts and recent advances of a risk-neutral mathematical framework called “stochastic programming” and its applications in solving process systems engineering problems under uncertainty. This review intends to provide both a tutorial for beginners without prior experience and a high-level overview of the current state-of-the-art developments for experts in process systems engineering and stochastic programming. The mathematical formulations and algorithms for two-stage and multistage stochastic programming are reviewed with illustrative examples from process industries. The differences between stochastic programming under exogenous uncertainty and endogenous uncertainties are discussed. The concepts and several data-driven methods for generating scenario trees are also reviewed.
The Role of Porphyromonas gingivalis Outer Membrane Vesicles in Periodontal Disease and Related Systemic Diseases
Authors: Zhang Zhiying , Liu Dongjuan , Liu Sai , Zhang Shuwei , Pan Yaping
Published: January 2021

Periodontal disease is a chronic infectious disease associated with a variety of bacteria, which can cause damage to the periodontal support structure and affect a variety of systemic system diseases such as cancer, cardiovascular disease, diabetes, rheumatoid arthritis, non-alcoholic fatty liver, and Alzheimer’s disease. Porphyromonas gingivalis (P. gingivalis) is the most important pathogenic bacteria for periodontal disease. It can produce outer membrane vesicles (OMVs) and release them into the environment, playing an important role in its pathogenesis. This article focuses on P. gingivalis OMVs, reviews its production and regulation, virulence components, mode of action and related diseases, with a view to providing new ideas for the prevention and treatment of diseases related to P. gingivalis infections.
Streptococcus pyogenes M1T1 Variants Induce an Inflammatory Neutrophil Phenotype Including Activation of Inflammatory Caspases
Authors: Williams Jonathan G. , Ly Diane , Geraghty Nicholas J. , McArthur Jason D. , Vyas Heema K. N. , Gorman Jody , Tsatsaronis James A. , Sluyter Ronald , Sanderson-Smith Martina L.
Published: January 2021

Invasive infections due to group AStreptococcus(GAS) advance rapidly causing tissue degradation and unregulated inflammation. Neutrophils are the primary immune cells that respond to GAS. The neutrophil response to GAS was characterised in response to two M1T1 isolates; 5448 and animal passaged variant 5448AP. Co-incubation of neutrophils with 5448AP resulted in proliferation of GAS and lowered the production of reactive oxygen species when compared with 5448. Infection with both strains invoked neutrophil death, however apoptosis was reduced in response to 5448AP. Both strains induced neutrophil caspase-1 and caspase-4 expressionin vitro, with inflammatory caspase activation detectedin vitroandin vivo. GAS infections involving strains such as 5448AP that promote an inflammatory neutrophil phenotype may contribute to increased inflammation yet ineffective bacterial eradication, contributing to the severity of invasive GAS infections.
Unraveling the Interconnection Patterns Across Lung Microbiome, Respiratory Diseases, and COVID-19
Authors: Stavropoulou Elisavet , Kantartzi Konstantia , Tsigalou Christina , Konstantinidis Theocharis , Voidarou Chrissoula , Konstantinidis Theodoros , Bezirtzoglou Eugenia
Published: January 2021

Albeit the lungs were thought to be sterile, recent scientific data reported a microbial microbiota in the lungs of healthy individuals. Apparently, new developments in technological approachesincluding genome sequencing methodologies contributed in the identification of the microbiota and shed light on the role of the gut and lung microbiomes in the development of respiratory diseases. Moreover, knowledge of the human microbiome in health may act as a tool for evaluating characteristic shifts in the case of disease. This review paper discusses the development of respiratory disease linked to the intestinal dysbiosis which influences the lung immunity and microbiome. The gastrointestinal–lung dialogue provides interesting aspects in the pathogenesis of the respiratory diseases. Lastly, we were further interested on the role of this interconnection in the progression and physiopathology of newly emergedCOVID-19.
Mobilizing Climate Information for Decision-Making in Africa: Contrasting User-Centered and Knowledge-Centered Approaches
Authors: Harvey Blane , Huang Ying-Syuan , Araujo Julio , Vincent Katharine , Roux Jean-Pierre , Rouhaud Estelle , Visman Emma
Published: January 2021

This study examined ways in which climate information was mobilized for use under Future Climate for Africa (FCFA), an applied research program to improve the use of climate information to support medium-term (5–40 years) policies and planning in sub-Saharan Africa. Past research has underscored the interdependent relationship between user engagement and knowledge mobilization in effective climate knowledge uptake. The study used a document analysis of 46 program ou tputs and semi-structured interviews with 13 FCFA researchers to contrast user-centered and knowledge-centered approaches to effectively mobilize climate information uptake for use. A total of 20 knowledge mobilization tools and approaches were identified across the program and analyzed. This analysis reveals a complex interplay between user engagement and knowledge mobilization processes, including the strategic or flexible use and re-use of knowledge products as the user engagement process evolved. These findings have important implications for future programmatic design and planning in promoting engagement and mobilization approaches that can contribute to long-term policy and decision-making.