bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating Decorin’s role in the preovulatory follicle
Authors: Kedem A. , Ulanenko-Shenkar K. , Yung Y. , Yerushalmi G. M. , Maman E. , Hourvitz A. 
Published: February 2020

Abstract
Background
DCN (decorin) is a proteoglycan known to be involved in regulating cell proliferation, collagen fibril organization and migration. In our global transcriptome RNA-sequencing approach to systematically identify new ovulation-associated genes, DCN was identified as one of the highly regulated genes. We therefore hypothesize that DCN may have a role in ovulatory processes such as cell migration and proliferation.

Aim
To characterize the expression, regulation and function of the proteoglycan DCN in the human ovarian follicles during the preovulatory period.

Methods
The in-vivo expression of DCN mRNA in mural (MGCs) and cumulus (CGCs) granulosa cells was characterized using quantitative RT-PCR and western blot.
A signaling study was performed by treating human MGCs cultures with gonadotropins and different stimulators and inhibitors to determine their effect on DCN expression by qRT- PCR and elucidate the pathways regulating these proteins.
In a functional study, KGN granulosa cell line was used to study cell migration with a scratch assay.

Results
DCN mRNA expression was significantly higher in MGCs compared to CGCs. DCN mRNA was significantly higher in CGCs surrounding mature metaphase II (MII) oocytes compared to CGCs of germinal vesicle (GV) and metaphase I (MI) oocytes.
hCG significantly increased DCN mRNA and protein expression levels in cultured MGCs. Using signal transduction activators and inhibitors, we demonstrated that DCN induction by LH/hCG is carried out via PKA, PKC, ERK/MEK, and PI3K pathways.
We showed that DCN expression is also induced in high-density cell cultures, in a dose-dependent pattern. In addition, progesterone induced a significant increase in DCN secretion to the media. MGCs from follicles of endometriosis patients exhibited reduced (about 20% of) mRNA transcriptions levels compared to MGCs follicles of control patients. More significantly, we found that DCN has an inhibiting effect on KGN cell migration.

Conclusions
Our study indicates that DCN is a unique ovulatory gene.
Our findings support the hypothesis that DCN plays an important new role during the preovulatory period and ovulation, and stress its involvement in endometriosis infertility. A better understanding of DCN role in ovulation and endometriosis may provide treatment for some types of infertility.
A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells
Authors: Lee Sooncheol , Micalizzi Douglas , Truesdell Samuel S. , Bukhari Syed I. A. , Boukhali Myriam , Lombardi-Story Jennifer , Kato Yasutaka , Choo Min-Kyung , Dey-Guha Ipsita , Ji Fei , Nicholson Benjamin T. , Myers David T. , Lee Dongjun , Mazzola Maria A. , Raheja Radhika , Langenbucher Adam , Haradhvala Nicholas J. , Lawrence Michael S. , Gandhi Roopali , Tiedje Christopher , Diaz-Muñoz Manuel D. , Sweetser David A. , Sadreyev Ruslan , Sykes David , Haas Wilhelm , Haber Daniel A. , Maheswaran Shyamala , Vasudevan Shobha 
Published: February 2020

Abstract
Background
Quiescence (G0) is a transient, cell cycle-arrested state. By entering G0, cancer cells survive unfavorable conditions such as chemotherapy and cause relapse. While G0 cells have been studied at the transcriptome level, how post-transcriptional regulation contributes to their chemoresistance remains unknown.

Results
We induce chemoresistant and G0 leukemic cells by serum starvation or chemotherapy treatment. To study post-transcriptional regulation in G0 leukemic cells, we systematically analyzed their transcriptome, translatome, and proteome. We find that our resistant G0 cells recapitulate gene expression profiles of in vivo chemoresistant leukemic and G0 models. In G0 cells, canonical translation initiation is inhibited; yet we find that inflammatory genes are highly translated, indicating alternative post-transcriptional regulation. Importantly, AU-rich elements (AREs) are significantly enriched in the upregulated G0 translatome and transcriptome. Mechanistically, we find the stress-responsive p38 MAPK-MK2 signaling pathway stabilizes ARE mRNAs by phosphorylation and inactivation of mRNA decay factor, Tristetraprolin (TTP) in G0. This permits expression of ARE mRNAs that promote chemoresistance. Conversely, inhibition of TTP phosphorylation by p38 MAPK inhibitors and non-phosphorylatable TTP mutant decreases ARE-bearing TNFα and DUSP1 mRNAs and sensitizes leukemic cells to chemotherapy. Furthermore, co-inhibiting p38 MAPK and TNFα prior to or along with chemotherapy substantially reduces chemoresistance in primary leukemic cells ex vivo and in vivo.

Conclusions
These studies uncover post-transcriptional regulation underlying chemoresistance in leukemia. Our data reveal the p38 MAPK-MK2-TTP axis as a key regulator of expression of ARE-bearing mRNAs that promote chemoresistance. By disrupting this pathway, we develop an effective combination therapy against chemosurvival.
Prevalence of 3.7 and 4.2 deletions in Sudanese patients with red cells hypochromia and microcytosis
Authors: Osman Hussam Ali , Hamid Muzamil Mahdi Abdel , Ahmad Rahimah Binti , Saleem Mohamed , Abdallah Sana Altahir 
Published: February 2020

Abstract
Objective
Alpha-thalassemia is a genetic disorder characterized by deletions of one or more α globin genes that result in deficient of α globin chains reducing haemoglobin concentration. The study aimed to screen 97 patients with microcytosis and hypochromasia for the 3.7 and 4.2 alpha thalassemia deletion mutations.

Results
Out of 97 patients screened, only 7 were carriers for the 3.7 deletion and all patients were negative for the 4.2 deletion. The 3.7 deletion was found in Foor, Hawsa and Rezagat Sudanese tribes. In the carriers of the 3.7 deletion, Red Blood Cells and Haematocrit were significantly increased. The Red Blood Cells were 7.23 ± 0.78 × 1012/L in adult males and 7.21 ± 0.67 × 1012/L in adult females while in children were 5.07 ± 0.87 × 1012/L. The mean cell volume and mean cell haemoglobin were significantly decreased, but the mean cell haemoglobin concentration slightly decreased. Haemoglobin levels didn’t revealed statistically significant decrease in adult males (11.7 ± 0.57 g/dL) and adult females (11.25 ± 0.64 g/dL), while in children were (11.6 ± 2.95 g/dL). Haemoglobin electrophoresis revealed two patients of the 3.7 and 4.2 negative were carriers for β-thalassemia. The study concluded that α3.7 deletion has frequency of 0.07 in Sudanese with hypochromasia and microcytosis.
Identification of hemolysin encoding genes and their association with antimicrobial resistance pattern among clinical isolates of coagulase-negative Staphylococci
Authors: Nasaj Mona , Saeidi Zahra , Asghari Babak , Roshanaei Ghodratollah , Arabestani Mohammad Reza 
Published: February 2020

AbstractObjectiveCoagulase-negativestaphylococci(CoNS) are as considered opportunistic pathogens which capable of producing several toxins, enzymes and resistance genes. The current study aimed to determine the occurrence of different hemolysins genes and patterns of antibiotic resistance among CoNS species.ResultsThe highest frequency of antibiotic resistance was observed against cefoxitin in 49 isolates (53.8%), and the lowest resistance was against novobiocin in 5 isolates (5.5%). None of the isolates was resistant to vancomycin. The prevalence ofhla, hla_yidD, hld,andhlbgenes was: 87.9%, 62.6%, 56%, and 47.3%, respectively. Thehla/yidDandhldgenes were detected in 69.4% ofS. epidermidisand thehlagene in 94.6% ofS. haemolyticusisolates; thehlbgene was detected in 53.1% of theS. epidermidisisolates. ThemecAgene was identified in 50 (55%) of the CoNS isolates. In conclusion, the results of statistical analysis showed that thehld genehad a significant association with resistance to levofloxacin and erythromycin antibiotics, thehlbwith clindamycin resistance and thehla/yidDwith rifampicin and novobiocin resistance. The results of this study showed that there is a significant relationship between hemolysin encoding genes and antibiotic resistance patterns; therefore, detection of virulence factors associated with antibiotic resistance has become a significant issue of concern.
Evaluation of deep and shallow learning methods in chemogenomics for the prediction of drugs specificity
Authors: Playe Benoit , Stoven Veronique 
Published: February 2020

AbstractChemogenomics, also called proteochemometrics, covers a range of computational methods that can be used to predict protein–ligand interactions at large scales in the protein and chemical spaces. They differ from more classical ligand-based methods (also called QSAR) that predict ligands for a given protein receptor. In the context of drug discovery process, chemogenomics allows to tackle the question of predicting off-target proteins for drug candidates, one of the main causes of undesirable side-effects and failure within drugs development processes. The present study compares shallow and deep machine-learning approaches for chemogenomics, and explores data augmentation techniques for deep learning algorithms in chemogenomics. Shallow machine-learning algorithms rely on expert-based chemical and protein descriptors, while recent developments in deep learning algorithms enable to learn abstract numerical representations of molecular graphs and protein sequences, in order to optimise the performance of the prediction task. We first propose a formulation of chemogenomics with deep learning, called the chemogenomic neural network (CN), as a feed-forward neural network taking as input the combination of molecule and protein representations learnt by molecular graph and protein sequence encoders. We show that, on large datasets, the deep learning CN model outperforms state-of-the-art shallow methods, and competes with deep methods with expert-based descriptors. However, on small datasets, shallow methods present better prediction performance than deep learning methods. Then, we evaluate data augmentation techniques, namely multi-view and transfer learning, to improve the prediction performance of the chemogenomic neural network. We conclude that a promising research direction is to integrate heterogeneous sources of data such as auxiliary tasks for which large datasets are available, or independently, multiple molecule and protein attribute views.
Magnetotelluric characterization of the Alhama de Murcia Fault (Eastern Betics, Spain) and study of magnetotelluric interstation impedance inversion
Authors: Martí Anna , Queralt Pilar , Marcuello Alex , Ledo Juanjo , Rodríguez-Escudero Emilio , Martínez-Díaz José Jesús , Campanyà Joan , Meqbel Naser 
Published: February 2020

AbstractThe Lorca earthquake (May 11th, 2011, Mw 5.2) stands as the most destructive one in Spain over the last 50 years, interpreted as having occurred in an intersegment zone of the strike–slip Alhama de Murcia Fault (AMF) (Eastern Betics, Spain). Magnetotelluric data were acquired along a profile to the SW of Lorca (La Torrecilla profile), to characterize its signature at depth, as part of the multidisciplinary project “INTERGEOSIMA”. Given the short distance between stations, some station pairs were recorded simultaneously, with magnetic sensors in only one of them. In order to properly understand the resulting impedances (called interstation impedances), and the effects of inverting them, we used synthetic models to compare the impedances and the interstation impedances and to analyze the corresponding inversion results, together with the inversion of the quasi-impedance (inversion of the interstation impedances, considering them as impedances). The results are sensitive to the location of the magnetic sensors and the resistivity underneath, but in general the use of the quasi-impedances in the inversion can be considered a valid procedure. Both the 2D and the 3D resistivity models obtained through the inversion allowed us to complement the previous ERT models and represent the continuation of the main fault gouge in depth showing its extension towards the SE.
Experimentation and numerical modeling on the response of woven glass/epoxy composite plate under blast impact loading
Authors: Gunaryo Kasmidi , Heriana Heri , Sitompul M. Rafiqi , Kuswoyo Andi , Hadi Bambang K. 
Published: February 2020

AbstractBackgroundComposite material is being used in vehicles for protective structures against blast loading. Limited data is available which compare experimental works and numerical analysis in the open field environment. More data is needed in this area in order to be able to predict and use composite materials safely.MethodsIn this work, the response of woven glass/epoxy composite plates under blast loading was investigated, both experimentally and numerically. The plate was manufactured using glass/epoxy woven Cytec 120 °C curing system. The explosive material was Tri-Nitro-Toluen (TNT) with different masses, which are 60, 80, and 100 g. The stand-off distance was also varied, ranging from 300 up to 1000 mm. In the experimental work, a sewing needle pin was put under the plate to record the maximum deformation of the plate during TNT explosion. In the numerical analysis, LS-DYNA was used extensively. The composite plate was modeled as shell elements using MAT54, and the failure criteria was Chang-Chang failure criteria. The explosive TNT material was modeled in two different ways. First, it was modeled using CONWEP and the second was modeled using Smooth Particle Hydrodynamics (SPH). The numerical analysis results were then compared with the experimental data for the case of maximum deformation.ResultsExperimentally, the sewing needle method was able to measure the plate maximum deformation during the explosion. The numerical analysis showed that the SPH model gave better agreement with experimental results compared with CONWEP method. The SPH results were in the range of 8–18% compared to experimental data, while the CONWEP results were in the range of 14–43%.ConclusionAlbeit its simplicity, sewing needle method was able to measure the maximum deformation for blast loading experimentation. The SPH model was better compared with CONWEP method in analyzing the response of composite plate subjected to blast loading.
Development of the informed health choices resources in four countries to teach primary school children to assess claims about treatment effects: a qualitative study employing a user-centred approach
Authors: Nsangi Allen , Semakula Daniel , Rosenbaum Sarah E. , Oxman Andrew David , Oxman Matt , Morelli Angela , Austvoll-Dahlgren Astrid , Kaseje Margaret , Mugisha Michael , Uwitonze Anne-Marie , Glenton Claire , Lewin Simon , Fretheim Atle , Sewankambo Nelson Kaulukusi 
Published: February 2020

Abstract
Background
People of all ages are flooded with health claims about treatment effects (benefits and harms of treatments). Many of these are not reliable, and many people lack skills to assess their reliability. Primary school is the ideal time to begin to teach these skills, to lay a foundation for continued learning and enable children to make well-informed health choices, as they grow older. However, these skills are rarely being taught and yet there are no rigorously developed and evaluated resources for teaching these skills.

Objectives
To develop the Informed Health Choices (IHC) resources (for learning and teaching people to assess claims about the effects of treatments) for primary school children and teachers.

Methods
We prototyped, piloted, and user-tested resources in four settings that included Uganda, Kenya, Rwanda, and Norway. We employed a user-centred approach to designing IHC resources which entailed multiple iterative cycles of development (determining content scope, generating ideas, prototyping, testing, analysing and refining) based on continuous close collaboration with teachers and children.

Results
We identified 24 Key Concepts that are important for children to learn. We developed a comic book and a separate exercise book to introduce and explain the Key Concepts to the children, combining lessons with exercises and classroom activities. We developed a teachers’ guide to supplement the resources for children.

Conclusion
By employing a user-centred approach to designing resources to teach primary children to think critically about treatment claims and choices, we developed learning resources that end users experienced as useful, easy to use and well-suited to use in diverse classroom settings.
Genotoxicity assessment of titanium dioxide nanoparticle accumulation of 90 days in the liver of gpt delta transgenic mice
Authors: Suzuki Tetsuya , Miura Nobuhiko , Hojo Rieko , Yanagiba Yukie , Suda Megumi , Hasegawa Tatsuya , Miyagawa Muneyuki , Wang Rui-Sheng 
Published: February 2020

Abstract
Backgound
A variety of in vivo and in vitro studies to assess the genotoxicity of titanium dioxide nanoparticles (TiO2 NPs) have been reported, but the results are inconsistent. Recently, we reported that TiO2 NPs exhibit no genotoxic effects in the liver and erythrocytes during a relatively brief period following intravenous injection into mice. However, there is no information about long-term genotoxicity due to TiO2 NP accumulation in tissues. In this study, we investigated the long-term mutagenic effects of TiO2 NPs and the localization of residual TiO2 NPs in mouse liver after multiple intravenous injections.

Results
Male gpt delta C57BL/6 J mice were administered with various doses of TiO2 NPs weekly for 4 consecutive weeks. The long-term mutagenic effects on the liver were analyzed using gpt and Spi− mutation assays 90 days after the final injection. We also quantified the amount of titanium in the liver using inductively coupled plasma mass spectrometry and observed the localization of TiO2 NPs in the liver using transmission electron microscopy. Although TiO2 NPs were found in the liver cells, the gpt and Spi− mutation frequencies in the liver were not significantly increased by the TiO2 NP administration.

Conclusions
These results clearly show that TiO2 NPs have no mutagenic effects on the liver, even though the particles remain in the liver long-term.
Sonallah Ibrahim and Miriam Naoum’sZaat
Authors: Salem Sara 
Published: February 2020

AbstractThis article explores the television adaptation of Sonallah Ibrahim’s novel Zaat, arguing that the series provides us with an interesting representation of the various ways in which national projects in Egypt are gendered. It adds to feminist debates around nationalism, capitalism, and gender. In particular, the focus on the intimate in Zaat reveals how political projects are depicted in the domestic sphere through the lens of women’s work. The article explores two themes: one, the increasing financial pressure and its effects on constructs of masculinity and femininity, and two, the steady decay of infrastructure and social services and how it renders middle-class life an impossibility. The article argues that by focusing on the intimate, Ibrahim’s novel and the TV adaptation both reveal the various forms of work women perform and make use of women’s work to critique or celebrate national projects.
Efficacy and safety of sacubitril/valsartan in the treatment of heart failure: protocol for a systematic review incorporating unpublished clinical study reports
Authors: Byrne David , Fahey Tom , Moriarty Frank 
Published: February 2020

Background: Sacubitril/valsartan is a first-in-class angiotensin-receptor neprilysin inhibitor used to treat heart failure with reduced ejection fraction. The evidence base for this novel medication is largely based on one pivotal phase III trial which was stopped early due to significant clinical benefits being shown. However potential limitations in the trial design have been highlighted in recent medical literature, necessitating a thorough review of the evidence base for sacubitril/valsartan. Methods: This review will be conducted using the PRISMA reporting guidelines. Relevant randomised controlled trials (RCTs) for sacubitril/valsartan will be systematically searched for in Medline (PubMed), Embase, Cochrane library, Google Scholar, Web of Science, Toxline and Scopus. Clinical trials registries will be searched, as will eight grey literature databases. In addition, unpublished clinical study reports (CSRs) of relevant trials will be requested from the European Medicines Agency (EMA) and the Clinical Study Data Request database. Studies will be included if they involve randomising adult patients with heart failure to either sacubitril/valsartan or usual care with either an active comparator or placebo as a control. All relevant clinical and safety outcomes will be reviewed, particularly hospitalisation due to heart failure and cardiovascular mortality. Two reviewers will assess eligibility of selected trials for inclusion. Data extraction will be performed separately for trial publications, clinical trial registries and for CSRs using a piloted form. Methodological quality of included trials from published sources will be assessed separately using the recently updated Cochrane Risk of Bias tool version 2. Narrative synthesis of included studies will be conducted and, if appropriate, meta-analysis for clinical efficacy and safety outcomes. Discussion: This review will collate all available RCT data on sacubitril/valsartan including published and unpublished sources in order to obtain a more complete picture of the evidence base for sacubitril/valsartan. Registration: This protocol has been submitted for registration on PROSPERO.
THE POSSIBILITY OF A BRIDGE. PERSPECTIVES AND LIMITATIONS OF NEUROAESTHETICS
Authors: Tatar Tõnis 
Published: February 2020

In the traditional study of humanities non-humanitarian inputinto the study of culture has usually been rejected. According tohumanist theories, only the meanings and values derived fromhistory and culture can be attributed to art. Recently a disciplineknown as neuroaesthetics has risen to the fore from among thevarious disciplines that use non-humanitarian methods to approachthe subject of aesthetics. Triggered by the invention of varioustechnological devices (EEG, fMRI, PET), neuroaesthetics is nowbeing used to tackle the role of the brain in the processes of creation,reception and even thinking about arts.When introducing new perspectives, such as neuroaesthetics, it isimportant to acknowledge the limitations of the different methods.A narrow reductional approach to art and the brain clearly does notsuffice – a satisfactory explanation must also involve non-physicalfactors, such as knowledge about the history of art. On the otherhand, as with any theoretical approach, the explanatory capacityof neuroaesthetics varies when applied to different kinds of art.Neuroaesthetic theories tend to stress the visual, mimetic andemotional nature of art, often associating artistic features with theactivity of the visual brain as well as evolutionary psychology.Instead of stressing historic and local differences and culturalexceptions, researchers with a natural sciences background tend to search for the universal qualities of art. This appears to beirreconcilable with the institutional theory of art that implicitlyunderlies the entire contemporary paradigm of art. It can be assumedthat some of the reasoning behind the sceptical attitude shared bymost mainstream humanitarian discourse is hidden in this conflict.It can even be claimed that, under the banner of institutionalist ideas,the art of the modernist period constituted a systematic negation ofthe conditions of art prescribed by the universal qualities of art basedon the laws of the brain. Therefore, one of the challenges in this earlyphase of the biologically and psychologically based analysis of artshould be to shed light on this inherent and ideological bias that isdeeply rooted in the humanistic discourse of arts.