bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of the effects of cinnamon bark fractions on Candida albicans and oral epithelial cells
Authors: Veilleux Marie-Pier , Grenier Daniel 
Published: November 2019

Abstract

Background
Candida albicans is an opportunistic pathogen that causes oral candidiasis and denture stomatitis. It has also been reported to infect oral mucositis lesions in patients who suffer from cancer affecting the head and neck and who receive chemotherapy and radiotherapy treatments. This study aimed to investigate the effects of two cinnamon bark fractions, i.e., an essential oil and an aqueous extract enriched in proanthocyanidins (Cinnulin PF®) on growth, biofilm formation, and adherence properties of C. albicans as well as on oral epithelial cells (barrier integrity, inflammatory response).

Methods
A microplate dilution assay was used to determine antifungal and anti-biofilm properties. A fluorescent assay was used to determine C. albicans adherence to oral epithelial cells. Cytotoxicity toward oral epithelial cells was assessed by determination of cell metabolic activity. Tight junction integrity of gingival keratinocytes was assessed by determination of transepithelial electrical resistance. IL-6 and IL-8 secretion by TNFα-stimulated oral epithelial cells was quantified by ELISA.

Results
While Cinnulin PF® did not reduce C. albicans growth, the cinnamon bark oil exhibited high antifungal activity with minimum inhibitory concentrations and minimum fungicidal concentrations in the range of 0.039 to 0.078%. The cinnamon oil was also active against a pre-formed C. albicans biofilm. Interestingly, Cinnulin PF® prevented biofilm formation by C. albicans and attenuated its adherence to oral epithelial cells. At their effective concentrations, the cinnamon oil and the Cinnulin PF® displayed no significant cytotoxicity against oral epithelial cells. In an in vitro model, both cinnamon fractions reinforced the integrity of the oral epithelial barrier. Lastly, Cinnulin PF® inhibited the secretion of interleukin-6 and interleukin-8 by oral epithelial cells stimulated with TNF-α.

Conclusion
By their ability to attenuate growth, biofilm formation and adherence property of C. albicans, to reinforce the epithelial barrier function, and to exert anti-inflammatory properties the two cinnamon fractions (essential oil, Cinnulin PF®) investigated in the present study may be promising agents for treating oral infections involving C. albicans.
Interpreting patient-Specific risk prediction using contextual decomposition of BiLSTMs: application to children with asthma
Authors: AlSaad Rawan , Malluhi Qutaibah , Janahi Ibrahim , Boughorbel Sabri 
Published: November 2019

Abstract

Background
Predictive modeling with longitudinal electronic health record (EHR) data offers great promise for accelerating personalized medicine and better informs clinical decision-making. Recently, deep learning models have achieved state-of-the-art performance for many healthcare prediction tasks. However, deep models lack interpretability, which is integral to successful decision-making and can lead to better patient care. In this paper, we build upon the contextual decomposition (CD) method, an algorithm for producing importance scores from long short-term memory networks (LSTMs). We extend the method to bidirectional LSTMs (BiLSTMs) and use it in the context of predicting future clinical outcomes using patients’ EHR historical visits.

Methods
We use a real EHR dataset comprising 11071 patients, to evaluate and compare CD interpretations from LSTM and BiLSTM models. First, we train LSTM and BiLSTM models for the task of predicting which pre-school children with respiratory system-related complications will have asthma at school-age. After that, we conduct quantitative and qualitative analysis to evaluate the CD interpretations produced by the contextual decomposition of the trained models. In addition, we develop an interactive visualization to demonstrate the utility of CD scores in explaining predicted outcomes.

Results
Our experimental evaluation demonstrate that whenever a clear visit-level pattern exists, the models learn that pattern and the contextual decomposition can appropriately attribute the prediction to the correct pattern. In addition, the results confirm that the CD scores agree to a large extent with the importance scores generated using logistic regression coefficients. Our main insight was that rather than interpreting the attribution of individual visits to the predicted outcome, we could instead attribute a model’s prediction to a group of visits.

Conclusion
We presented a quantitative and qualitative evidence that CD interpretations can explain patient-specific predictions using CD attributions of individual visits or a group of visits.
Estimating the effectiveness and cost-effectiveness of establishing additional endovascular Thrombectomy stroke Centres in England: a discrete event simulation
Authors: McMeekin Peter , Flynn Darren , Allen Mike , Coughlan Diarmuid , Ford Gary A. , Lumley Hannah , Balami Joyce S. , James Martin A. , Stein Ken , Burgess David , White Phil 
Published: November 2019

AbstractBackgroundWe have previously modelled that the optimal number of comprehensive stroke centres (CSC) providing endovascular thrombectomy (EVT) in England would be 30 (net 6 new centres). We now estimate the relative effectiveness and cost-effectiveness of increasing the number of centres from 24 to 30.MethodsWe constructed a discrete event simulation (DES) to estimate the effectiveness and lifetime cost-effectiveness (from a payer perspective) using 1 year’s incidence of stroke in England. 2000 iterations of the simulation were performed comparing baseline 24 centres to 30.ResultsOf 80,800 patients admitted to hospital with acute stroke/year, 21,740 would be affected by the service reconfiguration. The median time to treatment for eligible early presenters (< 270 min since onset) would reduce from 195 (IQR 155–249) to 165 (IQR 105–224) minutes. Our model predicts reconfiguration would mean an additional 33 independent patients (modified Rankin scale [mRS] 0–1) and 30 fewer dependent/dead patients (mRS 3–6) per year. The net addition of 6 centres generates 190 QALYs (95%CI − 6 to 399) and results in net savings to the healthcare system of £1,864,000/year (95% CI -1,204,000 to £5,017,000). The estimated budget impact was a saving of £980,000 in year 1 and £7.07 million in years 2 to 5.ConclusionChanges in acute stroke service configuration will produce clinical and cost benefits when the time taken for patients to receive treatment is reduced. Benefits are highly likely to be cost saving over 5 years before any capital investment above £8 million is required.
In vivo immunogenicity assessment and vaccine efficacy evaluation of a chimeric tandem repeat of epitopic region of OMP31 antigen fused to interleukin 2 (IL-2) against Brucella melitensis in BALB/c mice
Authors: Nazifi Narges , Tahmoorespur Mojtaba , Sekhavati Mohammad Hadi , Haghparast Alireza , Behroozikhah Ali Mohammad 
Published: November 2019

AbstractBackgroundDesigning a potent recombinant vaccine, using the appropriate subunits with the greatest effect on stimulating the immune system, especially in the case of intracellular pathogens such as gram negativeBrucella Melitensisbacteria, is of great importance. In this study, three repeats of 27 amino acids of the immunogenic epitope derived from OMP31 antigen (3E) from theBrucella melitensis, in a protective manner against Brucellosis have been used. To fortify the delivery system of recombinant antigens, IL-2 cytokine as a molecular adjuvant was fused to recombinant constructs. Recombinant proteins were evaluated for immunological studies in a mouse model (BALB/c).ResultsThe results showed that all recombinant proteins could stimulate the immune system to produce Th1 cytokines and antibodies in compare to the negative control treatments. 3E-IL2 and then OMP31-IL2 proteins stimulated higher levels of IFN-γ and IL-2 compared to the other treatments (p < 0.05). Also, the results indicated that experimental treatments produced a higher level of IgG2a isotype than IgG1 isotype. In addition, the findings of the experiment showed that the presence of chemical adjuvant (IFA) along with molecular adjuvant can play a significant role in stimulating the immune system. After determining the potency of recombinant structures, their efficacy in stimulating the immune system were also evaluated.B. melitensis M16strain was used to challenge 30 days after last immunization. The microbial load of the splenocyte in the treatments receiving chimeric proteins were significantly lower. Also, Wright serological test confirmed that these treatments had the lowest agglutination rate, as well as the positive treatment, while in the negative treatments in excess of blood serum dilutions, agglutination rate were more than 2 + .Conclusions3E-IL2 treatment showed the best performance compared to other recombinant proteins and could be considered as the suitable candidate for further research on the production of recombinant vaccine against Brucella.
Significant random signatures reveals new biomarker for breast cancer
Authors: Saberi Ansar Elnaz , Eslahchii Changiz , Rahimi Mahsa , Geranpayeh Lobat , Ebrahimi Marzieh , Aghdam Rosa , Kerdivel Gwenneg 
Published: November 2019

AbstractBackgroundIn 2012, Venet et al. proposed that at least in the case of breast cancer, most published signatures are not significantly more associated with outcome than randomly generated signatures. They suggested that nominalp-value is not a good estimator to show the significance of a signature. Therefore, one can reasonably postulate that some information might be present in such significant random signatures.MethodsIn this research, first we show that, using an empiricalp-value, these published signatures are more significant than their nominalp-values. In other words, the proposed empiricalp-value can be considered as a complimentary criterion for nominalp-value to distinguish random signatures from significant ones. Secondly, we develop a novel computational method to extract information that are embedded within significant random signatures. In our method, a score is assigned to each gene based on the number of times it appears in significant random signatures. Then, these scores are diffused through a protein-protein interaction network and a permutation procedure is used to determine the genes with significant scores. The genes with significant scores are considered as the set of significant genes.ResultsFirst, we applied our method on the breast cancer dataset NKI to achieve a set of significant genes in breast cancer considering significant random signatures. Secondly, prognostic performance of the computed set of significant genes is evaluated using DMFS and RFS datasets. We have observed that the top ranked genes from this set can successfully separate patients with poor prognosis from those with good prognosis. Finally, we investigated the expression pattern of TAT, the first gene reported in our set, in malignant breast cancer vs. adjacent normal tissue and mammospheres.ConclusionApplying the method, we found a set of significant genes in breast cancer, including TAT, a gene that has never been reported as an important gene in breast cancer. Our results show that the expression of TAT is repressed in tumors suggesting that this gene could act as a tumor suppressor in breast cancer and could be used as a new biomarker.
RETRACTED ARTICLE: Silencing of TRIM11 suppresses the tumorigenicity of chordoma cells through improving the activity of PHLPP1/AKT
Authors: Wang Bin , Wang Gang , Wang Qingfeng , Zhu Ziqiang , Wang Yunqing , Chen Kangwu , Yang Huilin 
Published: November 2019

Abstract
Background
Tripartite motif-containing protein 11 (TRIM11), a member of RING family of E3 ubiquitin ligases, is identified as an oncogene in certain human tumors. However, the detailed biological function of TRIM11 in chordoma is still unclear. The purpose of present research is to explore the role of TRIM11 in human chordoma cells.

Methods
TRIM11 was induced silencing and overexpression in human chordoma cells using RNA interference (RNAi) and lentiviral vector. qRT-PCR and western blot were used to determine gene expression in chordomas cells. Meanwhile, cell counting kit-8 (CCK-8) assay was used to examine the cell proliferation rate. Flow cytometry analysis was performed to quantify the cell apoptosis rate.

Results
We identified that TRIM11 was upregulated in chordomas tissues. Moreover, TRIM11 presented pro-proliferation and anti-apoptosis function in chordoma cells. Further, LY294002, a specific AKT inhibitor, was utilized to examine the connection between TRIM11 and AKT in human chordoma cells. Importantly, our findings elucidated that TRIM11 promoted the growth of chordoma cells and involved in AKT signaling. Much more importantly, knockdown of TRIM11 significantly upregulated the translation of PH domain leucine-rich repeats protein phosphatase 1 (PHLPP1), whereas did not affect its transcription. Results that obtained from co-immunoprecipitation (Co-IP) and ubiquitination assay demonstrated TRIM11 interacted with PHLPP1 and promoted its ubiquitination in chordoma cells. Moreover, overexpression of PHLPP1 inhibited the phosphorylation of AKT in human chordomas cells. These results suggested that TRIM11 mediated the post-translation modification of PHLPP1 and was a novel component in PHLPP1/AKT signaling pathway in human chordoma cells.

Conclusions
Taken together, the present research not only enhanced the understanding of TRIM11 but also indicated its potential target and signaling pathway in human chordoma cells.
Trial registration retrospectively registered.
The effect of ivermectin® on fertility, fecundity and mortality of Anopheles arabiensis fed on treated men in Ethiopia
Authors: Mekuriaw Wondemeneh , Balkew Meshesha , Messenger Louisa A. , Yewhalaw Delenasaw , Woyessa Adugna , Massebo Fekadu 
Published: November 2019

Abstract

Background
Insecticide resistance is a growing threat to malaria vector control. Ivermectin, either administered to humans or animals, may represent an alternate strategy to reduce resistant mosquito populations. The aim of this study was to assess the residual or delayed effect of administering a single oral dose of ivermectin to humans on the survival, fecundity and fertility of Anopheles arabiensis in Ethiopia.

Methods
Six male volunteers aged 25–40 years (weight range 64–72 kg) were recruited; four of them received a recommended single oral dose of 12 mg ivermectin and the other two individuals were untreated controls. A fully susceptible insectary colony of An. arabiensis was fed on treated and control participants at 1, 4, 7, 10 and 13 days post ivermectin-administration. Daily mosquito mortality was recorded for 5 days. An. arabiensis fecundity and fertility were measured from day 7 post treatment, by dissection to examine the number of eggs per mosquito, and by observing larval hatching rates, respectively.

Results
Ivermectin treatment induced significantly higher An. arabiensis mortality on days 1 and 4, compared to untreated controls (p = 0.02 and p < 0.001, respectively). However, this effect had declined by day 7, with no significant difference in mortality between treated and control groups (p = 0.06). The mean survival time of mosquitoes fed on day 1 was 2.1 days, while those fed on day 4 survived 4.0 days. Mosquitoes fed on the treatment group at day 7 and 10 produced significantly lower numbers of eggs compared to the untreated controls (p < 0.001 and p = 0.04, respectively). An. arabiensis fed on day 7 on treated men also had lower larval hatching rates than mosquitoes fed on days 10 and 13 (p = 0.003 and p = 0.001, respectively).

Conclusion
A single oral dose of ivermectin given to humans can induce mortality and reduce survivorship of An. arabiensis for 7 days after treatment. Ivermectin also had a delayed effect on fecundity of An. arabiensis that took bloodmeals from treated individuals on day 7 and 10. Additional studies are warranted using wild, insecticide-resistant mosquito populations, to confirm findings and a phase III evaluation among community members in Ethiopia is needed to determine the impact of ivermectin on malaria transmission.
The Pfs230 N-terminal fragment, Pfs230D1+: expression and characterization of a potential malaria transmission-blocking vaccine candidate
Authors: Lee Shwu-Maan , Wu Yimin , Hickey John M. , Miura Kazutoyo , Whitaker Neal , Joshi Sangeeta B. , Volkin David B. , Richter King C. , Plieskatt Jordan 
Published: November 2019

Abstract

Background
Control and elimination of malaria can be accelerated by transmission-blocking interventions such as vaccines. A surface antigen of Plasmodium falciparum gametocytes, Pfs230, is a leading vaccine target antigen, and has recently progressed to experimental clinical trials. To support vaccine product development, an N-terminal Pfs230 antigen was designed to increase yield, as well as to improve antigen quality, integrity, and homogeneity.

Methods
A scalable baculovirus expression system was used to express the Pfs230D1+ construct (aa 552–731), which was subsequently purified and analysed. Pfs230D1+ was designed to avoid glycosylation and protease digestion, thereby potentially increasing homogeneity and stability. The resulting Pfs230D1+ protein was compared to a previous iteration of the Pfs230 N-terminal domain, Pfs230C1 (aa 443–731), through physiochemical characterization and in vivo analysis. The induction of functional antibody responses was confirmed via the standard membrane feeding assay (SMFA).

Results
Pfs230D1+ was produced and purified to an overall yield of 23 mg/L culture supernatant, a twofold yield increase over Pfs230C1. The Pfs230D1+ protein migrated as a single band via SDS-PAGE and was detected by anti-Pfs230C1 monoclonal antibodies. Evaluation by SDS-PAGE, chromatography (size-exclusion and reversed phase) and capillary isoelectric focusing demonstrated the molecule had improved homogeneity in terms of size, conformation, and charge. Intact mass spectrometry confirmed its molecular weight and that it was free of glycosylation, a key difference to the prior Pfs230C1 protein. The correct formation of the two intramolecular disulfide bonds was initially inferred by binding of a conformation specific monoclonal antibody and directly confirmed by LC/MS and peptide mapping. When injected into mice the Pfs230D1+ protein elicited antibodies that demonstrated transmission-reducing activity, via SMFA, comparable to Pfs230C1.

Conclusion
By elimination of an O-glycosylation site, a potential N-glycosylation site, and two proteolytic cleavage sites, an improved N-terminal Pfs230 fragment was produced, termed D1+, which is non-glycosylated, homogeneous, and biologically active. An intact protein at higher yield than that previously observed for the Pfs230C1 fragment was achieved. The results indicate that Pfs230D1+ protein produced in the baculovirus expression system is an attractive antigen for transmission-blocking vaccine development.
The population randomization observation process (PROP) assessment method: using systematic habitation observations of street segments to establish household-level epidemiologic population samples
Authors: Smart Mieka , Sadler Richard , Harris Alan , Buchalski Zachary , Pearson Amber , Debra Furr-Holden C. 
Published: November 2019

Abstract

Background
Identifying and intervening on health disparities requires representative community public health data. For cities with high vacancy and transient populations, traditional methods of population estimation for refining random samples are not feasible. The aim of this project was to develop a novel method for systematic observations to establish community epidemiologic samples.

Results
We devised a four-step population randomization observation process for Flint, Michigan, USA: (1) Use recent total population data for community areas (i.e., neighborhoods) to establish the proportional sample size for each area, (2) Randomly select street segments of each community area, (3) Deploy raters to conduct observations about habitation for each randomly selected segment, and (4) Complete observations for second and third street segments, depending on vacancy levels. We implemented this systematic observation process on 400 randomly selected street segments. Of these, 130 (32.5%) required assessment of secondary segments due to high vacancy. Among the 130 primary segments, 28 (21.5%) required assessment of tertiary (or more) segments. For 71.5% of the 400 primary street segments, there was consensus among raters on whether the dwelling inhabited or uninhabited.

Conclusion
Houses observed with this method could have easily been considered uninhabited via other methods. This could cause residents of ambiguous dwellings (likely to be the most marginalized residents with highest levels of unmet health needs) to be underrepresented in the resultant sample.
A simple and rapid protocol for the genetic transformation of Ensete ventricosum
Authors: Matheka Jonathan , Tripathi Jaindra Nath , Merga Ibsa , Gebre Endale , Tripathi Leena 
Published: November 2019

Abstract
Enset (Ensete ventricosum), also known as Ethiopian banana, is a food security crop for more than 20 million people in Ethiopia. As conventional breeding of enset is very challenging, genetic engineering is an alternative option to introduce important traits such as enhanced disease resistance and nutritional value. Genetic transformation and subsequent regeneration of transgenic enset has never been reported mainly due to challenges in developing transformation protocols for this tropical species. Agrobacterium-mediated transformation could be a practical tool for the genetic improvement of enset. However, the efficiency of the transformation system depends on several parameters such as plant regeneration, genotype, explant, selection agent and Agrobacterium strains. As a first step towards the development of transgenic enset, a simple and rapid plant regeneration system was developed using multiple buds as explants. Induction and proliferation of multiple buds from shoot tip explants was achieved on Murashige and Skoog (MS) medium supplemented with 5 and 10 mg/l of 6-benzylaminopurine (BAP), respectively. Shoots were regenerated from multiple buds on MS media containing 2 mg/l BAP and 0.2% activated charcoal. Based on the optimized regeneration protocol, an Agrobacterium-mediated transformation method was developed using multiple buds as explants and the binary plasmid pCAMBIA2300-GFP containing the green florescent protein (gfp) reporter gene and neomycin phosphotransferase II (nptII) selection marker gene. Transgenic plantlets were obtained within 4 months at a frequency of about 1.25%. The transgenic lines were validated by PCR analysis using primers specific to the nptII gene. To obtain uniformly transformed plantlets, chimerism was diluted by subculturing and regenerating the transgenic shoots on a selective medium containing kanamycin (150 mg/l) for five cycles. The uniformity of the transgenic plants was confirmed by Southern blot hybridization and RT-PCR analyses on different tissues such as leaf, pseudostem and root of same transgenic plant. In the present study, we report a simple Agrobacterium-mediated transformation system for generating transgenic events of enset. To the best of our knowledge, this is the first report on the stable transformation and regeneration of transgenic events of enset. The transformation system established in this study can be used for the generation of transgenic enset with important traits such as disease resistance.