bluuebunny/crossref_metadata_2025 huggingface dataset:
Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study
Authors: Sugino Shigekazu , Konno Daisuke , Kawai Yosuke , Nagasaki Masao , Endo Yasuhiro , Hayase Tomo , Yamazaki-Higuchi Misako , Kumeta Yukihiro , Tachibana Shunsuke , Saito Katsuhiko , Suzuki Jun , Kido Kanta , Kurosawa Nahoko , Namiki Akiyoshi , Yamauchi Masanori
Published: June 2020

Background: Genetic factors such as single nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study is to identify causal SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. associations between 659,636 SNPs and the incidence of PONV 24 h after surgery in a limited sample of 24 female patients using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. Results: The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). Conclusions: We identified a novel causal SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. Trial registration: This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903, date of registration: June 27th, 2016, retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026392).
Health variations among breast-cancer patients from different disease states: Evidence from China
Authors: Yang Qing , Yu Xuexin , Zhang Wei
Published: June 2020

Background: The aim of this study was to obtain health utility data for Chinese breast cancer patients in different disease states to obtain important parameters for health economics modelling and to explore the feasibility of establishing a breast cancer health utility mapping model in China.Methods: Multiple patient-reported health attributes were assessed, including quality of life, which was measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument; health utility and self-rated health, which were measured by the EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire. Multivariate regression models, including a linear regression model, an ordinal logistic regression model and a Tobit model, were employed to analyse health differences among 446 breast cancer patients. Subgroup analyses were performed to analyse differences in the dimensions of health derived from the FACT-B and EQ-5D-5L instruments. A mapping function was used to estimate health utility from quality of life. Rank correlation analyses were employed to examine the correlation between estimated and observed health utility values.Results: A total of 446 breast cancer patients with different disease states were analysed. The health utility values of breast cancer patients in the P state (without cancer recurrence and metastasis), R state (with cancer recurrence within a year), S state (with primary and recurrent breast cancer for the second year and above), and M state (metastatic cancer) were 0.81 (SD±0.23), 0.90 (SD±0.12), 0.78 (SD±0.31), and 0.74 (SD±0.27), respectively. There were positive correlations between all scores, including each domain of the FACT-B instrument (p<0.001). Multivariate analysis suggested that patients in the R and M states had lower scores for overall quality of life (R, β = -9.45, p< 0.01; M, β = -6.72, p<0.05). Patients in the M state had lower health utility values than patients in the P state (β = -0.11, p< 0.05). Estimated health utility values, which were derived from quality of life using a mapping function, were significantly correlated with directly measured health utility values (p<0.001).Conclusions: We obtained the health utility and health-related quality of life (HRQoL) scores of Chinese breast cancer patients with different disease states. Mapping health utility values from quality of life using four disease states could be feasible in health economic modelling, but the mapping function may need further revision.
A high-throughput drug combination screen identifies an anti-glioma synergism between TH588 and PI3K inhibitors
Authors: Chen Zhen , Chen Chao , Zhou Tingting , Duan Chao , Wang Qianqian , Zhou Xiaohui , Zhang Xia , Wu Fangrong , Hua Yunfen , Lin Fan
Published: June 2020

Background: Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor. More than half of GBMs contain mutation(s) of PTEN/PI3K/AKT, making inhibitors targeting the PI3K pathway very attractive for clinical investigation. However, so far, PI3K/AKT/mTOR inhibitors have not achieved satisfactory therapeutic effects in clinical trials of GBM. In this study, we aimed to develop a high-throughput screening method for high-throughput identification of potential targeted agents that synergize with PI3K inhibitors in GBM.Methods: A Sensitivity Index (SI)-based drug combination screening method was established to evaluate the interactions between BKM120, a pan-PI3K inhibitor, and compounds from a library of 606 target-selective inhibitors. Proliferation, colony and 3D spheroid formation assays, western blotting, comet assay, γ-H2AX staining were used to evaluate the anti-glioma effects of the top-ranked candidates. The drug combination effects were analyzed by the Chou-Talalay method. Results: Six compounds were successfully identified from the drug screen, including three previously reported compounds that cause synergistic antitumor effects with PI3K/mTOR inhibitors. TH588, an MTH1 inhibitor exhibited significant synergy with BKM120 in suppressing the proliferation, colony formation and 3D spheroid formation of GBM cells. Further investigation revealed that both DNA damage and apoptosis were markedly enhanced upon combination treatment with TH588 and BKM120. Finally, activation of PI3K or overexpression of AKT compromised the anti-glioma efficacy of TH588.Conclusions: The screening method developed in this study demonstrated its usefulness in the rapid identification of synergistic drug combinations of PI3K inhibitors and targeted agents.
The expression of miRNA-146a-5p and its mechanism of treating dry eye syndrome
Authors: Yin Liang , Zhang Mingxue , He Tiangeng , Chen Song
Published: June 2020

BACKGROUND
Dry eye syndrome in which tear fluid quality or abnormality or kinetic abnormality is caused by many causes, resulting in decreased tear film stability. In recent years, more and more results from the studies indicate that miRNA alterations are involved in dry eye syndrome. And miRNA-146a-5p is a key regulator to regulate the inflammatory response. In this paper, we demonstrated whether miRNA-146a-5p could cure dry eye syndrome by regulating target genes based on network analysis.
METHODS
In this paper, we collected the blood of patients with dry eye disease served as model group, the blood of healthy people was served as control group. The expression of miRNA-146a-5p in the patients were detected by RT-PCR, the genes controled by miRNA-146a-5p were predicted by Targetscan, miRDB, miRWalk and PicTar databases, the genes regulated by miRNA-146a-5p which relative with dry eye disease were selected by draw venn diagram;
RESULTS
The comparison of the general information between patients and healthy people were no significant difference, and it indicated that the two groups were comparable. The results of databases showed that IRAK1 was one of the target genes regulated by miRNA-146a-5p and it is related to dry eye disease. The expression of miRNA-146a-5p was negatively related to IRAK1 mRNA and protein. While IRAK1 had positive correlation with IL-6, TNF-α and CBP proteins.
CONCLUSIONS
These results emphasized that miRNA-146a-5p could inhibit the expression of IRAK1, IL-6, TNF-α and CBP so as to help reduce the inflammatory response in dry eye syndrome.
The role of Interleukin-33 in patients with mild cognitive impairment and Alzheimer’s disease
Authors: Liang Chih-Sung , Su Kuan-Pin , Tsai Chia-Lin , Lee Jiunn-Tay , Chu Che-Sheng , Yeh Ta-Chuan , Su Ming-Wei , Lin Guan-Yu , Lin Yu-Kai , Chu Hsuan-Te , Tsai Chia-Kuang , Yang Fu-Chi
Published: June 2020

Background: The neuroprotective role of interleukin (IL)-33 is supported by numerous pre-clinical studies, but it remains uninvestigated in clinical studies of Alzheimer’s disease (AD). We aimed to examine the association between human blood levels of IL-33 and cognitive preservation in amnestic mild cognitive impairment (aMCI) and AD.Methods: A total of 100 participants (26 controls, 35 aMCI patients, and 39 AD patients) completed two Mini Mental State Examination (MMSE) over a 1-year interval. In all 100 participants at the second MMSE, we examined the plasma levels of IL-33, IL-β, IL-1 receptor agonist (IL-1RA), beta amyloid (Aβ), and tau and apolipoprotein E (ApoE) genotyping; we also performed Hopkins Verbal Learning Test, Trail Making Test, forward and backward digit span, and Clinical Dementia Rating. Results: IL-33 expression showed a positive trend among controls (1/26 = 3.8%), aMCI (9/35 = 25.7%), and AD (17/39 = 43.6%) (trend analysis: P < 0.001). Patients expressing IL-33 preserved their cognitive function compared with IL-33 non-expressing patients (1-year ΔMMSE: 0.16 ± 1.6 vs -1.5 ± 2.6; P = 0.006). The cognitive preservation was not associated with the lower levels of Aβ, tau, and ApoE ε4, while higher levels of ApoE ε4 and phosphorylated tau were indeed associated with cognitive decline. The aMCI patients with AD conversion during study period had higher proportion of IL-33(-) than non-AD converters (90.9% vs 53.3%, P = 0.04).Conclusions: IL-33 or its associated signaling pathways may represent a new treatment paradigm for aMCI and AD.
Quantification of epicardial fat using 3D cine Dixon MRI
Authors: Henningsson Markus , Brundin Martin , Scheffel Tobias , Edin Carl , Viola Federica , Carlhäll Carl-Johan
Published: June 2020

Background: There is an increased interest in quantifying and characterizing epicardial fat which has been linked to various cardiovascular diseases such as coronary artery disease and atrial fibrillation. Recently, three-dimensional single-phase Dixon techniques have been used to depict the heart and to quantify the surrounding fat. The purpose of this study was to investigate the merits of a new high-resolution cine 3D Dixon technique for quantification of epicardial adipose tissue and compare it to single-phase 3D Dixon in patients with cardiovascular disease. Methods: Fifteen patients referred for clinical CMR examination of known or suspected heart disease were scanned on a 1.5T scanner using single-phase Dixon and cine Dixon. Epicardial fat was segmented by three readers and intra- and inter-observer variability was calculated per slice. Cine Dixon segmentation was performed in the same cardiac phase as single-phase Dixon. Subjective image quality assessment of water and fat images were performed by three readers using a 4-point Likert scale (1=severe; 2=significant; 3=mild; 4=no blurring of cardiac structures).Results: Intra-observer variability was excellent for cine Dixon images (ICC=0.96), and higher than single-phase Dixon (ICC=0.92). Inter-observer variability was good for cine Dixon (ICC=0.76) and moderate for single-phase Dixon (ICC=0.63). The intra-observer measurement error (mean ± standard deviation) per slice for cine was -0.02±0.51 ml (-0.08±0.4%), and for single-phase 0.39±0.72 ml (0.18±0.41%). Inter-observer measurement error for cine was 0.46±0.98 ml (0.11±0.46%) and for single-phase 0.42±1.53 ml (0.17±0.47%). Visual scoring of the water image yielded median of 2 (interquartile range = [Q3-Q1] 2-2) for cine and median of 3 (interquartile range = 3-2) for single-phase (P < 0.05) while no significant difference was found for the fat images, both techniques yielding a median of 3 and interquartile range of 3-2. Conclusion: Cine Dixon can be used to quantify epicardial fat with lower intra- and inter-observer variability compared to standard single-phase Dixon. The time-resolved information provided by the cine acquisition appears to support the delineation of the epicardial adipose tissue depot.
Underestimation of astigmatism without cycloplegic refraction in preschool children
Authors: lin jian
Published: June 2020

Significance: It is generally believed that cycloplegia optometry had no effect on astigmatism. The comparison was all made on the spectacle plane. There is a dearth of studies on the influence from corneal plane. Purpose: Study on the difference between cycloplegic and noncycloplegic measurements of astigmatism on corneal plane. Methods: This is a retrospective study. Vertexing the total ocular astigmatism to the corneal plane. To transpose astigmatism into J0 and J45 components by Fourier transformation. The changes of astigmatism measured with and without cycloplegic were compared from corneal plane. Data were compared by paired t test. Results: The changes of the total ocular astigmatism were significantly different on corneal plane (total ocular astigmatism: t = -2.31, P < .05; J0 components: t = -2.71, P < .01; J45 components: t = -1.09, P༞.05). The magnitude of total ocular astigmatism generally increased after cycloplegia (2.12 ± .87 D vs 2.07 ± .89 D). 37 eyes (32.17%) had a change value greater than 0.25 D. The proportion of with-the-rule total ocular astigmatism increased (from 90.43–92.17%) and that of oblique total ocular astigmatism decreased (from 9.57–7.83%). While the changes of anterior corneal astigmatism were no significantly different . Conclusion: There were underestimation of total ocular astigmatism without cycloplegic refraction in preschool children. The proportion of with-the-rule astigmatism increases after cycloplegia.
Advancing integrated care evaluation in shifting contexts: Blending implementation research with case study design in Project SUSTAIN.
Authors: Billings Jenny , de Bruin Simone R. , Baan Caroline , Nijpels Giel
Published: June 2020

Background
Despite many studies evaluating the effectiveness of integrated care, evidence remains inconsistent. There is increasing commentary pointing out the mismatch between the ability to capture the somewhat ‘illusive’ impact of integrated care initiatives and programmes, and the most appropriate way to do this. Focusing on methodology, this paper describes and critically reviews the experiences of SUSTAIN, a Horizon 2020 funded project (2015–2019) with the purpose of advancing knowledge and understanding of cross-European integrated care evaluation. SUSTAIN sought to improve integrated care initiatives for older people in seven countries, and to maximise the potential for knowledge transfer and application across Europe. The methods approach drew from implementation research, employing the participative Evidence Integration Triangle (EIT) and incorporating a mixed method, multiple embedded case study design. A core set of qualitative and quantitative indicators, alongside context and process data, were created and tested within four key project domains (person-centredness, prevention-orientation, safety and efficiency). The paper critically discusses the overall approach, highlighting the value of the EIT and case study design, and signalling the challenges of data collection with frail older people and stakeholder involvement at the sites, as well as difficulties developing the core set of indicators.
Conclusions
Lessons learned and recommendations for advancing integrated care evaluation are put forward that focus on the status of integrated care as a complex intervention and a process. The use of implementation research methods and case study design are recommended, alongside suggested ways of improving methods of data collection with frail populations and cost analysis.
A case-control study on psychotropic substance use and risk of Axis I psychiatric disorders in HIV-infected gay or bisexual men in Hong Kong
Authors: Lee Chi Kei Krystal , Chung Kar Kin Albert
Published: June 2020

Background: Psychotropic substance use is common in HIV-infected gay or bisexual men (GBM). This study examined the association between Axis I psychiatric disorders and active psychotropic substance use, and identified factors affecting the prevalence of psychiatric disorders in HIV-infected GBM.Methods: This is a cross-sectional case-control study taken place in an HIV clinic and community organisations serving people living with HIV or GBM in Hong Kong. Participants were 62 HIV-infected self-identified GBM who reported psychotropic substance use in the past 1 year (cases), and 55 HIV-infected self-identified GBM without psychotropic substance use in the past 1 year and had negative toxicology tests at recruitment (controls).The Chinese-bilingual Structured Clinical Interview for DSM-IV (Axis I, Patient version) was followed to establish the psychiatric diagnoses. Socio-demographic data, level of social support, HIV-related data, and pattern of psychotropic substance use were collected. Results: Cases had lower level of social support (p=0.02), more depressive disorders (AOR 3.4, 95% CI 1.3-8.7, p=0.01) and psychotic disorders (AOR 7.2, 95% CI 1.2-41, p=0.03) but not anxiety disorders. Significant difference in the prevalence of psychiatric disorders was only evident for disorders with onset after HIV diagnosis. Methamphetamine dependence (AOR 6.63, 95% CI 1.53-228.72, p<0.01), weekly methamphetamine use for 2 years or more (AOR 18.6, 95% CI 1.26-274.69, p=0.03), using methamphetamine beyond chemsex (AOR 4.76, 95% CI 1.17-19.41, p=0.03) were significant predictors for psychiatric disorders in the cases in separate logistic regression models. Duration of HIV diagnosis was a significant independent predictor in all three models. Conclusions: Active psychotropic substance use in HIV-infected gay or bisexual men was associated with a 3-fold increase in Axis I psychiatric disorders. This increase in psychiatric disorders was predicted by the severity, duration and context of methamphetamine use and the duration of HIV diagnosis.
Draw your heart disease: a graphic assessment of the knowledge of congenital heart disease of patients and their parents
Authors: García Paula Mariño , Moure Ángeles Fuertes , Bendayán Isaac Martínez , Barreiro Vanesa Balboa , Núñez Fernando Rueda
Published: June 2020

Background
Patients with congenital heart disease are a chronically ill population. Knowledge of the disease is a key factor in promoting an appropriate attitude towards health. The aim of this study is to evaluate the understanding of heart involvement by describing the heart disease and drawing a picture of the heart by patients and parents.
Methods
Descriptive cross-sectional study over an 8-month period in a tertiary pediatric cardiology center, involving 201 parents and 123 patients, of whom 74 were between 8 and 14 years old and 49 were older than 14 years old. A questionnaire was used in which they had to name and describe the disease, and where a blank box was included in which they were asked to draw their congenital heart disease.
Results
68.8% of the patients correctly named their heart disease, however only 32.4% described it adequately and only 3.5% drew a correct picture of it. Divided by age groups, of the patients between 8 and 14 years old 45.9% named their cardiopathy correctly, 28.2% described it adequately and 4.1% drew a correct picture of it. Of those over 14 years of age, 83.6% correctly named their cardiopathy, 26.5% knew how to describe it and only 2% managed to draw it properly. In the group of parents, 79.1% correctly named their child's congenital heart disease, 45.8% described it adequately and only 3.5% drew a correct picture (p value 0.55).
Conclusions
Most parents and patients with congenital heart disease are unaware of fundamental aspects of their heart disease. An effort should be made by the professionals to try to explain congenital heart disease in an illustrative way, in order to achieve a better understanding of the disease and thus optimize the behavior in terms of health.
Some Notable Records of Mayflies (Insecta: Ephemeroptera) from Big Rivers in Indiana
Authors: Jacobus Luke M.
Published: June 2020

Objectives: Mayflies (Insecta: Ephemeroptera) were collected from the Ohio River, White River and Wabash River in Indiana during July and August 2019, with the goals of confirming the continued existence of historic populations of species and discovering previously undocumented populations.Data description: Notable new data for Ephoron album (Say) (Polymitarcyidae), Heptagenia elegantula (Eaton) (Heptageniidae), Pentagenia vittigera (Walsh) (Palingeniidae), and Tortopsis primus (McDunnough) (Polymitarcyidae) are reported.
The Top 100 Most Cited Articles on Bronchoscopy: A Bibliometric Analysis
Authors: He Boxue , Zhang Pengfei , Shi Shuai , Xie Hui , Zhang Yuqian , Peng Xiong , Zhao Zhenyu , Yin Wei , Cai Qidong , Wang Xiang
Published: June 2020

Background: The applications of bronchoscopy are broad and involve different aspects of diagnosis and treatment. Over the past few decades, an increasing number of studies about bronchoscopy have been published. However, little is known about their qualities and characteristics.Methods: The databases of Web of Science Core Collection, MEDLINE, etc. were utilized to identifying articles published from 1990 to 2020. The top 100 most cited articles about bronchoscopy were selected for analysis of publication time, total citation number, the citation density, time-related flux, first author, geographic origin, research theme, published journals, and network analysis.Results: The selected articles were published mainly in the 2000s and 1990s. Citations per article ranged from 731 to 196. The leading country was the USA, followed by the United Kingdom. The most frequent study themes were bronchoalveolar lavage (BAL) fluid and biopsy. The network analysis connoted that “BAL, inflammation, diagnosis” had a high degree of centrality in the 1990s, while “diagnosis, BAL, biopsy, prospective” in the 2000s.Conclusions: The time, area, and theme distribution of the 100 most cited articles on bronchoscopy have been thoroughly analyzed. It is noticeable that researches based on BAL and endobronchial or transbronchial biopsies currently plays a major role.
A novel age-structured mosquito model for assessing the mechanisms behind vector control success
Authors: Davis Emma L , Hollingsworth T Déirdre , Keeling Matt J
Published: June 2020

Background: Vector control is a vital tool utilised by malaria control and elimination programmes worldwide, and as such it is important that we can accurately quantify the expected public health impact of a range of vector control methods. There are very few previous models that consider vector control induced changes in the age-structure of the vector population and the resulting impact this will have on transmission.Methods: The steady-state solution of a novel age-structured deterministic compartmental model describing the mosquito gonotrophic cycle is analytically derived, with the age of each mosquito measured in the number of gonotrophic cycles (or successful blood meals) completed. From this model we derive analytical expressions for key transmission measures, such as the effective reproductive ratio under control, Rc, and investigate the impact of commonly used vector control methods on the age-structure of the vector population.Results: We derive and analyse a novel model with an explicit solution that can be used to directly quantify key transmission statistics and investigate the age-structured impact of vector control. Application of this model confirms current knowledge that adult-acting interventions, such as IRS or LLINs, are highly effective at reducing transmission, particularly in comparison to larvicide usage at the same coverage. We also find that scaling up coverage results in a wider gap in transmission reduction between adult-active and larval-based interventions. For LLINs and IRS the effective reproductive ratio under control, Rc, decreases exponentially with coverage, whereas for larvicides the relationship is linear. We also find that mid-ranges of LLIN coverage see the largest effect of reduced net integrity on transmission.Conclusions: Well-maintained, adult-acting vector control measures are substantially more effective than larval-based action at reducing the transmission potential of the mosquito population, particularly at medium to high coverage levels.
Carbon Stock Variation Along Altitudinal Gradient of Wacho Forest in Hawa Galan District, Kellem Wollega Zone, Oromia Region, Ethiopia
Authors: Gashu Gezahegn , Gidey Gebre , Deressa Sime , Fekansa Zame , Awoke Halid
Published: June 2020

Background: Forest ecosystem plays a crucial role in the global carbon cycle; as such, mitigating high atmospheric concentrations of carbon dioxide and other greenhouse gases by naturally taking carbon from the atmosphere through photosynthesis. Verification and accounting of carbon stock in forest ecosystem have been renowned as a potential strategy to reduce and stabilize atmospheric concentrations of greenhouse gas. Forest sequesters and store more carbon than any other terrestrial ecosystem and it is an important natural break on climate change. It acts as a carbon reservoir by storing large amount of carbon in trees, undergrowth vegetation, forest floor and soil. Result: The mean carbon stock of each carbon pool was changed along altitudinal class of the study area. The largest mean above and below ground carbon stock was found in the second altitudinal class(1560.01-1643m) followed by first altitudinal class(1435-1560m) and the third altitudinal class (1643.01-1704m) of the study area. The largest mean dead tree and dead wood carbon stock was also stored in the first altitudinal class followed by the third and the second altitudinal class of the study area. The largest mean litter carbon stock was found in the first altitudinal class followed by the second and the third altitudinal class of the study area. The largest mean soil organic carbon was found in the third altitudinal class followed by the second and the first altitudinal class of the study area.Conclusions: The carbon stock variation along altitudinal gradients indicated that, altitude had no a statistically significant effect on any of the carbon pools except litter carbon of the study area at 95% of confidence interval.
A comparative study on effect of different methods of recycling orthodontic brackets on shear bond strength
Authors: Khanal Purna Prasad , Shrestha Basanta Kumar , Yadav Rajiv , Gupta Sanjay Prasad
Published: June 2020

Background: Recycling the old or debonded bracket is one possible alternative to the replacement with new bracket. The aim of this study was to evaluate and compare the effect of different methods of recycling stainless steel orthodontic brackets on shear bond strength.Methods: One hundred twenty human premolars extracted for orthodontic purpose were randomly divided into four groups. Standard MBT (0.022”) brackets, (Leone co., Sesto, Florentine, Florence, Italy) were bonded on buccal surface of all samples with light cured adhesive primer Orthosol (Enlight, Ormco corp., USA) using LED curing unit for 10 seconds. Group I was assigned as control and the brackets of Group II, Group III and Group IV were subjected to recycling by flaming (Gas microtorch: RS Pro, Nozzle, MT 790) ,flaming with sandblasting (Bio-Art sandblaster; Rua Teotônio Vilela, Brazil) and flaming with ultrasonic cleaning (Ultrasonic cleaning unit ,Confident dental equipments Ltd, India) respectively. The recycled brackets were rebonded and final debonding of all brackets was done with universal testing machine (AG-IC/100 KN, Shimadzu, Japan) at a crosshead speed of 0.5mm/min and shear bond strength (MPa) was determined. The adhesive remnant index was evaluated by stereomicroscope at 10X magnification (Olympus corp., Japan). Results: The highest shear bond strength was obtained with Group I (10.35 ± 0.46 MPa), followed by Group III (9.36 ± 0.55 MPa), Group IV (5.97 ± 0.66 MPa) and the least value was obtained with Group II (4.30 ± 0.55 Mpa). Significant differences among the groups were detected by analysis of variance. Tukey post hoc multiple comparison test showed that the shear bond strength of each group was significantly different from one another (p < 0.001). The Chi-square showed statistically significant differences in the adhesive remnant index of the 4 groups (p < 0.001). Conclusions: Shear bond strength of new brackets was significantly higher than that of the recycled brackets. Among recycled brackets, flaming with sandblasting provided adequate shear bond strength, flaming with ultrasonic cleaning provided borderline value for clinical use while flaming alone led to significantly lower value.
Epigenomic evolution in chronic lymphocytic leukaemia cells from patients treated with ibrutinib and showing disease progression
Authors: Holmes Katie , Sadreev Ildar , Evans Charlotte , Thomas Fraser , Rawstron Andy , Hillmen Pete , Newton Darren James , Lefevre Pascal
Published: June 2020

BackgroundThe Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib provided a breakthrough in the treatment of chronic lymphocytic leukaemia (CLL), but cases of resistance are now emerging. Whilst resistance is commonly associated with mutations in BTK itself and the downstream signalling molecule PLCg2, this is not always the case. In a recent study, we have detected some epigenomic plasticity correlated with the dynamics of CLL cell response to ibrutinib. To understand the mechanisms mediating resistance in CLL, it is important to be able to determine whether the observed phenotypic changes are driven solely by resistance cues (e.g. clonal evolution, activation of signalling bypassing BTK inhibition), or if they could also be the consequence of unrelated events.MethodsTo answer to this question, we have monitored chromatin changes happening in response to ibrutinib from the start of treatment until relapse in CLL cells from both a patient carrying a previously identified BTK C481S mutation and from a relapsing patient, for whom none of the classical genetic lesions associated with ibrutinib relapse was detected.ResultsWe established that the epigenome and gene expression in CLL cells from patients on ibrutinib changes with time independently of disease progression and identified two patterns of chromatin alterations, which are independent of resistance mechanisms; one ibrutinib-dependent and the other related to quiescence. Furthermore, by defining the main characteristics of resistance-independent epigenomic plasticity and excluding them from the analysis, we identified candidate genes potentially mediating disease progression.ConclusionThis two-step strategy could fundamentally alter the understanding of resistance to treatment in CLL.
Baseline Well-being, Perceptions of Critical Incidents, and Openness to Debriefing in Community Hospital Emergency Department Clinical Staff Before COVID-19, A Cross-Sectional Study
Authors: Cantu Laura Ashley , Thomas Listy
Published: June 2020

Background: Emergency department personnel routinely bear witness to traumatic experiences and critical incidents that can affect their own well-being. Peer support through debriefing has demonstrated positive impacts on clinicians’ well-being following critical incidents. This study explored community hospital emergency department staff’s perceptions of critical incidents, assessed openness to debriefing and measured baseline well-being. Our analysis provides a baseline of provider well-being immediately prior to the local onset of COVID-19. The potential need for additional resources to support frontline providers during the pandemic can be evaluated. Method: We conducted a cross-sectional study for 4-weeks prior to the first COVID-19 case in Connecticut using a survey offered to an interprofessional group of emergency department clinical staff. The main outcome measures were the Hospital Anxiety and Depression Scale (HADS) and the Professional Quality of Life (ProQOL) scale. Pearson’s chi-square test was used to identify significant differences in perceptions of critical incidents and debriefings between professional categories. One-way ANOVA and Tukey’s test were used to analyze significant differences in well-being between professional categories. Results: Thirty-nine clinical personnel from St. Vincent’s Emergency Department responded to the survey. Events frequently selected as critical incidents were caring for critically ill children (89.7%), mass casualty events (84.6%), and death of a patient (69.2%). Critical incidents were commonly reported (81.6%) as occurring once per week. Additionally, 76.2% of participants reported wanting to discuss a critical incident with their team. Across all respondents, 45.7% scored borderline or abnormal for anxiety, 55.9% scored moderate for burnout, and 55.8% scored moderate to high for secondary traumatic stress.Conclusions: At baseline, providers reported caring for critically ill children, mass casualty events, and death of a patient as critical incidents, which typically occurred once per week. Death of a patient occurs at increased frequency during the protracted mass casualty experience of COVID-19 and threatens provider well-being. Receptiveness to post-event debriefing is high but the method is still underutilized. With nearly half of staff scoring borderline or abnormal for anxiety, burnout, and secondary traumatic stress at baseline, peer support measures should be implemented to protect frontline providers’ well-being during and after the pandemic.
Tyrosine Supplement Ameliorates Murine aGVHD by Modulation of Gut Microbiome and Metabolome
Authors: Li Xiaoqing , Lin Yu , Li Xue , Xu Xiaoxiao , Zhao Yanmin , Xu Lin , Gao Yang , Li Yixue , Tan Yamin , Qian Pengxu , Huang He
Published: June 2020

Background
The microbial communities and their metabolic components in gut are essential for immune homeostasis and profoundly influence the host susceptibility to many immune-mediated diseases including acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the functional connections between microbiome and metabolites in aGVHD are poorly understood because of the complexity of gastrointestinal environment. Thus, we initially performed 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics to unleash the gut microbiota and fecal metabolic phenotype in aGVHD murine model.
Results
A Lachnospiraceae_unclassified was significantly downregulated while the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus were increased in aGVHD happened group. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites inversely correlated with Clostridium XIVa, Blautia and Enterococcus in aGVHD condition. In addition to explore the importance and function of tyrosine, we supplied different tyrosine content diets to mice during transplantation. Additional tyrosine supplements could improve overall survival, ameliorate symptoms at the early stage of aGVHD and changed the structure and composition of gut microbiota and fecal metabolic phenotype, while mice with aGVHD deprived from tyrosine displayed worse manifestations than vehicle.
Conclusions
Overall, a better understanding of the roles of gut microbiota-metabolomes interconnectedness in aGVHD could help identify disease biomarkers and offer better targets for diagnosis and treatment.
Associating the COVID-19 Severity with Urban Factors: A Case Study of Wuhan
Authors: Li Xin , Zhou Lin , Jia Tao , Peng Ran , Fu Xiongwu , Zou Yuliang
Published: June 2020

Wuhan encountered a serious attack in the first round of the COVID-19 pandemic which has resulted in serious worldwide consequences politically and economically. Based on the Weibo help data, we inferred the spatial distribution pattern of the epidemic situation and its impacts. Seven urban factors, i.e. urban growth, general hospital, commercial facilities, subway station, landuse mixture, aging ratio, and road density, were selected for validation with the ordinary linear model, and the former six presented globally significant association with the epidemic severity; thereafter, the geographically weighted regression model was further adopted for local test to identify their unevenly distributed effects in urban space. Among the six, the place where general hospitals exert effects on epidemic situation highly is associated with their distribution and density; commercial facilities appear the most prevalently distributed factor over the city; newly developed residential quarters with high-rise buildings face greater risks, mainly distributed around the waterfront area of Hanyang and Wuchang; the influence of subway stations concentrates at the adjacency place where the three towns meet and near-terminal locations; aging ratio dominantly affects the hinterland of Hankou in a broader extent than other areas in the city. Upon the result, a series of managerial implications that coordinate various urban factors have been proposed. This research is conductive to developing specific planning and design responses for different areas in the city based on a better understanding of the occurrence, transmission, and diffusion of the COVID-19 epidemic in the metropolitan area.
Construction and Validation of a Machine Learning-based Nomogram: A TOOL to Predict the Risk of Getting Severe Corona Virus Disease 2019 (COVID-19)
Authors: Zheng Xinyi , Yao Zhixian , Zheng Zhong , Wu Ke , Zheng Junhua
Published: June 2020

Background

Identifying patients who may develop severe coronavirus disease 2019 (COVID-19) will facilitate personalized treatment and optimize the distribution of medical resources.
Methods

In this study, 590 COVID-19 patients during hospitalization were enrolled (Training set: n = 285; Internal validation set: n = 127; Prospective set: n = 178). After filtered by 2 machine learning methods in the training set, 5 out of 31 clinical features were selected into model building to predict the risk of developing severe COVID-19 disease. Multivariate logistic regression was applied to build the prediction nomogram and validated in 2 different sets. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were used to evaluate its performance.
Results

From 31 potential predictors in the training set, 5 independent predictive factors were identified and included in the risk score: C-reactive protein (CRP), Lactate dehydrogenase (LDH), Age, Charlson/Deyo comorbidity score (CDCS) and Erythrocyte sedimentation rate (ESR). Subsequently, we generated the nomogram based on the above features for predicting severe COVID-19. In the training cohort, the Area under curves (AUCs) were 0.822 (95% CI 0.765–0.875) and the internal validation cohort was 0.762 (95% CI 0.768–0.844). Further, we validated it in a prospective cohort with the AUCs of 0.705 (95% CI 0.627–0.778). The internally bootstrapped calibration curve showed favorable consistency between prediction by nomogram and actual situation. And DCA analysis also conferred high clinical net benefit.
Conclusion

In this study, our predicting model based on 5 clinical characteristics of COVID-19 patients will enable clinicians to predict the potential risk of developing critical illness and thus optimize medical management.
Toll-Like Receptor 4 Mediated Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation in Vascular Smooth Muscle Cells
Authors: Chen Zhongli , Xue Qiqi , Cao Lijuan , Wang Yanpin , Chen Yuanyuan , Zhang Xiaojie , Xiao Fan , Yang Ying , Hayden Melvin R. , Yan Liu , Yang Ke
Published: June 2020

Background: Oxidized low-density lipoprotein (oxLDL) induced a foam-cell like phenotype of the vascular smooth muscle cells (VSMCs), leading to the inflammatory responses incorporating Toll-like receptors (Tlrs)-mediated cellular alterations. We previously found that Tlr4 participated in inflammation response in VSMCs under oxLDL stimulation. However, the role of Tlr4 in foam-cell formation and underlying molecular pathways has not been comprehensively elucidated. This study aimed to investigate the role of Tlr4-mediated mechanisms in oxLDL induced foam-cell formation within VSMCs. Methods: After incubated with different dose of oxLDL, the lipid, reactive oxygen species (ROS) accumulation and foam-cell phenotype of the VSMCs were detected. The alteration of Tlr family, ROS and lipid accumulation regulators including the Src kinase, Nox2, Nox4, Mnsod and sirtuins were measured. Then the Tlr4 was knock down and underlying cellular change and altered molecules were detected. Results: We showed that oxLDL induced foam-cell like phenotype in VSMCs and led to lipid and ROS accumulation in a dose-dependent manner. OxLDL induced the strongest upregulation of Tlr4 in the Tlrs family and initiated change of Src activation, Nox2, Mnsod, sirt1 and sirt3 expression. The effect of oxLDL was abolished by Tlr4 knockdown. Furthermore, knocking down of Tlr4 reduced Src activation and led to restored Sirt1/Sirt3 expression. Moreover, inhibiting or knocking down the Src kinase diminished lipid accumulation in VSMCs under oxLDL treatment. And overexpression of Sirt1/3 relieved the oxLDL induced ROS accumulation and foam-cell phenotype in VSMCs.Conclusions: These results demonstrated that Tlr4 is a critical regulator in oxLDL induced foam cell formation of VSMCs via mediating Src kinase as well as Sirt1 and Sirt3. Beyond the role of Tlr4 in inflammation response of VSMCs, we provide an integrated mechanism about TLR4 in VSMCs phenotype transition under oxLDL stimulation.
Can medication mitigate the need for a strict lock down?: A mathematical study of control strategies for COVID-19 infection
Authors: Ali Mohsin , Imran Mudassar , Khan Adnan
Published: June 2020

BackgroundCOVID-19 is a pandemic that has swept across the world in 2020. To date the only effective control mechanisms were non-pharmaceutical interventions, however there have been encouraging reports regarding possible medication in the literature, with emergency approval given to some drugs in various countries.MethodsWe formulate a deterministic epidemic model to study the effects of medication on the transmission dynamics of Corona Virus Disease (COVID-19). We are especially interested in how the availability of medication could change the necessary quarantine measures for effective control of the disease. We model the transmission by extending the SEIR model to include asymptomatic, quarantined, isolated and medicated population compartments.ResultsWe calculate the basic reproduction number R0 and show that for R0<1 the disease dies out and for R0>1 the disease is endemic. Using sensitivity analysis we establish that R0 is most sensitive to the rates of quarantine and medication. We also study how the effectiveness and the rate of medication along with the quarantine rate affect R0. We devise optimal quarantine, medication and isolation strategies, noting that availability of medication reduces the duration and severity of the lock-down needed for effective disease control.ConclusionOur study also reinforces the idea that with the availability of medication, while the severity of the lock downs can be eased over time some social distancing protocols need to be observed, at least till a vaccine is found. We also analyze the COVID-19 outbreak data for four different countries, in two of these, India and Pakistan the curve is still rising, and in he other two, Italy and Spain, the epidemic curve is now falling due to effective quarantine measures. We provide estimates of R0 and the proportion of asymptomatic individuals in the population for these countries.
Inhibitory control training improves ADHD symptoms and externalizing behavior
Authors: Nejati Vahid , Fallah Fateme
Published: June 2020

Background: The majority of cognitive and behavioral deficit in children with attention deficit- hyperactivity disorder (ADHD) originates form the impaired inhibitory control. Methods: In the present study, thirty preschoolers with ADHD are requited in an experimental design in two equal control and intervention groups. The Color- word Stroop test, GO/No- Go task, Swanson, Nolan, and Pelham Rating Scale, and Child Behavior Checklist were used for assessment in baseline, after intervention, and one- month follow- up sessions. The program for attentive rehabilitation of inhibition and selective attention (PARISA) was used for intervention in 12-15 sessions. Results: The result found improvement in prepotent inhibition and interference control in intervention group. Furthermore, the hyperactivity/ impulsivity symptoms were ameliorated and the externalizing behavioral problem were improved after intervention. Conclusion: The inhibitory control in preschooler with ADHD is trainable and the benefit of training could be transferred to the ADHD symptoms and externalizing behavior.Trial registration: IR.IAU.TMU.REC.1398.046.
Immune Normalization Strategy Against Suboptimal Health Status: Safe and Effective Mixed-Natural Killer Cell Therapy
Authors: Li Ying , Fu Shihu , Xing Fuyuan , Wu Huanwan , Wang Juan , Chen Aihua , Ren Xinhua , Peng Dawei , Ling Xia , Shi Ming , Wu Hongjin
Published: June 2020

Background: Immune normalization has emerged as a new paradigm in immunotherapy, which is proposed in cancer patients instead of the traditional immune enhancement therapy. The immune normalization strategy may also be implemented in cancer prevention of sub-healthy individuals.Methods: We established in vitro cultured mixed-Natural Killer cells (NKM), which could be used to achieve immune normalization. We defined the sub-healthy individuals after analyzing the PD-1 ratio in PBMCs from 95 donors over 50 years of age.Results: NKM were composed by approximately 20% NK cells (CD3-CD16+ or CD56+), 30% NKT-like cells (CD3+CD16+ or CD56+) and other T cells. The in vitro cytotoxicity of NKM was ten times higher than the peripheral blood mononuclear cells (PBMC). NKM cytotoxicity was negatively correlated with the ratio of regulatory T cells (CD3+CD4+ T), and positively correlated with the ratio of NK cells, especially CD56brightCD16bright NK cells. We found the sub-healthy individuals displayed significantly higher ratio of CD3+PD-1+ T cells in PBMC (Ratio > 4%) and higher ratio of CD3+CD8+PD-1+ T cells in CD3+CD8+ T cells (Ratio > 10%) than the healthy controls. Then, we evaluated the potential clinical application of NKM therapy in one pancreatic cancer patient and four sub-healthy individuals.Conclusions: NKM therapy showed good tolerance and no side effects were found. In sub-healthy individuals, the ratio of CD3+PD-1+ T cells and CD3+CD8+PD-1+ T cells was significantly reduced after NKM treatment, which indicated that NKM therapy could potentially be used for cancer prevention and health care, thereby achieving the immune normalization.Trial registration: International Research Center for Regenerative Medicine, BIH-2018-1001. 01 August 2018, BOAO International Hospital.International Research Center for Regenerative Medicine, BIH-2018-1002. 01 August 2018, BOAO International Hospital.