bluuebunny/crossref_metadata_2025 huggingface dataset:
A SNP-mediated lncRNA (LOC146880) and microRNA (miR-539-5p) interaction and its potential impact on the NSCLC risk
Authors: Feng Tienan , Feng Nannan , Zhu Tengteng , Li Qiang , Zhang Qi , Wang Yu , Gao Ming , Zhou Baosen , Yu Herbert , Zheng Min , Qian Biyun
Published: August 2020

Background

Many cancer-associated single nucleotide polymorphisms (SNPs) are located in the genomic regions of long non-coding RNAs (lncRNAs). Mechanisms of these SNPs in connection to cancer risk are not fully understood.

Methods

Association of SNP (rs140618127) in lncRNALOC146880with non-small cell lung cancer (NSCLC) was evaluated in a case-control study of 2707 individuals. The mechanism of the SNP’s biologic influence was explored with in vitro and in vivo experiments, including plasmid transfection, siRNA knockdown, flow cytometry assessment, and assays of cell proliferation, migration, invasion, and colony formation.

Results

Association analysis showed that A allele of SNP rs140618127 was associated with low risk of NSCLC in the Chinese population. Lab experiments indicated that SNP rs140618127 contained a binding site for miR-539-5p and the binding between miR-539-5p andLOC146880resulted in declined phosphorylation of an oncogene, ENO1. The reduced phosphorylation of ENO1 led to decreased phosphorylation of PI3K and Akt, which is further linked to the decline in cell proliferation and tumor progression.

Conclusion

The study demonstrates that SNP rs140618127 in lncRNA loc146880 provides an alternate binding site for microRNA miR-539-5p which affects the phosphorylation of ENO1 and activation of the PI3K and Akt pathway.
TNFAIP8 promotes AML chemoresistance by activating ERK signaling pathway through interaction with Rac1
Authors: Pang Yihua , Zhao Yanan , Wang Yan , Wang Xinlu , Wang Ruiqing , Liu Na , Li Peng , Ji Min , Ye Jingjing , Sun Tao , Li Jingxin , Ma Daoxin , Lu Fei , Ji Chunyan
Published: August 2020

Background

Chemoresistance is emerging as a major barrier to successful treatment in acute myeloid leukemia (AML), and evasion of apoptosis is among the fundamental underlying mechanisms. Therefore, unraveling molecular networks that drive this process constitutes an urgent unmet need. Herein, we aim to characterize the role and molecular mechanism of the tumor necrosis factor ɑ-induced protein 8 (TNFAIP8), a novel anti-apoptotic molecule, in AML chemoresistance.

Methods

The expression levels of TNFAIP8 were assessed in AML patients and cell lines by RT-qPCR and western blots. The transcriptional regulation of TNFAIP8 was analyzed with luciferase reporter assay and ChIP followed by RT-qPCR. Functional experiments were conducted to evaluate the effects of TNFAIP8 on apoptosis, drug sensitivity and proliferation of AML cells. Potential effects of TNFAIP8 on the activation of extracellular signal-regulated kinase (ERK) pathway were detected by western blots. CoIP and P21-activated kinase (PAK) pull-down assay were performed to ascertain the upstream target. The overall effects of TNFAIP8 on AML were examined in murine models.

Results

Upregulated TNFAIP8 expression was first confirmed in human AML patients and cell lines. E74 like ETS transcription factor 1 (ELF1) was then identified to contribute to its aberrant expression. Through manipulating TNFAIP8 expression, we described its role in protecting AML cells from apoptosis induced by chemotherapeutic agents and in promoting drug resistance. Notably, the leukemia-promoting action of TNFAIP8 was mediated by sustaining activity of the ERK signaling pathway, through an interaction with Rac family small GTPase 1 (Rac1). In addition, in vivo experiments confirmed that TNFAIP8 suppression lowered leukemia infiltration and improved survival.

Conclusion

Our data provide a molecular basis for the role of TNFAIP8 in chemoresistance and progression of AML and highlight the unique function of TNFAIP8 as an attractive therapeutic target.
Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma
Authors: He Hui , Wang Yawei , Ye Peng , Yi Dehui , Cheng Ying , Tang Haibo , Zhu Zhi , Wang Xun , Jin Shi
Published: August 2020

Background

Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained.

Methods

The expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments.

Results

The expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis.

Conclusions

ZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.
Pre-hospital blood transfusion – an ESA survey of European practice
Authors: Thies Karl-Christian , Truhlář Anatolij , Keene Damian , Hinkelbein Jochen , Rützler Kurt , Brazzi Luca , Vivien Benoît
Published: August 2020

Background

Blood products are a lifesaving commodity in the treatment of major trauma.

Although there is little evidence for use of pre-hospital blood products (PHBP) in seriously injured patients, an increasing number of emergency medical services have started using PHBP for treatment of major haemorrhage.

The primary aim of this survey was to establish the degree of prehospital blood product use throughout Europe and discover main indications. The secondary aim was to evaluate opinions about PHBP and also the experience and the personal views of its users.

Methods

The subcommittee for Critical Emergency Medicine of the European Society of Anaesthesiology (ESA) held an online survey of European Helicopter Emergency Services (HEMS) and all French Services d’Aide Médicale Urgente (SAMU) regions. It contained 13 questions both open and multiple-choice about the frequency transfusions are carried out, the PHBP used and the perceived benefit. The survey was distributed to the corresponding HEMS leads in 14 European countries.

Results

In total there were 172 valid responses; overall 48% of all respondents have prehospital access to packed red cells, 22% to fresh plasma and 14% use lyophilised plasma. Besides blood product administration, 94% of all services use tranexamic acid. Sixty five percent of all replies came from French and from German services (37 and 28% respectively). PHBP were mainly used for trauma related emergencies. France has the highest uptake of use of blood products at 89%, whereas the rate in Germany was far lower at 6%.

Fifty five percent of the service leads felt that PHBP are beneficial, and even lifesaving in individual cases despite being needed infrequently.

Conclusions

We found remarkable dissimilarities in practice between the different European countries. Even if there is not an absolute consensus amongst providers on the benefit of PHBP, the majority feel they are beneficial. The difference in practice is possibly related to the perceived lack of evidence on prehospital blood transfusion. We suggest to include the use of PHBP in trauma registries in order to consolidate the existing evidence.
Evaluation of Mental Health First Aid from the Perspective Of Workplace End UseRs—EMPOWER: protocol of cluster randomised trial phase
Authors: Atanda Opeyemi , Callaghan Patrick , Carter Tim , Durcan Graham , O’Shea Nick , Brown Steve D. , Reavey Paula , Vangeli Eleni , White Sarah , Wood Kerry V.
Published: August 2020

Background

Mental Health First Aid (MHFA) is a mental health intervention that teaches people how to identify, understand and help someone who may be experiencing a mental health issue. Reviews of the implementation of MHFA found between 68 and 88% of trained Mental Health First Aiders had used their skills when in contact with someone experiencing mental health difficulties. Reviews evaluating the impact of MHFA suggest positive outcomes. However, to date, there has been no systematic, rigorous evaluation of the impact of MHFA on recipients of the intervention, the organisations providing it and the cost-effectiveness of MHFA overall. This trial will evaluate the effectiveness and cost-effectiveness of MHFA.

Methods

The study is a multi-centred, two-arm clustered randomised controlled trial. Organisations will be randomly allocated to the control or intervention (estimated sample size 800 recipients). The intervention is the standard MHFA intervention provided by Mental Health First Aid England (MHFAE). The control condition will be organisations having a brief consultation from MHFAE on promoting mental health and well-being in the workplace. The primary outcome is health seeking behaviour, measured using the Actual Help Seeking Questionnaire, at 6 months’ follow-up. Data collection will be undertaken at baseline (T0), post-intervention—up to 3 months (T1), at 6 months (T2), 12 months (T3) and 24 months (T4). The primary analysis will be conducted on those participants who receive MHFA, a per protocol analysis.

Discussion

The study is the first to evaluate the effect of MHFA in the workplace on employees with direct and indirect experience of the intervention, when compared with usual practice. Being also the first to assess, systematically, the social impact of MHFA and investigate its cost-effectiveness adds to the originality of the study. The study promises to yield important data, as yet unknown, regarding the effectiveness, cost-effectiveness, implementation issues, and the sustainability of MHFA in the workplace.

Trial registration

Clinicaltrials.govNCT04311203. Registered on 17 March 2020.
Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study
Authors: Sharma Shefali Khanna , Jain Siddharth , Bahl Pooja , Potturi Pragna , Rathi Manish , Naidu Shankar , Sachdeva Naresh , Dhir Varun , Jain Sanjay
Published: August 2020

Background

Ovarian toxicity is a dreaded complication of cyclophosphamide (CYC). With the use of lower cumulative doses of intravenous CYC (modified NIH regimens) and availability of better markers of ovarian toxicity, the incidence of ovarian dysfunction needs reassessment. Lupus disease activity, by itself, is also believed to affect ovarian function negatively.

Methods

This single-centre prospective cohort study recruited 50 female patients of severe lupus aged 18–40 years. Twenty-five patients each received induction with either monthly intravenous CYC (0.5–0.75 g/m2) for 6–9 months or daily oral mycophenolate mofetil (MMF). Details of menstrual irregularities; serum levels of FSH, LH, estradiol, AMH, and inhibin B; and sonographic assessment of ovarian volume and antral follicular count were done at baseline and 6 months after treatment. Amenorrhoeic patients were re-evaluated at 1 year.

Results

Mean (SD) age of subjects in the CYC and MMF groups was 31.4 (6.3) and 28.4 (4.4) years, respectively. Mean (SD) SLEDAI at the initiation of therapy was 7.2 (2.5) in the CYC group and 5.8 (3.4) in the MMF group. The mean cumulative dose of CYC used was 4.6 (1.8) g. Three patients in the CYC group (versus none in MMF) had amenorrhoea at 6 months—two of these regained menses within 6 months, while only one (4%) developed sustained amenorrhoea (lasting more than 12 months) at 41 years of age, likely menopause. Serum FSH levels increased (p = 0.03), while AMH (p = 0.002) and inhibin B (p < 0.001) levels decreased significantly with 6 months of CYC therapy. Ovarian volume also reduced significantly (p = 0.005) with 6 months of CYC therapy, while antral follicular count reduced numerically (p = 0.32). Levels of AMH, inhibin-B, estradiol, ovarian volume, and antral follicular count after 6 months therapy were significantly lesser in the CYC group compared to the MMF group, despite being similar before the start of therapy.

Conclusions

Ovarian dysfunction with monthly intravenous CYC (modified NIH regimen) was predominantly subclinical, with a negative effect on ovarian reserve. No premature ovarian failure was noted at 1 year. No ovarian dysfunction occurred in the MMF group, despite having patients with severe background lupus. Use of intravenous CYC for induction may thus not be restricted in young lupus females with incomplete families for fear of gonadotoxicity, especially in life- or organ-threatening situations, where the benefits outweigh this subclinical risk.
Molecular characteristics of the VP1 region of enterovirus 71 strains in China
Authors: Sun Haiyan , Gao Min , Cui Dawei
Published: August 2020

Background

Enterovirus 71 (EV71) is the most commonly implicated causative agent of severe outbreaks of paediatric hand, foot, and mouth disease (HFMD).VP1 protein, a capsid protein of EV71, is responsible for the genotype of the virus and is essential for vaccine development and effectiveness. However, the genotypes of EV71 isolates in China are still not completely clear.

Methods

The VP1 gene sequences of 3712 EV71 virus strains from China, excluding repetitive sequences and 30 known EV71 genotypes as reference strains, between 1986 and 2019 were obtained from GenBank. Phylogenetic tree, amino acid homology, genetic variation and genotype analyses of the EV71VP1 protein were performed with MEGA 6.0 software.

Results

The amino acid identity was found to be 88.33%–100% among the 3712 EV71 strains, 93.47%–100% compared with vaccine strain H07, and 93.04%–100% compared with vaccine strains FY7VP5 or FY-23 K-B. Since 2000, the prevalent strains of EV71 were mainly of the C4 genotype. Among these, the C4a subgenotype was predominant, followed by the C4b subgenotype; other subgenotypes appeared sporadically between 2005 and 2018 in mainland China. The B4 genotype was the main genotype in Taiwan, and the epidemic strains were constantly changing. Some amino acid variations in VP1 of EV71 occurred with high frequencies, including A289T (20.99%), H22Q (16.49%), A293S (15.95%), S283T (15.11%), V249I (7.76%), N31D (7.25%), and E98K (6.65%).

Conclusion

The C4 genotype of EV71 in China matches the vaccine and should effectively control EV71. However, the efficacy of the vaccine is partially affected by the continuous change in epidemic strains in Taiwan. These results suggest that the genetic characteristics of the EV71-VP1 region should be continuously monitored, which is critical for epidemic control and vaccine design to prevent EV71 infection in children.
Arterial endothelium creates a permissive niche for expansion of human cord blood hematopoietic stem and progenitor cells
Authors: Li Huilin , Pei Haiyun , Wang Sihan , Zhang Bowen , Fan Zeng , Liu Yiming , Xie Xiaoyan , Yang Zhou , Xu Lei , Jia Yali , Bai Yun , Han Yi , Chen Lin , He Lijuan , Nan Xue , Yue Wen , Pei Xuetao
Published: August 2020

Background

Although cord blood (CB) offers promise for treatment of patients with high-risk hematological malignancies and immune disorders, the limited numbers of hematopoietic stem cell (HSC)/progenitor cell in a CB unit and straitened circumstances in expanding ex vivo make it quite challenging to develop the successful cell therapies.

Methods

In this study, a novel strategy has been developed to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) by coculture with engineered human umbilical arterial endothelial cells (HuAECs-E4orf1-GFP), which expressesE4ORF1stably by using a retroviral system.

Results

Coculture of CD34+hCB cells with HuAECs-E4orf1-GFP resulted in generation of considerably more total nucleated cells, CD34+CD38−, and CD34+CD38−CD90+HSPCs in comparison with that of cytokines alone or that of coculture with human umbilical vein endothelial cells (HuVECs) after 14-day amplification. The in vitro multilineage differentiation potential and in vivo repopulating capacity of the expanded hematopoietic cells cocultured with HuAECs-E4orf1-GFP were also markedly enhanced compared with the other two control groups. DLL4, a major determinant of arterial endothelial cell (EC) identity, was associated with CD34+hCB cells amplified on HuAECs-E4orf1-GFP.

Conclusions

Collectively, we demonstrated that HuAECs acted as a permissive niche in facilitating expansion of HSPCs. Our study further implicated that the crucial factors and related pathways presented in HuAECs may give a hint to maintain self-renewal of bona fide HSCs.
Quantitative comparison of pre-treatment predictive and post-treatment measured dosimetry for selective internal radiation therapy using cone-beam CT for tumor and liver perfusion territory definition
Authors: Jafargholi Rangraz Esmaeel , Tang Xikai , Van Laeken Charlotte , Maleux Geert , Dekervel Jeroen , Van Cutsem Eric , Verslype Chris , Baete Kristof , Nuyts Johan , Deroose Christophe M.
Published: August 2020

Background

Selective internal radiation therapy (SIRT) is a promising treatment for unresectable hepatic malignancies. Predictive dose calculation based on a simulation using 99mTc-labeled macro-aggregated albumin (99mTc-MAA) before the treatment is considered as a potential tool for patient-specific treatment planning. Post-treatment dose measurement is mainly performed to confirm the planned absorbed dose to the tumor and non-tumor liver volumes. This study compared the predicted and measured absorbed dose distributions.

Methods

Thirty-one patients (67 tumors) treated by SIRT with resin microspheres were analyzed. Predicted and delivered absorbed dose was calculated using 99mTc-MAA-SPECT and 90Y-TOF-PET imaging. The voxel-level dose distribution was derived using the local deposition model. Liver perfusion territories and tumors have been delineated on contrast-enhanced CBCT images, which have been acquired during the 99mTc-MAA work-up. Several dose-volume histogram (DVH) parameters together with the mean dose for liver perfusion territories and non-tumoral and tumoral compartments were evaluated.

Results

A strong correlation between the predicted and measured mean dose for non-tumoral volume was observed (r = 0.937). The ratio of measured and predicted mean dose to this volume has a first, second, and third interquartile range of 0.83, 1.05, and 1.25. The difference between the measured and predicted mean dose did not exceed 11 Gy. The correlation between predicted and measured mean dose to the tumor was moderate (r = 0.623) with a mean difference of − 9.3 Gy. The ratio of measured and predicted tumor mean dose had a median of 1.01 with the first and third interquartile ranges of 0.58 and 1.59, respectively. Our results suggest that 99mTc-MAA-based dosimetry could predict under or over dosing of the non-tumoral liver parenchyma for almost all cases. For more than two thirds of the tumors, a predictive absorbed dose correctly indicated either good tumor dose coverage or under-dosing of the tumor.

Conclusion

Our results highlight the predictive value of 99mTc-MAA-based dose estimation to predict non-tumor liver irradiation, which can be applied to prescribe an optimized activity aiming at avoiding liver toxicity. Compared to non-tumoral tissue, a poorer agreement between predicted and measured absorbed dose is observed for tumors.
Effects of exercise therapy in patients with acute low back pain: a systematic review of systematic reviews
Authors: Karlsson Marc , Bergenheim Anna , Larsson Maria E. H. , Nordeman Lena , van Tulder Maurits , Bernhardsson Susanne
Published: August 2020

Background

Acute low back pain is associated with pain and disability, but symptoms are often self-healing. The effectiveness of exercise therapy for acute low back pain remains uncertain with conflicting evidence from systematic reviews. The aim of this systematic review of systematic reviews was to assess the overall certainty of evidence for the effects of exercise therapy, compared with other interventions, on pain, disability, recurrence, and adverse effects in adult patients with acute low back pain.

Methods

PubMed, the Cochrane library, CINAHL, PEDro, Open Grey, Web of Science, and PROSPERO were searched for systematic reviews of randomized controlled trials. Methodological quality was assessed independently by two authors using AMSTAR. Meta-analyses were performed if possible, using data from the original studies. Data for pain, disability, recurrence, and adverse effects were analyzed. Certainty of evidence was assessed using GRADE.

Results

The searches retrieved 2602 records, of which 134 publications were selected for full-text screening. Twenty-four reviews were included, in which 21 randomized controlled trials (n= 2685) presented data for an acute population, related to 69 comparisons. Overlap was high, 76%, with a corrected covered area of 0.14. Methodological quality varied from low to high. Exercise therapy was categorized into general exercise therapy, stabilization exercise, and McKenzie therapy. No important difference in pain or disability was evident when exercise therapy was compared with sham ultrasound, nor for the comparators usual care, spinal manipulative therapy, advice to stay active, and educational booklet. Neither McKenzie therapy nor stabilization exercise yielded any important difference in effects compared with other types of exercise therapy. Certainty of evidence varied from very low to moderate.

Conclusions

The findings suggest very low to moderate certainty of evidence that exercise therapy may result in little or no important difference in pain or disability, compared with other interventions, in adult patients with acute low back pain. A limitation of this systematic review is that some included reviews were of low quality. When implementing findings of this systematic review in clinical practice, patients’ preferences and the clinician’s expertise also should be considered, to determine if and when exercise therapy should be the intervention of choice.

Systematic review registration

PROSPERO: CRD46146, available at:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=46146.
Boundary shape function method for nonlinear BVP, automatically satisfying prescribed multipoint boundary conditions
Authors: Liu Chein-Shan , Chang Chih-Wen
Published: August 2020

It is difficult to exactly and automatically satisfy nonseparable multipoint boundary conditions by numerical methods. With this in mind, we develop a novel algorithm to find solution for a second-order nonlinear boundary value problem (BVP), which automatically satisfies the multipoint boundary conditions prescribed. A novel concept of boundary shape function (BSF) is introduced, whose existence is proven, and it can satisfy the multipoint boundary conditions a priori. In the BSF, there exists a free function, from which we can develop an iterative algorithm by letting the BSF be the solution of the BVP and the free function be another variable. Hence, the multipoint nonlinear BVP is properly transformed to an initial value problem for the new variable, whose initial conditions are given arbitrarily. The BSF method (BSFM) can find very accurate solution through a few iterations.
Further generalizations of Hadamard and Fejér–Hadamard fractional inequalities and error estimates
Authors: Rao Yongsheng , Yussouf Muhammad , Farid Ghulam , Pečarić Josip , Tlili Iskander
Published: August 2020

The aim of this paper is to generalize the fractional Hadamard and Fejér–Hadamard inequalities. By using a generalized fractional integral operator containing extended Mittag-Leffler function via monotone function, for convex functions we generalize well known fractional Hadamard and Fejér–Hadamard inequalities. Also we study the error bounds of these generalized Hadamard and Fejér–Hadamard inequalities. We also obtain some published results from presented inequalities.
Dynamics of a fractional order mathematical model for COVID-19 epidemic
Authors: Zhang Zizhen , Zeb Anwar , Egbelowo Oluwaseun Francis , Erturk Vedat Suat
Published: August 2020

In this work, we formulate and analyze a new mathematical model for COVID-19 epidemic with isolated class in fractional order. This model is described by a system of fractional-order differential equations model and includes five classes, namely, S (susceptible class), E (exposed class), I (infected class), Q (isolated class), and R (recovered class). Dynamics and numerical approximations for the proposed fractional-order model are studied. Firstly, positivity and boundedness of the model are established. Secondly, the basic reproduction number of the model is calculated by using the next generation matrix approach. Then, asymptotic stability of the model is investigated. Lastly, we apply the adaptive predictor–corrector algorithm and fourth-order Runge–Kutta (RK4) method to simulate the proposed model. Consequently, a set of numerical simulations are performed to support the validity of the theoretical results. The numerical simulations indicate that there is a good agreement between theoretical results and numerical ones.
Estimates of quantum bounds pertaining to new q-integral identity with applications
Authors: Awan Muhammad Uzair , Talib Sadia , Kashuri Artion , Noor Muhammad Aslam , Chu Yu-Ming
Published: August 2020

In this article, we establish a new generalized q-integral identity involving a q-differentiable function. Using this new auxiliary result, we obtain some new associated quantum bounds essentially using the class of preinvex functions. At the end, we present some applications to the special bivariate means to show the significance of the obtained results. Our approaches and obtained results may lead to further applications in physics.
Analysis of dengue model with fractal-fractional Caputo–Fabrizio operator
Authors: Fatmawati  , Khan Muhammad Altaf , Alfiniyah Cicik , Alzahrani Ebraheem
Published: August 2020

In this work, we study the dengue dynamics with fractal-factional Caputo–Fabrizio operator. We employ real statistical data of dengue infection cases of East Java, Indonesia, from 2018 and parameterize the dengue model. The estimated basic reduction number for this dataset is$\mathcal{R}_{0}\approx2.2020$R0≈2.2020. We briefly show the stability results of the model for the case when the basic reproduction number is$\mathcal{R}_{0} <1$R0<1. We apply the fractal-fractional operator in the framework of Caputo–Fabrizio to the model and present its numerical solution by using a novel approach. The parameter values estimated for the model are used to compare with fractal-fractional operator, and we suggest that the fractal-fractional operator provides the best fitting for real cases of dengue infection when varying the values of both operators’ orders. We suggest some more graphical illustration for the model variables with various orders of fractal and fractional.
A seven-year surveillance study of the epidemiology, antifungal susceptibility, risk factors and mortality of candidaemia among paediatric and adult inpatients in a tertiary teaching hospital in China
Authors: Zeng Zhangrui , Ding Yinhuan , Tian Gang , Yang Kui , Deng Jian , Li Guangrong , Liu Jinbo
Published: August 2020

Background

There are no current national estimates of the candidaemia burden in China, and epidemiological candidaemia data from the underdeveloped region of China are lacking.

Methods

A 7-year retrospective study was carried out to analyse the prevalence, species distribution, antifungal susceptibility, risk factors and inpatient mortality of candidaemia among paediatric and adult patients in a regional tertiary teaching hospital in China.

Results

During the seven-year study period, a total of 201 inpatients with candidaemia were identified. The median age of the patients was 65 years (range, 1 day to 92 years), and 114 of the patients (56.7%) were male. The mean annual incidence of candidaemia was 0.26 cases per 1000 admissions (0.42 cases per 1000 paediatric admissions vs 0.24 cases per 1000 adult admissions, P < 0.05). Candida albicans was the most common fungal species (81/201, 40.3%) in all patients, Candida glabrata was the most common fungal species (18/35, 51.4%) in paediatric patients. Most isolates were susceptible to flucytosine (99.0%) and amphotericin B (99.0%), and the activity of antifungal agents against Candida species was no significant difference in satisfaction between paediatric and adult patients (P > 0.05). The all-cause mortality rate was 20.4% (paediatric patients: 11.4% vs adult patients:22.3%, P > 0.05). Fewer univariate predictors of poor outcomes were identified for paediatric patients than for adult patients (4 vs 11 predictors). Respiratory dysfunction and septic shock were independent predictors of 30-day mortality for all patients.

Conclusions

The epidemiological data of candidaemia in paediatric and adult patients are only different in the distributions of Candida species and the mean annual incidence of candidaemia. Flucytosine and amphotericin B can be used as first-choice agents when no antifungal susceptibility test results are available.
Rapid determination of S-(+)-linalool in leaf of Cinnamomum osmophloeum ct. linalool using ultrasound-assisted microextraction
Authors: Chang Ting-Kuang , Lin Chun-Ya , Chen Ying-Ju , Yeh Ting-Feng , Chang Shang-Tzen
Published: August 2020

Cinnamomum osmophloeum ct. linalool is one chemotype of indigenous cinnamon in Taiwan. Its leaf essential oil (LEO) and main component S-(+)-linalool both possess great anxiolytic activities. The aim of this study was to establish ultrasound-assisted microextraction (UAME) for extracting LEO from C. osmophloeum ct. linalool. The absolute content of S-(+)-linalool and chemical composition of LEO were analyzed using GC-MS and GC-FID. To obtain the optimal conditions for UAME, four parameters (ultrasonic extraction duration, power of ultrasound, times of extraction, and leaf weight of extraction) were investigated according to the S-(+)-linalool content extracted. Results showed that the optimal condition was 10 mg of leaf extracted using n-hexane in an ultrasonicator with ultrasonic power of 80 W for 1 min. Furthermore, the absolute content of S-(+)-linalool obtained by UAME (28.3 ± 0.5 mg/g leaf) was comparable with that extracted by the 30-min hydrodistillation (HD) (26.9 ± 2.7 mg/g leaf). UAME was then employed to extract S-(+)-linalool from leaves at different stages of maturity (young, semi-mature, and mature). Results indicated that only mature leaf contains large amounts of S-(+)-linalool. Of note is that the LEO extracted by UAME contains coumarin, while that extracted by HD does not. Coumarin is an important ingredient in a number of cosmetic products due to its odor-fixing properties. With UAME, the leaf of C. osmophloeum ct. linalool has potential to be used as an aromatic material for further applications. In conclusion, UAME established in the present study provides a simple and rapid method for the determination of S-(+)-linalool and chemical composition of LEO from C. osmophloeum ct. linalool.
Effects of aqueous extract of fruit pulp of Adansonia digitata L. on the oxidative stress profile against Trypanosoma brucei brucei infection in albino rats
Authors: Ogunleye Oluyomi Olajumoke , Jatau Isa Danladi , Natala Audu Joseph , Ola-Fadunsin Shola David
Published: August 2020

Background

Chemotherapy is the most widely used means of controlling trypanosomosis, however, effectiveness of the drugs available is limited by a number of factors. This study investigates the oxidative stress profile of aqueous extract of the fruit pulp of Adansonia digitata on some organs in rats infected with Trypanosoma brucei brucei.

Methods

Thirty-five male albino rats were divided into 7 groups of 5 rats each. Groups B, C, D, E, F and G were inoculated with 0.20 ml of suspension containing 106 T. b. brucei. Group A were neither infected nor treated. Group B were infected but not treated. At onset of parasitaemia, rats in group C were treated with diminazene aceturate at 3.5 mg/kg body weight once, while rats in group D were treated with vitamin C at 200 mg/kg body weight for 3 days consecutively. Rats in groups E, F and G were treated orally for 3 days with the aqueous extract of fruit pulp of A. digitata at a dosage of 40 mg/kg, 80 mg/kg and 160 mg/kg body weight respectively. Liver and kidney tissues of the rats were collected at necropsy (10 days PI) for oxidative stress analysis.

Results

There was a significant (p < 0.05) effect in the concentration levels of malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase among the different groups treated with aqueous extract of fruit pulp of A. digitata.

Conclusion

The extract of A. digitata exert protective effects against tissue peroxidation in albino rats experimentally infected with T. b. brucei.
Suppression of platelet reactivity during dialysis by addition of a nitric oxide donor to the dialysis fluid
Authors: Urabe Shunichiro , Kokubo Kenichi , Tsukao Hiroshi , Kobayashi Kozue , Hirose Minoru , Kobayashi Hirosuke
Published: August 2020

Background

Dialysis membranes that release nitric oxide (NO) from their surface, mimicking one of the functions of endothelial cells, may suppress platelet reactivity during hemodialysis treatment. The aim of the present study was to examine whether the addition of a NO donor to the dialysis fluid can suppress platelet reactivity during dialysis.

Methods

Porcine whole blood was circulated for 4 h through a polysulfone (PS) dialyzer or polymethylmethacrylate (PMMA) dialyzer. After the blood was circulated through the blood circuit and dialyzer, sodium nitroprusside was added to the dialysis fluid as a NO donor. The changes in the platelet reactivity, measured by the platelet aggregation activity by the addition of adenosine diphosphate or collagen in the blood sample, were evaluated during ex vivo dialysis experiments in the presence of a dialysis fluid containing or not containing a NO donor.

Results

The platelet aggregation activity was significantly decreased at 30 min after the start of the experiment in the case where nitroprusside was added to the dialysis fluid (the NO (+) condition) as compared to the case where no nitroprusside was added to the dialysis fluid (the NO (−) condition), for both the PS and PMMA membranes. The suppression of the platelet reactivity in the NO (+) condition was sustained until the end of the experimental period (240 min). The platelet cyclic guanosine monophosphate level was also significantly increased in the NO (+) condition as compared to the NO (−) condition.

Conclusions

NO in the dialysis fluid appears to be capable of suppressing the increase of the platelet reactivity observed during dialysis.
Decisions on marriage? Couples’ decisions on union transition in Sweden
Authors: Duvander Ann-Zofie , Kridahl Linda
Published: August 2020

Marriage is an institution that has become optional for many. This study investigates how decisions are taken regarding marriage among Swedish cohabiting couples in the twenty-first century, specifically focusing on whose intentions to marry are most decisive. We use the Young Adult Panel Study conducted in 2009 with augmented register data for 2009–2014 in order to observe both partners’ intentions and to then follow up on which couples ultimately married. The study finds that women’s and men’s intentions to marry seem to be equally important, but that there are gendered differences by educational level: women’s intentions carry more weight among highly educated couples, while men’s intentions carry more weight among lower educated couples.
The holistic way of tackling the COVID-19 pandemic: the one health approach
Authors: Mushi Vivian
Published: August 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is causing a global pandemic had a zoonotic origin in China. Considering the inter-connectedness between human, environment, and animal health, the One Health approach is the appropriate strategy to control and mitigate the effects of the ongoing coronavirus disease 2019 (COVID-19). This letter explains the benefits of the One Health approach and recommends specific measures that could be taken to accelerate the fight against COVID-19 and prevent the spread of newly emerging infectious diseases.
Eye spy a liar: assessing the utility of eye fixations and confidence judgments for detecting concealed recognition of faces, scenes and objects
Authors: Millen Ailsa E. , Hope Lorraine , Hillstrom Anne P.
Published: August 2020

Background

In criminal investigations, uncooperative witnesses might deny knowing a perpetrator, the location of a murder scene or knowledge of a weapon. We sought to identify markers of recognition in eye fixations and confidence judgments whilst participants told the truth and lied about recognising faces (Experiment 1) and scenes and objects (Experiment 2) that varied in familiarity. To detect recognition we calculated effect size differences in markers of recognition between familiar and unfamiliar items that varied in familiarity (personally familiar, newly learned).

Results

In Experiment 1, recognition of personally familiar faces was reliably detected across multiple fixation markers (e.g. fewer fixations, fewer interest areas viewed, fewer return fixations) during honest and concealed recognition. In Experiment 2, recognition of personally familiar non-face items (scenes and objects) was detected solely by fewer fixations during honest and concealed recognition; differences in other fixation measures were not consistent. In both experiments, fewer fixations exposed concealed recognition of newly learned faces, scenes and objects, but the same pattern was not observed during honest recognition. Confidence ratings were higher for recognition of personally familiar faces than for unfamiliar faces.

Conclusions

Robust memories of personally familiar faces were detected in patterns of fixations and confidence ratings, irrespective of task demands required to conceal recognition. Crucially, we demonstrate that newly learned faces should not be used as a proxy for real-world familiarity, and that conclusions should not be generalised across different types of familiarity or stimulus class.
Isokinetic evaluation of the trunk muscle strength in housewives with fibromyalgia: a cross-sectional study
Authors: Mülkoğlu Cevriye , Taşkın Sühan , Vural Seçil , Mansız Kaplan Başak , Selvi Ahmet Buğra , Genç Hakan
Published: August 2020

Background

It is known that physical activity and muscular performance are reduced in fibromyalgia (FM) syndrome. This study aims to compare the performance of trunk muscles in women with FM and healthy controls and evaluate the correlation between trunk muscle strength and FM severity.

Methods

Forty-six patients with FM and 42 age- and body mass index-matched healthy housewives without FM were included in the FM and control groups, respectively. The Fibromyalgia Impact Questionnaire (FIQ) was used for the assessment of FM severity. The pain intensity was evaluated using the visual analogical scale (VAS). An isokinetic dynamometer was used to measure the isokinetic trunk muscle strength. The peak torque (PT) values were recorded. The psychological status of the patients was evaluated using the Beck Depression Inventory.

Results

There was no statistically significant difference in terms of age, BMI, and BDI scores in two groups (p > 0.05, for all). The isokinetic trunk extensor PT values were significantly lower in the FM group (p = 0.002 for 60°/s, and p < 0.001 for 90°/s and 120°/s) than control group. There was a statistically significant negative correlation between FIQ score and isokinetic extensor muscle parameters.

Conclusion

The results indicate that trunk extensor muscles were significantly weaker in FM patients. Trunk extensor muscle strength decreased as FM severity increased in FM patients.
Accuracy and clinical feasibility of 3D-myocardial thickness map measured by cardiac computed tomogram
Authors: Kwon Oh-Seok , Lee Jisu , Lim Sehwan , Park Je-Wook , Han Hee-Jin , Yang So-Hyun , Hwang Inseok , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: August 2020

Background

Although myocardial thickness is an important variable for therapeutic catheter ablation of cardiac arrhythmias, quantification of wall thickness has been overlooked. We developed a software (AMBER) that measures 3D-myocardial thickness using a cardiac computed tomogram (CT) image, verified its accuracy, and tested its clinical feasibility.

Methods

We generated 3D-thickness maps by calculating wall thickness (WT) from the CT images of 120 patients’ hearts and a 3D-phantom model (PhM). The initial vector field of the Laplace equation was oriented to calculate WT with the field lines derived from the 3D mesh. We demonstrate the robustness of the Laplace WT algorithm by comparing with the real thickness of 3D-PhM, echocardiographically measured left ventricular (LV) WT, and regional left atrial (LA) WT reported from previous studies. We conducted a pilot case of catheter ablation for atrial fibrillation (AF) utilizing real-time LAWT map-guided radiofrequency (RF) energy titration.

Results

AMBER 3D-WT had excellent correlations with the real thickness of the PhM (R = 0.968,p < 0.001) and echocardiographically measured LVWT in 10 patients (R = 0.656,p = 0.007). AMBER 3D-LAWT (n = 120) showed a relatively good match with 12 previously reported regional LAWT. We successfully conducted pilot AF ablation utilizing AMBER 3D-LAWT map-guided real-time RF energy titration.

Conclusion

We developed and verified an AMBER 3D-cardiac thickness map measured by cardiac CT images for LAWT and LVWT, and tested its feasibility for RF energy titration during clinical catheter ablation.
An open-source phase correction toolkit for transcranial focused ultrasound
Authors: Jin Changzhu , Moore David , Snell John , Paeng Dong-Guk
Published: August 2020

Background

The phase correction on transcranial focused ultrasound is essential to regulate unwanted focal point shift caused by skull bone aberration. The aim of the current study was to design and investigate the feasibility of a ray-based phase correction toolkit for transcranial focused ultrasound.

Results

The peak pressure at focal area was improved by 140.5 ± 7.0% on target I and 134.8 ± 19.1% on target II using proposed phase correction toolkit, respectively. A total computation time of 402.1 ± 24.5 milliseconds was achieved for each sonication.

Conclusion

The designed ray-based phase correction software can be used as a lightweight toolkit to compensate aberrated phase within clinical environment.
Progress in exosome associated tumor markers and their detection methods
Authors: Shen Mengjiao , Di Kaili , He Hongzhang , Xia Yanyan , Xie Hui , Huang Rongrong , Liu Chang , Yang Mo , Zheng Siyang , He Nongyue , Li Zhiyang
Published: August 2020

Exosomes are secreted by cells and are widely present in body fluids. Exosomes contain various molecular constituents of their cells of origin such as proteins, mRNA, miRNAs, DNA, lipid and glycans which are very similar as the content in tumor cells. These contents play an important role in various stages of tumor development, and make the tumor-derived exosome as a hot and emerging biomarker for various cancers diagnosis and management in non-invasive manner. The present problems of exosome isolation and detection hinder the application of exosomes. With the development of exosome isolation and detection technology, the contents of exosomes can be exploited for early cancer diagnosis. This review summarizes the recent progress on exosome-associated tumor biomarkers and some new technologies for exosome isolation and detection. Furthermore, we have also discussed the future development direction in exosome analysis methods.
Developing fluorescence sensor probe to capture activated muscle-specific calpain-3 (CAPN3) in living muscle cells
Authors: Ojima Koichi , Hata Shoji , Shinkai-Ouchi Fumiko , Oe Mika , Muroya Susumu , Sorimachi Hiroyuki , Ono Yasuko
Published: August 2020

Calpain-3 (CAPN3) is a muscle specific type of calpain whose protease activity is triggered by Ca2+. Here, we developed CAPN3 sensor probes (SPs) to detect activated-CAPN3 using a fluorescence/Förster resonance energy transfer (FRET) technique. In our SPs, partial amino acid sequence of calpastatin, endogenous CAPN inhibitor but CAPN3 substrate, is inserted between two different fluorescence proteins which cause FRET. Biochemical and spectral studies revealed that CAPN3 cleaved SPs and changed emission wavelengths of SPs. Importantly, SPs were scarcely cleaved by CAPN1 and CAPN2. Furthermore, our SP successfully captured the activation of endogenous CAPN3 in living myotubes treated with ouabain. Our SPs would become a promising tool to detect the dynamics of CAPN3 protease activity in living cells.
Inhibition of Alk signaling promotes the induction of human salivary-gland-derived organoids
Authors: Yoshimoto Shohei , Yoshizumi Junko , Anzai Hiromasa , Morishita Koichiro , Okamura Kazuhiko , Hiraki Akimitsu , Hashimoto Shuichi
Published: August 2020

Hyposalivation and xerostomia are the cause of several morbidities, such as dental caries, painful mucositis, oral fungal infections, sialadenitis and dysphagia. For these reasons, preservation of normal saliva secretion is critical for the maintenance of functionally normal oral homeostasis and for keeping good health. Several strategies for restoring salivary gland function have been reported, from different points of view, based on the use of salivary-gland-derived epithelial stem/progenitor cells and tissue engineering approaches to induce organoids that mimic in vivo salivary glands. In this study, we clarified that inhibition of activin receptor-like kinase (Alk) signaling was essential for the induction of human salivary-gland-derived organoids, and demonstrated the usefulness of such organoids as an inflammatory disease model. In inflammatory conditions like sialadenitis, in general, pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α, also known as TNF) are upregulated, but their function is still unclear. In our established human salivary-gland-derived organoid culture system, we successfully induced organoid swelling by stimulation with carbachol, a non-selective cholinergic agonist, and forskolin, an activator of cystic fibrosis transmembrane conductance regulator (CFTR). Furthermore, we found that this organoid swelling was inhibited by TNF-α. From these results, we could clarify the inhibitory function of TNF-α on saliva secretion in vitro. Thus, our established human salivary-gland-derived organoids would be useful for in vitro analyses of the morphological and functional changes involved in salivary gland dysfunctions in several research fields, such as pathobiology, inflammation and regenerative medicine.

This article has an associated First Person interview with the first author of the paper.