bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-200c Overexpression in Cancer-Associated Fibroblasts Reduces the Invasive Properties of Breast Cancer Cells: An Approach to Molecular Therapy
Authors: Shenavar Nasim , Shariati Laleh , Hakimian Mohammad Reza , Javanmard Shaghayegh Haghjooy
Published: March 2021

BackgroundThe most common malignancy is breast cancer, among women in the world. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Cancer associated fibroblasts (CAFs) play a critical role to support tumor cells in all aspect of cancer development such as cell proliferation, migration and angiogenesis. MiRNAs are one of the regulatory molecules that regulate the genes contributing to cell growth, differentiation, migration and apoptosis. Based on other studies, miR-200c, as a tumor suppressor, has low expression levels in cancer associated fibroblasts. In this investigation, effect of miR-200c overexpression was evaluated on proliferation, migration and angiogenesis of TNBC cells. MethodsThe fibroblasts were isolated from normal and cancer breast tissue. MiR-200c expression was assessed using RT PCR in cancer associated fibroblasts (CAFs) and normal fibrobalasts (NFs) and then, were transfected using miR-200c. Finally, its effect on proliferation, migration and angiogenesis of TNBC cells were evaluated. ResultsOur results confirm that in presence of miR-200c transfected fibroblasts, the proliferation, migration and angiogenesis of cancer cells significantly decreased. This effect may be due to the reduction of growth factors provided by CAFs after miRNAs dysregulation. ConclusionThese results suggest miR-200c act as an effective tumor suppressor in many aspects of TNBC cancer development and can be regarded as a potential therapeutic tool for breast cancer in the future.
Allogeneic Hematopoietic Stem Cell Transplantation, Especially Haploidentical, May Improve Long-term Survival for Children With High-risk T-cell Acute Lymphoblastic Leukemia in First Complete Remission
Authors: Zhang Yongzhan , Bai Lu , Huang Xiao-jun , Lu Ai-dong , Wang Yu , Wu Jun , Zhang Xiao-hui , Zuo Ying-xi , Xu Lan-ping , Jia Yue-ping , Cheng Yi-fei , Zhang Le-ping
Published: March 2021

Purpose The role of hematopoietic stem cell transplantation (HSCT) for children with high-risk (HR) T- cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under critical discussion. This study explored the hierarchical criteria, prognostic factors of childhood T-ALL, and the role of HSCT, especially haplo-HSCT, for children with HR T-ALL in CR1. Methods Seventy-four pediatric T-ALL patients were included in this study and stratified into low-risk chemotherapy cohort (n=16), high-risk chemotherapy cohort (n=31) and high-risk transplant cohort (n=24). Results Patient prognosis in the high-risk chemotherapy cohort was significantly inferior to the low-risk chemotherapy cohort (5-year overall survival (OS): 51.2%±10% vs. 100%, P = 0.003; 5-year event-free survival (EFS): 48.4%±9.8% vs. 93.8%±6.1%, P = 0.01; 5-year cumulative incidence of relapse (CIR): 45.5%±0.8% vs. 6.3%±0.4%, P = 0.043). The 5-year OS, EFS, and CIR of the high-risk transplant cohort were 77.0%±8.3%, 77.0%±8.3%, and 11.9%±0.4%, respectively. When compared to the high-risk chemotherapy cohort, the P values were 0.084, 0.041, and 0.011, respectively. Minimal residual disease (MRD) re-emergence, initial white blood cell (WBC) count, and age≥10 years were independent risk factors for prognosis. ConclusionsHSCT, especially haplo-HSCT, might effectively improve the survival outcomes for HR childhood T-ALL in CR1.
Predictive Approaches to Guide the Expression of Recombinant Vaccine Targets in Escherichia Coli: A Case Study Presentation Utilising Absynth Biologics Ltd Proprietary C.Difficile Vaccine Antigens
Authors: HUSSAIN HIRRA , McKenzie Edward A , Robinson Andrew M , Gingles Neill A , Marston Fiona , Warwicker Jim , Dickson Alan J
Published: March 2021

Background: Bacterial expression systems remain a widely used host for recombinant protein production. However, overexpression of recombinant target proteins in bacterial systems such as Escherichia coli can result in poor solubility and the formation of insoluble aggregates, termed inclusion bodies. As a consequence, different and numerous strategies or alternative engineering approaches have been employed to increase recombinant protein production. In this case study, we present the strategies used to increase the recombinant production and solubility of ‘difficult-to-express’ bacterial antigens, termed Ant2 and Ant3, from Absynth Biologics Ltd’s Clostridium difficile vaccine programme. Results: Single recombinant antigens (Ant2 and Ant3) and fusion proteins (Ant2-3 and Ant3-2) formed insoluble aggregates (inclusion bodies) when overexpressed in BL21 CodonPlus (DE3) cells. Further, proteolytic cleavage of Ant2-3 was observed, potentially due to the presence of a large un-structured loop between the protein boundaries. Optimisation of culture conditions such as varying the induction temperature and addition of heat-shock inducer benzyl alcohol to the growth media had no significant effect on the processing and protein production pattern for all four antigen molecules. Changes to the construct design to include N-terminal solubility tags (Thioredoxin and N utilisation substance protein A) did not improve solubility. Screening of different buffer/additives to improve stability showed that the addition of 1-15mM dithiothreitol (DTT) alone improved the stability of both Ant2 and Ant3. Structural models were generated for Ant2 and Ant3 and solubility-based prediction tools were employed to determine the role of charge and hydrophobicity on protein production. The results showed that both Ant2 and Ant3 contained unfavorable features associated with poor solubility. A large non-polar region was detected on the surface of Ant2 structures, whereas, positively charged regions were observed for Ant3.Conclusions: Commonly used strategies to enhance recombinant protein production in bacterial systems did not act to increase production of model ‘difficult-to-express’ antigens, Ant2 and Ant3 and their fusion proteins. Sequence and structural analysis of antigens identified unfavorable features that potentially result in the increased tendency of these antigens to aggregate and/or lead to improper processing. We present a guide of strategies and predictive approaches that aim to guide the construct design, prior to expression studies, to define and engineer sequences/structures that could lead to increased expression of single and potentially multi-domain (or fusion) antigens in bacterial expression systems.
miR-466 Regulates the Migration of ADSCs in Repairing Cutaneous Wound via Targeting SCF/c-kit/ERK Signaling Axis
Authors: xia sizhan , zhang wei , jin ronghua , weng tingting , yu meirong , yang min , shao jiaming , wang xingang , han chunmao
Published: March 2021

BackgroundWound healing is a complex process and the treatment of chronic non-healing wounds still remains a tough challenge. Mesenchymal stem cell (MSC) based therapy has emerged as a promising therapeutic strategy for wound healing. Stem cell factor/stem cell factor receptor (SCF/c-kit) interaction activates downstream signal pathways in stem cells. microRNAs (miRNAs) regulate the effect of adipose tissue-derived stem cells (ADSCs) in cutaneous wound, but the associated cellular mechanisms are not fully understood. In the research, we investigate the inhibitory effect of miR-466 in ADSC migration induced by SCF/c-kit/ERK axis.MethodsHuman ADSCs were tested by scratch assay and Transwell assay to evaluate the migration ability. MicroRNA sequencing was used to find the discrepancy miRNA in ADSCs with or without SCF pretreatment. The ERK signaling pathway was investigated by pharmacological disruption of PD98059. In addition, siRNA, RT-qPCR, western blotting, and luciferase reporter assay were used to investigate the mechanism of miR-466 regulating migration via the SCF/c-kit/ERK pathway. In the in vivo study, the wound healing ability of miR-466 and SCF was evaluated in a nude mouse full-thickness skin wound model.ResultsADSCs incubated with SCF induces the expression of c-kit and promotes ADSC migration, whereas siRNA c-kit inhibited the effects. microRNAs microarray showed that miR-466 was upregulated in SCF pretreatment ADSCs compared to ADSCs. The luciferase reporter assay indicated that miR-466 may target c-kit and suppress SCF/c-kit-mediated migration of ADSCs. The ERK signaling pathway was confirmed to be involved in SCF/c-kit induced migration. In addition, pre-treatment with PD98059 reversed the effects of SCF/c-kit on the ERK signaling and migration-related proteins. Furthermore, miR-466 inhibits ADSC migration to wound site and defects cutaneous wound healing in vivo.Conclusions﻿Taken together, our data suggested that SCF/c-kit signal axis can enhance the activation of ERK signal pathway, which will promote ADSC migration. miR-466 regulates ADSC migration by targeting SCF/c-kit/ERK signaling and defects wound healing.
Infection Prevention and Control (IPC) Implementation in Low-Resource Settings: A Qualitative Analysis
Authors: Tomczyk Sara , Storr Julie , Kilpatrick Claire , Allegranzi Benedetta
Published: March 2021

BackgroundThe coronavirus disease-2019 (COVID-19) pandemic has again demonstrated the critical role of effective infection prevention and control (IPC) implementation to combat infectious disease threats. Standards such as the World Health Organization (WHO) IPC minimum requirements offer a basis, but robust evidence on effective IPC implementation strategies in low-resource settings remains limited. We aimed to qualitatively assess IPC implementation themes in these settings.MethodsSemi-structured interviews were conducted with IPC experts from low-resource settings, using a standardised questionnaire. Applying a qualitative inductive thematic analysis, IPC implementation examples from interview transcripts were coded, collated into sub-themes, grouped again into broad themes, and reviewed to ensure validity. Sub-themes appearing ≥3 times in data were highlighted as frequent IPC implementation themes and all findings were summarised descriptively.ResultsInterviews were conducted with IPC experts from 29 countries in six WHO regions. Frequent IPC implementation themes to achieve the WHO IPC core components included: 1) To develop IPC programmes: continuous advocacy with leadership, initial external technical assistance, stepwise approach to build resources, use of catalysts, linkages with other programmes, role of national IPC associations and normative legal actions; 2) To develop guidelines: early planning for their operationalization, initial external technical assistance and local guideline adaption; 3) To establish training: attention to methods, fostering local leadership, and sustainable health system linkages such as developing an IPC career path; 4) To establish health care-associated (HAI) surveillance: feasible but high-impact pilots, multidisciplinary collaboration, mentorship, careful consideration of definitions and data quality, and “data for action”; 5) To implement multimodal strategies: clear communication to explain multimodal strategies, attention to certain elements, and feasible but high-impact pilots; 6) To develop monitoring, audit and feedback: feasible but high-impact pilots, attention to methods such as positive (not punitive) incentives and “data for action”; 7) To improve staffing and bed occupancy: participation of national actors to set standards and attention to methods such as use of data; and 8) To promote built environment: involvement of IPC professionals in facility construction, attention to multimodal strategy elements, and long-term advocacy.ConclusionsThese IPC implementation themes offer important qualitative evidence for IPC professionals to consider.
Prognostic Prediction, Immune Microenvironment, and Drug Resistance Value of Collagen Type I Alpha 1 Chain (COL1A1) in Pan-Cancer Analysis
Authors: Yi Liu , Xue Jinmin , Zhong Maoxi , Wang Zhi , Li Jie , Yuxi Zhu
Published: March 2021

Objective

The protein encoded by collagen type I alpha 1 chain(COL1A1)is a component of the extracellular matrix, and critical for tumor microenvironments. However, it remains unclear that the expression level, prognostic prediction, and immunological value of COL1A1 in multiple cancers.
Methods

4 profiles and 6 hub genes were found by bioinformatics analysis. We further analyzed one of the hub genes, the COL1A1. And, we comprehensively analyzed gene expression and genetic alteration patterns among 33 types of malignancies from The Cancer Genome Atlas(TCGA). Besides, we explored the correlation of COL1A1 with cancer prognosis, immune infiltrates, tumor mutational burden (TMB)/ microsatellite instability status (MSI), pathway and drug sensitivity analysis of co-expressed genes.
Results

COL1A1 was highly expressed and associated with poor prognosis in the majority of cancer. On the other hand, COL1A1 expression was closely related to high TMB in THYM, LAML, ACC, KICH, PRAD, and LGG. High MSI was observed in TGCT, MESO, PRAD, COAD, SARC, and CESC. In addition, COL1A1 was positively correlated with the abundance of CAFs, macrophages, and tumor-infiltrating lymphocytes. However, it was negatively correlated with CD8 + T cells mainly in CESC, HNSC-HPV+, and SKCM.
Conclusion

COL1A1 can serve as a prognostic and immunological biomarker in multiple cancers.
Clinical Presentation and Genetic Variants in Autoinflammatory Diseases: Results From the German anti-IL1 Registry for Orphan Diseases (GARROD)
Authors: Blank Norbert , Kötter Ina , Tony Hans-Peter , Rech Jürgen , Krause Karoline , Köhler Birgit , Kaudewitz Dorothee , Nitschke Martin , Haas Christian , Lorenz Hanns-Martin , Krusche Martin
Published: March 2021

Background: To investigate the clinical presentation and genetic variants in patients of the German anti-IL1 registry for autoinflammatory orphan diseases (GARROD) between 2013-2019.Methods: Multicenter, retrospective analysis of demographic, clinical and genetic data of 231 patients with autoinflammatory diseases (AID) who received anti-IL1 targeted therapy.Results: Inflammatory attacks started before the age of 18 years in 44% of the patients. Symptom onset was on average 17.8 years prior to the initiation of anti-IL1 targeted therapy. AID spectrum comprised familial Mediterranean fever (FMF; n=71; 30.7%), cryopyrin-associated periodic syndromes (CAPS; n=43; 18.6%), adult-onset Still’s disease (AOSD, n=32; 13.8%) or other AID (n=85; 36.8%). Monogenetic AID were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 65% of patients with FMF, 14% with CAPS and 47% with TNF receptor-associated periodic syndrome (TRAPS). Heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 23% of patients with FMF, 51% with CAPS and 47% with TRAPS. Patients with VUS were older at disease onset, indicating a milder phenotype.Twenty-nine patients (12.5%) had secondary AA amyloidosis at initiation of anti-IL1 therapy. Primary Diseases were FMF (n=22), TRAPS (n=1) and idiopathic AA amyloidosis (n=6).Conclusions: Molecular genetic analyses might substantiate the clinical diagnosis of a monogenetic AID. In the absence of a known pathogenic variant, the functional role of VUS can be discussed. Our data support the concept of a variable penetrance of VUS, leading to late-onset AID.Anti-IL1 targeted drugs are used to control systemic inflammation, prevent disease flares and AA amyloidosis.
Ultrasensitive broadband photodetectors based on two-dimensional Bi2O2Te films
Authors: Tian Pin , Wu Hongbo , Tang Libin , Xiang Jinzhong , Ji Rongbin , Lau Shu Ping , Teng Kar , Guo Wei , Yao Yugui , Li Lain-Jong
Published: March 2021

Two-dimensional (2D) materials exhibit many unique optical and electronic properties that are highly desirable for application in optoelectronics. Here, we report the study of photodetector based on 2D Bi2O2Te grown on n-Si substrate. The 2D Bi2O2Te material was transformed from sputtered Bi2Te3 ultrathin film after rapid annealing at 400 ℃ for 10 min in air atmosphere. The photodetector was capable of detecting a broad wavelength from 210 nm to 2.4 μm with excellent responsivity of up to 3x105 and 2x104 AW-1, and detectivity of 4x1015 and 2x1014 Jones at deep ultraviolet (UV) and short-wave infrared (SWIR) under weak light illumination, respectively. The effectiveness of 2D materials in weak light detection was investigated by analysis of the photocurrent density contribution. Importantly, the facile growth process with low annealing temperature would allow direct large-scale integration of the 2D Bi2O2Te materials with complementary metal-oxide–semiconductor (CMOS) technology.
Genetic Characterization and Diversity Assessment in ‘Bhangor’ Indigenous Swamp Buffalo Population using Heterologous Microsatellite Markers
Authors: Singh Karan Veer , Das Ramendra , Sodhi Monika , Kataria Ranjit Singh
Published: March 2021

The present study was aimed at genetic characterization and diversity analysis of newly identified swamp buffalo population ‘Bhangor’ using the Food and Agriculture Organization (FAO) recommended bovine microsatellite markers. Genomic DNA was isolated from blood samples of 76 unrelated animals. Of the 24 markers, 15 markers (CSSM33, BM1818, CSRM60, HEL13, ILSTS019, ILSTS025, ILSTS028, ILSTS029, ILSTS030, ILSTS033, ILSTS036, ILSTS056, ILSTS058, ILSTS061, ILSTS089 and ETH003) were found to be highly polymorphic in the population. A total of 114 alleles were secured, with an overall average of 7.60 alleles per locus. The number of alleles ranged from 3 (CSRM60 and ILSTS025) to 12 (ILSTS056 and ILSTS061). The mean effective number of alleles across all polymorphic loci was found to be 3.76. The overall mean expected heterozygosity and unbiased expected heterozygosity values were 0.67 and 0.68, ranging from 0.067 (ILSTS025) to 0.85 (ILSTS058) and 0.068 (ILSTS025) to 0.86 (ILSTS058), respectively. The average PIC estimate across all polymorphic loci was 0.63. The population was found to be in optimum diversity based on polymorphic microsatellite markers. This is the newly characterized buffalo population from north-east India.
Impact of the COVID-19 Pandemic on UK Medical School Widening Access Schemes: Disruption, Support and a Virtual Student Led Initiative
Authors: Bligh Emily R , Courtney Ellie , Stirling Rebecca , Rajananthanan Asveny , Society Sheffield Neuroscience
Published: March 2021

BackgroundCOVID-19 has disrupted medical education in the United Kingdom (UK). The pandemic may result in a long-term disproportionate negative impact to students applying to Medical School from a low-socioeconomic background. In addition, the upsurge in Medical School applications increases the likelihood of stricter University entry criteria over the coming years. There is no current research to determine how widening participation of Medicine to students from low-socioeconomic backgrounds can be improved virtually. The aim of this study is to establish the impact of COVID-19 on students enrolled in UK widening access schemes and the role of virtual student led initiatives in widening participation.MethodsA voluntary online survey was distributed to UK Sixth Form students (N=31) enrolled in a widening access scheme who attended Sheffield Neuroscience Society International Virtual Conference in February 2021. The event was free to attend. The five-domain survey consisted of questions determining demographics, career aspirations, impact of COVID-19, academic skillsets and an educational manipulation check.ResultsThere were 30 pre-conference and 26 post-conference responses. 76.7% (N=23) had work experience cancelled due to COVID-19. A total of 36.7% (N=11) of participants reported participating in virtual work experience. ‘Observe GP’ and ‘Medic Mentor’ were each specified as attended virtual opportunities in 20% (N=6) of answers. Post conference, students felt significantly more confident in applying to Medical School (p=0.008) and more prepared to undertake a presentation (p=0.002). Educational manipulation check scores increased significantly (p=0.003). 100% of students felt inspired to do further CV building activities. ConclusionCOVID-19 has negatively impacted pupils enrolled in UK Medical School widening access schemes. Virtual student led initiatives can instill confidence in delegates from low socio-economic backgrounds, increase their career knowledge and inspire them to take part in further CV building exercises. Both Medical Schools and medical students play a key role in widening participation. This study recommends Medical Schools promote access to virtual events and act mindfully when determining student’s academic potential in the context of their socioeconomic and/or educational background.
D-Cystine di(m)ethyl Ester Reverses the Deleterious Effects of Morphine on Ventilation and Arterial Blood Gas Chemistry While Promoting Analgesia
Authors: Gaston Ben , Baby Santhosh M. , May Walter J. , Young Alex P. , Grossfield Alan , Bates James N. , Seckler James M. , Wilson Christopher G. , Lewis Stephen J.
Published: March 2021

We have identified thiolesters that reverse the negative effects of opioids on breathing without compromising analgesia. Here we report the effects of D-cystine diethyl ester (D-cystine diEE) or D-cystine dimethyl ester (D-cystine diME) on morphine-induced changes in ventilation, arterial-blood gas chemistry, A-a gradient (index of gas-exchange in the lungs) and analgesia in freely moving rats. Injection of morphine (10 mg/kg, IV) elicited negative effects on breathing (e.g., depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive). Subsequent injection of D-cystine diEE (500 mmol/kg, IV) elicited an immediate and sustained reversal of these effects of morphine. Injection of morphine (10 mg/kg, IV) also elicited pronounced decreases in arterial blood pH, pO2 and sO2 accompanied by pronounced increases in pCO2 (all indicative of a decrease in ventilatory drive) and A-a gradient (mismatch in ventilation-perfusion in the lungs). These effects of morphine were reversed in an immediate and sustained fashion by D-cystine diME (500 mmol/kg, IV). Finally, the duration of morphine (5 and 10 mg/kg, IV) analgesia was augmented by D-cystine diEE. D-cystine diEE and D-cystine diME may be clinically useful agents that can effectively reverse the negative effects of morphine on breathing and gas-exchange in the lungs while promoting analgesia.
A Multicenter Study of Short-Term Changes in Mental Health Emergency Services Use During Lockdown in Kitchener-Waterloo, Ontario During the COVID-19 Pandemic
Authors: Dainton Christopher , Donato-Woodger Simon , Chu Charlene
Published: March 2021

Background

The COVID-19 pandemic and subsequent lockdown measures have led to increasing mental health concerns in the general population. We aimed to assess the short-term impact of the pandemic lockdown on mental health emergency services use in the Kitchener-Waterloo region of Ontario, Canada.
Methods

We conducted an observational study during the 6-month period between March 5 and September 5, 2020 using National Ambulatory Care Reporting System metadata from mental health visits to three regional Emergency Departments (ED); mental health and substance related police calls; and calls to a regional mental health crisis telephone line, comparing volumes during the pandemic lockdown with the same period in 2019. Poisson regressions were used to determine significant differences between numbers of each visit or call type during the lockdown period versus the previous year.
Results

Involuntary admissions, substance related visits, mood related visits, situational crisis visits, and self-harm related mental health visits to the EDs were significantly reduced during the lockdown period compared to the year before. Psychosis-related and alcohol-related visits were not significantly reduced. Among police calls, suicide attempts were significantly decreased during the period of lockdown, but intoxication, assault, and domestic disputes were not significantly different. Mental health crisis telephone calls were significantly decreased during the lockdown period.
Conclusions

Contrary to our hypothesis, the decrease in most types of mental health ED visits, mental health and substance-related police calls, and mental health crisis calls largely mirrored the overall decline in emergency services usage during the lockdown period. This finding is unexpected in the context of increased attention to acutely deteriorating mental health during the COVID-19 pandemic.
Detection of Missed Fractures of Hand and Forearm in Whole-Body CT in a Blinded Reassessment
Authors: Kim Simon , Gölz Leonie , Münn Friederike , Kim Damon , Millrose Michael , Eisenschenk Andreas , Thelen Simon , Lautenbach Martin
Published: March 2021

Background: We examined the visibility of fractures of hand and forearm in whole-body CT and its influence on delayed diagnosis. This study is based on a prior study on delayed diagnosis of fractures of hand and forearm in patients with suspected polytrauma.Methods: Two blinded radiologists examined CT-scans of patients with fractures of hand or forearm that were diagnosed later than 24 hrs after admission and control cases with unremarkable imaging of those areas. They were provided with clinical information that was documented in the admission report and were asked to examine forearm and hands. After unblinding, the visibility of fractures was determined. We examined if time of admission or slice thickness was a factor for late or missed diagnoses.Results: We included 72 known fractures in 36 cases. Of those 65 were visible. Sixteen visible fractures were diagnosed late during hospital stay. Eight more fractures were detected on revision by the radiologists. Both radiologists missed known fractures and found new fractures that were not reported by the other. Missed and late diagnoses of fractures occurred more often around 5 pm and 1 am. Slice thickness was not significantly different between fractures and cases with fractures found within 24 hrs and those found later.Conclusions: The number of late diagnosis or completely missed fractures of the hand and forearm may be reduced by a repeated survey of WBCT with focus on the extremities in patients with suspected polytrauma who are not conscious.Level of Evidence III
Clinical Depression in Children and Adolescents With Sickle Cell Anaemia: Influencing Factors in a Resource-limited Setting
Authors: Ezenwosu Osita Uchenna , Chukwu Barth Friday , Ezenwosu Ifeyinwa Lilian , Uwaezuoke Ndubuisi Anyaele , Eke Christopher Bismarck , Udorah Maria Ifechukwu , Idoko Chinedu Arthur , Ikefuna Anthony Nnaemeka , Emodi Ifeoma Josephine
Published: March 2021

Background: Sickle cell anaemia (SCA) is the commonest monogenic haematologic disorder resulting from the inheritance of homozygous mutant haemoglobin genes from both parents. Some factors have been identified as important in explaining the variability in depression in sickle cell anaemia (SCA). Information on this is limited in a resource-limited setting like Nigeria. This study aims to determine factors which influence depression in children and adolescents with sickle cell anaemia in a resource-limited setting.Methods: Systematic random sampling technique was used in this cross-sectional study to select children and adolescents aged 7-17 years at the weekly sickle cell clinic of the University of Nigeria Teaching hospital (UNTH) Enugu, Nigeria. Pretested, structured questionnaire was used to collect sociodemographic and disease severity data while depression was assessed using the Children’s Depression Inventory.Results: Age and educational level had significant positive linear relationships with depression (r = 0.253, p = 0.02; r = 0.225, p = 0.04 respectively) while gender (χ2 = 0.531, p = 0.466), socioeconomic status (χ2 = 0.451, p = 0.798) and disease severity (χ2 = 0.422, p = 0.810) had no relationship with depression in children and adolescents with SCA.Conclusion: Depression in children and adolescents with SCA increased with increasing age and educational level. Psychological evaluation should be integrated into routine assessment of children with SCA during their follow up visits as they get older and progress in class.
Effect of Cu Incorporation on Optoelectronic Properties of e-Beam Evaporated ZnO thin Films by Ellipsometric Investigations
Authors: Ali Gharieb A , moustafa said H. , Amer M. I. , Shaban H. , Emam-Ismail M. , Shaaban E. R. , El-Hagary M.
Published: March 2021

Electron beam deposition technique has been used to deposit a series of Zn1-xCuxO nanocrystalline thin film on silica substrate with a variety of Cu concentrations. The microstructural, surface morphology and spectroscopic ellipsometry (SE) were used to examine the physical properties of the deposited films. The nanocrystalline nature of the Zn1-xCuxO (0.0≤x≤0.20) thin film has been confirmed by surface morphology studies. The XRD spectrum of the Zn1-xCuxO nanocrystalline film showed a hexagonal wurtzite type structure, and no extra phase was detected. Our results show that as the Cu content increases, the direct optical energy gap Eg decreases without any sign of solubility limit up to x≤0.2. The decrease in Eg can be attributed to the sp-d exchange coupling. In addition, exploring the spectral behavior of the refractive index dispersion from SE of the Cu-doped ZnO shows that as the Cu dopant increments; the refractive index of the deposited film enhances. Further, understand the refractive index dispersion of the deposited film has been performed using a single oscillator model proposed by Wemple-DiDomenico (WDD). Our calculations show that as the Cu concentration increases, the values of oscillator energy Eo decreases however, the dispersion energy Ed increases. As a result, the variation of the optical energy band gap and the tunability of the dispersive oscillator parameters values Eo, Ed, n0, e0, M-1 and M-3 with the increase of the Cu doping level confirm that Cu doped ZnO films are a good candidate for optoelectronic device applications.
An Application of Slow Feature Analysis to the Genetic Sequences of Coronaviruses and Influenza viruses
Authors: Tsonis Anastasios , Wang Geli , Zhang Lvyi , Lu Wenxu , Kayafas Aristotle , Rio-Tsonis Katia Del
Published: March 2021

BackgroundMathematical approaches have for decades used to probe the structure of DNA sequences. This has led to the development of Bioinformatics. In this exploratory work, a novel mathematical method is applied to probe the DNA structure of two related viral families; those of coronaviruses and those of influenza viruses. The coronaviruses are SARS-CoV-2, SARS-CoV-1, and MERS. The influenza viruses include H1N1-1918, H1N1-2009, H2N2-1957, and H3N2-1968.MethodsThe mathematical method used is the Slow Feature Analysis (SFA), a rather new but promising method to delineate complex structure in DNA sequences.ResultsThe analysis indicates that the DNA sequences exhibit an elaborate and convoluted structure akin to complex networks. We define a measure of complexity and show that each DNA sequence exhibits a certain degree of complexity within itself, while at the same time there exists complex inter-relationships between the sequences within a family and between the two families. From these relationships, we find evidence, especially for the coronavirus family, that increasing complexity in a sequence is associated with higher transmission rate but with lower mortality.ConclusionsThe complexity measure defined here may hold a promise and could become a useful tool in the prediction of transmission and mortality rates in future new viral strains.
Study on Mechanical Behavior and Failure Network of Deep Roadway under Different Lateral Pressure Coefficients
Authors: Luo Feng , Guo Yijun , Xu Peidong , Diao Yanglong , Li Meng
Published: March 2021

The failure and instability of roadway is a main disaster with the highest frequency in coal mines. The development of surrounding rock control technology is an important way to ensure mine safety. In order to obtain the failure characteristics of surrounding rock and optimize the support method of the roadway, the numerical simulation and physical simulation were used to investigate the mechanical behavior of deep roadway under different lateral pressure coefficients. The evolution mechanism of meso tensile-shear cracks in excavation damaged zone (EDZ) were deeply revealed. The results show that the shear bands which are basically in the form of sliding spiral extends from the two sidewalls to the roof and floor with the increase of lateral pressure coefficient, and develop to the deep surrounding rock. The “crescent-shaped” tensile failure zones generate in the roof and floor when λ < 1, and gradually decrease with the increase of horizontal stress. When λ = 1, the failure pattern around the arch and right angle sides are different influenced by the shape of different side. Under the special stress environment of high deviatoric stress, the pattern of plastic zone will lead to butterfly-like failure mode induced by the stress relief of excavation. Judged from the curves of tangential and deviatoric stress, the surrounding rock in the two sidewalls, the roof and floor are greatly damaged under λ < 0.75 and λ > 1.5 respectively. The verification of the numerical simulation experiment is proved by the similar material simulation experiment.
Liver Stiffness for Predicting Adverse Cardiac Events in Chinese Patients With Heart Failure: A Two-year Prospective Study
Authors: Wang Qian , Song Yuqing , Wu Qiming , Dong Qian , Yang Song
Published: March 2021

Background. To investigate whether liver stiffness (LS) can predict adverse cardiac events in Chinese patients with heart failure (HF). Methods. Total of 53 hospitalized patients with HF were enrolled and LS and tricuspid annual plane systolic excursion (TAPSE)were determined before discharge with Fibroscan® and Echocardiography. The patients were divided into two groups: High LS group(LS >6.9Kpa, n=23) and Low LS group(LS ≤6.9Kp, n=30) . Patients were followed up for 24 months at interval of 3 months. The endpoint of follow-up is death or rehospitalization for HF. Results. All patients were followed up for 24 months or until the endpoint. Patients in High LS group had lower platelet count(P=0.014), lower creatine clear rate (P=0.014), higher level of B-type natriuretic peptide at discharge(P=0.012), and lower tricuspid annual plane systolic excursion (P<0.001). During 24 months follow-up, 3(5.7%) deaths and 21(39.6%) hospitalization were observed. Patients in high LS group had a higher rate of death/rehospitalization when compared with patient in low LS group (Hazard ratio: 4.81; 95% confidence interval:1.69-13.7, P=0.003) after adjustment for age, sex, platelet count, creatine clear rate, and B-type natriuretic peptide level. Also, TAPSE≤16 can predict adverse cardiac events with HR of 6.63 (95% confidence interval:1.69-13.7, P=0.004) for age, sex, platelet count, creatine clear rate, and B-type natriuretic peptide level.Conclusion. LS and TAPSE may be considered for predicting worse outcomes for patients with heart failure.
Comparative Study of Cefixime and Tetracycline: Measuring Effectiveness of Strategies to Improve Appropriate Antibiotic Use in the Treatment of Acute Respiratory Tract Infections (ARTIs) in Urban Population Indonesia.
Authors: Ramdhani Danni , Kusuma Sri Agung Fitri , Sediana Dede , A.P Hilarius Bima , Khumairoh Ika
Published: March 2021

Objective. Antibiotic resistance is a serious threat that occurs globally in the health sector due to increased consumption of inappropriate antibiotics. Guidelines for prescribing antibiotics for ARTIs have been issued in general practice to promote rational antibiotic prescribing. This study was conducted to compare the effectiveness of cefixime and tetracycline as a solution to improve monitoring of appropriate antibiotic use in the treatment of ARTIs.Methods. All stock isolates were rejuvenated first, and cultured on standard media and Kirby-Bauer disc diffusion method was used for susceptibility testing in accordance with the Clinical and Laboratory Standard Institute's (CLSI) recommendations. Identification of bacteria from a single isolate was carried out to determine which bacteria were resistant to cefixime and tetracycline.Results. A total of 466 single isolates of bacteria were analyzed, which showed a percentage of resistance to cefixime 38.0 %, and tetracycline 92.86 %. Bacterial isolates were resistant to cefixime and tetracycilne was a genus of Haemophilus, Streptococcus, Corynebacterium, Staphylococcus, and bordetella. Conclusions. Cefixime compared to tetracycline was proven to be superior in terms of the effectiveness of ARIs treatment.
Biophysical and Computational Landscapes of Mycobacterial Pyrophosphatase: A Closer View of Drug Repurposing With Different Natural and Synthetic Compounds.
Authors: Shivangi Shivangi , Meena Laxman
Published: March 2021

Mycobacterial pyrophosphatase (Mt-ppa) play essential role in bacterial in vitro and in vivo survival. This family of proteins reacts on pyrophosphates to release orthophosphates and protect bacteria from pyrophosphates toxicity. Rv3628 encodes pyrophosphate protein which is a type I pyrophosphate protein. This protein is engaged in hydrolysis of tri and diphosphates (majorly GTP, ATP and GDP) and its catalysis is metal ion dependent. Mt-ppa was showed efficient interaction with GTP molecule, whose Kd was 37.9µM, ΔH was -11Kcal/mol and ΔG was -6.06Kcal/mol. The protein was interacted with ATP family genes that resemble that it is participator in conversion of diphosphates moiety to the residual monophosphates. W102G, V150G, F44G, I119G, L93F, F3G, F122G, I108G, L32G, M82G, Y17G, L59G, V5G, V26G, I7G, W140D, W140G, W140A, F80G, W140S, L49G, L56G, I9G, V60G, V19G, V92G, L28G, L61G, Y126E and F123G are the top 30 mutation hits and Y126G, Y42G, R30G, E8G, K16G are top mutational hits in active site of Mt-ppa. Mt-ppa is temperature and pH sensitive as increasing temperature and pH decreases protein stability. It is also the receptor for several kinases that phosphorylate this protein at different Ser/Thr/Tyr sites. Virtual screening of 700 compounds from herbal ingredient targets (HITs) subset of zinc database give ZINC000003979028, ZINC000003870413, ZINC000003870412, ZINC000150338758, ZINC0000070450948, ZINC000150338754, ZINC000095098891, ZINC000000119985, ZINC000005085286 as the top target hits and Mac0182344 and NAV_2729 as the top GTPase inhibitor that can target and hinders Mt-ppa activity.
Effect of Polystyrene Treatment on the Efficiency and Stability of Fully Printable Mesoscopic Perovskite Solar Cells With Carbon Electrode
Authors: Sonu Kyong Su , Kim Pyol , Ko Song Guk , So Hak Son , Ri Jin Hyok , Ryu Kwon Il
Published: March 2021

Hole conductor-free, fully printable mesoscopic perovskite solar cells with carbon electrode (PM-PSCs) have a good commercialization prospect because of low-cost production and high power conversion efficiency (PCE). Currently, the problem of improving the stability of perovskite solar cells (PSCs) is very important for commercialization. Interfacial engineering using polymers is an effective method to improve the efficiency and stability of PSCs. We prepared PM-PSCs by treatment with the toluene solution containing PS on the carbon electrode of the PM-PSCs, which would improve the charge transfer and greatly suppressed charge recombination in polystyrene (PS)-treated PM-PSCs, and also could greatly prevent degradation of perovskite into PbI2. The PS-treated PM-PSCs showed higher stability to light and moisture than the control, and the PCE was improved from 11.31% (control) to 14.03%.
The Impact of PbF2-Based Glasses on Radiation Shielding and Mechanical Concepts: An Extensive Theoretical and Monte Carlo Simulation Study
Authors: El-Denglawey A. , Issa Shams A.M. , Saddeek Yasser B. , Tekin Huseyin O. , Zakaly Hesham M.H.
Published: March 2021

This work aimed to investigate the impact of Lead-fluoride based glasses via theoretical and simulation techniques on mechanical and radiation shielding parameters. Accordingly, a glass composition PbF2 blended with TeO2-B2O3-Bi2O3 glasses were synthesised by using melt-quenching method. Using Fluka Monte Carlo code, the radiation shielding properties have measured. Moreover. Comparatively higher density PbF80= 6.163g/cm3 with 80 mol % Bi2O3, greater µ, µm and Zeff and lower T1/2, l, tenth value layer values achieved for TeO2-B2O3-Bi2O3/PbF2 glass pointed it out as the best shield of gamma. Besides, the computed effective removal cross-sections against fast neutrons (ΣR) observed that the PbF80 sample has commensurately greater with value 5.2954 (cm-1) The results observed that the variation Bi2O3/PbF2 improves the gamma protection ability of Lead-fluoride based glasses. The longitudinal modulus-L, shear modulus-S, bulk modulus-K, and Young’s modulus-Y raised from 15.89 to 25.9 -GPa, from 8.49 to 12.09 -GPa, from 4.58 to 9.77 -GPa, and from 15.74 to 25.69 -GPa, respectively. The results indicate that the highest Bi2O3/PbF2 ratio encoded PbF80 has the best shielding and mechanical competence with measurable physical properties.
Implementation and Success Factors from Thailand’s 1-3-7 Surveillance Strategy for Malaria Elimination
Authors: Lertpiriyasuwat Cheewanan , Sudathip Prayuth , Kitchakarn Suravadee , Areechokchai Darin , Naowarat Sathapana , Shah Jui A. , Sintasath David , Pinyajeerapat Niparueradee , Young Felicity , Thimasarn Krongthong , Gopinath Deyer , Prempree Preecha
Published: March 2021

Thailand’s National Malaria Elimination Strategy 2017–2026 introduced the 1-3-7 strategy as a robust surveillance and response approach for elimination that would prioritize timely, evidence-based action. Under this strategy, cases are reported within 1 day, cases are investigated within 3 days, and foci are investigated and responded to within 7 days, building on Thailand’s long history of conducting case investigation since the 1980s. However, the hallmark of the 1-3-7 strategy is timeliness, with strict deadlines for reporting and response to accelerate elimination. This paper outlines Thailand’s experience adapting and implementing the 1-3-7 strategy, including success factors such as a cross-sectoral Steering Committee, participation in a collaborative regional partnership, and flexible local budgets. The program continues to evolve to ensure prompt and high-quality case management, capacity maintenance, and adequate supply of lifesaving commodities based on surveillance data. Results from implementation suggest the 1-3-7 strategy has contributed to Thailand’s decline in malaria burden; this experience may be useful for other countries aiming to eliminate malaria.
Application of Deep Learning-Based Neural Networks Using Theoretical Seismograms as Training Data for Locating Earthquakes in the Hakone Volcanic Region, Japan
Authors: Sugiyama Daisuke , Tsuboi Seiji , Yukutake Yohei
Published: March 2021

In the present study, we propose a new approach for determining earthquake hypocentral parameters. This approach integrates computed theoretical seismograms and deep machine learning. The theoretical seismograms are generated through a realistic three-dimensional Earth model, and are then used to create spatial images of seismic wave propagation at the Earth’s surface. These snapshots are subsequently utilized as a training dataset for a convolutional neural network. Neural networks for determining hypocentral parameters such as the epicenter, depth, occurrence time, and magnitude are established using the temporal evolution of the snapshots. These networks are applied to seismograms from the seismic observation network in the Hakone volcanic region in Japan to demonstrate the suitability of the proposed approach for locating earthquakes. We demonstrate that the determination accuracy of hypocentral parameters can be improved by including theoretical seismograms for different earthquake locations and sizes, in the learning dataset for the deep machine learning. Using the proposed method, the hypocentral parameters are automatically determined within seconds after detecting an event. This method can potentially serve in monitoring earthquake activity in active volcanic areas such as the Hakone region.
Alteration of Payload in Extracellular Vesicles by Crosstalk With Mesenchymal Stem Cells From Different Origin
Authors: Park Dong Jun , Park Jeong-Eun , Kong Tae Hoon , Seo YoungJoon
Published: March 2021

BackgroundThe application of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) requires customized materials to target disease or cell damage. We hypothesized that EVs exert different inflammatory effects on one recipient cell, although stem cells of different origins in humans have similar payloads.ResultsHere, the payload of EVs released by crosstalk between MSCs and human middle ear epithelial cells (HMEECs) extracted from adipose tissue, bone marrow and tonsils significantly increased the level of anti-inflammatory factors. EVs derived from the co-culture medium decreased TNF-α, COX-2, IL-1β, and IL-6 levels to approximately zero within 3 h in HMEECs. Expression of miR-638 and amyloid-β A4 precursor protein-binding family A member 2 was analyzed using microarrays and gene ontology analysis, respectively.ConclusionsIn conclusion, stem cells of different origins have different payloads through crosstalk with recipient-specific cells. Inducing specific factors in EVs by co-culture with MSCs could be valuable in regenerative medicine.
Characterization and Adsorption Applications of Composite Biochars of Clay Minerals and Biomass
Authors: Gao Lihui , Goldfarb Jillian L.
Published: March 2021

Composite mineral-biochars of a homogeneous biomass (cellulose) and heterogeneous biomass (oak leaves) were fabricated with either 5wt% or 10wt% minerals (montmorillonite (MMT), kaolinite, and sand), and then pyrolyzed at 600 °C for 60 min. Characterizations including proximate analysis, ultimate analysis, surface area and porosity, morphology and surface chemistry confirmed that minerals were present on the surface of biochar, and MMT/kaolinite-biochar composites showed a strengthening in the chars’ aromatic structures, as well as increases in oxygen-containing surface functional groups. Methylene blue adsorption isotherms indicated that the MMT/kaolinite-biochars had higher adsorption capacities than pure biomass or biomass-sand biochars (110 mgMB/gchar and 24 mgMB/gchar for MMT-cellulose char and cellulose char, respectively). A multilinear model relating adsorption capacity and adsorbent properties was developed to measure the relative contribution of biochar properties to adsorption behavior. The model indicates that pore volume and hydrogen bonding were the dominant properties in controlling the adsorption of methylene blue onto the biochars. Findings from this work indicate that composite biochars prepared from biomass and inexpensive clay minerals are a promising adsorbent for remediating organic contaminants from water.