bluuebunny/crossref_metadata_2025_split 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.