bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production and Purification of A Cell-Penetrating Peptide-Erythropoietin Fusion Protein and Optimization of an in Vitro Blood-Brain Barrier Model for Central Nervous System Drug Delivery
Authors: Chiu Po-Chuan , Shen Li-Jiuan 
Published: October 2020

Abstract
Drug delivery into the central nervous system (CNS) is a brilliant research field, and the development of protein production and purification procedures for novel therapeutic proteins is crucial. Erythropoietin (EPO) is a glycoprotein with tremendous neuroprotective potential, but its bulky size prevents easy penetration across the blood-brain barrier (BBB). EPO-HBHAc is a promising cell-penetrating peptide modified protein for CNS diseases, necessitating an appropriate in vitro BBB model for further evaluation. The plasmid of EPO-HBHAc was constructed by DNA recombinant technology, and the Chinese Hamster Ovary (CHO-K1) cell expression system was selected to generate target proteins. His-tag and size exclusion purification were used to purify the target protein from the cell-conditioned medium; target proteins were further evaluated by western blotting and Coomassie blue staining. Moreover, the endothelial cells (bEnd.3) and astrocytes (CTX TNA2) were used to generate the in vitro BBB model, and transepithelial electrical resistance (TEER) and paracellular diffusion were measured to evaluate barrier integrity. The EPO-HBHAc plasmid was successfully constructed, and a stable cell line expressing EPO-HBHAc was generated. A higher protein expression level was observed in serum-containing medium than in serum-free medium. His-tag purification is not sufficient to remove impurities from target proteins, and thus size exclusion purification was performed to increase the purity of the protein of interest. In contrast, a higher TEER value and lower paracellular diffusion were observed in the co-culture model than in the mono-culture model. Furthermore, the higher TEER value was observed in inserts with a larger growth area (4.67 cm2) than in those with a smaller area (0.33 cm2). In conclusion, we demonstrated that some critical points might impact protein production and the in vitro BBB model construction in this study. Importantly, our research will provide valuable information in the field of CNS drug delivery.
Biomarkers for BCR-ABL1 as a Potential Therapeutic Option Among Adult Chronic Myeloid Leukaemia Treated With Tyrosine Kinase Inhibitors at Molecular Response in Multi-racial Malaysia: Hsa-mir-181a-5p for Decrement; hsa-mir-182-5p and hsa-mir-26a-5p for Increment.
Authors: Yacob Aliza Mohd , Muhammad Nor Asiah , Chang Kian Meng , Hisham Hamidah Akmal , Yusoff Yuslina Mat , Ibrahim Latifah 
Published: October 2020

Abstract
BackgroundTyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukaemia (CML) show a high success rate. However, low number of patients with long-term treatment-free remission (TFR) is observed. Molecular relapse after imatinib discontinuation occurred at 50% at 24 months with 80% occurrence within the first 6 months. One of the reasons for relapse is untimely TKIs discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranted new biomarkers for CML. MethodsNext Generation Sequencing (NGS) was used to identify microRNAs (miRNAs) at molecular response in CML adult patients receiving TKIs treatment. A total of 86 samples were collected, 30 from CML patients responsive and 28 from non-responsive to imatinib therapy, and 28 from blood donors. NGS was conducted whereby 18 miRNAs were selected and validated by real time RT-qPCR in triplicate. ResultsHsa-miR-181a-5p was expressed significantly (p-value<0.05) with 2.14 and 2.3 fold down-regulation in both patient groups respectively while hsa-miR-182-5p and hsa-miR-26a-5p were significant only in the non-responsive group with 2.08 and 2.39 fold up-regulation respectively. The down-regulation was consistent with decreased amount of BCR-ABL1 in patients taking TKIs regardless of molecular responses. The up-regulation was consistent with substantial presence of BCR-ABL1 in CML patients treated with TKIs at molecular response. ConclusionTherefore, these miRNAs have potential as new therapeutic biomarkers for BCR-ABL1 status in adult CML patients treated with TKIs at molecular responses. These could improve current approaches and require further analysis to look for targets of these miRNAs in CML.
A Geospatial Examination of Specialist Care Accessibility and Impact on Health Outcomes for Patients With Acute Traumatic Spinal Cord Injury in Nsw, Australia: A Whole&nbsp;&nbsp;Population Record Linkage Study
Authors: Sharwood Lisa Nicole , Whyatt David , Vaikuntam Bharat P , Cheng Christiana L , Noonan Vanessa K , Joseph Anthony P , Ball Jonathon , Stanford Ralph E , Kok Mei-Ruu , Withers Samuel R , Middleton James W 
Published: October 2020

Abstract
BackgroundTimely treatment is essential for achieving optimal outcomes after traumatic spinal cord injury, and expeditious transfer to a specialist spinal cord injury unit is recommended within 24 hours from injury. Previous research in New South Wales found only 57% of TSCI patients were admitted to specialist spinal cord injury unit for acute post-injury care; 73% transferred within 24 hours from injury. We evaluated pre-hospital and inter-hospital transfer practices to identify opportunities for improving care delivery. MethodsThis record linkage study included administrative pre-hospital, admissions and costs data for all patients aged ≥16 years with incident traumatic spinal cord injury in New South Wales (2013-2016). We investigated impacts of geographical disparities on pre-hospital and inter-hospital transport decisions from injury location using geospatial methods to better understand the post-injury care pathways impact on patient outcomes.ResultsInclusion criteria identified 316 patients, geospatial analysis showed that over half (53%, n=168) of all patients were injured within 60 minutes road travel of a SCIU, yet only 28.6% (n=48) were directly transferred to a specialist spinal cord injury unit. Direct transfers received earlier operative intervention (median (IQR) 12.9(7.9) hours), compared with patients transferred indirectly to specialist spinal cord injury unit (median (IQR) 19.5(18.9) hours), and had lower risk of complications (OR 3.2 v 1.4, p<0.001).ConclusionsGetting patients with acute traumatic spinal cord injury patients to the right place at the right time is dependent on numerous factors; some are still being triaged directly to non-trauma services which delays specialist and surgical care and increases complication risks. More stringent adherence to recommended guidelines would prioritise direct specialist spinal cord injury unit transfer for patients injured within 60 minutes radius, enabling the benefits of specialised care.
A Simple and Efficient Automated Microvolume Radiosynthesis of [18F]Florbetaben
Authors: Lisova Ksenia , Wang Jia , Chao Philip H. , Dam R. Michael van 
Published: October 2020

Abstract
Background: Current automated radiosynthesizers are generally optimized for producing large batches of PET tracers. Preclinical imaging studies, however, often require only a small portion of a regular batch, which cannot be economically produced on a conventional synthesizer. Alternative approaches are desired to produce small to moderate batches to reduce cost and the amount of reagents and radioisotope needed to produce PET tracers with high molar activity. In this work we describe the first reported microvolume method for production of [18F]Florbetaben for use in imaging of Alzheimer’s disease.Procedures: The microscale synthesis of [18F]Florbetaben was adapted from conventional-scale synthesis methods. Aqueous [18F]fluoride was azeotropically dried with K2CO3/K222 (275/383 nmol) complex prior to radiofluorination of the Boc-protected precursor (80 nmol) in 10 μL DMSO at 130°C for 5 min. The resulting intermediate was deprotected with HCl at 90°C for 3 min and recovered from the chip in aqueous acetonitrile solution. The crude product was purified via analytical scale HPLC and the collected fraction reformulated via solid-phase extraction using a miniature C18 cartridge.Results: Starting with 270 ± 100 MBq (n=3) of [18F]Fluoride, the method affords formulated product with 49 ± 3% (decay-corrected) yield,> 98% radiochemical purity and a molar activity of 338 ± 55 GBq/μmol. The miniature C18 cartridge enables efficient elution with only 150 μL of ethanol which is diluted to a final volume of 1.0 mL, thus providing a sufficient concentration for in vivo imaging. The whole procedure can be completed in 55 min.Conclusions: This work describes an efficient and reliable procedure to produce [18F]Florbetaben in quantities sufficient for large-scale preclinical applications. This method provides very high yields and molar activities compared to reported literature methods. This method can be applied to higher starting activities with special consideration given to automation and radiolysis prevention.
Violence and Discrimination Among Ugandan Residents During the COVID-19 Lockdown
Authors: Katana Elizabeth , Amodan Bob Omoda , Bulage Lilian , Ario Alex R. , Fodjo Joseph Nelson Siewe , Colebunders Robert , Wanyenze Rhoda K. 
Published: October 2020

Abstract
Background: In March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic. Many countries in Sub Saharan Africa, Uganda inclusive, implemented lockdowns, curfew, banning of both private and public transport systems and mass gatherings to minimize spread. Media reports indicated that cases of violence and discrimination had increased in Uganda’s communities following the lockdown. We estimated the incidence and factors associated with experiencing violence and discrimination among Ugandans during the COVID-19 lockdown to inform control and prevention measures.Methods: In April 2020, we conducted a cross-sectional study under the International Citizen Project (ICP) to assess adherence to public health measures and their impact on the COVID-19 outbreak in Uganda. We abstracted and analyzed data on violence and discrimination from the ICP study. We performed descriptive statistics for all the participants’ characteristics and created a binary outcome variable called experiencing violence and/or discrimination. We performed logistic regression analysis to identify the factors associated with experiencing violence and discrimination.Results: Of the 1,726 ICP study participants, 1,051 (58.8%) were males, 841 (48.7%) were currently living with a spouse or partner, and 376 (21.8%) had physically attended work for more than 3 days in the past week. Overall, 145 (8.4%) experienced any form of violence and/or discrimination by any perpetrator, and 46 (31.7%) of the 145 reported that it was perpetrated by a law enforcement officer. Factors associated with experiencing violence or discrimination were: being male (AOR= 1.60 CI:1.10-2.33), having attended work physically for more than 3 days in the past week (AOR=1.52 CI:1.03-2.23), and inability to access social or essential health services since the epidemic started (AOR=3.10 CI:2.14-4.50).Conclusion: A substantial proportion of Ugandan residents experienced violence and/or discrimination during the COVID-19 lockdown, mostly perpetrated by law enforcement officers. Mitigation of violence and/or discrimination, as well as increased access to health and social services should be integrated into control measures in large-scale public health emergencies.
Transportation Route Optimization of Municipal Solid Waste Using Network Analyst tool, Case of Jimma town, Southwestern Ethiopia
Authors: Gudeta Beekan Gurmessa , Feyisa Fikadu Fufa , Kitesa Wagari Mosisa 
Published: October 2020

Abstract

Transportation of municipal solid waste to disposal sites takes a large percentage of its overall management costs. The objective of this study is to optimize the transportation route of municipal solid waste using the Network Analyst tool for Jimma town. The input data in the present study were coordinates of individual municipal solid waste collection container location and disposal site location, master plan, and road shapefile. Network Analyst, an extension of ArcGIS was the main software used in the study. The result obtained includes the proposed number and location of MSW container and the best possible route for the evacuation of municipal solid waste from individual container location to the disposal site. The minimum average distance to transport loaded containers from individual collection container locations to the disposal site and empty container to its location that optimized by the network analyst tool was 17.94 km. It is therefore recommended that the urban authority should do route planning for municipal solid waste collection vehicles within the urban area.
Metabolome and Transcriptome Profiling Reveals Anthocyanin Contents and Anthocyanin-Related Genes of Chimeric Leaves in Ananas comosus Var. Bracteatus
Authors: Zhou Xuzixin , Xue Yanbin , Mao Meiqin , He Yehua , Adjei Mark Owusu , Yang Wei , Hu Hao , Liu Jiawen , Feng Lijun , Zhang Huiling , Luo Jiaheng , Li Xi , Sun Lingxia , Huang Zhuo , Ma Jun 
Published: October 2020

Abstract
Background: Ananas comosus var. bracteatus is a colorful plant used as a cut flower or landscape ornamental. The unique foliage color of this plant includes both green and red leaves and, as a trait of interest, deserves investigation. In this study, green and red parts of chimeric leaves of Ananas comosus var. bracteatus were sampled and anthocyanin accumulation differences were comparatively analyzed at phenotypic, cellular and molecular levels.Results: A CIELAB results indicated that the a* values and L* values samples had significant differences between two parts. Freehand sections showed that anthocyanin presented limited accumulation in the green leaf tissues but obviously accumulation in the epidermal cells of red tissues. Transcriptomic and metabolomic analyses were performed by RNA-seq and LC-ESI-MS/MS. Among the 508 identified metabolites, 10 kinds of anthocyanins were detected, with 6 significantly different between the two samples. The cyanidin-3,5-O-diglucoside content that accounts for nearly 95.6% in red samples was significantly higher than green samples. RNA-Seq analyses showed that 11 out of 40 anthocyanin-related genes were differentially expressed between the green and red samples. Transcriptome and metabolome correlations were determined by nine quadrant analyses, and 9 anthocyanin-related genes, including MYB5 and MYB82, were correlated with 7 anthocyanin-related metabolites in the third quadrant in which genes and metabolites showing consistent change. Particularly, the PCCs between these two MYB genes and cyanidin-3,5-O-diglucoside were above 0.95. Conclusion: Phenotypic colors are closely related to the tissue structures of different leaf parts of Ananas comosus var. bracteatus, and two MYB transcription factors might contribute to differences of anthocyanin accumulation in two parts of Ananas comosus var. bracteatus chimeric leaves. This study lay a foundation for further researches on functions of MYBs in Ananas comosus var. bracteatus and provides new insights to anthocyanin accumulation in different parts of chimeric leaves.
Effect of Antiangiogenic-Based Treatment and Systemic Inflammatory Factors on Outcomes in Patients With BRAF v600-Mutated Metastatic Colorectal Cancer: A Real-World Study in Spain
Authors: Lago Nieves Martinez , Montes Ana Fernández , Rúa Marta Covela , Vázquez Elena M. Brozos , Gómez Juan C. De la Cámara , Méndez Jose C. Méndez , Fernández Mónica Jorge , Castiñeiras Antía Cousillas , Rendo Cristina Reboredo , Ron David Arias , Campos Marta Carmona , Insua Yolanda Vidal , Augusto Maria L. Pellón , Villarroel Paula González , Suarez Begoña Graña , Fernández Mercedes Salgado , Maseda Alberto Carral , Rivera Francisca Vázquez , Folgar Sonia Candamio , López Margarita Reboredo 
Published: October 2020

Abstract
Background Outcomes are poorer in metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations than those without it, but the effect of these mutations on treatment response is unclear. This real-world study assessed the effects of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF V600-mutated mCRC.Methods/patients This real-world, multicenter, retrospective, observational study included patients with BRAF V600-mutated mCRC treated in eight hospitals in Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS); overall response rate (ORR) and disease control rate (DCR) were also assessed. The effect of first- and second-line treatment type on OS, PFS, ORR, and DCR were evaluated, plus the impact of systemic inflammatory markers on these outcomes. A systemic inflammation score (SIS) of 1–3 was assigned based on one point each for platelet-lymphocyte ratio (PLR) ≥200, neutrophil-lymphocyte ratio (NLR) ≥3, and serum albumin <3.6 g/dL.Results Of 72 patients, data from 64 were analyzed. After a median of 69.1 months, median OS was 11.9 months and median first-line PFS was 4.4 months. First-line treatment was triplet chemotherapy-antiangiogenic (12.5%), doublet chemotherapy-antiangiogenic (47.2%), doublet chemotherapy-anti-EGFR (11.1%), or doublet chemotherapy (18.1%). Although first-line treatment showed no significant effect on OS, antiangiogenic-based regimens were associated with prolonged median PFS versus non-antiangiogenic regimens. Negative predictors of survival with antiangiogenic-based treatment were NLR, serum albumin, and SIS 1–3, but not PLR. Patients with SIS 1–3 showed significantly prolonged PFS with antiangiogenic-based treatment versus non-antiangiogenic-based treatment, while those with SIS=0 showed no PFS benefit.Conclusions Antiangiogenic-based regimens, SIS, NLR, and albumin were predictors of survival in patients with mCRC, while SIS, NLR and serum albumin may predict response to antiangiogenic-based chemotherapy.Trial registration GIT-BRAF-2017-01.
Sustained CO2-photoreduction activity and high selectivity over C, Mn-codoped ZnO core-triple shell hollow spheres
Authors: Sayed Mahmoud , Kuang Panyong , Low Jingxiang , Zhang Liuyang , Yu Jiaguo 
Published: October 2020

Abstract
Solar conversion of CO2 into energy-rich products is one of the sustainable solutions to lessen the global energy shortage and environmental crisis. Pitifully, it is still challenging to attain reliable and affordable CO2 conversion. Herein, we demonstrate a facile one-pot approach to design core-triple shell Mn, C-codoped ZnO hollow spheres as efficient photocatalysts for CO2 reduction. The Mn ions, with switchable valance states, function as “ionized cocatalyst” to promote the CO2 adsorption and light harvesting of the system. Besides, they can capture photogenerated electrons from the conduction band of ZnO and provide the electrons for CO2 reduction. This process is continuous due to the switchable valence states of Mn ions. Benefiting from such unique features, the prepared photocatalysts demonstrated remarkably selective CO2 conversion into CH3OH (yielding ten times higher than that of commercial ZnO). This work is endeavoured to shed light on the role of ionized cocatalyst towards sustainable energy production.
Composition and spatio-temporal variation of soil arthropods in the wetland of the Daxia River on the Qinghai-Tibet Plateau
Authors: Delai Chen , Liu Changzhong , Ma Zhengxue , Su Jingjing 
Published: October 2020

Abstract
The Daxia River Basin on the eastern edge of the Chinese Qinghai-Tibetan Plateau is one of the typical distribution regions of alpine wetlands and a global biodiversity hotspot. The aim of this study is to analyze the composition and spatio-temporal distribution of the soil arthropods, and to use them as an indicator for the soil environment in the wetland. The soil arthropods of 32 taxa and 7706 individuals were collected from the soil samples at two soil layers (0–10 and 10–20 cm depth) in each habitat of six habitats along the Daxia River in cold season and warm season between 2016 and 2017. The habitat of Tumenguan had a greater arthropod abundance than all other habitats in both cold season and warm season. A significant seasonal variation was observed in the composition, abundance and diversity of the soil arthropod community in each habitat. In cold season the dominant groups were Chironomidae larvae, Sejidae and Trombidiidae. In warm season the dominant groups were Chironomidae larva, Onychiurus, Pygmephorus and Tullbergia. The soil arthopod communities exhibited significant differences among the habitats at the 0–10 and 10–20 cm depth. The multivariate tests with the linear model redundancy analysis (RDA) revealed the significant impact of soil physical and chemical factors on the seasonal change of soil arthropod community. The results demonstrate that soil arthropods in the study area respond more actively to temporal changes than to habitat changes.
Positive Selection on Two Mitochondrial Coding Genes and Adaptation Signals in Hares (Genus Lepus) from China
Authors: Awadi Asma , Slimen Hichem Ben , Schaschl Helmut , Knauer Felix , Suchentrunk Franz 
Published: October 2020

Abstract
Background: Animal mitochondria play a central role in energy production in the cells through the oxidative phosphorylation (OXPHOS) pathway. Recent studies of selection on different mitochondrial OXPHOS genes have revealed the adaptive implications of amino acid changes in these subunits. In hares, climatic variation and/or introgression were suggested to be at the origin of such adaptation. Here we looked for evidence of positive selection in three mitochondrial OXPHOS genes, using tests of selection, protein structure modelling and effects of amino acid substitutions on the protein function and stability. We also used statistical models to test for climate and introgression effects on sites under positive selection. Results: Our results revealed seven sites under positive selection in ND4 and three sites in Cytb. However, no sites under positive selection were observed in the COX1 gene. All three subunits presented a high number of codons under negative selection. Sites under positive selection were mapped on the tridimensional structure of the predicted models for the respective mitochondrial subunit. Of the ten amino acid replacements inferred to have evolved under positive selection for both subunits, six were located in the transmembrane domain. On the other hand, three codons were identified as sites lining proton translocation channels. Furthermore, four codons were identified as destabilizing with a significant variation of Δ vibrational entropy energy between wild and mutant type. Moreover, the PROVEAN analysis suggested that among all positively selected sites two fixed amino acid replacements altered the protein functioning. The statistical model runs indicated significant effects of climate on the presence of ND4 and Cytb protein variants, but no effect by trans-specific mitochondrial DNA introgresson.Conclusions: Positive selection was observed in several codons in two OXPHOS genes. We found that substitutions in the positively selected codons have structural and functional impacts on the encoded proteins. Our results are concordantly suggesting that adaptations have strongly affected the evolution of mtDNA of hare species with potential effects on the protein function. Environmental/climatic changes appear to be a major trigger of this adaptation, whereas trans-specific introgressive hybridization seems to play no major role for the occurrence of protein variants.