bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Role of Renin-Angiotensin System Inhibitors in Bevacizumab -induced Hypertension
Authors: Ren Tianshu , Jia Hui , Wu Qiong , Zhang Yan , Ma Qun , Yao Dong , Gao Xudong , Xie Danni , Xu Zihua , Zhang Yingshi , Zhao Chun Qing 
Published: August 2021

Abstract
Bevacizumab (Bev) is a humanized vascular endothelial growth factor monoclonal antibody that is used with chemotherapeutic drugs for the treatment of metastatic colorectal cancer (mCRC). Bev-induced hypertension (HT) is the most common adverse reaction during clinical practice. However, at present, appropriate antihypertensive agents for Bev-induced HT are unavailable. In this study, retrospective analysis of clinical data from mCRC patients who received renin-angiotensin system inhibitors (RASIs) showed significant survival benefits of overall survival (OS) and progression-free survival (PFS) over patients who received calcium channel blockers (CCBs) and patients who received no antihypertensive drug. An experiment in HCT116 colon cancer cell xenografts in mice confirmed that combined treatment with Bev and lisinopril (Lis), a RASI, synergistically inhibited subcutaneous tumor growth and enhanced the concentration of 5-fluorouracil (5-Fu) in tumor tissues. Our results showed that the addition of Lis did not interfere with the vascular normalization effect promoted by Bev, but also inhibited collagen and hyaluronic acid (HA) deposition and significantly downregulated the expression of TGF-β1 and downstream SMAD signaling components which were enhanced by Bev, ultimately remodeling primary ECM components. In conclusion, RASIs might be the optimal choice for the treatment of Bev-induced HT in mCRC patients.
The Clinicopathological Features of BRG1-deficient Non-small Cell Lung Cancer and Its Response to Immunotherapy: A Single-center Retrospective Study
Authors: Chen Xiaoyan , Zhang Jing , Zhao Runze , Xu Haimin , Dong Lei 
Published: August 2021

Abstract
PurposeBRG1-deficient NSCLCs have been more intriguing recently for its highly aggressive clinical behavior and no effective therapies. This study characterized the clinical and pathological features of BRG1-deficient NSCLCs and investigated their response to immunotherapy.MethodsForty-seven cases with BRG1-deficient NSCLC were included. Immunohistochemical markers such as CK7, TTF-1, NapsinA, P40, HepPar-1, Ki-67, BRM, ARID1A and ARID1B were stained. Meanwhile, the PD-L1 expression level, overall survival, progression-free survival and disease control rate of patients received immunotherapy were evaluated.ResultsThis study revealed that: (1) Patients with BRG1-deficient NSCLC have a male predominance(89.4%), smoker enrichment(76.6%) and poor prognosis(median OS: 7.0 months for advanced stage). (2) Histologically, BRG1-deficient NSCLCs presented significant morphological diversity and no lepidic pattern. Inflammatory infiltration and tumor necrosis was a prominent feature. Immunohistochemical analyses showed a distinctive uniform immunophenotype (TTF-1-/NapsinA-/CK7+) in 60.9% (28/46) of cases and HepPar-1 positive in 46.5% (20/43) of cases. BRM loss or significant reduction coexisted in 11.8% (4/34) of cases. No case (0/37) showed loss of ARID1A or ARID1B. (3) For twenty-nine patients with advanced stage, eight patients had received immunotherapy and 4 cases achieved a sustainable clinical response with the disease control rate of 50%. ICIs treated patients had better OS than those who received non-ICIs treatment settings (median OS, 27.0m versus 6.0m, p=0.02). Moreover, patients received ICIs have a median PFS of 17.0 months, while, median PFS on platinum doublet chemotherapy were only 6.0 months(p=0.04). Conclusion﻿BRG1-deficient NSCLC showed diverse histopathological patterns and a unique immunohistochemical phenotype. ICIs–based immunotherapy was a beneficial therapy for BRG1- deficient NSCLC.
Manufacturing Parameters Optimization and Modeling of PxGyEz Hybrid Composite for High Flexural Strength Using Taguchi Robust Experimental Design Technique and General Regression Analysis
Authors: Samuel Bassey Okon 
Published: August 2021

Abstract
With the continuous need for sustainable, environmentally friendly, and low-cost systems, processes, and materials, natural fibers have been a major topic of discussion in the materials science community as it has increasingly found acceptance in material development as an alternative to synthetic fibers due to environmental concerns. Although many studies have been carried out in this regard, the optimal flexural performance of pineapple leaf fiber/synthetic fiber hybrid reinforced composite has not been studied even with its promising application in aviation, health, and fitness, marine, etc. In this study, a Pineapple Leaf fiber (PALF)/Glass fiber Epoxy hybrid composite PxGyEz (with x, y, and z representing the volume fraction of pineapple leaf fiber, the volume fraction of glass fiber, and fiber length respectively) was developed and its flexural properties optimized and modeled with regards to the variable manufacturing parameters of x, y, and z respectively. For the quality characteristics (flexural strength) investigated, the Minitab®19 software was used to analyze the Taguchi robust experiment design technique on a higher the better basis. The optimum combination of the control factors was found at x = 20%, y = 20%, and z = 25mm. The optimized composite P20G20E25 possessed a flexural strength of 144.4994MPa which was only a 7.17% deviation from the predicted optimum flexural strength. Analysis of variance showed that the PALF had the highest contribution of 23.97% to the flexural strength of the PxGyEz, glass fiber 7.13%, and fiber length 12.79%. SEM Images of the PALF, glass fiber, and the fractured surface of the optimized material P20G20E25 revealed the surface structure which explained their different contribution to the flexural strength of the materials. An equation for the prediction of the flexural properties of PxGyEz was derived from the regression model and it had an approximately 77.57% agreement with experimentation.
Adenine Base-Editing-Mediated Exon Skipping Induces Gene Knockout in Cultured Pig Cells
Authors: ZHU XIANGXING , Pan Jia-sheng , Lin Tao , Yang Ye-cheng , Huang Qiu-yan , Yang Shuai-peng , Qu Zi-xiao , Lin Zi-sheng , Wen Jian-cong , Yan Ai-fen , Feng Juan , Liu Lian , Zhang Xiao-li , Lu Jia-hong , Tang Dong-sheng 
Published: August 2021

Abstract
Gene-knockout pigs have important applications in agriculture and medicine. Compared with CRISPR/Cas9, Adenine base editor (ABE) convert single A·T pairs to G·C pairs in the genome without generating DNA double-strand breaks, and this method has higher accuracy and biosafety in pig genetic modification. However, the application of ABE in pig gene knockout is limited by protospacer-adjacent motif (PAM) sequences and the base-editing window. Alternative mRNA splicing is an important mechanism underlying the formation of proteins with diverse functions in eukaryotes. Spliceosome recognizes the conservative sequences of splice donors and acceptors in a precursor mRNA. Mutations in these conservative sequences induce exon skipping, leading to proteins with novel functions or to gene inactivation due to frameshift mutations. In this study, adenine base-editing-mediated exon skipping was used to expand the application of ABE in the generation of gene knockout pigs. We first constructed a modified “all-in-one” ABE vector suitable for porcine somatic cell transfection that contained an ABE for single-base editing and an sgRNA expression cassette. The “all-in-one” ABE vector induced efficient sgRNA-dependent A-to-G conversions in porcine cells during single base-editing of multiple endogenous gene loci. Subsequently, an ABE system was designed for single adenine editing of the conservative splice acceptor site (AG sequence at the 3’ end of the intron 5) and splice donor site (GT sequence at the 5’ end of the intron 6) in the porcine gene GHR; this method achieved highly efficient A-to-G conversion at the cellular level. Then, porcine single-cell colonies carrying a biallelic A-to-G conversion in the splice acceptor site in the intron 5 of GHR were generated. RT-PCR indicated exon 6 skipped at the mRNA level. Western blotting revealed GHR protein loss, and gene sequencing showed no sgRNA-dependent off-target effects. These results demonstrate accurate adenine base-editing-mediated exon skipping and gene knockout in porcine cells. This is the first proof-of-concept study of adenine base-editing-mediated exon skipping for gene regulation in pigs, and this work provides a new strategy for accurate and safe genetic modification of pigs for agricultural and medical applications.
Intravenous Immunoglobulin Suppresses Chemotherapy-induced Peripheral Neurotoxicity via Macrophage Modulation in Rats and Mice
Authors: Tanaka Jun , Kajii Masahiko 
Published: August 2021

Abstract
Chemotherapy-induced peripheral neurotoxicity (CIPN) is a serious adverse effect that leads to treatment discontinuation by patients receiving anticancer therapy. Treatment discontinuation is a serious and life-threatening problem for patients with cancer; hence, there is a need for drugs that suppress the induction of CIPN by anticancer drugs. Intravenous immunoglobulin (IVIg) reportedly suppresses bortezomib-induced CIPN in a rat model. Here, using rodent models, we showed that IVIg can also suppress peripheral neurotoxicity induced by anticancer drugs other than bortezomib. Furthermore, the suppressive effect of IVIg disappeared when macrophages were depleted. These findings indicate two novel independent possibilities of alleviating CIPN using IVIg. First, CIPN can be controlled by macrophage modulation. Second, IVIg directly combined with anti-cancer drugs can avoid restrictions on the use of anti-cancer drugs due to CIPN inductions. However, further research is necessary for the bench-to-bedside translation of these novel applications of IVIg. Our findings lay a strong foundation for research on IVIg therapeutics.
Antimicrobial Sensitivity Profile of Bacteria Isolated in Babitonga Bay
Authors: Vecchia Maria Tereza Dalla , Schneider Andréa , de França Paulo Henrique Condeixa , Gern Regina Maria Miranda 
Published: August 2021

Abstract
Antimicrobial resistance is one of the main and growing public health concerns. However, the analysis of the expansion of this phenomenon in the environment is limited. Thus, the objective of this work was to determine the antimicrobial susceptibility profile of bacteria isolated from Baía Babitonga. Isolation and identification of microorganisms were carried out from the mangrove sediment sample, collected at two sampling points in Baía Babitonga. Microbial identification analyzes demonstrated the presence of Gram-negative microorganisms, for which the antimicrobial susceptibility profile analysis showed the presence of resistance to Aztreonam, Ciprofloxacin, Cefuroxim, Nitrofurantoin, Meropenem, Tetracyclin, Cefotaxime, and Ceftazidime. For the identified Gram-positive microorganisms, the presence of resistance to Ampicillin and Clindamycin was evidenced. The genotypic investigation showed that the resistances found were not caused by the researched genes (blaSHV, blaCTX-M, blaOXA-48-like, blaKPC, blaNDM-1, blaVIM e blaIMP).
Automated Machine Learning: a case study of genomic “image-based” prediction in maize hybrids
Authors: Galli Giovanni , Sabadin Felipe , Yassue Rafael Massahiro , de Souza Cassia Galves , Carvalho Humberto Fanelli , Fritsche-Neto Roberto 
Published: August 2021

Abstract
Machine learning methods such as Multilayer perceptrons (MLP) and Convolutional Neural Networks (CNN) have emerged as promising methods for genomic prediction (GP). In this sense, we assess the performance of MLP and CNN on regression and classification tasks in a case study with maize hybrids. The genomic information was provided to the MLP as a relationship matrix and to the CNN as “genomic images”. In the regression task, the machine learning models were compared along with GBLUP. Under the classification task, MLP and CNN were compared. In this case, the traits (plant height and grain yield) were discretized in such a way to create balanced (moderate selection intensity) and unbalanced (extreme selection intensity) datasets for further evaluations. An automatic hyperparameter search for MLP and CNN was performed, and the best models were reported. For both task types, several metrics were calculated under a validation scheme to assess the effect of the prediction method and other variables. Overall, MLP and CNN presented competitive results to GBLUP but improved a little using only the additive genomic layer. It is expected that the average effect of allele substitution is mostly linear. Nevertheless, the methodology’s potential for GP is unprecedented because we can create “multispectral genome images,” including other effects and layers of data, such as dominance, epistasis, g × e, transcriptome, and so on, capturing linear and non-linear effects and boosting prediction accuracies. Hence, we bring new insights on automated machine learning for genomic prediction and its implications to plant breeding.
Erucin Inhibits Osteoclast Formation via Suppressing Cell-cell Fusion Molecule DC-STAMP Without Influencing Mineralization by Osteoblasts
Authors: Takagi Tomohiro , Inoue Hirofumi , Fujii Shungo , Takahashi Nobuyuki , Uehara Mariko 
Published: August 2021

Abstract
Objective: Erucin (ERN), an isothiocyanate, is derived from the vegetable arugula. Although ERN has antitumor and antioxidant activity, the effect of ERN on osteoclast and osteoblast differentiation is not well documented. In this study, we evaluated the effects of ERN on osteoclast and osteoblast differentiation in vitro. Results: ERN significantly reduced the formation of 1α,25(OH)2D3-induced tartrate-resistant acid phosphatase (TRAP)-positive cells at non-cytotoxic concentrations. Furthermore, ERN downregulated the mRNA expression of osteoclast-associated genes, such as nuclear factor of activated T cells cytoplasmic-1, TRAP, and cathepsin K. In addition, ERN suppressed dendritic cell specific transmembrane protein (DC-STAMP), which encodes cell-cell fusion. However, ERN did not affect mineralization by osteoblasts. Thus, our data suggest that ERN may attenuate osteoclastic bone resorption by inhibiting multinucleation of mononuclear pre-osteoclasts and by suppressing mRNA expression of DC-STAMP in bone marrow cells without influencing mineralization by osteoblasts.
Fatigue is associated with physical inactivity in people with multiple sclerosis despite different environmental backgrounds: merging and comparing cohorts from Turkey and Israel
Authors: Ozdagar Asiye Tuba , Kahraman Turhan , Ozakbas Serkan , Achiron Anat , Kalron Alon 
Published: August 2021

Abstract
Background Examining physical activity in people with multiple sclerosis (PwMS) from different environmental backgrounds might increase understanding and awareness of inactivity in PwMS.Objectives To compare the level of physical activity in PwMS in Israel and Turkey and to examine the relationship between the level of physical activity with common disease-related symptoms and demographical characteristics of PwMS. Methods Cross-sectional data collected by two centers were combined. The physical activity level was determined by the Godin Leisure-Time Exercise Questionnaire, and subsequently, classified into one of three subgroups: "active", "moderately active" and "insufficiently active". Logistic regressions determined the risks of insufficiently active PwMS, according to age, gender, body mass index, disability, impact of walking impairment, disease duration, type of MS and perceived fatigue. The analysis of variance test determined the differences between countries in terms of outcome variables.Results The study comprised 458 patients from Israel and 575 from Turkey; 68.2% Turkish PwMS were classified as insufficiently active compared with 52.0% of Israeli PwMS. The percentage of insufficiently active PwMS was significantly higher in those categorized as fatigued compared to non-fatigued in the total cohort (72.4% vs. 51.9%, p<0.001) and in each country separately. Based on the regression analysis, fatigue was the main factor associated with the insufficiently physically active group; odds ratio=1.968. Interpretation PwMS with increased fatigue tend to be physically inactive compared with the non-fatigued. This observation is supported by the merged data collected from two countries, Turkey and Israel, representing PwMS from different environmental backgrounds.
Association of extracranial carotid artery stenosis in ischemic stroke in a Sri Lankan cohort of patients - An analytical cross-sectional study
Authors: Rajapakshe Ishani , Wijesundara Devasmitha , Chandrakumara Amila , Senanayake Bimsara 
Published: August 2021

Abstract
Background and Objectives

: The burden of stroke in Sri Lanka is on the increase with the current demographic transition toward an ageing population [1]. However, the association of symptomatic extracranial carotid artery stenosis (CAS) in ischemic stroke has not been prospectively evaluated in a Sri Lankan cohort of patients. Globally population-based studies have estimated about 15% of ischemic strokes are caused by large vessel occlusions. It is commonly believed that the prevalence of significant extracranial CAS is low in Sri Lanka compared to western populations [2, 3]. The purpose of the study is to systematically analyses and assess this long held notion and to search for other associated causative factors.
Methods

The study population comprised 164 acute ischemic stroke patients admitted to the National hospital of Sri Lanka over a period of 3 months. Carotid artery duplex scans were done by a single well-trained operator within 2 weeks of presentation and degree of CAS was classified as low (< 50%), moderate (50–69%), severe (> 70%) and complete occlusion according to NASCET criteria. Factors associated with CAS were identified by stepwise multiple logistic regression analysis.
Results

Out of 164 ischemic stroke patients 104 (63.4%) were male and 60 (36.6%) were female. The mean age of stroke patients was 62.2+- 14.21 years. 139 (84.8%) had low grade stenosis, 10 (6.1%) had moderate stenosis, 7 (4.2%) had severe stenosis and 8 (4.9%) had complete stenosis of carotid artery. Older age and presence of previous TIAs were significantly associated with CAS. Gender, hypertension, diabetes mellitus, hypercholesterolemia, IHD, previous stroke, previous TIA, previous use of antiplatelets, family history of stroke, previous use of statins and presence of carotid bruit were not significantly associated.
Conclusion

Extracranial carotid artery occlusion previously considered a rare cause of ischemic stroke in Sri Lanka was found to be having a prevalence similar to western populations in this study with over 15% having significant stenosis. Hence, we emphasize that early carotid doppler studies must be performed in all ischemic strokes at least within two weeks and necessary interventions carried out where it is deemed necessary.
What works to improve school lunch nutritional quality - legislation or self-audit? Medium-term results from Sweden
Authors: Patterson Emma , Andersson Filip , Elinder Liselotte Schäfer 
Published: August 2021

Abstract
BackgroundPoor monitoring and evaluation leads to a lack of evidence regarding what works in terms of improving school meal quality. Sweden has a long-standing policy of universal free school meals but updated legislation regarding nutritional quality came into effect in 2011. To coincide with this, we built a fully automated web-based self-audit tool for schools, called School Food Sweden, in order to i) establish a national database on overall meal quality, covering six domains, and ii) help schools and municipalities improve, based on the implementation strategy of audit and feedback. We have previously examined the pre- and post-legislation period. In this paper we describe changes in one domain – nutritional quality – in the years since the new legislation and examine if repeated use of the tool was associated with improvements.MethodsPrimary schools in Sweden self-selected to use the tool between March 2012 and July 2019 and audited a four-week lunch menu. Date of audit, number of audits per school (1-9), how often schools accessed their feedback (% of times) and school characteristics were noted. Factors associated with meeting nutritional criteria were examined using variance weighted least squares regression and logistic regression, using both repeated cross-sectional and longitudinal design.ResultsAlmost half of all ca 4800 primary schools in Sweden signed up to the tool. Nutritional quality was audited by 1500 schools at least once. Repeated cross-sectional analyses showed the proportion of all schools meeting the criteria increased significantly between 2012/13 and 2018/19 (from 11% to 34%). For all schools, each extra audit completed increased the odds of meeting nutritional criteria by 1.30 (CI 1.20-1.41), controlling for region and time since the introduction of legislation. In a longitudinal analysis (schools with repeat audits, n=774), both number of audits and the frequency of accessing previous feedback reports were predictors of meeting the nutritional criteria (OR 2.02, CI 1.23-3.31), even after adjusting for time since the introduction of legislation and number of days since the previous audit.ConclusionsBoth legislation and self-audit with automatic feedback appear effective in helping schools to improve school meal quality. Self-audit may be an essential complement to legislation, or a promising alternative in settings where regulation is not an option.
PENGALIHAN HAK ATAS TANAH UNTUK KEPENTINGAN UMUM MENURUT HUKUM ISLAM
Authors: Latif Faozi , Sunarko Asep 
Published: August 2021

Transfer of land rights for public interest in the community often occurs. The transfer of land is done for various purposes, including the construction of roads, hospitals, places of education, places of worship and others. This research is pursued in the discussion of the process of transferring land rights in the public interest according to Islamic law and the consequences for the transfer of ownership rights to land in the public interest. This research uses library research. The results of the study explained that in Islamic law the transfer of land rights was carried out in the time of the Prophet and also shahaba. Transfer of land rights for public interest in Islam can be done through buying and selling or compensation and endowments. After the transfer of land rights, the rights to manage and use the land are transferred to the second party.
Keywords: Land, Public Interests, Waqf.