bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexpected Detection of a Sub-millimeter Early Hepatocellular Carcinoma Focus by Intraoperative Near-infrared Fluorescence Imaging
Authors: Dai Bo , Wang Ziyang , Lu Qian , Ma Hucheng , Guissi Nida El Islem , Cai Huiming , Wu Xinyu , Wang Yiqing , Wang Dongjin 
Published: October 2020

Abstract
Background: Intraoperative near-infrared fluorescence (NIRF) imaging became a great assistance to surgeons for precision cancer surgeries. Here, we demonstrate that NIRF was capable of detecting ultra-small hepatocellular carcinoma focus of about 430µm during real time monitored liver cancer surgery. Prognosis of hepatocellular carcinoma is closely related to residual tumor cells and tissues after tumor resection. Thus, close monitoring to ensure a complete removal of residual tumor is primordial. However, up to now, the identification of tiny lesions has not been reported. Herein, we report our findings about a case where tiny lesions were successfully identified by real-time ICG-NIRF imaging. Case presentation: A 55-year-old man, with chronic hepatitis B infection, was preoperatively diagnosed with liver space-occupying lesion. A fluorescence signal was detected on the surface of the liver through the NIRF imaging system. We then tested the residual liver surface and observed a high signal point, less than 1 mm in the right anterior lobe of the liver. Histopathological examination revealed that the tiny fluorescent spot belongs to an early hepatocellular carcinoma focus. Conclusion: Results strongly suggest that ICG-NIRF imaging system should be used as a routine intraoperative detection method for liver cancer surgery, in order to remove any residual tumor cells and tissue, hence minimizing further risk of remnant tumor regrowth.
Construction of NEIL3&nbsp;as a Prognostic Biomarker and Co-expressed Prognostic Signature in Lung Adenocarcinoma
Authors: Zhao Cui , Liu Jian , Zhou Haomiao , Qian Xin , Sun Hui , Chen Xuewen , Zheng Miaosen , Bian Tingting , Liu Lei , Zhang Jianguo , Liu Yifei 
Published: October 2020

Abstract
Background: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death. This study aimed to develop and validate reliable prognostic biomarkers and signature.Methods: Differentially expressed genes were identified based on three Gene Expression Omnibus (GEO) datasets. Based on three LUAD cohorts’ data included 1052 samples and extracted from our cohort, GEO, The Cancer Genome Atlas, we explored clinicopathological features and the expression of NEIL3 to determine its clinical effect in LUAD. Western blotting, Real-time quantitative PCR; (22 pairs of tumor and normal tissues), and immunohistochemical analyses (406-tumor tissues subjected to microarray) were conducted. TIMER and ImmuCellAI analyzed relationship between NEIL3 expression and the abundance of tumor-infiltrating immune cells in LUAD. The co-expressed-gene prognostic signature was established based on the Cox regression analysis.Results: This study identified 502 common differentially expressed genes and confirmed that NEIL3 was significantly overexpressed in LUAD samples(P<0.001). Increased NEIL3 expression was related to advanced stage, larger tumor size and poor overall survival (p < 0.001) in three LUAD cohorts. The proportions of natural T regulatory cells and induced T regulatory cells increased in the high NEIL3 group, whereas those of B cells, Th17 cells and dendritic cells decreased. Gene set enrichment analysis indicated that NEIL3 may activate cell cycle progression and P53 signaling pathway, leading to poor outcomes. We identified nine prognosis-associated hub genes among 370 genes co-expressed with NEIL3. A 10-gene prognostic signature including NEIL3 and nine key co-expressed genes was constructed. Higher risk-score was correlated with more advanced stage, larger tumor size and worse outcome (p<0.05). Finally, the signature was verified in test cohort (GSE50081) with superior diagnostic accuracy. Conclusions: This study suggested that NEIL3 has the potential to be an immune-related therapeutic target and an independent predictor for LUAD. We also developed a prognostic signature for LUAD with a precise diagnostic accuracy.
Effect and Mechanism of PLSCR4 in The Injury of Human Pulmonary Microvascular Endothelial Cells Induced by LPS
Authors: Liu Xiaobin , Wang Dong , Zhang Xiaoning , Gu Changping , Yang Fan , Wang Yuelan 
Published: October 2020

Abstract
Background: Previous experiments have revealed that Phospholipid scramblase 4 (PLSCR4) mRNA significantly increased in ARDS model of human pulmonary microvascular endothelial cells (HPMECs) stimulated by lipopolysaccharide (LPS) , but the specific effect and mechanism have not been reported to date.In consideration of the function of PLSCR4 that has been reported, we infer that PLSCR4 may have impact on cell death through pyroptosis. Methods: To investigate the effect and mechanism of PLSCR4 in ARDS in vitro, HPMECs were cultured in 6-well plates and divded into four groups: control group, LPS group ,siRNA+LPS group and transfection reagent group. After 4 h of LPS stimulation, western blot was used to detect the expression of PLSCR4 and pyroptosis – relevant proteins; Using ELISA to exame IL-1β and IL-18; Tracer flux assays was used to evaluate the barrier function of endothelium, and fluorescence assays to observe the distribution of phospholipid and the degree of pyroptosis. At last we used DNA pull-down and protein profiling to study the potential transcription factor of PLSCR4.Results: It was found that when the expression of PLSCR4 was elevated, the concentration of IL-1β and IL-18 decreased, together with barrier damage ( P < 0.05), and HPMECs injury was reduced with more distribution of phospholipid on the external sie of cells, but the pyroptosis-relevant proteins did not change obviously ( P < 0.05); then we found P62280 remarkably increased in the DNA pull-down assay, and it could impact the pyroptosis by regulating the expression of PLSCR4. Conclusion: We found that PLSCR4 alleviated pyroptosis by transporting phosphatidylserine (PS) to the outside of the membrane, blocking the forming of pyroptosis pores composed of gasdermin D, it was further found that the expression level of PLSCR4 during LPS stimulation was regulated by P62280. This study for the first time explains the protective effect of PLSCR4 in the ARDS model, and its possible mechanism, providing a new research idea for the clinical treatment of ARDS.
Does Application of 'phosphogypsum Organic’ to a Sandy BRIS Soil Has an Impact on Soil-plants-water Systems?
Authors: Hanafi Mohamed M. , Azizi Parisa , Sahibin Abdul Rahim , Razi Idris Wan Mohd , Fazli Ismail Aznan 
Published: October 2020

Abstract
BackgroundPredominant sandy, Beach Ridges Interspersed with Swales (BRIS) soil is a problematical soil for agriculture. It requires structure and capacity improvement due to its weak composition, low water retention capacity and high leaching of nutrients. However, there are hopes to improve it using different fertilizers in combination with organic matter. Phosphogypsum organic (PG organic) is an agricultural soil conditioner formulated from industrial by-products and organic filler material. This research was carried out to investigate the accumulated levels of heavy metals and radionuclides in water, soil and plants between BRIS soil under PG organic conditioner treatment and normal BRIS soil.ResultsThe result revealed that the PG organic’s particles are as similar to the reported pattern for calcium sulfate hydrate through powder X-ray diffraction (XRD). The heavy metals measured in the surface and borehole water, and soils were below the target values for raw drinking water and in the Dutch list, respectively. The values for biological accumulation coefficients, contamination factors, I-geo index and pollution load index (PLI) showed that there was no accumulation of metals in grain, no contamination and no pollution in the BRIS soil that received from the PG organic. Natural radioactivity concentrations, 226Ra (238U series), 228Ra (232Th series), and 40K in the collected samples were also measured. Naturally occurring radionuclide concentrations, such as 226Ra, 228Ra, and 40K, in soil and plant tissue were found to be lower than the average value reported by several earlier studies in Malaysia. There was no leaching of natural occurring radionuclides to the groundwater, nor was there discharge to the nearest river. The calculated radium equivalent (Raeq) in soil for this study was lower than the recommended value of 370 Bq/kg soil.ConclusionTherefore, the application of PG organic to the studied soil had no impact on the soil, plants and water and suitable as a soil conditioner in BRIS soil.
Genotoxicity and Gene Expression in the Rat Lung Tissue Following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NMs)
Authors: Brandão Fátima , Costa Carla , Bessa Maria João , Dumortier Elise , Debacq-Chainiaux Florence , Hubaux Roland , Salmon Michel , Laloy Julie , Stan Miruna S. , Hermenean Anca , Gharbia Sami , Dinischiotu Anca , Bannuscher Anne , Hellack Bryan , Haase Andrea , Fraga Sónia , Teixeira João Paulo 
Published: October 2020

Abstract
The authors have requested that this preprint be removed from Research Square.
One-Tube SARS-CoV-2 Detection Platform Based on RT-RPA and CRISPR/Cas12a
Authors: Sun Yangyang , Yu Lei , Liu Chengxi , Chen Wei , Li Dechang , Huang Weiren 
Published: October 2020

Abstract
Background: COVID-19 has spread rapidly around the world, affecting almost every person. When lifting certain mandatory measures for an economic restart, robust surveillance must be established and implemented, with nucleic acid detection for SARS-CoV-2 as an essential component. Methods: We designed RT-RPA (Reverse Transcription and Recombinase Polymerase Isothermal Amplification) primers of RdRp gene and N gene according to the SARS-CoV-2 gene sequence. We optimized the components in the reaction so that the detection process could be carried out in one tube. The specificity was demonstrated through detecting nucleic acid samples from seven human coronaviruses. Clinical samples were used to validate the platform and all results were compared to rRT-PCR. RNA standards diluted by different gradients were used to demonstrate the limit of detection. Furthermore, we have developed a lateral flow assay based on OR-DETECTR for the detection of COVID-19. Results: We have developed a o ne-tube detection platform based on R T- R PA and DNA Endonuclease-Targeted CRISPR Trans Reporter ( DETECTR ) technology, termed OR-DETECTR, to detect SARS-CoV-2. The detection process is completed in one tube, and the time is 50min. The method can specifically detect SARS-CoV-2 from seven human coronaviruses with a low detection limit of 2.5 copies/µl input. Results from six SARS-CoV-2 patient samples, eight samples from patients with fever but no SARS-CoV-2 infection, and one mixed sample from 40 negative controls showed that OR-DETECTR is 100% consistent with rRT-PCR. Furthermore, we have developed a lateral flow assay based on OR-DETECTR for the detection of COVID-19. Conclusions: OR-DETECTR detection platform is rapid, accurate, tube closed, easy-to-operate, and free of large instruments for COVID-19 detection.
Dual-Source Dual-Energy Thin-Section CT Combined with Small Field of View Technique for Diagnosing Small Lymph Node in Thyroid Cancer
Authors: Zhuo Shuiqing , Sun Jiayuan , Chang Jinyong , Liu Longzhong , Li Sheng 
Published: October 2020

Abstract
Background To evaluate the diagnostic performance of quantitative special CT parameters derived from dual-source dual-energy CT at small field of view (FOV) for small lymph node metastasis in thyroid cancer. Methods This was a retrospective study. From 2016 to 2019, 280 patients with thyroid disease underwent thin-section dual-source dual-energy thyroid CT and thyroid surgery. The data of patients with lymph nodes having a short diameter of 2-6 mm were analyzed. The targeted lymph nodes were sketched, their quantitative dual-energy CT parameters were measured, and all parameters between metastatic and nonmetastatic lymph nodes were compared. These parameters were then fitted to univariable and multivariable binary logistic regression models. The diagnostic role of spectral parameters was analyzed by receiver operating characteristic curves and compared with the McNemar test. Small FOV CT images and a mathematical model were used to judge the lymph nodes status respectively and then compared with pathological results.Results Of the 216 lymph nodes investigated in this study, 52.3% and 23.6% had a short diameter of 2-3 mm and 4 mm, respectively. Multiple quantitative CT parameters were found to be significantly different between benign and malignant lymph nodes and binary regression analysis was performed. The mathematical model was: p=ey/(1+ ey), y= = -23.119+0.033×precontrast electron cloud density+0.076×arterial phase normalized iodine concentration+2.156×arterial phase normalized effective atomic number -0.540×venous phase slope of the spectral Hounsfield unit curve +1.676×venous phase iodine concentration. This parameter model has an AUC of 92%, with good discrimination and consistency, and the diagnostic accuracy was 90.3%. The diagnostic accuracy of CT image model was 43.1%, and for lymph nodes with short-diameter 2-3 mm, the diagnostic accuracy was 22.1%.Conclusions Parameter model show higher diagnostic accuracy than CT image model for diagnosing small lymph node metastasis in thyroid cancer, and quantitative dual-energy CT parameters were very useful for small lymph nodes that were difficult to be diagnosed only on conventional CT images.Trial registration This study is retrospectively registered, and we have registered a prospective study (Registration number: ChiCTR2000035195;http://www.chictr.org.cn)
Gene4PD: a comprehensive genetic database of Parkinson's disease
Authors: Li Bin , Zhao Guihu , Zhou Qiao , Xie Yali , Wang Zheng , Fang Zhenghuan , Lu Bin , Qin Lixia , Zhao Yuwen , Zhang Rui , Jiang Li , Pan Hongxu , He Yan , Wang Xiaomeng , Luo Tengfei , Zhang Yi , Wang Yijing , Chen Qian , Liu Zhenhua , Guo Jifeng , Tang Beisha , Li Jinchen 
Published: October 2020

Abstract
BackgroundParkinson's disease (PD) is a complex neurodegenerative disorder with a strong genetic component. A growing number of variants and genes have been reported to be associated with PD; however, there is no database that integrate different type of genetic data, and support analyzing of PD-associated genes (PAGs).MethodsBy systematic review and curation of multiple lines of public studies, we integrate multiple layers of genetic data (rare variants and copy-number variants identified from patients with PD, associated variants identified from genome-wide association studies, differential expression genes, and differential DNA methylation genes) and clinical data in PD. A weighted scoring system was employed to prioritize PAGs. Permutation test and protein-protein interaction network was used to evaluate the interconnectivity and functional correlation among the PAGs. The relationship between AAO and PAGs was further analyzed. A PHP-based web framework was used to construct a database. ResultWe integrated five layers of genetic data with different levels of evidences from more than 3,000 studies and prioritized 124 PAGs with strong or suggestive evidences. These PAGs were identified to be significantly interacted with each other and formed an interconnected functional network enriched in several functional pathways involved in PD, suggesting these genes may contribute to the pathogenesis of PD, which also highlighting the reliability of these genetic data for PD. Furthermore, we identified 10 genes were associated with a juvenile-onset (age ≤ 30 years), 11 genes were associated with an early-onset (age of 30–50 years), whereas another 10 genes were associated with a late-onset (age > 50 years). Notably, the AAOs of patients with loss of function variants in five genes (GCH1, PINK1, PRKN, FBXO7, ATP13A2) were significantly lower than that of patients with deleterious missense variants, while patients with VPS13C (P = 0.01) was opposite. Finally, we developed an online database named Gene4PD (http://genemed.tech/gene4pd) which integrated published genetic data in PD, the PAGs, and 63 popular genomic data sources, as well as an online pipeline for prioritize risk variants in PD.ConclusionGene4PD provides researchers and clinicians comprehensive genetic knowledge and analytic platform for PD, and would also improve the understanding of pathogenesis in PD.Availability and Implementation: Gene4PD can be freely accessed at http://genemed.tech/gene4pd.
Reconciling ACEA and MCDA: Is There a Way Forward for Measuring Cost-Effectiveness in the U.S. Healthcare Setting?
Authors: Zamora Bernarda , Garrison Louis , Unuigbe Aig , Towse Adrian 
Published: October 2020

Abstract
Background The ISPOR Special Task Force (STF) on US Value Assessment Frameworks. The STF was agnostic about exactly how to implement the quality-adjusted life year (QALY) as the denominator in the overall cost-effectiveness metric of the cost-per-QALY gained as a starting point in their deliberations on the issue of including a new technology in the health plan benefit. The STF offered two major alternative approaches—augmented cost-effectiveness analysis (ACEA) and MCDA—while emphasizing the need to apply either a willingness-to-pay (WTP) or opportunity cost threshold rule to operationalize the inclusion decision.Methods The MCDA model uses the multi-attribute utility function. The ACEA model is based on the expected utility theory. In both ACEA and MCDA models, value trade-offs are derived in a hierarchical model with two high-level objectives which measure overall health gain separately from financial attributes affecting consumption.ResultsEven though value trade-offs can be elicited or revealed without considering budget constraints, we demonstrate that they can be used similarly to willingness-to-pay-based cost-effectiveness thresholds for resource allocation decisions. The consideration of how costs of medical technology, income, and severity of disease affect value trade-offs demonstrates, however, that reconciling decisions in ACEA and MCDA requires that health and consumption are either complements or independent attributes. ConclusionsWe conclude that value trade-offs derived either from ACEA or MCDA move similarly with changes in main factors considered by enrollees and decision makers—costs of the medical technology, income, and severity of disease. Consequently, this complementarity between health and consumption is a necessary condition for reconciling ACEA and MCDA.
A Novel Process to Recruit Community Partners for a Hybrid Implementation-Effectiveness Study
Authors: Leone Lucia A. , Kasprzak Christina , Lally Anne , Haynes-Maslow Lindsey , Vermont Leah N. , Horrigan-Maurer Caroline , Tumiel-Berhalter Laurene , Ammerman Alice , Raja Samina 
Published: October 2020

Abstract
BackgroundCreating strong partnerships with community organizations is essential to testing implementation of evidence-based interventions. Given the time and investment needed build relationships, partners are often chosen based on convenience, rather than capacity or diversity. Streamlined processes are needed to identify qualified, diverse, and invested partners to conduct community-based implementation research. Currently there is a gap in the literature on effective and efficient methods for recruiting implementation partners. The goal of this paper is to fill that gap by describing a novel process for identifying a diverse group of community organizations to participate in implementation research.MethodsWe used a community-guided Request for Partners (RFP) approach to recruit implementation partners to participate in a cluster-randomized hybrid implementation-effectiveness study of the Veggie Van mobile produce market model. The multi-state RFP process included formative work to inform RFP development, creation of an outside selection committee, an intent-to-apply round, a full application round, and an in-person training and selection process. Chosen implementation partners receive a toolkit, training, technical assistance and funding to offset the costs of implementing the Veggie Van model and assisting with research. Data was collected to characterize applicant size, location and experience; pre-post surveys were conducted to understand the utility of the in-person training.ResultsWe received 59 intent-to-apply submissions, of which we invited 28 organizations to complete full applications: 17 submitted applications and 12 finalists were invited to the in-person training and selection process. The RFP process took approximately eight months to recruit nine organizations and 32 community sites across five states with a range of size and experience. The process increased understanding of the intervention and implementation partner responsibilities; 63.6% of finalists reported being very to extremely familiar with the Veggie Van model post-training compared to 28.6% pre-training. Only one finalist dropped out (due to significant organizational change).ConclusionsAn RFP process is familiar to even small community organizations that compete for grant funding, but may not have prior research experience. This RFP process streamlined partner recruitment timelines, increased partner diversity and cultivated community among mobile market organizations. It may also improve research transparency, study completion and intervention fidelity.
A Distributed Framework Based on Publish-Subscribe to Monitor Beyond 5G Networks
Authors: Perez Ramon , Garcia-Reinoso Jaime , Zabala Aitor , Serrano Pablo , Banchs Albert 
Published: October 2020

Abstract
The Fifth-Generation (5G) of mobile networks is designed to accommodate different types of use cases, each of them with different and stringent requirements and Key Performance Indicators (KPIs). To support the optimization of the network performance and validation of the KPIs, there exists the necessity of a flexible and efficient monitoring system, capable of realizing multi-site and multi-stakeholder scenarios. Nevertheless, for the evolution from 5G to 6G, the network is envisioned as a user-driven, distributed Cloud computing system where the resource pool is foreseen to integrate the participating users. In this scope, current monitoring solutions are limited, as they have to be able to maintain 5G performance in a distributed system with heterogeneous resources and still be efficient and sustainable. In this paper, we present a distributed monitoring architecture for Beyond 5G multi-site platforms, where different stakeholders share the resource pool in a distributed environment. Taking advantage of the usage of publish-subscribe mechanisms adapted to the Edge, the developed lightweight monitoring solution can manage large amounts of real-time traffic generated by the applications located in the resource pool. We assess the performance of the implemented paradigm, to confirm that it suits the requirements of the proposed scenarios, and discuss how the architecture could be mapped to other 5G or Beyond 5G scenarios.