bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pathological significance of abnormal RON and PD-L1 expression in colorectal cancer
Authors: Liu Yi-Zhi , Han Da-Ting , Shi Dan-Rong , Hong Bo , Qian Yun , Wu Zhi-Gang , Yao Shu-Hao , Tang Tao-Ming , Xu Xiang-Ming , Wang Ming-Hai , Yao Hangping 
Published: June 2020

Abstract
Background: PD-L1 immunotherapy remains poorly efficacious in colorectal cancer. The RON receptor tyrosine kinase plays an important role in regulating tumor immunity. Here, we identify patterns of RON and PD-L1 expression and explore the clinical significance of these patterns in colorectal cancer.
Methods: Gene expression data were obtained from the Gene Expression Omnibus database (GEO; n = 290) and patients at the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZUSM; n = 381) and were analyzed to determine the prognostic value of RON and PD-L1 expression within the tumor cells and the tumor microenvironment of colorectal cancer. Human colorectal cancer cell lines were treated with BMS-777607 to explore the relationship between RON activity and PD-L1 protein expression. Signaling pathways and protein expression perturbed by RON inhibition were evaluated by cellular immunofluorescence and western blot.
Results: In the GEO cohort, cut-off values for RON and PD-L1 expression of 7.70 and 4.30, respectively, were determined. Stratification of patients based on these cutoffs demonstrated that high expression of RON and PD-L1 associated with poor prognosis. In the FAHZUSM cohort, rates of high expression of RON in tumor cells, high PD-L1 expression in tumor cells and in tumor infiltrating monocytes, and both high RON and high PD-L1 expression in the tumor microenvironment were 121 (32%), 43 (11%), 91 (24%), and 51 (13.4%), respectively. High expression of RON and high expression of PD-L1 in the tumor cell compartment was significantly correlated (p < 0.001). High expression of RON and PD-L1 were independent prognostic factors for poorer overall survival. Concurrent high expression of both RON and PD-L1 in the tumor microenvironment was significantly associated with poor prognosis. In vitro , BMS-777607 inhibited the phosphorylation of RON, inhibited PD-L1 expression, and attenuated activation of the ERK1/2 and AKT signaling pathways in colorectal cancer cells.
Conclusions: RON, PD-L1 and the crosstalk between these proteins plays an important role in predicting the prognostic value of colorectal cancer. Moreover, phosphorylation of RON upregulates the expression of PD-L1, which provides a novel approach to immunotherapy in colorectal cancer.
Urban-rural differences in catastrophic health expenditure among households with chronic non-communicable disease patients : evidence from China Family Panel Studies
Authors: Fu Xianzhi , Sun Qi-wei , Sun Chang-qing , Xu Fei , He Jun-jian 
Published: June 2020

Abstract
Background: The prevalence of chronic non-communicable diseases (NCDs) challenges the Chinese health system reform. Little is known for the differences in catastrophic health expenditure (CHE) between urban and rural households with NCD patients. This study aims to measure the differences above and quantify the contribution of each variable in explaining the urban-rural differences.Methods: The second and the fourth waves of the China Family Panel Studies (CFPS) data, conducted in 2012 and 2016, were employed in this cross-sectional study. The techniques of Fairlie nonlinear decomposition and Blinder-Oaxaca decomposition were employed to measure the contribution of each independent variable to the urban-rural differences.Results: The CHE incidence and intensity of households with NCD patients were significantly higher in rural areas than in urban areas. The explained disparity of CHE incidence increased from 3.15% in 2012 to 27.04% in 2016, and the corresponding values of CHE intensity rose from 21.30% in 2012 to 53.37% in 2016. The major contribution to the urban-rural differences in CHE was associated with household economic status, education level, health status and supplementary medical insurance (SMI).Conclusions: Compared with urban households with NCD patients, rural households with NCD patients have higher risk of incurring CHE and heavier economic burden of diseases. Policy interventions should give priority to decreasing the urban-rural disparity in observable characteristics.
The Inhibition of Long Non-Coding RNA CAR10 and The Regulation of miR-203 Expression Suppresses Cell Viability and Induces Cell Apoptosis in Prostate Cancer
Authors: Zhang Liansheng , Chen Yougan , Wang Zhenjie , Xia Qiang 
Published: June 2020

Abstract
Background: Prostate cancer (PC) is one of the most common malignant tumors. Recently, it has been reported that long noncoding RNAs (lncRNAs) play key roles in tumor progression. Studies have revealed that long non-coding RNA CAR10 (CAR10) can regulate tumor cell behaviors through sponging miR-203. In this study, we examined the effects of CAR10 in PC cells. Methods: Firstly, real time-quantitative polymerase chain reaction (qRT-PCR) was used to explore CAR10 expression in tumor tissues, peripheral blood of PC patients, and PC cells. We used the dual-luciferase reporter gene assay to analyze the relationship between CAR10 and miR-203. Moreover, flow cytometry, MTT assay, and western blot assay were used to determine cell apoptosis, cell viability, and apoptosis-related protein expression. Results: The results showed that CAR10 expression was remarkably higher in PC samples compared with that of control, and CAR10 regulated miR-203 negatively in PC cells. The qRT-PCR results also showed that miR-203 expression was significantly decreased in PC samples. Moreover, knockdown of CAR10 inhibited PC cell viability and promoted cleaved caspase-3 expression but induced PC cell apoptosis and, reduced pro-caspase-3 expression; miR-203 inhibitor reversed these effects. Conclusion: Our study found that CAR10 is a potential oncogene in PC and suggests that CAR10 inhibition could inhibit PC cell viability but promote PC cell apoptosis through regulating miR-203 expression. Our results show that CAR10 is a potential target for the treatment of PC.
Identifying hub genes associated with clinical characteristics in IgA nephropathy by WGCNA
Authors: Yang Chengyu , Li Chenyu , Zhao Long , Zhou Bin , Luo Congjuan , Jiang Wei , Luan Hong , Xu Yan 
Published: June 2020

Abstract
Background

Clinically, IgA nephropathy (IgAN) has a variety of symptoms including paroxysmal gross hematuria, nephritic syndrome and nephrotic syndrome. However, the currently research of IgAN research is not thoroughly enough. This study was aimed at investigating hub genes and genes modulars related to IgAN clinical characteristics.

Results

We collected microarray data from 66 human samples to construct the gene co-expression network by weighted gene co-expression network analysis and identify the hub genes associated with clinical characteristics. The GO-enriched analysis, pathway analysis and protein-protein interaction network were used to study the specific clinically relevant hub genes. The results showed there were 1470 differentially expressed genes (DEGs) in IgAN glomeruli, of which 48 hub genes associated with blood pressure (Bp) and enriched in ERK1 and ERK2 cascade and Rap1 signaling pathway, 223 hub genes associated with body Mass Index (BMI) and related to organic acid catabolic process and fatty acid degradation pathway, 136 hub genes associated glomerular filtration rate (GFR) enriched in immune response and PI3K-Akt signaling pathway, 82 hub genes associated with proteinuria enriched in extracellular matrix organization and PI3K-Akt signaling pathway. Moreover, there were 480 DEGs IgAN in tubulointerstitium. Among 480 DEGs, 35 hub genes associated with Bp which enriched in positive regulation of apoptotic process, 87 hub genes associated with GFR which related in negative regulation of macromolecule metabolic process and RNA transport, 33 hub genes associated with proteinuria and enriched in regulation of apoptotic process and FoxO signaling pathway.

Conclusions

We made a preliminary investigation of the transcriptome of IgAN and identified hub genes and pathways closely related to BMI, GFR and proteinuria in IgAN.
One-Step Heating Strategy for Efficient Solubilization of Recombinant Spider Silk Protein From Inclusion Bodies
Authors: Cai Hui , Chen Gefei , Yu Hairui , Tang Ying , Xiong Sidong , Qi Xingmei 
Published: June 2020

Abstract
Background: Spider silk is a proteinaceous fiber with remarkable mechanical properties spun from spider silk proteins (spidroins). Engineering spidroins have been successfully produced in a variety of heterologous hosts and the most widely used expression system is Escherichia coli (E. coli). So far, recombinantly expressed spidroins often form insoluble inclusion bodies (IBs), which will often be dissolved under extremely harsh conditions in a traditional manner, e.g. either 8 mol/L urea or 6 mol/L guanidine hydrochloride, highly risking to poor recovery of bioactive proteins as well as unexpected precipitations during dialysis process. Results: Here, we present a mild solubilization strategy—one-step heating method to solubilize spidroins from IBs, with combining spidroins’ high thermal stability with low concentration of urea. A 430-aa recombinant protein (designated as NM) derived from the minor ampullate spidroin of Araneus ventricosus was expressed in E. coli, and the recombinant proteins were mainly present in insoluble fraction as IBs. The isolated IBs were solubilized parallelly by both traditional urea-denatured method and one-step heating method, respectively. The solubilization efficiency of NM IBs in Tris-HCl pH 8.0 containing 4 mol/L urea by one-step heating method was already comparable to that of 7 mol/L urea with using traditional urea-denatured method. The effects of buffer, pH and temperature conditions on NM IBs solubilization of one-step heating method were evaluated, respectively, based on which the recommended conditions are: heating temperature 70–90°C for 20 min, pH 7.0–10, urea concentration 2–4 mol/L in normal biological buffers. The recombinant NM generated via the one-step heating method held the potential functions with self-assembling into sphere nanoparticles with smooth morphology.Conclusions: The one-step heating method introduced here efficiently solubilizes IBs under relatively mild conditions compared to the traditional ones, which might be important for the downstream applications. Further, this method can be applied under broad buffer, pH and temperature conditions, conferring the potential to apply to other thermal stable proteins.
Are We Contented in Achieving Universal Health Coverage in Treating Dengue Patients in Sri Lanka?
Authors: Perera Nadeeka , Silva Amala De , Wass Dulshika Amarasinghe , Wijewickrama Ananda , Prathapan Shamini 
Published: June 2020

Abstract
BackgroundAmong infectious diseases, Dengue illness causes a major public health threat in Sri Lanka. The preventive and the curative services place a financial burden on the state health sectorand household cost and out of pocket expenditure also are important cost components embedded with Dengue infection. ObjectiveTo estimate the household costs andout of pocket expenditure incurred due to Dengue infection among adults who received institutional care.MethodsA longitudinal study was conducted from July to December 2018. Fifty patients each from DF and DHF categories were recruited with systematic sampling admitted to an institution in Colombo District, Sri Lanka.Adults residing in Colombo District of Sri Lanka for more than six months prior to Dengue/DHF episode, were recruited based on a systematic sampling method. Details were obtained via an interviewer administered questionnaire. They were interviewed on day of discharge from the hospital and were followed up for two weeks. Unit cost per patient was calculated. The household costs were calculated for three phases; ambulatory cost, costs incurred during hospitalization and post hospitalization costs. These components were described using mean, median, standard deviation and inter-quartile range and out of pocket expenditure were calculatedResultsThe median age in DF group was 38.5 years and in DHF group was 28.5 years.Average household cost was US$127.69(SD=93.32) and US$134.71(SD=94.31) for DF and DHF patients respectively. Among DF patients 98.03% was borne using OOPE and among DHF patients it was 95.57%. In 2016, the average monthly income of a household in Colombo was US$571.82. Thereforenearly 25% of the monthly income had been spent on a single adult with Dengue.Conclusions and RecommendationsIf an adult member is hospitalized with Dengueinfection the Out of pocket expenditure is high, which is nearly 25% of a family’s monthly income.Strengthening the Dengue control programme is the key towards Universal Health Coverage.
Retinal Microvascular Alterations in Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Chua Jacqueline , Hu Qinglan , Ke Mengyuan , Tan Bingyao , Hong Jimmy , Yao Xinwen , Hilal Saima , Venketasubramanian Narayanaswamy , Garhöfer Gerhard , Cheung Carol Y. , Wong Tien Yin , Chen Christopher Li-Hsian , Schmetterer Leopold 
Published: June 2020

Abstract
Background: The retina and brain share many neuronal and vasculature characteristics developmentally and potential biomarkers may be present in the retina. We investigated the retinal microvasculature in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) using optical coherence tomography angiography (OCTA).Methods: In this cross-sectional study, 24 AD participants, 37 MCI participants, and 29 controls were diagnosed according to internationally accepted criteria. OCTA images of the superficial and deep capillary plexus (SCP, DCP) of the retinal microvasculature were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 with AngioPlex, Carl Zeiss Meditec, Dublin, CA). The main outcome measures were vessel density (VD) and fractal dimension (FD) in the SCP and DCP within a 2.5-mm ring around the fovea were compared between groups. Perfusion density of large vessels and foveal avascular zone (FAZ) area were additional outcome parameters.Results: Age, gender and race did not differ among groups. However, there was a significant difference in diabetes status (P=0.039), and systolic blood pressure (P=0.008) among the groups. After adjusting for confounders, AD participants showed significantly decreased VD in SCP and DCP (P = 0.005 and P = 0.016, respectively) and decreased FD in SCP (P = 0.008), compared to controls. MCI participants showed significantly decreased VD and FD only in SCP (P = 0.005 and P < 0.001, respectively) and not the DCP (P > 0.05) compared with controls. There was no difference in the OCTA variables between AD and MCI (P > 0.05). Perfusion density of large vessels and FAZ area did not differ significantly between groups (P > 0.05).Conclusions and relevance: Eyes of patients with AD have significantly reduced macular VD in both plexuses whereas MCI participants only showed reduction in the superficial plexus. Changes in the retinal microvasculature and capillary network may mirror small vessel cerebrovascular changes in AD.
The Impact of A Multi-Domain Intervention on Cerebral Glucose Metabolism: Analysis from the Randomized Ancillary FDG PET MAPT trial
Authors: Delrieu Julien , Voisin Thierry , Saint-Aubert Laure , Carrie Isabelle , Cantet Christelle , Vellas Bruno , Payoux Pierre , Andrieu Sandrine 
Published: June 2020

Abstract
Background: The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism.Methods: MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented, and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to « MI group » or « No MI group ». The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months and 12 months, and cerebral Magnetic Resonance Imaging scans at baseline The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis.Results: The intention-to-treat population included 67 subjects (34 in the « MI group » and 33 in the « No MI group ». No significant MI effect was observed on primary outcome at 6 and 12 months. In the exploratory voxel-wise analysis, we observed a difference in favor of « MI group » on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months.Conclusions: MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression.Trial registration: ClinicalTrials.gov Identifier, NCT01513252.
Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy for uterus weighing ≥ 1kg
Authors: Wang Xiaojuan , LI Junwei , Hua Keqin , Chen Yisong 
Published: June 2020

Abstract
Background: The transvaginal natural orifice transluminal endoscopic surgery (vNOTES) applied in gynecology has been developed recent years and been evolving. In this study, we aimed to evaluate the feasibility and effect of the transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy for uterus ≥ 1 kilogram (kg). Methods: From January 2019 to March 2020, 39 patients with benign indications in cases of uterus weighing ≥ 1kg, underwent vNOTES hysterectomy were studied retrospectively. The patient demographics, indications for surgery, operation outcomes and patient follow-up details were recorded.Results: The mean age was 48 years (range 42-66); the mean BMI was 24 kg/m 2 (range 18.4-38); the mean operating time was 123.3 minutes (rang 40-400), mean estimated blood loss was 206.7 milliliters (range 10-1300); the mean uterus weight was 1141.8 gram (g) (range 1000-1720). The mean pain assessment was 2.1 (range 0-5). The mean length of stay was 2.4 nights (1-11). 1 patient experienced ureteral injury and was performed ureteral anastomosis. 3 patients were converted to vaginal-assisted trans-umbilicus single-port laparoscopy. The learning curve was analyzed to show that 20 cases were needed to achieve proficiency in vNOTES hysterectomy for large uterus ≥ 1 kg. Conclusion: Our preliminary experience suggested that vNOTES hysterectomy for large uterus weighing ≥ 1kg was feasible and safe, meanwhile this procedure had the advantages of all the minimal invasive approach such as fast recovery and aesthetic advantage.
Global Research Trends at the Intersection of Coronavirus Disease 2019 (COVID-19) and Traditional, Integrative, and Complementary and Alternative Medicine: A Bibliometric Analysis
Authors: Ng Jeremy Y. 
Published: June 2020

Abstract
Background: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2, and responsible for a global pandemic. Despite there being no known vaccines or medicines that prevent or cure COVID-19, many traditional, integrative, complementary and alternative medicines (TICAMs) have been touted as the solution, as well as researched as a potential remedy globally. This study presents a bibliometric analysis of global research trends at the intersection of TICAM and COVID-19. Methods: SCOPUS, MEDLINE, EMBASE, AMED and PSYCHINFO databases were searched on June 5, 2020, with results being exported on the same day. All publication types were included, however, articles were only deemed eligible if they made mention of one or more TICAMs for the potential prevention, treatment, and/or management of COVID-19. The following eligible article characteristics were extracted: title; author names, affiliations, and countries; DOI; publication language; publication type; publication year; journal (and whether it is TICAM-focused); impact factor, and TICAMs mentioned. Results: A total of 178 eligible articles were published by 856 unique authors at 541 affiliations across 43 countries. The most common countries associated with author affiliation included China, United States, Italy and India. The vast majority of articles were published in English, followed by Chinese. Eligible articles were published across 100 journals, of which 24 were TICAM-focussed; only 69 journals had a 2018 impact factor, which ranged from 0.672-59.102. A total of 180 TICAMs were mentioned across eligible articles, with the most common ones including: Traditional Chinese Medicine (n=64), vitamin D (n=44), melatonin (n=10), general herbal medicine (n=9), and vitamin C (n=8). Conclusions: This study provides researchers and clinicians with a greater knowledge of the characteristics of articles that been published globally at the intersection of COVID-19 and TICAM to date. At a time where safe and effective vaccines and medicines for the prevention and treatment of COVID-19 have yet to be discovered, this study may aid to guide the identification and exploration of understudied TICAM therapies that may hold potential in combatting the COVID-19 pandemic.
Plasmons in holographic graphene
Authors: Gran Ulf , Tornsö Marcus , Zingg Tobias 
Published: June 2020

We demonstrate how self-sourced collective modes – of which the
plasmon is a prominent example due to its relevance in modern
technological applications – are identified in strongly correlated
systems described by holographic Maxwell theories. The characteristic
\omega \propto \sqrt{k}ω∝k
plasmon dispersion for 2D materials, such as graphene, naturally emerges
from this formalism. We also demonstrate this by constructing the first
holographic model containing this feature. This provides new insight
into modeling such systems from a holographic point of view, bottom-up
and top-down alike. Beyond that, this method provides a general
framework to compute the dynamical charge response of strange metals,
which has recently become experimentally accessible due to the novel
technique of momentum-resolved electron energy-loss
spectroscopy (M-EELS). This framework therefore opens up the exciting
possibility of testing holographic models for strange metals against
actual experimental data.