bluuebunny/crossref_metadata_2025_split huggingface dataset:
A broad-range survey of Borrelia burgdorferi sensu lato infection in small mammals in Yunnan Province, China
Authors: He Zhihai , Jiang Baogui , Gao Zihou , Shao Zongti , Zhang Yun , Liu Zhengxiang , Li Yuqiong , Pu Ennian , Tang Li , Yao Mingguo , Jia Na , Fricken Michael E. von , Jiang Jiafu , Du Chunhong 
Published: December 2020

Abstract
Background: Lyme disease, caused by Borrelia burgdorferi sensu lato (BBSL), is commonly found in wild and domestic mammals worldwide. In China, human cases of B. burgdorferi infections have been identified across a wide distribution, but little direct surveillance of potential small mammal reservoirs has been performed in Yunnan Province, a tropical region in southwestern China. Here we report a thorough investigation of BBSL in small mammals collected from 2011 to 2016 from this region.Methods: Small mammals were captured using snap traps in 23 counties located in Yunnan Province. DNA was extracted from spleen tissue using DNA blood and tissue kits. A nested PCR targeting the 5S-23S rRNA intergenic spacer gene of BBSL was used for pathogen detection. Amplicons of 252bp expected sizes were sequenced directly and analyzed using BLAST algorithm. A phylogenetic tree was constructed using MEGA software and statistical analysis were conducted using SPSS version 17.0.Results: Overall, 3659 mammals belonging to 57 species were captured at 159 sample sites located in 23 counties in Yunnan Province. Borrelia burgdorferi s.l. was found in 146 mammals (3.99%), from 30 different species, 20 of which represent the first reported detection in that species. Sequence analysis revealed five genotypes of B. burgdorferi s.l., including B. afzelii, B. burgdorferi sensu stricto, B. japonica, B. garinii and B. valaisiana.Conclusions: Significant differences in prevalence rates of BBSL were observed at varying landscape types and altitudes. Small mammals in forested areas had higher prevalence rates than other landscape types, as did small mammals found at altitudes greater than 2500 meters. The five genotypes of BBSL detected, suggests high genetic diversity within this province.
The Effect of Talaromyces Marneffei Infection on CD86 Expression in THP-1 Cells
Authors: Yang Di , Shen Lin , Chen Ri , Fu Yu , Zhang Li , Xu Hong , Liu Dong 
Published: December 2020

Abstract
Background: Talaromyces Marneffei (T.marneffei) is an destructive opportunistic dimorphic fungal which can cause lethiferous Talaromycosis, but the clearance of T.marneffei mainly depends on the innate immune response. Objectives: To investigate the effect of T.marneffei on CD86 expression in THP-1 cells after infection and discuss the potential mechanisms. Methods: Western blot and immunoelectron microscopy were used to detect the CD86 expression on T.marneffei cultured on BHI medium at 37℃. Western blot、enzyme-linked immunoassay and immunofluorescence were used to detect the change of CD86 expression on macrophages incubating with T.marneffei. Enzyme-linked immunoassay was used to detect the content of CD86 in supernatant in the co-culture system. Immunohistochemistry and immunoelectron microscopy were used to detect the expression of CD86 on T.marneffei incubating with macrophages. Results: T.marneffei didn’t express CD86 when cultured separately at 37℃ detected by western blot and immunoelectron microscopy, but it did express CD86 when incubated with macrophages detected by immunohistochemistry and immunoelectron microscopy. The CD86 expression of macrophages significantly decreased at 72 hours when infected with T.marneffei while the content of CD86 in supernatant significantly increased at 72 hours compared with the control group which were detected by western blot, enzyme-linked immunoassay and immunofluorescence. Conclusion: 1.After T.marneffei infection，CD86 expression on THP-1 decreased，and with the progression of infection, insufficient polarization of M1 macrophages gradually appeared；2.T.marneffei may adsorb or uptake CD86 in supernatant produced by macrophages during the contact with THP-1 cells, thus leading to the consumption of CD86 in macrophages.
Advance Research Directives: Avoiding Double Standards
Authors: Heinrichs Bert 
Published: December 2020

Abstract
Background: Advance research directives (ARD) have been suggested to facilitate research with incapacitated subjects, in particular in the context of dementia research. However, established disclosure requirements for study participation raise an ethical problem for the application of ARDs: While regular consent procedures call for detailed information on a specific study (“token disclosure”), ARDs can typically only include generic information (“type disclosure”). ARDs, therefore, run the risk of introducing an ethically problematic double standard. Methods: This paper provides an ethical analysis of ARDs, taking into account the results of numerous empirical studies that have been performed so far. It will be argued that a revised understanding of informed consent can allow for context-sensitive disclosure standards. As a consequence, ARDs that include “type disclosure” can be acceptable under suitable circumstances. Discussion: Such an approach raises objections, two of which are especially important. A thorough examination shows, however, that they are not sufficient to justify a rejection of the approach. Conclusion: The approach presented in this paper avoids introducing a double-standard for particular types of research such as dementia research. It is, therefore, more suitable for the implementation of ARDs than established approaches.
Evaluation of HER&nbsp;2-overexpression Status in Breast Cancer Patients: Results From a Breast Cancer Registry
Authors: Nourmohammadi Hassan , Beigi Seyedeh Negin Mir , Bonyadi Mahtab , Shafiei Elham 
Published: December 2020

Abstract
Background: The expression level of HER2 gene is low in normal breast tissue, but levels of these receptors are higher in half of cases of breast cancer. Different expression levels of HER2 gene in normal and malignant cells have made this gene an ideal biomarker for therapeutic purposes. In this study, the extent of HER2 overexpression and its relationship with the age and the occurrence of metastasis were evaluated in breast cancer patients. Methods: In this cross-sectional study, 62 patients with breast cancer were evaluated at oncology clinics in Ilam province. Clinical examination for metastasis, examination of tissue samples for HER2 gene expression, and information related to variables were recorded in a breast cancer registry. The obtained data were analyzed using SPSS 20 statistical software by appropriate statistical tests.Results: The mean age of the participants was 48.37 ± 10.98, and 98.4% were women. The prevalence of increased HER2 gene expression was 37.1% in patients. There was an inverse relationship between patients' age and HER2 positivity (P value = 0.02). The chance of metastasis was 9 times higher (OR = 9.82) in cancer patients who had the HER2 gene expression Conclusion: In Ilam province, the prevalence of HER2 positivity in breast cancer patients is almost similar to other parts of the country and is associated with the occurrence of metastasis and low age of breast cancer patients.
WITHDRAWN: TP53 Drives Abscopal Effect by Secretion of Senescence-associated Molecular Signals in Non Small Cell Lung Cancer
Authors: Tesei Anna , Arienti Chiara , Bossi Gianluca , Santi Spartaco , De Santis Ilaria , Bevilacqua Alessandro , Zanoni Michele , Pignatta Sara , Cortesi Michela , Zamagni Alice , Storci Gianluca , Bonafè Massimiliano , Sarnelli Anna , Romeo Antonino , Cavallo Carola , Bartolazzi Armando , Rossi Stefania , Soriani Antonella , Strigari Lidia 
Published: December 2020

Abstract
Background. Recent developments in abscopal effect strongly support the use of radiotherapy for the treatment of metastatic disease. However, deeper understanding of the molecular mechanisms underlying the abscopal effect are required to best benefit a larger proportion of patients with metastasis. Several groups including ours, reported the involvement of wild-type (wt) p53 in radiation-induced abscopal effects, however very little is known on the role of wtp53 dependent molecular mechanisms. Methods. We investigated through in vivo and in vitro approaches how wtp53 orchestrates radiation-induced abscopal effects. Wtp53 bearing (A549) and p53-null (H1299) NSCLC lines were xenotransplanted in nude mice, and cultured in 2D monolayers and 3D tumor spheroids. Extracellular vesicles (EVs) were isolated from medium cell culture by ultracentrifugation protocol followed by Nanoparticle Tracking Analysis. Gene expression was evaluated by RT-Real Time, digital qRT-PCR, and dot blot technique. Protein levels were determined by immunohistochemistry, confocal anlysis, western blot techniques, and immunoassay.Results. We demonstrated that single high-dose irradiation (20 Gy) induces significant tumor growth inhibition in contralateral non-irradiated (NIR) A549 xenograft tumors but not in NIR p53-null H1299 or p53-silenced A549 (A549sh/p53) xenografts. We further demonstrates that irradiation of A549 cells in vitro induces a senescence-associated secretory phenotype (SASP) producing extracellular vesicles (EVs) expressing CD63 and carrying DNA:RNA hybrids and LINE-1 retrotransposon. IR-A549 EVs also hamper the colony-forming capability of recipient NIR A549 cells, induce senescent phenotype, nuclear expression of DNA:RNA hybrids, and M1 macrophage polarization. Conclusions. In our models, we demonstrate that p53-mediated abscopal effect was accompanied by the onset of SASP and was mediated by CD63+ EVs conveying in NIR counterpart as abscopal messengers DNA:RNA hybrids and LINE-1 retrotransposons.
The Anti-Dysenteric Drug Fraxetin Enhances Anti-Tumor Efficacy of Gemcitabine and Suppresses Pancreatic Cancer Development by Antagonizing STAT3&nbsp;Activation
Authors: Guo Yangyang , Xiao Yanyi , Guo Hangcheng , Zhu Hengyue , Chen Dong , Wang Jilong , Deng Junjie , Xu Zheng , Lan Junjie , Liu Xiaodong , Zhang Qiyu , Bai Yongheng 
Published: December 2020

Abstract
BackgroundFraxetin, a natural product isolated and purified from the bark of Fraxinus bungeana A.DC., has anti-inflammatory, analgesic and anti-dysenteric activities. This study aimed to investigate the anti-tumor effects of fraxetin in pancreatic ductal adenocarcinoma (PDA) and elucidate the underlying molecular mechanism. MethodsThe effects of quercetin on the proliferation, apoptosis, migration and invasion of pancreatic cancer cells (PCCs), and tumor growth and metastasis in PDA xenograft mouse models were evaluated. Besides, the effects of fraxetin on the sensitivity of PCCs to gemcitabine were evaluated. Moreover, angiogenesis, glucose metabolism, the epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS), and STAT3 activity were analyzed.ResultsIn PCCs, fraxetin inhibited the proliferation, induced mitochondrial-dependent apoptosis, and suppressed the invasion and migration by reversing the EMT. In nude mouse models, PDA growth and metastasis were reduced by fraxetin treatment. Moreover, fraxetin enhanced the sensitivity of PCCs to the chemotherapy drug gemcitabine. Mechanically, oncogenic KRAS-triggered STAT3 activation in PCCs and PDA tissues was suppressed by fraxetin treatment. Fraxetin shows important interactions with STAT3 Src Homology 2 (SH2) domain residues to occupy the pTyr‐recognition site of its SH2 domain of another STAT3 monomer, thereby preventing its homo-dimer formation, which then blocks the activation of downstream signal pathways. The anti-tumor activity of fraxetin in PDA was functionally rescued by a STAT3 activator colivelin. As a result, fraxetin hindered hypoxia-induced angiogenesis by decreasing HIF-1α and VEGFA expression, controlled glucose metabolism by reducing GLUT1 expression, inhibited the EMT by blocking the Slug-E-cadherin axis, and drove ROS-mediated apoptosis by regulating STAT3-Ref1 axis.Conclusion﻿These findings indicate that fraxetin enhances anti-tumor activity of gemcitabine and suppresses pancreatic cancer development by antagonizing STAT3 activation.
The XBP1-MARCH5-MFN2&nbsp;Axis Confers ER&nbsp;Stress Resistance by Coordinating Mitochondrial Fission and Mitophagy in Melanoma
Authors: Wang Huina , Yi Xiuli , Guo Sen , Wang Sijia , Ma Jinyuan , Zhao Tao , Shi Qiong , Tian Yangzi , Wang Hao , Jia Lintao , Gao Tianwen , Li Chunying , Guo Weinan 
Published: December 2020

Abstract
Background: Melanoma cells are relatively resistant to ER stress, which contributes to tumor progression under stressful conditions and renders tolerance to ER stress-inducing therapeutic agents. Mitochondria are tightly interconnected with ER. However, whether mitochondria play a role in regulating ER stress resistance in melanoma remains elusive.Methods: Integrative bioinformatics was employed to figure out the implication of mitochondria in the resistance of melanoma cells to ER stress. A panel of biochemical assays and pre-clinical xenograft mouse model were used to investigate the role of mitochondrial fission and mitophagy in affecting ER stress sensitivity and the underlying mechanisms. Results: Our integrative bioinformatics analysis revealed that the down-regulation of mitochondrial genes was highly correlated with UPR activation in melanoma. Then we proved that mitochondrial fission and mitophagy were prominently induced in melanoma cells upon ER stress. Pharmacological inhibition of either mitochondrial fission or mitophagy effectively restored the sensitivity of melanoma cells to ER stress both in vitro and in vivo. Mechanistically, the down-regulation of MFN2 was essential for rendering the resistance by promoting mitochondrial fission and mitophagy. XBP1-mediated transcriptional up-regulation of E3 ligase MARCH5 contributed to the ubiquitination and degradation of MFN2 in ER stress-resistant cells, whereas the impaired transduction of this axis indicated the fragile to ER stress. Finally, the relationships among UPR pathway molecules, MARCH5 and mitochondrial genes were confirmed in both publicly accessible databases and tumor specimens.Conclusions: Together, our findings demonstrate a novel regulatory axis that links mitochondrial fission and mitophagy to the resistance to ER stress. Targeting mitochondrial quality control machinery can be exploited as an approach to reinforce the efficacy of ER stress-inducing agents against cancer.
Surufatinib Plus Toripalimab in Patients with Advanced Solid Tumors: A Single-Arm, Open-Label, Phase 1 Trial
Authors: Cao Yanshuo , Lu Ming , Sun Yu , Gong Jifang , Li Jie , Lu Zhihao , Li Jian , Zhang Xiaotian , Li Yan , Peng Zhi , Zhou Jun , Wang Xicheng , Shen Lin 
Published: December 2020

Abstract
BackgroundPreclinical studies have supported a potential synergistic antitumor activity between surufatinib and anti-programed death ligand-1 (PD-L1). We describe here the results of a single-arm, open-label phase 1 trial to evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) in patients with advanced solid tumors treated with surufatinib combined with toripalimab, an inhibitor of PD-L1.MethodsThis is an open-label, dose escalation and expansion study in patients with solid tumors who had failed standard therapies or had no effective treatment. In the dose escalation stage, 3 cohorts of patients were treated with surufatinib, at dose levels of 200, 250, or 300 mg once daily (QD) in combination with a fixed dose of toripalimab 240 mg, every 3 weeks (Q3W), to evaluate maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Additional patients were enrolled in the dose expansion phase to further assess the efficacy, safety, and PK profile.ResultsFrom April 1, 2019 to July 10, 2020, 31 patients were screened, of which 28 patients were enrolled. One patient in the 300 mg cohort experienced dose limited toxicity (DLT), a grade 3 hyperthyroidism. The top 3 most common treatment-related adverse events of ≥ grade 3 were transaminases increased (17.9%), hypertension (14.3%) and blood bilirubin increased (10.7%). No treatment-related death or treatment discontinuation was identified. The RP2D was determined to be surufatinib 250 mg QD plus toripalimab 240 mg Q3W. Overall objective response rate was 22.2% [95% confidential interval (CI) 8.6‒42.3], and disease control rate reached 81.5% (95% CI 61.9‒93.7). ConclusionsSurufatinib plus toripalimab was well-tolerated, with no unexpected safety signals, and showed promising antitumor activity in patients with advanced solid tumors. Trial registrationclinicaltrials.gov, NCT03879057; Registered March 18, 2019, https://clinicaltrials.gov/ct2/show/NCT03879057
Pirfenidone Modulates Macrophage Polarization and Ameliorates Radiation-induced Lung Fibrosis by Inhibiting the TGF-β1/Smad3 Pathway
Authors: ying hangjie , Fang min , Hang Qing Qing , Chen Ya mei , Qian Xu , Chen Ming 
Published: December 2020

Abstract
Background：Radiation-induced lung injury (RILI) mainly contributes to the complications of thoracic radiotherapy. RILI can be divided into early-stage radiation pneumonia (RP) and late-stage radiation-induced lung fibrosis (RILF). Once RILF occurs, patients will eventually develop irreversible respiratory failure; thus, a new treatment strategy to prevent RILI is urgently needed. This study explored the therapeutic effect of pirfenidone (PFD), a Food and Drug Administration (FDA)-approved drug for idiopathic pulmonary fibrosis (IPF) treatment, and its mechanism in the treatment of RILF. Methods：A series of in vitro and in vivo assays were performed to explore the role and mechanism of PFD in the prevention and treatment of RILF. Results：Collagen deposition and fibrosis in the lung were reversed by PFD treatment, which was associated with reduced M2 macrophage infiltration and inhibition of the transforming growth factor-β1(TGF-β1) /drosophila mothers against decapentaplegic 3 (Smad3) signaling pathway. Moreover, PFD treatment decreased the radiation-induced expression of TGF-β1 and phosphorylation of Smad3 in alveolar epithelial cells (AECs) and vascular endothelial cells (VECs). Furthermore, IL-4- and IL13-induced M2 macrophage polarization was suppressed by PFD treatment in vitro, resulting in reductions in the release of arginase-1(ARG-1), chitinase 3-like 3 (YM-1) and TGF-β1. Notably, the PFD-induced inhibitory effects on M2 macrophage polarization were associated with downregulation of nuclear factor kappa-B (NF-κB) p50 activity. Additionally, PFD could significantly inhibit ionizing radiation-induced chemokine secretion in MLE-12 cells and consequently impair the migration of RAW264.7 cells. PFD could also eliminate TGF-β1 from M2 macrophages by attenuating the activation of TGF-β1/Smad3. Conclusion：PFD is a potential therapeutic agent to ameliorate fibrosis in RILF by reducing M2 macrophage infiltration and inhibiting the activation of TGF-β1/Smad3.
Impact of Albumin-bilirubin (ALBI) score on the Prognostic Significance of Patients with Heart Failure:A Retrospective Cohort Study
Authors: Han Su , Wang Chuanhe , Tong Fei , Li Ying , Li Zhichao , Sun Zhaoqing , Sun Zhijun 
Published: December 2020

Abstract
Objectives Liver dysfunction is prevalent in heart failure (HF) patients and it can bring a poor prognosis. Presently, albumin-bilirubin (ALBI) score has been designed as an effective and convenient scoring system for assessing liver function, but the correlation linking ALBI and in-hospital mortality in HF patients remains unclear.Methods and Results A total of 9749 patients with HF (from January 2013 to December 2018) was enrolled and retrospectively analyzed. The main outcome is in-hospital death. We examined and analyzed ALBI as a continuous variable as well as according to 3 categories. Following adjustment for multivariable, patients which occurred in-hospital death was remarkably elevated in Tertile 3 group (ALBI>-2.27) (OR=1.670, 95% CI: 1.231~2.265, p=0.001), relative to the other two groups (Tertile 1: <-2.59; Tertile 2: -2.59~-2.27). When ALBI was inspected as a continuous variable, the incidence of HF patients with in-hospital death will increase by 8.2%. (For ALBI score per 0.1 score increasing, OR=1.082, 95% CI: 1.052~1.113, p<0.001). ALBI score for estimating in-hospital mortality under C-statistic was 0.650 (95% CI: 0.641~0.660, p<0.001) and the cut-off value of ALBI score was -2.32 with a specificity of 0.630 and a sensitivity of 0.632. Moreover, ALBI score can enhance the estimation potential of NT-proBNP (NT-proBNP+ALBI vs NT-proBNP: C-statistic: z=1.990, p=0.0467; net reclassification improvement=0.4012, p<0.001; integrated discrimination improvement= 0.0082, p<0.001). Conclusions In patients with HF, ALBI score was an independent prognosticator of in-hospital death. The predictive significance of NT-proBNP +ALBI was superior to NT-proBNP, and ALBI score can enhance the estimation potential of NT-proBNP.
Prediction of Recurrence Patterns in Glioblastoma Using DSC-MRI Radiomics-Based Deep Learning
Authors: Shim Ka Young , Chung Sung Won , Jeong Jae Hak , Hwang Inpyeong , Park Chul-Kee , Kim Tae Min , Park Sung-Hye , Won Jae Kyung , Lee Joo Ho , Lee Soon-Tae , Yoo Roh-Eul , Kang Koung Mi , Yun Tae Jin , Kim Ji-Hoon , Sohn Chul-Ho , Choi Kyu Sung , Choi Seung Hong 
Published: December 2020

Abstract
Glioblastoma remains the most devastating brain tumor despite optimal treatment, because of the high rate of recurrence. Distant recurrence has distinct genomic alterations compared to local recurrence, which requires different treatment planning both in clinical practice and trials. To date, perfusion-weighted MRI has revealed that perfusional characteristics of tumor are associated with prognosis. However, not much research has focused on recurrence patterns in glioblastoma: namely, local and distant recurrence. Here, we propose two different neural network models to predict the recurrence patterns in glioblastoma that utilizes high-dimensional radiomic profiles based on perfusion MRI: area under the curve (AUC) (95% confidence interval), 0.969 (0.903-1.000) for local recurrence; 0.864 (0.726-0.976) for distant recurrence for each patient in the validation set. This creates an opportunity to provide personalized medicine in contrast to studies investigating only group differences. Moreover, interpretable deep learning identified that salient radiomic features for each recurrence pattern are related to perfusional intratumoral heterogeneity. We also demonstrated that the combined salient radiomic features, or “radiomic risk score”, increased risk of recurrence/progression (hazard ratio, 1.61; p=0.03) in multivariate Cox regression on progression-free survival.
Dispersion Scan Frequency Resolved Optical Gating For Evaluation of Pulse Chirp Instability
Authors: Guesmi Mariem , Veselá Petra , Žídek Karel 
Published: December 2020

Abstract
The commonly used methods to characterize ultrafast laser pulses, such as frequency-resolved optical gating (FROG) and dispersion scan (d-scan), face problems when they are used on pulses varying within the acquisition time or laser beam. Such chirp variation can be identified by a discrepancy between the measured FROG and d-scan traces and their reconstructed counterparts. Nevertheless, quantification of the instability from the experimental data is a more complex task. In this work, we evaluate the precision of chirp instability quantification based on three different pulse characterization techniques. Two commonly used techniques FROG and d-scan are compared to a new method dispersion scan FROG (D-FROG) that combines the idea of dispersion scanning with the FROG method. We demonstrate the characterization of pulses generated from NOPA together with pulses processed by a 4f-pulse shaper without and with SLM-adjusted phase. In this paper, we validate the performance of the new method to estimate the chirp instability and, therefore, to improve the reconstruction of the measured results. Furthermore, we discuss the instability origin of each measurement case by using fast-scan autocorrelation traces.