bluuebunny/crossref_metadata_2025_split huggingface dataset:
CpG Oligodeoxynucleotide Developed For Activating Primate Immune Responses Promotes Anti-Tumoral Effect Combine With Neo-Antigen Based mRNA Cancer Vaccine
Authors: Hu Rongkuan , Li Qin , Ren Jie , Liu Wei , Jiang Guoqin 
Published: January 2021

Abstract
Synthetic phosphorthiolate modified CPG-oligodeoxynucleotides (CPG-ODN) activate innate and adaptive immune responses, which being exploited as a therapeutic approach. Here, we first screened and identified a new CpG-B class ODN (CpG2018B) that effectively stimulates type II interferon both in mouse Plasmacytoid dendritic cells (p-DC) and human PBMC. In addition, CpG2018B promotes cytokine production mainly via toll-like receptor 9 (TLR9) pathways. We further demonstrated that intratumoral (IT) injection of CpG2018B inhibits melanoma growth in syngeneic models and could turn “cold” tumors into “hot” tumors. Then, CpG2018B and mRNA based neo-antigen cancer vaccine were encapsulated into lipid-nanoparticle (LNP) and intratumoral injected into melanoma mice models. Interestingly, vaccination with CpG or mRNA vaccine alone could inhibit tumor growth respectively, while, CpG combine with mRNA vaccine enhanced the anti-tumor effect. At last, we described the long-term safety and tolerability of CpG2018B and mRNA therapy in mice models. In conclusion, we identified a novel CpG-B ODNs to promote immune response and CpG combine with mRNA cancer vaccines are attractive candidate for immune stimulatory sequences (ISS) based therapeutic strategies.
Symptomatic Features of 932 Hospitalized Patients with COVID-19 in Wuhan
Authors: Sun Liang-Liang , Wang Jian , Wang Yu-Sheng , Hu Ping-Fang , Zhao Zheng-Qing , Chen Wei , Ning Bei-Fang , Yin Chuan , Hao Yu-Shi , Wang Qiong , Wang Chen , Liu Ya-Long , Chen Cheng , Yin Ji-Zhong , Huang Hai , Xie Wei-Fen 
Published: January 2021

Abstract
BackgroundMuch remains unknown about COVID-19 onset and rehabilitation's symptomatic features, especially the long-term health consequences of patients with COVID-19 who have been discharged from the hospital.MethodsIn this cohort study, we collected the first pandemic data of hospitalized patients in Wuhan from February 20 to March 31, 2020. All patients completed a 3-month follow-up after discharge. We carefully analyzed the detailed symptomatic characteristics of severe COVID-19 at illness onset and three months after discharge, compared it with non-severe patients, and used multiple logistic regression to determine potential symptomatic risk factors for severe COVID-19.ResultsA total of 932 hospitalized patients with COVID-19 were enrolled, including 52 severe cases and 880 non-severe cases. Fever (60%), cough (50.8%), and fatigue (36.4%) were the most common symptoms, followed by anorexia (21.8%) and dyspnea (19.2%). The median duration of fever was seven days, which was characterized by persistent low fever. The median duration of cough was 17 days, characterized by dry cough without sputum. Most dyspnea occurred on the fourth day after symptom onset, with a median duration of 16 days. The incidences of taste loss and olfactory disturbance were only 6.2% and 3.1%, respectively. Multivariate logistic regression analysis showed that age over 65 years old (OR 6.52, 95% CI 3.27-13.02, P<0.0001), male sex (3.71, 1.90-7.26, P = 0.0001), fever lasting for more than five days (1.90, 1.00-3.62, P=0.0498), anorexia at onset (2.61, 1.26-5.40, P=0.0096), and modified Medical Research Council level above grade 2 when dyspnea occurred (14.19,7.01-28.71, P<0.0001) were symptomatic risk factors for severe COVID-19. Three months after discharge from the hospital, 6.2% of patients still cough, 7.2% of patients still dyspnea, and 1.8% still fatigue, and 1.5% of patients had olfactory or taste disorders.ConclusionsCOVID-19 caused clusters of symptoms, with multiple systems involved. Specific symptomatic features at the onset of illness have predictive value for severe COVID-19. Persistent legacy symptoms are more frequent in severe COVID-19 patients.
Platelets and Pro-Angiogenic Circulating Cells Accelerate Skin Wound Healing
Authors: Erratico Silvia , Belicchi Marzia , Meregalli Mirella , Silvestre Dario Di , Tripodi Luana , Palma Antonella De , Jones Rebecca , Ferrari Emanuele , Porretti Lura , Trombetta Elena , Merlo Giorgio R. , Mauri Pierluigi , Torrente Yvan 
Published: January 2021

Abstract
BackgroundDelayed wound healing and chronic skin lesions represent a major health problem. Over the past years, growth factors mediated by platelet-rich plasma (PRP) and cell-based therapies were developed as effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which PRP exhibits its beneficial effects remains unrevealed. Herein we show that a combination of PRP and pro-angiogenic cells (AngioPRP) could exert a synergistic positive effect on keratinocyte proliferation and angiogenesis accelerating wound healing.MethodWe designed a sterile and closed class IIa device (NovySep) for single use only to collect blood-derived mononucleated cells and the plasma phase after centrifugation without opening the system. We performed in vitro and in vivo wound healing experiments to assess the angiogenic potential of AngioPRP; we evaluated the extracellular matrix remodeling and the physical properties of treated wounds through mechanical (stress-strain test) and proteomics analysis.ResultAngioPRP enhanced wound healing by promoting uniform regeneration of the basal and granular layers and vessel remodeling. We coupled this effect with normalization of mechanical properties of rescued mouse wounds, which is sustained by a correct arrangement of elastin and collagen fibers. The network analysis-based protein–protein interactions of AngioPRP-treated wounds demonstrated a fingerprint of AngioPRP-related proteins that may provide the signal for a faster wound healing response which include Caveolin and EGFR/TGFβ/β-catenin pathways.ConclusionA combined treatment composed of PRP and a pool of pro-angiogenic/keratogenic cells (AngioPRP) may provide a more integrated method to supports wound healing, by promoting a cascade of events leading to the reduction of TGFβ1/β-catenin up-downstream signaling pathways. The molecular mechanism undergoing the support of AngioPRP to wound healing opens new perspectives in the treatment of skin injuries.
MicroRNA-21 Promotes Allergic Airway Inflammation and AHR&nbsp;and Inhibits Mesenchymal Stem Cell Migration in Cockroach Allergen Induced Asthma Model
Authors: Cheng Tianli , heng jianfu , Mei Quanhui , Chen Lijun , Zeng Feng 
Published: January 2021

Abstract
BackgroundMesenchymal stem cells (MSCs) have been used to treat asthma in a mouse model. However, the efficacy and mechanism of MSCs are not elucidated. MicroRNAs (miRNAs) play a key rolein asthma and related to the aim of this study was to illustrate the role of miR21 and its influence on MSC migration in asthma model. MethodsA mouse model of asthma was established using cockroach extract (CRE), and miR-21 expression was examined. A miR-21 lentivirus construct was used to investigate the role of miR-21 in vivo and in vitro in mouse bone marrow-derived (BM-) MSCs. A TOPFlash reporter gene assay was used to study the signaling downstream of miR-21. IL-4, IL-5, IL-13, IgE, and IgG1 levels in bronchoalveolar lavage fluids were determined by enzyme-linked immunosorbent assays.ResultsMiR-21 was upregulated in CRE-induced asthmatic mice. MiR-21 promoted allergic airway inflammation and airway hyperreactivity by inhibiting BM-MSC migration. β-Catenin was found to act downstream of miR-21 as a negative regulator of miR-21. Rescue experiments verified that miR-21 inhibited BM-MSC migration by suppressing Wnt/β-catenin signaling.ConclusionMiR-21 promotes allergic airway inflammation and AHR and inhibits BM-MSC migration through Wnt/β-catenin signaling, which may serve as an effective therapeutic target for asthma.
Construction and Validation of a Nomogram for The Prediction of Overall Survival in Intrahepatic Cholangiocarcinoma
Authors: Yang Yong-jing , Cao Ling , Yan Ling , Zhu Jing , Li Qiang , Wu Chun-jiao 
Published: January 2021

Abstract
Objective: This study aimed to establishand validates a nomogram to predict the overall survival (OS) of patients with intrahepatic cholangiocarcinoma (ICC).Patients and methods: The ICC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Then, the independent prognosis-related factors were obtained from the training set using the Cox regression model for the establishment of a nomogram.Results: We identified 3675 eligible patients with a median survival time of 9 months (0–153 months). According to multivariate analysis, age, sex, marital status, grade, T stage, N stage, M stage, surgery, chemotherapy and radiotherapy were identified as the factors to independently predictthe prognosis for ICC (all P<0.05). Thereafter, the above factors were incorporated for the construction of a nomogram. In comparison with the AJCC 8th TNM classification system and the SEER summary stage system, our constructed nomogram showed higher ability in discrimination, as revealed by the C-index (all P<0.001).Besides, the internal as well as external calibration curve analysis demonstrated that the predicted results were highly consistent with the actual ones. On the other hand, our nomogram outperformed the AJCC 8th TNM classification system and the SEER summary stage system in predicting the 3- and 5-year OS, as suggested by time-independent area under the curve (tAUC) values.Conclusion: Our constructed nomogram performs well, indicating its potential as an efficient approach to evaluate the prognosis of ICC patients.
Refractive Outcomes of Table-Mounted and HandheldAuto-Refractometers in Children: An Observational Cross-Sectional Study
Authors: karab müjdat , karabulut sinem , karalezli Aylin 
Published: January 2021

Abstract
Background: To compare the refractive results of two autorefractors.Methods: We designed this study as an observational, cross-sectional study. We compared the mean spheric and cylinder power, spherical equivalent, Jackson cross-cylinder values, determined the limits of agreement (LoA), and evaluated reliability.Results: Nidek HandyRef-K autorefractor measured more astigmatism and myopia in terms of the mean cylindrical power (P<.001) and spherical equivalent (P=.024). Nidek HandyRef-K showed significantly more myopic results in subgroups with spherical power more than +1.50 Diopters (D) hyperopia and -3.00 D myopia (P=.031; P=.045; P=.026; respectively) and higher astigmatism in the subgroup with the cylindric power less than -1.00 D (P<.001). The mean differences and 95% LoA were 0.06 D ± 0.47 D (-0.82 D to 0.98 D) in spherical power, 0.08 D ± 0.28 D (-0.47 D to 0.64 D) in cylindrical power, 0.11 D ± 0.47 D (-0.81 D to 1.01 D) in spherical equivalent, 0.02 D ± 0.36 D (-0.73 D to 0.69 D) in Jackson cross-cylinder power at 0°, 0.005 D ± 0.54 D (-1.07 D to 1.06 D) in Jackson cross-cylinder power at 45°. There was a strong correlation for spherical power (Spearman’s rho=0.99, P<.001), cylindrical power (Spearman’s rho=0.88, P<.001), spherical equivalent (Spearman’s rho=0.98, P<.001).Conclusion: Nidek HandyRef-K showed more myopic results regarding spherical equivalent and cylindrical power. Nidek HandyRef-K showed significantly more myopia in spherical power more than +1.50 D hyperopia, -3.00 D myopia, and more prominent astigmatism in cylindrical power less than -1.00 D subgroups.
Identification of a 10-Gene Signature Model to Predict Efficacy of Neoadjuvant Therapy in Patients With HER2&nbsp;Positive Breast Cancer.
Authors: Wang Yusong , Wang Mozhi , Sun Xiangyu , Yao Litong , Wang Mengshen , Dong Haoran , Li Xinyan , He Mingcong , Xu Yingying 
Published: January 2021

Abstract
BackgroundPatients with human epidermal growth factor receptor 2 (HER2) positive breast cancer represent a poor prognosis, which are recommended to be treated with neoadjuvant therapy (NAT). Tumor immune microenvironment, especially tumor infiltrating cells (TILs), are proved to predict the efficacy of NAT. However, validated immune-related multi-gene signatures for HER2-positive BC are still lacking.MethodsWe collected gene expression arrays of pre-NAT samples from the National Center for Biotechnology Information Gene Expression Omnibus. Totally 4 studies are included in our study (n=295, no. of train =207, no. of validation=95) to construct the signature. Single Sample Gene Set Enrichment Analysis (ssGSEA)and weighted gene co-expression network analysis (WGCNA)were used to quantify immune-infiltrating components in tumor environment and to identify immune related modules. We used spline regression to evaluate non-linear effect of genes and to construct the signature.ResultsImmune infiltration status was significantly related to pathological complete response (pCR) (p=0.02). We filtered 80 differential expression genes according to immune infiltration status, and identified two gene modules correlated to pCR and immune infiltration status. CCL5, CD72, PTGDS, CYTIP, PAX5, and estrogen receptor (ER)status were significantly related with pCR in linear multivariate analysis. In spline regression, non-linear aspects of MAP7, IL2RB, CD3G, PTPRC, TRAC were relevant to pCR. We constructed a signature concerning both linear and non-linear effect of genes, which was validated in 5-fold cross validation (AUC=0.81) and an external validation cohort (n=88) (AUC=0.797).ConclusionsIn HER2 positive BC, immune infiltration status should be involved into consideration to make optimal regimens. A ten-gene generalized non-linear signature including ER status could predict the efficacy of NAT.
microRNA-1915-3p Promotes Cell Metastasis and Progression by Targeting Bcl2L11 in Hepatocellular Carcinoma
Authors: Huang Wenjie , Li Sufen , Chen Xianhua , Sun Lin , Pan Gangxi , Chen Jianlin , Sun Xiujuan , Shen Yongqi , Lu Yonggang , Sun Yifan 
Published: January 2021

Abstract
BackgroundIncreasing evidence suggests that miR-1915-3p plays vital regulatory roles in metastasis and progression of several types of cancer. However, the roles and underlying mechanism of miR-1915-3p in hepatocellular carcinoma (HCC) remains largely unclear. MethodsWe carried out a bioinformatic meta-analysis to investigate a possible role of miR-1915-3p as prognostic biomarkers. In vitro cellular models of HCC were used for functional studies exploring the role of miR-1915-3p in HCC development and progression. Finally, in vivo studies were performed to demonstrate that miR-1915-3p is a viable therapeutic target.ResultsThis study showed that miR-1915-3p was significantly increased in HCC tissue samples and cell lines, and high miR-1915-3p expression was associated with a poor overall survival (OS) and disease-free survival (DFS) time of HCC patients. Overexpression or ablation of miR-1915-3p expression resulted in accelerated or inhibited cell proliferation, migration, and invasion respectively in HCC cells. In addition, miR-1915-3p induced downregulation of proapoptotic factors, including caspase3, caspase8, BAD, Bcl2L11, and P53. It also induced upregulation of antiapoptotic Bcl-2, protecting HCC cells from apoptosis. A biological analysis indicated that miR-1915-3p could be directly targeted to Bcl2L11 to regulate the proliferation, invasion, and migration of HCC cells. Furthermore, in vivo studies confirmed that treatment with miR-1915-3p retarded the growth of tumor in nude mice. Conclusionour study provided the evidence for the regulatory role of miR-1915-3p in HCC, which was causally linked to targeting of Bcl2L11. Medications that abrogate excessively expressed miR-1915-3p may offer novel targets for the management of HCC.
Use of Vasopressors Increases the Risk of Mortality in Severe Traumatic Brain Injury: A Nationwide Retrospective Cohort Study in Japan
Authors: Hosomi Sanae , Sobue Tomotaka , Kitamura Tetsuhisa , Hirayama Atsushi , Ogura Hiroshi , Shimazu Takeshi 
Published: January 2021

Abstract
BackgroundPharmacological elevation of blood pressure is frequently incorporated in severe traumatic brain injury management algorithms. However, there is limited evidence on prevalent clinical practices regarding resuscitation for severe traumatic brain injury using vasopressors. We conducted a nationwide retrospective cohort study to determine the association between the use of vasopressors and mortality following hospital discharge in patients with severe traumatic brain injury, and to determine whether the use of vasopressors affects emergency department mortality or the occurrence of cognitive dysfunction.MethodsData were collected between January 2004 and December 2018 from the Japanese Trauma Data Bank, which includes data from 272 emergency hospitals in Japan. Adults aged ≥16 years with severe traumatic brain injury, without other major injuries, were examined. A severe traumatic brain injury was defined based on the Abbreviated Injury Scale code and a Glasgow Coma Scale score of 3–8 on admission. Multivariable analysis and propensity score matching were performed. Statistical significance was assessed using 95% confidence intervals (CIs).ResultsIn total, 10 284 patients were eligible for analysis, with 650 patients (6.32%) included in the vasopressor group and 9634 patients (93.68%) included in the non-vasopressor group. The proportion of deaths on hospital discharge was higher in the vasopressor group than in the non-vasopressor group (81.69% [531/650] vs. 40.21% [3,874/9,634]). This finding was confirmed by multivariable logistic regression analysis (adjusted odds ratio [OR], 5.71; 95% CI: 4.56–7.16). Regarding propensity score-matched patients, the proportion of deaths on hospital discharge remained higher in the vasopressor group than in the non-vasopressor group (81.66% [530/649] vs. 50.69% [329/649]) (OR, 4.33; 95% CI: 3.37–5.57). The vasopressor group had a higher emergency department mortality rate than the non-vasopressor group (8.01% [52/649] vs. 2.77% [18/649]) (OR, 3.05; 95% CI: 1.77–5.28). There was no reduction in complications of cognitive disorders in the vasopressor group (5.39% [35/649] vs. 5.55% [36/649]) (OR, 0.97; 95% CI: 0.60–1.57).ConclusionsIn this population, the use of vasopressors for severe traumatic brain injury was associated with higher mortality on hospital discharge. Our results suggest that vasopressors should be avoided in most cases of severe traumatic brain injury.
The management and outcome of paediatric splenic injuries in the Netherlands
Authors: Grootenhaar Maike , Lamers Dominique , Ulzen Karin Kamphuis-van , de Blaauw Ivo , Tan Edward C 
Published: January 2021

Abstract
Background: Non-operative management (NOM) is generally accepted as a treatment method of traumatic paediatric splenic rupture. However, considerable variations in management exist. This study analyses local trends in aetiology and management of paediatric splenic injuries and evaluates the implementation of the guidelines proposed by the American Paediatric Surgical Association (APSA) in a level 1 trauma centre. Methods: The charts of paediatric patients with blunt splenic injury (BSI) who were admitted or transferred to a level 1 trauma centre between 2003 and 2020 were retrospectively assessed. Information pertaining to demographics, mechanism of injury, injury description, associated injuries, intervention and outcomes were analysed and compared to international literature.Results: There were 130 patients with BSI identified (63.1% male), with a mean age of 11.3 ± 4.0 and a mean injury severity score (ISS) of 21.6 ± 13.7. Bicycle accidents were the most common trauma mechanism (23.1%). Sixty-four percent were multi-trauma patients, 25% received blood transfusions, and 31% were hemodynamically unstable. Mean injury grade was 3.0, with 30% of patients having a high-grade injury. In total, 75% of patients underwent NOM with a 100% efficacy rate. Total splenectomy rate was 6.2%. Four patients died due to brain damage. Patients with a high-grade BSI (grade IV-V) had a significantly higher ISS and longer bedrest and more often presented with an active blush on computed tomography (CT) scans than patients with a low-grade BSI (grade I-III). Non-operative management was mainly the choice of treatment in both groups (76.6% and 79.5%, respectively). Hemodynamic instability was a predictor for operative management (OM) (p=0.001). Predictors for a longer length of stay (LOS) included concomitant injuries, hemodynamic instability and OM (all p < 0.02). Interobserver agreement in the grading of BSI is moderate, with a Cohens Kappa coefficient of 0.493.Conclusion: Non-operative management has proven to be a realistic management approach in both low- and high-grade splenic injuries. Consideration for operative management should be based on hemodynamic instability. Compared to the anticipated length of bedrest and hospital stay outlined in the APSA guidelines, the Netherlands can reduce the length of bedrest and hospital stay through their non-operative management.Level of evidence: Therapeutic study, level III
Alterations in The Gut Microbiota and Metabolite Profiles in The Context of Neuropathic Pain
Authors: Chen Peng , Wang Chen , Ren Yan-na , Ye Zeng-jie , Jiang Chao , Wu Zhi-bing 
Published: January 2021

Abstract
The aim of this study was to explore the relationships among gut microbiota disturbances and serum and spinal cord metabolic disorders in neuropathic pain. 16S rDNA amplicon sequencing and serum and spinal cord metabolomics were used to identify alterations in the microbiota and metabolite profiles in the sham rats and the chronic constriction injury (CCI) model rats. Correlations between the abundances of gut microbiota components at the genus level, the levels of serum metabolites, and pain-related behavioural parameters were analysed. Ingenuity pathway analysis (IPA) was applied to analyse the interaction networks of the differentially expressed serum metabolites. First, we found that the composition of the gut microbiota was different between rats with CCI-induced neuropathic pain and sham controls. At the genus level, the abundances of Helicobacter, Phascolarctobacterium, Christensenella, Blautia, Streptococcus, Rothia and Lactobacillus were significantly increased, whereas the abundances of Ignatzschineria, Butyricimonas, Escherichia, AF12, and Corynebacterium were significantly decreased. Additionally, 72 significantly differentially expressed serum metabolites and 17 significantly differentially expressed spinal cord metabolites were identified between the CCI rats and the sham rats. Finally, correlation analysis showed that changes in the gut microbiota was significantly correlated with changes in serum metabolite levels, suggesting that dysbiosis of the gut microbiota is an important factor in modulating metabolic disturbances in the context of neuropathic pain. In conclusion, our research provides a novel perspective on the potential roles of the gut microbiota and related metabolites in neuropathic pain.