bluuebunny/crossref_metadata_2025_split huggingface dataset:
Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success
Authors: Silvis Max J. M. , Kaffka genaamd Dengler Selma E. , Odille Clémence A. , Mishra Mudit , van der Kaaij Niels P. , Doevendans Pieter A. , Sluijter Joost P. G. , de Kleijn Dominique P. V. , de Jager Saskia C. A. , Bosch Lena , van Hout Gerardus P. J. 
Published: December 2020

In the setting of myocardial infarction (MI), ischemia reperfusion injury (IRI) occurs due to occlusion (ischemia) and subsequent re-establishment of blood flow (reperfusion) of a coronary artery. A similar phenomenon is observed in heart transplantation (HTx) when, after cold storage, the donor heart is connected to the recipient’s circulation. Although reperfusion is essential for the survival of cardiomyocytes, it paradoxically leads to additional myocardial damage in experimental MI and HTx models. Damage (or danger)-associated molecular patterns (DAMPs) are endogenous molecules released after cellular damage or stress such as myocardial IRI. DAMPs activate pattern recognition receptors (PRRs), and set in motion a complex signaling cascade resulting in the release of cytokines and a profound inflammatory reaction. This inflammatory response is thought to function as a double-edged sword. Although it enables removal of cell debris and promotes wound healing, DAMP mediated signalling can also exacerbate the inflammatory state in a disproportional matter, thereby leading to additional tissue damage. Upon MI, this leads to expansion of the infarcted area and deterioration of cardiac function in preclinical models. Eventually this culminates in adverse myocardial remodeling; a process that leads to increased myocardial fibrosis, gradual further loss of cardiomyocytes, left ventricular dilation and heart failure. Upon HTx, DAMPs aggravate ischemic damage, which results in more pronounced reperfusion injury that impacts cardiac function and increases the occurrence of primary graft dysfunction and graft rejection via cytokine release, cardiac edema, enhanced myocardial/endothelial damage and allograft fibrosis. Therapies targeting DAMPs or PRRs have predominantly been investigated in experimental models and are potentially cardioprotective. To date, however, none of these interventions have reached the clinical arena. In this review we summarize the current evidence of involvement of DAMPs and PRRs in the inflammatory response after MI and HTx. Furthermore, we will discuss various current therapeutic approaches targeting this complex interplay and provide possible reasons why clinical translation still fails.
Pregnancy Outcomes in Patients With Adult-Onset Still's Disease: A Cohort Study From China
Authors: Wang Zhihong , Chi Huihui , Feng Tienan , Du Qinwen , Zeng Ting , Teng Jialin , Liu Honglei , Cheng Xiaobing , Ye Junna , Shi Hui , Sun Yue , Hu Qiongyi , Jia Jinchao , Liu Tingting , Wan Liyan , Wu Xinyao , Zhou Zhuochao , Yang Chengde , Su Yutong 
Published: December 2020

Objective: Adult-onset Still's disease (AOSD) is an autoinflammatory disease with a higher prevalence rate in young females. The purpose of this study is to investigate whether AOSD has an adverse impact on pregnancy outcomes, or conversely exacerbated by pregnancy.Methods: The outcomes of 191 pregnancies were evaluated in 86 female patients with AOSD. The generalized linear mixed model and propensity score matching method were conducted to evaluate the influence of AOSD on pregnancy outcomes. A dependent sample sign test was applied to assess the impact of pregnancy on the relapse of AOSD.Results: The results showed that the post-AOSD group had a lower proportion of normal delivery (25.0 vs. 52.4%, p = 0.036) and a higher proportion of spontaneous abortion (STA) (18.8 vs. 0.6%, p = 0.002) compared with the pre-AOSD group. Moreover, pregnancy after being diagnosed with AOSD was a significant high risk factor of STA (adjusted OR = 4.577, 95% CI: 4.166–845.119; p = 0.003). Disease flare upon conception was observed in one of 16 post-AOSD pregnancies (p = 1.000). There were 11 patients with new-onset AOSD during gestation or postpartum, among which five (45.4%) evolved into the polycyclic course.Conclusions: AOSD patients might suffer from a higher risk of STA, however, pregnancy might not be related with the exacerbation of diagnosed AOSD. New-onset AOSD during gestation or postpartum tend to evolve into the polycyclic course.
Fast-Track Ultrasound Clinic for the Diagnosis of Giant Cell Arteritis Changes the Prognosis of the Disease but Not the Risk of Future Relapse
Authors: Monti Sara , Bartoletti Alice , Bellis Elisa , Delvino Paolo , Montecucco Carlomaurizio 
Published: December 2020

Background: Color Duplex sonography (CDS) of temporal arteries and large vessels (LV) is a recently validated diagnostic methodology for Giant Cell Arteritis (GCA). CDS combined with a fast-track approach (FTA) has improved the early diagnosis of the disease.Objectives: To assess FTA effects on the prevention of permanent visual loss (PVL), relapse and late complications of GCA compared to conventional practice. To assess the impact of COVID-19 pandemic on outcomes of GCA patients assessed with FTA.Methods: GCA patients diagnosed up to June 2020 at the Rheumatology Department, University of Pavia, were included. FTA was implemented since October 2016. FTA consists in the referral within 1 working day of a suspected GCA case to an expert rheumatologist who performs clinical evaluation and CDS.Results: One hundred sixty patients were recruited [female 120 (75%), mean age 72.4 ± 8.2 years]. Sixty-three (39.4%) evaluated with FTA, 97 (60.6%) with conventional approach. FTA patients were older (75.1 ± 7.6 vs. 70.6 ± 8.2 years old; p &lt; 0.001). Median follow-up duration was shorter in the FTA group compared to the conventional one (0.9 vs. 5.0 years; p &lt; 0.001). There was no difference between the two cohorts regarding major vessel district involvement (LV-GCA 17.5% vs. 22.7%; p = 0.4). PVL occurred in 8 (12.7%) FTA patients and 26 (26.8%) conventional ones (p = 0.03). The relative risk of blindness in the conventional group was 2.11 (95% C.I. 1.02–4.36; P = 0.04) as compared to FTA. Median symptom latency of patients experiencing PVL was higher in the conventional group (23 days IQR 12–96 vs. 7 days IQR 4–10, p = 0.02). During COVID-19 there was a significant increase in the occurrence of PVL (40%) including bilateral blindness despite a regularly operating FTA clinic. Cumulative incidence of relapses and time to first relapse did not change after FTA introduction (P = 0.2). No difference in late complications (stenosis/aneurysms) was detected.Conclusions: FTA including CDS evaluation contributed to a substantial reduction of PVL in GCA by shortening the time to diagnosis and treatment initiation. Relapse rate did not change upon FTA introduction, highlighting the need for better disease activity monitoring and treatment strategies optimization based on risk stratification that would predict the occurrence of relapse during glucocorticoid de-escalation.
Prognostic Value of Local Treatment in Prostate Cancer Patients With Different Metastatic Sites: A Population Based Retrospective Study
Authors: Jin Shengming , Wei Jiaming , Wang Junjie , Wang Beihe , Wu Junlong , Gan Hualei , Dai Bo , Qin Xiaojian , Lin Guowen , Wei Yu , Yang Chen , Shen Yijun , Zhu Yiping , Zhu Yao , Ye Dingwei 
Published: December 2020

PurposeOur study aims to examine the impact of definitive local therapy in prostate cancer patients with different metastatic sites.MethodsTotally, 5,849 patients diagnosed with metastatic prostate carcinoma from 2010 to 2014 were selected from Surveillance, Epidemiology, and End Results (SEER). Log-rank analyses, multivariable regression analysis, and Kaplan–Meier methods were used to assess prognostic impact of local treatment in patients with different metastatic sites. Survival curves and forest plots were also plotted to describe the prognostic value of definitive local therapy.ResultsIn our study, 159 patients received radical prostatectomy, and 62 received brachytherapy, while 5,628 did not receive local definitive local therapy. Survival analysis revealed that patients who received definitive local therapy had a better 5-year overall survival (OS) (P = 0.011) and cancer-specific survival (CSS) (P = 0.012). Multivariate regression analyses demonstrated that type of treatment was an independent prognostic indicator for OS (P = 0.011) and CSS (P = 0.012), along with age at diagnosis, chemotherapy, PSA level, and Gleason score. According to subgroup analysis, patients with bone metastasis or distant lymph node (LN) metastasis were significantly more likely to benefit from definitive local therapy. In addition, forest plots demonstrated that RP group had significant favorable OS and CSS in subgroups of younger age at diagnosis, T2–3 stage, N0–1 stage, Gleason score =7 or ≥8, bone metastasis, and distant LN metastasis.ConclusionsOur study suggested that local therapy improved survival in prostate cancer patients with bone or distant LN metastasis. Furthermore, patients who were at T2–3 stage or Gleason score ≥7 also significantly benefit from definitive local therapy.
A Hematological-Related Prognostic Scoring System for Patients With Newly Diagnosed Glioblastoma
Authors: Zhao Chao , Li Long-Qing , Yang Feng-Dong , Wei Ruo-Lun , Wang Min-Kai , Song Di-Xiang , Guo Xiao-Yue , Du Wei , Wei Xin-Ting 
Published: December 2020

BackgroundGlioblastoma is the most common primary malignant brain tumor. Recent studies have shown that hematological biomarkers have become a powerful tool for predicting the prognosis of patients with cancer. However, most studies have only investigated the prognostic value of unilateral hematological markers. Therefore, we aimed to establish a comprehensive prognostic scoring system containing hematological markers to improve the prognostic prediction in patients with glioblastoma.Patients and MethodsA total of 326 patients with glioblastoma were randomly divided into a training set and external validation set to develop and validate a hematological-related prognostic scoring system (HRPSS). The least absolute shrinkage and selection operator Cox proportional hazards regression analysis was used to determine the optimal covariates that constructed the scoring system. Furthermore, a quantitative survival-predicting nomogram was constructed based on the hematological risk score (HRS) derived from the HRPSS. The results of the nomogram were validated using bootstrap resampling and the external validation set. Finally, we further explored the relationship between the HRS and clinical prognostic factors.ResultsThe optimal cutoff value for the HRS was 0.839. The patients were successfully classified into different prognostic groups based on their HRSs (P &lt; 0.001). The areas under the curve (AUCs) of the HRS were 0.67, 0.73, and 0.78 at 0.5, 1, and 2 years, respectively. Additionally, the 0.5-, 1-y, and 2-y AUCs of the HRS were 0.51, 0.70, and 0.79, respectively, which validated the robust prognostic performance of the HRS in the external validation set. Based on both univariate and multivariate analyses, the HRS possessed a strong ability to predict overall survival in both the training set and validation set. The nomogram based on the HRS displayed good discrimination with a C-index of 0.81 and good calibration. In the validation cohort, a high C-index value of 0.82 could still be achieved. In all the data, the HRS showed specific correlations with age, first presenting symptoms, isocitrate dehydrogenase mutation status and tumor location, and successfully stratified them into different risk subgroups.ConclusionsThe HRPSS is a powerful tool for accurate prognostic prediction in patients with newly diagnosed glioblastoma.
Non-Invasive Estimation of Glioma IDH1 Mutation and VEGF Expression by Histogram Analysis of Dynamic Contrast-Enhanced MRI
Authors: Hu Yue , Chen Yue , Wang Jie , Kang Jin Juan , Shen Dan Dan , Jia Zhong Zheng 
Published: December 2020

ObjectivesTo investigate whether glioma isocitrate dehydrogenase (IDH) 1 mutation and vascular endothelial growth factor (VEGF) expression can be estimated by histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).MethodsChinese Glioma Genome Atlas (CGGA) database was wined for differential expression of VEGF in gliomas with different IDH genotypes. The VEGF expression and IDH1 genotypes of 56 glioma samples in our hospital were assessed by immunohistochemistry. Preoperative DCE-MRI data of glioma samples were reviewed. Regions of interest (ROIs) covering tumor parenchyma were delineated. Histogram parameters of volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (Ve) derived from DCE-MRI were obtained. Histogram parameters of Ktrans, Ve and VEGF expression of IDH1 mutant type (IDH1mut) gliomas were compared with the IDH1 wildtype (IDH1wt) gliomas. Receiver operating characteristic (ROC) curve analysis was performed to differentiate IDH1mut from IDH1wt gliomas. The correlation coefficients were determined between histogram parameters of Ktrans, Ve and VEGF expression in gliomas.ResultsIn CGGA database, VEGF expression in IDHmut gliomas was lower as compared to wildtype counterpart. The immunohistochemistry of glioma samples in our hospital also confirmed the results. Comparisons demonstrated statistically significant differences in histogram parameters of Ktransand Ve [mean, standard deviation (SD), 50th, 75th, 90th. and 95th percentile] between IDH1mutand IDH1wtgliomas (P &lt; 0.05, respectively). ROC curve analysis revealed that 50th percentile of Ktrans (0.019 min−1) and Ve (0.039) provided the perfect combination of sensitivity and specificity in differentiating gliomas with IDH1mutfrom IDH1wt. Irrespective of IDH1 mutation, histogram parameters of Ktransand Ve were correlated with VEGF expression in gliomas (P &lt; 0.05, respectively).ConclusionsVEGF expression is significantly lower in IDH1mut gliomas as compared to the wildtype counterpart, and it is non-invasively predictable with histogram analysis of DCE-MRI.
A Novel Model Incorporating Tumor Stiffness, Blood Flow Characteristics, and Ki-67 Expression to Predict Responses After Neoadjuvant Chemotherapy in Breast Cancer
Authors: Zhang Jing , Gao Song , Zheng Qiaojin , Kang Ye , Li Jianyi , Zhang Shuo , Shang Cong , Tan Xueying , Ren Weidong , Ma Yan 
Published: December 2020

ObjectiveTo investigate the ability of tumor stiffness, tumor blood flow, and Ki-67 expression alone or in combination in predicting the pathological response to neoadjuvant chemotherapy (NACT) in breast cancer.Patients and MethodsThis prospective cohort study included 145 breast cancer patients treated with NACT. Tumor stiffness (maximum stiffness (Emax), mean stiffness (Emean)), blood score (BS), and their relative changes, were evaluated before (t0), during (t1–t5), and at the end of NACT (t6) by shear-wave elastography and optical imaging. Ki-67 expression was quantitatively evaluated by immunohistochemistry using core biopsy specimens obtained before NACT. Pathological responses were evaluated by residual cancer burden. The ability of tumor stiffness, BS, Ki-67, and predRCB—which combined ΔEmean (t2) (the relative changes in Emean after the second NACT cycle), BS2 (BS after the second NACT cycle), and Ki-67—in predicting tumor responses was compared using receiver operating characteristic curves and the Z-test.ResultsTumor stiffness and BS decreased during NACT. ΔEmean (t2), BS2, and Ki-67 had better predictive performance than other indexes in identifying a favorable response (AUC = 0.82, 0.81, and 0.80) and resistance responses (AUC = 0.85, 0.79, and 0.84), with no significant differences between the three (p &gt; 0.05). PredRCB had better predictive performance than any parameter alone for a favorable response (AUC = 0.90) and resistance (AUC = 0.93).ConclusionTumor stiffness, BS, and Ki-67 expression showed good and similar abilities for predicting the pathological response to NACT, and predRCB was a significantly better predictor than each index alone. These results may help design therapeutic strategies for breast cancer patients undergoing NACT.
RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer
Authors: Wang Danping , Wang Yifan , Wu Xuebiao , Kong Xiangxing , Li Jun , Dong Chenfang 
Published: December 2020

BackgroundE-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often repressed due to Snail-mediated epigenetic modification; however, the exact mechanism remains unclear. There is an urgent need to understand the determinants of tumor aggressiveness and identify potential therapeutic targets in breast cancer.Experimental designWe studied the association of RNF20 with Snail and G9a by co-immunoprecipitation. We employed quantitative real-time PCR, ChIP, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the repression of E-cadherin in human breast cancer. We used a proteogenomic dataset that contains 105 breast tumor samples to determine the clinical relevance of RNF20 by Kaplan-Meier analyses.ResultsIn this study, we identified that Snail interacted with RNF20, an E3 ubiquitin-protein ligase responsible for monoubiquitination of H2BK120, and G9a, a methyltransferase for H3K9me2. RNF20 expression led to the inhibition of E-cadherin expression in the human breast cancer cells. Mechanically, we showed that RNF20 and H3K9m2 were enriched on the promoter of E-cadherin and knockdown of Snail reduced the enrichment of RNF20, showing a Snail-dependent manner. RNF20 expression enhanced breast cancer cell migration, invasion, tumorsphere and colony formation. Clinically, patients with high RNF20 expression had shorter overall survival.ConclusionRNF20 expression contributes to EMT induction and breast cancer progression through Snail-mediated epigenetic suppression of E-cadherin expression, suggesting the importance of RNF20 in breast cancer.
Linear Growth in Pediatric Kidney Transplant Population
Authors: Lopez-Gonzalez Mercedes , Munoz Marina , Perez-Beltran Victor , Cruz Alejandro , Gander Romy , Ariceta Gema 
Published: December 2020

Introduction: Growth retardation is one of the main complications of chronic kidney disease (CKD) in children and induces a negative impact on quality of life.Materials and Methods: Retrospective analysis of all consecutive patients younger than 18 years old who received a first KT in our center between 2008 and 2018.Results: 95 first KT recipients, median age at KT of 7.83 years. At the time of KT, 65.52% of males and 54.05% females showed normal height. After transplantation, linear growth improved from −1.53 at transplant to −1.37 SDS height at the last visit. We detected a different linear growth pattern according to patient age at KT. Children younger than 3 years old exhibited the most significant growth retardation at baseline and the greatest linear growth over time (−2.29 vs. −1.82 SDS height), whereas catch-up was not observed in older patients. Multivariate analysis showed that use of corticosteroids was negatively related to SDS height at 1 year after transplantation and final SDS height only was positively associated with SDS height at KT. 44.2 and 22.1% patients received rhGH treatment before and after KT. 71.88% patients reached adulthood with normal final height.Conclusions: In our study, pediatric KT recipients exhibited a normal height in more than half of cases at KT and in more than two thirds at the final adult height. Only children younger than 6 years old presented a relevant growth catch-up after KT. Treatment with rhGH was used before and after KT with significant improvement in height.
One-Year Quality of Life Trends in Early-Stage Lung Cancer Patients After Lobectomy
Authors: Marzorati Chiara , Mazzocco Ketti , Monzani Dario , Pavan Francesca , Casiraghi Monica , Spaggiari Lorenzo , Monturano Massimo , Pravettoni Gabriella 
Published: December 2020

Objective: Quality of Life (QoL) is an important predictor of patient's recovery and survival in lung cancer patients. The aim of the present study is to identify 1-year trends of lung cancer patients' QoL after robot-assisted or traditional lobectomy and investigate whether clinical (e.g., pre-surgery QoL, type of surgery, and perioperative complications) and sociodemographic variables (e.g., age) may predict these trends.Methods: An Italian sample of 176 lung cancer patients undergoing lobectomy completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire—Core 30 (QLQ-C30) at the pre-hospitalization (t0), 30 days (t1), 4 months (t2), 8 months (t3), and 12 months (t4) after surgery. Sociodemographic and clinical characteristics (age, gender, perioperative complications, and type of surgery) were also collected. The individual change over time of the 15 dimensions of the EORTC QLQ-C30 and the effects of pre-surgery scores of QoL dimensions, type of surgery, perioperative complications, and age on patients' QoL after surgery were studied with the individual growth curve (IGC) models.Results: Patients had a good recovery after lobectomy: functioning subscales improved over time, while most of the symptoms became less severe over the care process. Perioperative complications, type of surgery, pre-surgery status, and age significantly affected these trends, thus becoming predictors of patients' QoL.Conclusion: This study highlights different 1-year trends of lung cancer patients' QoL. The measurement of pre- and post-surgery QoL and its clinical and sociodemographic covariables would be necessary to better investigate patients' care process and implement personalized medicine in lung cancer hospital divisions.
COVID-19 Outbreak Can Change the Job Burnout in Health Care Professionals
Authors: Liu Xinghuang , Chen Jie , Wang Dongke , Li Xin , Wang Erchuan , Jin Yu , Ma Yanling , Yu Cheng , Luo Chang , Zhang Lei , Liu Chuang , Zhou Yangshiyu , Yang Ling , Song Jun , Bai Tao , Hou Xiaohua 
Published: December 2020

Background: The outbreak of COVID-19 in China was a sudden bio-disaster, which may bring a negative impact on the job burnout of health care professionals (HCPs).Objective: We aim to find out the association factors, especially those closely related to this outbreak, of job burnout in Chinese HCPs.Method: The cross-sectional survey about HCPs' job burnout based on a network platform was conducted in high and low infection regions during the COVID-19 outbreak in China. The demographic characteristics, medical-work-related factors, risk of getting infected due to occupational exposure, and family factors were collected by the self-reported questionnaire. The Chinese version of the Maslach Burnout Inventory (CMBI) and the Trait Coping Style Questionnaire (TCSQ) were employed in this study to evaluate the job burnout and coping style, respectively. Furthermore, statistical analysis was done to find out the associated factors of job burnout.Results: We collected 880 complete questionnaires from doctors and nurses from February 9, 2020 to February 11, 2020. In this study, the positive rates of three dimensions of burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) and overall burnout were 9.09, 50.57, 56.59, and 73.98%, respectively. After the statistical analysis, we found that several factors can independently affect the dimensions. Working in the high infection region and negative coping styles can affect all three dimensions at once. More night shift quantity and having symptoms could increase emotional exhaustion and depersonalization, while higher work intensity and senior title could increase emotional exhaustion and reduce personal accomplishment, respectively.Conclusion: The rate of moderate and severe burnout had increased due to the outbreak. More attention should be paid to burnout in HCPs, especially those with negative coping. There were some potential ways to reduce burnout, such as reducing their workload and providing better protection from the virus.