bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Arginine Methyltransferase 5 Promotes Esophageal Squamous Cell Carcinoma Proliferation and Metastasis via LKB1/AMPK/mTOR Signaling Pathway
Authors: Chen Yu-ru , Li Hua-ni , Zhang Lian-jun , Zhang Chong , He Jin-guang 
Published: May 2021

Background: Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer in the world. Protein arginine methyltransferase 5 (PRMT5), an enzyme that catalyzes symmetric and asymmetric methylation on arginine residues of histone and non-histone proteins, is overexpressed in many cancers. However, whether or not PRMT5 participates in the regulation of ESCC remains largely unclear.Methods: PRMT5 mRNA and protein expression in ESCC tissues and cell lines were examined by RT-PCR, western blotting, and immunohistochemistry assays. Cell proliferation was examined by RT-PCR, western blotting, immunohistochemistry assays, MTT, and EdU assays. Cell apoptosis and cell cycle were examined by RT-PCR, western blotting, immunohistochemistry assays, and flow cytometry. Cell migration and invasion were examined by RT-PCR, western blotting, immunohistochemistry assays, and wound-healing and transwell assays. Tumor volume, tumors, and mouse weight were measured in different groups. Lung tissues with metastatic foci, the number of nodules, and lung/total weight were measured in different groups.Results: In the present study, the PRMT5 expression level was dramatically upregulated in ESCC clinical tissues as well as ESCC cell lines (ECA109 and KYSE150). Furthermore, knocking down PRMT5 obviously suppressed cell migration, invasion, proliferation, and cell arrest in G1 phase and promoted cell apoptosis in ESCC cells. Meanwhile, downregulating PRMT5 also increased the expression levels of Bax, caspase-3, and caspase-9, while expression levels of Bax-2, MMP-2, MMP-9, and p21 were decreased, which are members of the cyclin-dependent kinase family. Furthermore, knocking down PRMT5 could increase the expression of LKB1 and the phosphorylation (p)-AMPK expression and decrease the p-mTOR level. Additionally, overexpression of LKB1 could reveal anti-tumor effects in ESCC cell lines by inhibiting ESCC cell, migration, invasion, and proliferation and accelerating cell apoptosis. Besides, upregulating LKB1 expression could increase the levels of Bax, caspase-3, and caspase-9 and weaken the levels of Bax-2, MMP-2, and MMP-9. Moreover, knocking down PRMT5 could weaken the tumor growth and lung metastasis in vivo with upregulating the LKB1 expression and the p-AMPK level and downregulating the p-mTOR expression.Conclusion: PRMT5 may act as a tumor-inducing agent in ESCC by modulating LKB1/AMPK/mTOR pathway signaling.
Association of Clinical and Immunological Characteristics With Disease Severity and Outcomes in 211 Patients With COVID-19 in Wuhan, China
Authors: Wang Man , Fan Yongzhen , Chai Yuqiong , Cheng Wenlin , Wang Kun , Cao Jianlei , Hu Xiaorong 
Published: May 2021

BackgroundCoronavirus disease 2019 (COVID-19) has posed a great threat to global public health. There remains an urgent need to address the clinical significance of laboratory finding changes in predicting disease progression in COVID-19 patients. We aimed to analyze the clinical and immunological features of severe and critically severe patients with COVID-19 in comparison with non-severe patients and identify risk factors for disease severity and clinical outcome in COVID-19 patients.MethodsThe consecutive records of 211 patients with COVID-19 who were admitted to Zhongnan Hospital of Wuhan University from December 2019 to February 2020 were retrospectively reviewed.ResultsOf the 211 patients with COVID-19 recruited, 111 patients were classified as non-severe, 59 as severe, and 41 as critically severe cases. The median age was obviously higher in severe and critically severe cases than in non-severe cases. Severe and critically severe patients showed more underlying comorbidities than non-severe patients. Fever was the predominant presenting symptom in COVID-19 patients, and the duration of fever was longer in critically severe patients. Moreover, patients with increased levels of serum aminotransferases and creatinine (CREA) were at a higher risk for severe and critical COVID-19 presentations. The serum levels of IL-6 in severe and critically severe patients were remarkably higher than in non-severe patients. Lymphopenia was more pronounced in severe and critically severe patients compared with non-severe patients. Lymphocyte subset analysis indicated that severe and critically severe patients had significantly decreased count of lymphocyte subpopulations, such as CD4+ T cells, CD8+ T cells and B cells. A multivariate logistic analysis indicated that older age, male sex, the length of hospital stay, body temperature before admission, comorbidities, higher white blood cell (WBC) counts, lower lymphocyte counts, and increased levels of IL-6 were significantly associated with predicting the progression to severe stage of COVID-19.ConclusionOlder age, male sex, underlying illness, sustained fever status, abnormal liver and renal functions, excessive expression of IL-6, lymphopenia, and selective loss of peripheral lymphocyte subsets were related to disease deterioration and clinical outcome in COVID-19 patients. This study would provide clinicians with valuable information for risk evaluation and effective interventions for COVID-19.
Early vs. Late Onset Cardiac Injury and Mortality in Hospitalized COVID-19 Patients in Wuhan
Authors: Sun Wei , Zhang Yanting , Wu Chun , Wang Shuyuan , Xie Yuji , Zhang Danqing , Yuan Hongliang , Zhang Yongxing , Cui Li , Li Meng , Zhang Yiwei , Li Yuman , Wang Jing , Yang Yali , Lv Qing , Zhang Li , Haines Philip , Wu Wen-Chih , Xie Mingxing 
Published: May 2021

Background: Increasing evidence points to cardiac injury (CI) as a common coronavirus disease 2019 (COVID-19) related complication. The characteristics of early CI (occurred within 72 h of admission) and late CI (occurred after 72 h of admission) and its association with mortality in COVID-19 patients is unknown.Methods: This retrospective study analyzed patients confirmed with COVID-19 in Union Hospital (Wuhan, China) from Jan 29th to Mar 15th, 2020. Clinical outcomes (discharge, or death) were monitored to April 15, 2020, the latest date of follow-up. Demographic, clinical, laboratory, as well as treatment and prognosis were collected and analyzed in patients with early, late CI and without CI.Results: A total of 196 COVID-19 patients were included for analysis. The median age was 65 years [interquartile range (IQR) 56–73 years], and 112 (57.1%) were male. Of the 196 COVID-19 patients, 49 (25.0%) patients had early and 20 (10.2%) patients had late CI, 56.6% developed Acute-Respiratory-Distress-Syndrome (ARDS) and 43 (21.9%) patients died. Patients with any CI were more likely to have developed ARDS (87.0 vs. 40.2%) and had a higher in-hospital mortality than those without (52.2 vs. 5.5%, P &lt; 0.001). Among CI subtypes, a significantly higher risk of in-hospital death was found in patients with early CI with recurrence [19/49 patients, adjusted odds ratio (OR) = 7.184, 95% CI 1.472–35.071] and patients with late CI (adjusted OR = 5.019, 95% CI 1.125–22.388) compared to patients with early CI but no recurrence.Conclusions: CI can occur early on or late after, the initial 72 h of admission and is associated with ARDS and an increased risk of in-hospital mortality. Both late CI and recurrent CI after the initial episode were associated with worse outcomes than patients with early CI alone. This study highlights the importance of early examination and periodical monitoring of cardiac biomarkers, especially for patients with early CI or at risk of clinical deterioration.
Sulfonylureas Use Is Not Associated With Increased Infarct Size in Patients With Type 2 Diabetes and ST-Segment Elevation Myocardial Infarction
Authors: Shi Fang-Hong , Li Hao , Kong Ling-Cong , Shen Long , Jiang Yi-Hong , Gu Zhi-Chun , Ge Heng 
Published: May 2021

Aims: This retrospective study assessed the association between sulfonylureas use and infarct size in patients with type 2 diabetes (T2DM) and ST-segment elevation myocardial infarction (STEMI) by myocardial enzymology indexes and cardiac magnetic resonance (CMR) imaging.Methods: Patients presenting STEMI between July 2013 and August 2019 were included in a retrospective database at our institution. Antidiabetic agents used before STEMI were recorded. Patients with maximum recorded troponin I (max cTNI) and creatine phosphokinase isoenzyme (CK-MB) within the first 72 h of chest pain onset were selected. Infarct size was quantified by CMR imaging, and cardiovascular outcomes were also obtained at 30 days and 6 months follow-up. Multivariable regression models explored potential risk factors associated with infarct size and clinical outcomes.Results: A total of 254 T2DM and STEMI patients were included, with 101 sulfonylurea users and 153 non-users. Sulfonylureas users were not associated with higher max cTnI and max CK-MB compared to non-users. Among 65 CMR patients, no significant differences in infarct size were detected between sulfonylureas users and non-users. Whereas, the incidence of microvascular obstruction (MVO) was higher in patients receiving sulfonylureas than those taking non-sulfonylureas (88.0 vs. 62.5%, p = 0.023). No higher cardiovascular events of sulfonylureas users vs. non-users were observed, except for heart failure events (24.0 vs. 2.5% at 30 days, p = 0.011; 28.0 vs. 2.5% at 6 months, p = 0.004). Multivariable regression analyses verified that sulfonylureas users increased the risks of MVO.Conclusions: Sulfonylureas use did not associate with larger infarct size in patients with T2DM and STEMI. A potentially higher incidence of MVO in sulfonylurea users was found. Notably, since most patients presented after a relatively long period of ischemia and glibenclamide was not used by the included patients in this observational study, the results of this study should not be extrapolated to clinical settings with short periods of ischemia or to patients using glibenclamide.
Development and Validation of a Risk Score for Predicting Post-acute Myocardial Infarction Infection in Patients Undergoing Percutaneous Coronary Intervention: Study Protocol for an Observational Study
Authors: Liu Yuanhui , Wang Litao , Lin Yaowang , Chen Wei , Xu Zhengrong , Chen Pengyuan , Dai Yining , Zeng Lihuan , Fan Hualin , Xue Ling , Chen Jiyan , Tan Ning , Duan Chongyang , He Pengcheng 
Published: May 2021

Background: Post-acute myocardial infarction (post-AMI) infection is an infrequent but important and serious complication in patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). Predicting its occurrence is essential for future prevention. However, little is known about the prediction of post-AMI infection in such patients to date. This study aims to develop and validate a new risk score based on risk factors for early prediction of infection in STEMI patients undergoing PCI.Methods: This prospective, multi-center and observational study assesses the predictive value of risk score for post-AMI infection among a cohort of patients hospitalized due to STEMI. The STEMI patients undergoing PCI enrolled between January 1st 2010 and May 31st 2016 were served as a development cohort while those enrolled from June 1st 2016 to May 31st 2018 were served as validation cohort. The primary endpoint was post-AMI infection during hospitalization, defined as infection requiring antibiotics (reflecting the clinical influence of infection compatible with the necessity for additional treatment), and all-cause death and major adverse cardiovascular events (MACE) including all-cause death, recurrent myocardial infarction, target vessel revascularization, and stroke were considered as secondary endpoints. The risk score model based on risk factors was established using stepwise logistic regression, and will be validated in other centers and external patients with non-ST-elevation acute coronary syndrome (NSTE-ACS).Results: This study will provide evidence on prognostic property, reliability of scoring, comparative performance, and suitability of the novel model for screening purpose in order to be recommended for clinical practice.Discussion: Our study is designed to develop and validate a clinical risk score for predicting infection in participants with STEMI who have undergone PCI. This simple tool may therefore improve evaluation of post-AMI infection and enhance future researches into the best practices to prevent or reduce infection in such patients.Clinical Trial Registration:www.chictr.org.cn, identifier: ChiCTR1900028278.
Multi-Parametric Field Experiment Links Explosive Activity and Persistent Degassing at Stromboli
Authors: Thivet Simon , Harris Andrew J. L. , Gurioli Lucia , Bani Philipson , Barnie Talfan , Bombrun Maxime , Marchetti Emanuele 
Published: May 2021

Visually unattainable magmatic processes in volcanic conduits, such as degassing, are closely linked to eruptive styles at the surface, but their roles are not completely identified and understood. To gain insights, a multi-parametric experiment at Stromboli volcano (Aeolian Islands, Italy) was installed in July 2016 focusing on the normal explosive activity and persistent degassing. During this experiment, gas-dominated (type 0) and particle-loaded (type 1) explosions, already defined by other studies, were clearly identified. A FLIR thermal camera, an Ultra-Violet SO₂ camera and a scanning Differential Optical Absorption Spectroscopy were deployed to record pyroclast and SO2 masses emitted during individual explosions, as well as persistent SO₂ fluxes, respectively. An ASHER instrument was also deployed in order to collect ash fallouts and to measure the grain size distribution of the samples. SO2 measurements confirm that persistent degassing was far greater than that emitted during the explosions. Further, we found that the data could be characterized by two periods. In the first period (25–27 July), activity was mainly characterized by type 0 explosions, characterized by high velocity jets. Pyroclast mass fluxes were relatively low (280 kg/event on average), while persistent SO2 fluxes were high (274 t/d on average). In the second period (29–30 July), activity was mainly characterized by type 1 explosions, characterized by low velocity jets. Pyroclast mass fluxes were almost ten times higher (2,400 kg/event on average), while persistent gas fluxes were significantly lower (82 t/d on average). Ash characterization also indicates that type 0 explosions fragments were characterized by a larger proportion of non-juvenile material compared to type 1 explosions fragments. This week-long field experiment suggests that, at least within short time periods, Stromboli’s type 1 explosions can be associated with low levels of degassing and the mass of particles accompanying such explosive events depends on the volume of a degassed magma cap sitting at the head of the magma column. This could make the classic particle-loaded explosions of Stromboli an aside from the true eruptive state of the volcano. Instead, gas-dominated explosions can be associated with high levels of degassing and are indicative of a highly charged (with gas) system. We thus suggest that relatively deep magmatic processes, such as persistent degassing and slug formation can rapidly influence the superficial behavior of the eruptive conduit, modulating the presence or absence of degassed magma at the explosion/fragmentation level.
Hints on the Late Miocene Evolution of the Tonale-Adamello-Brenta Region (Alps, Italy) Based on Allochtonous Sediments From Raponzolo Cave
Authors: Sauro Francesco , Fellin Maria Giuditta , Columbu Andrea , Häuselmann Philipp , Borsato Andrea , Carbone Cristina , De Waele Jo 
Published: May 2021

Raponzolo is a paleo-phreatic cave explored in 2011 in the Brenta Dolomites (Trentino, Italy), at the remarkable altitude of 2,560 m a.s.l. Differently to all other caves of the area, it hosts well-cemented fine to medium sands of granitic-metamorphic composition. The composition suggests a sediment source from the Adamello and Tonale Unit, separated from the Brenta by one of the most important tectonic lineaments of the Alps (Giudicarie Line). The fine-sand sediment was sampled to determine burial time and thus a minimum age of the cave. Cosmogenic isotopes (26Al and 10Be) in quartz grains allowed to estimate a minimum burial age of 5.25 Ma based on the mean sediment transport time at the surface and infer original altitude of the catchment area. Detrital apatite fission-track (AFT) and U-Pb dating on zircons provide information on the source, both from a regional and altitude (exhumation) perspective. Two populations of detrital AFT ages center at 17 (−2.3 + 2.6) Ma and 23 (−3.3 + 3.9) Ma, whereas the main detrital zircon U-Pb age populations are younger than 40 Ma. These correspond to intrusive and metamorphic sources nowadays outcropping exclusively above 2,200–2,300 m a.s.l. in Northern Adamello and Tonale. The results point to a late Miocene erosion and infilling of the cave by allochtonous sediments, with important implications on the timing of cave speleogenesis, as well as the paleogeographical connection, tectonic evolution and uplift of different structural units of the Alps. The roundness and the well sorted size of the quartz grains suggest a fluvial or aeolian origin, possibly recycled by glacial activity related to cold events reported in high latitude areas of the world at 5.75 and 5.51 Ma. These glacial phases have never been documented before in the Alps. This information confirms that the valleys dividing these geological units were not yet deeply entrenched during the onset of the Messinian Salinity Crisis (5.6–5.5 Ma), allowing an efficient transport of sediments across major tectonic lineaments of the Alps. This study shows the potential of cave sediments to provide information not only on the age of speleogenesis but also on the paleogeography of a wide area of the Alps during the late Miocene.
Prognostic Value of Pre-Treatment CT Radiomics and Clinical Factors for the Overall Survival of Advanced (IIIB–IV) Lung Adenocarcinoma Patients
Authors: Hong Duo , Zhang Lina , Xu Ke , Wan Xiaoting , Guo Yan 
Published: May 2021

PurposeThe purpose of this study was to investigate the prognostic value of pre-treatment CT radiomics and clinical factors for the overall survival (OS) of advanced (IIIB–IV) lung adenocarcinoma patients.MethodsThis study involved 165 patients with advanced lung adenocarcinoma. The Lasso–Cox regression model was used for feature selection and radiomics signature building. Then a clinical model was built based on clinical factors; a combined model in the form of nomogram was constructed with both clinical factors and the radiomics signature. Harrell’s concordance index (C-Index) and Receiver operating characteristic (ROC) curves at cut-off time points of 1-, 2-, and 3- year were used to estimate and compare the predictive ability of all three models. Finally, the discriminatory ability and calibration of the nomogram were analyzed.ResultsThirteen significant features were selected to build the radiomics signature whose C-indexes were 0.746 (95% CI, 0.699 to 0.792) in the training cohort and 0.677 (95% CI, 0.597 to 0.766) in the validation cohort. The C-indexes of combined model achieved 0.799 (95% CI, 0.757 to 0.84) in the training cohort and 0.733 (95% CI, 0.656 to 0.81) in the validation cohort, which outperformed the clinical model and radiomics signature. Moreover, the areas under the curve (AUCs) of the radiomic signature for 2-year prediction was superior to that of the clinical model. The combined model had the best AUCs for 2- and 3-year predictions.ConclusionsRadiomic signatures and clinical factors have prognostic value for OS in advanced (IIIB–IV) lung adenocarcinoma patients. The optimal model should be selected according to different cut-off time points in clinical application.
Identifying Periampullary Regions in MRI Images Using Deep Learning
Authors: Tang Yong , Zheng Yingjun , Chen Xinpei , Wang Weijia , Guo Qingxi , Shu Jian , Wu Jiali , Su Song 
Published: May 2021

BackgroundDevelopment and validation of a deep learning method to automatically segment the peri-ampullary (PA) region in magnetic resonance imaging (MRI) images.MethodsA group of patients with or without periampullary carcinoma (PAC) was included. The PA regions were manually annotated in MRI images by experts. Patients were randomly divided into one training set, one validation set, and one test set. Deep learning methods were developed to automatically segment the PA region in MRI images. The segmentation performance of the methods was compared in the validation set. The model with the highest intersection over union (IoU) was evaluated in the test set.ResultsThe deep learning algorithm achieved optimal accuracies in the segmentation of the PA regions in both T1 and T2 MRI images. The value of the IoU was 0.68, 0.68, and 0.64 for T1, T2, and combination of T1 and T2 images, respectively.ConclusionsDeep learning algorithm is promising with accuracies of concordance with manual human assessment in segmentation of the PA region in MRI images. This automated non-invasive method helps clinicians to identify and locate the PA region using preoperative MRI scanning.
The Application of the Lymphoma International Prognostic Index to Predict Venous Thromboembolic Events in Diffuse Large B-Cell Lymphoma Patients
Authors: Abdel-Razeq Hikmat , Ma’koseh Mohammad , Abdel-Razeq Rashid , Amarin Rula , Abufara Alaa , Mansour Razan , Manasrah Mohammad , Al-Rwashdeh Mohammad , Bater Rayan 
Published: May 2021

BackgroundVenous thromboembolic events (VTE) are commonly encountered in patients with lymphoma. Several risk assessments models (RAM) had attempted to identify higher risk patients with varying success. The International Prognostic Index (IPI) is a clinicopathological tool developed to help predict both response to treatment and prognosis of patients with diffuse large B-cell lymphoma (DLBCL).ObjectiveIn this study, we utilize the IPI index to identify group of patients with DLBCL at higher risk for VTE.Patients/MethodsPatients with pathologically-confirmed diagnosis of DLBCL and with image-confirmed VTE, treated and followed at our institution were included. Rates of VTE was calculated for each risk category.ResultsA total of 373 patients, median age 49 (range: 18-90) years were included. VTE were reported in 56 (15.0%) patients; 51 (91.1%) had active disease while 29 (51.8%) were ambulatory at time of VTE diagnosis. VTE rates were particularly high among patients with poor performance status (26.2%, P=0.028) and high LDH (19.0%, P=0.023). Applying the age-adjusted IPI separated patients into two risk categories; VTE were diagnosed in 9.7% in patients with “low and low-intermediate” scores compared to 19.8% in patients with “high and high-intermediate” scores, P=0.020.ConclusionsThe original IPI and its modified versions, routinely used at diagnosis as a prognostic and predictive tool for patients with DLBCL, can also be utilized to define high risk patients for VTE; the risk of whom might be high enough to recommend thromboprophylaxis even in the ambulatory settings. More work is needed to refine and improve currently available RAMs.