bluuebunny/crossref_metadata_2025_split huggingface dataset:
The integration of single-cell sequencing, TCGA, and GEO data analysis revealed that PRRT3-AS1 is a biomarker and therapeutic target of SKCM
Authors: Zhang Wancong , Xie Xuqi , Huang Zijian , Zhong Xiaoping , Liu Yang , Cheong Kit-Leong , Zhou Jianda , Tang Shijie 
Published: September 2022

IntroductionSkin cutaneous melanoma (SKCM) is the world’s fourth deadliest cancer, and advanced SKCM leads to a poor prognosis. Novel biomarkers for SKCM diagnosis and prognosis are urgently needed. Long non-coding RNAs (lncRNAs) provide various biological functions and have been proved to play a significant role in tumor progression. Single-cell RNA sequencing (scRNA-seq) enables genome analysis at the single-cell level. This study explored prognostic lncRNAs in SKCM based on scRNA-seq and bulk RNA sequencing data.Materials and methodsThe TCGA cohort and melanoma samples in the GEO database (GSE72056, GSE19234, GSE15605, GSE7553, and GSE81383) were included in this study. Marker genes were filtered, and ensemble lncRNAs were annotated. The clinical significance of selected lncRNAs was verified through TCGA and GEO dataset analysis. SiRNA transfection, wound−healing and transwell assays were performed to evaluate the effect of PRRT3-AS1 on cellular function. Immune infiltration of the selected lncRNAs was also exhibited.ResultsA 5-marker-lncRNAs model of significant prognostic value was constructed based on GSE72056 and the TCGA cohort. PRRT3-AS1 combined with DANCR was then found to provide significant prognostic value in SKCM. PRRT3-AS1 was filtered for its higher expression in more advanced melanoma and significant prognosis value. Cellular function experiments in vitro revealed that PRRT3-AS1 may be required for cancer cell migration in SKCM. PRRT3-AS1 was found to be related to epithelial-mesenchymal transition (EMT) signaling pathways. DNA methylation of PRRT3-AS1 was negatively related to PRRT3-AS1 expression and showed significant prognosis value. In addition, PRRT3-AS1 may suppress immune infiltration and be involved in immunotherapy resistance.ConclusionPRRT3-AS1 may be a diagnostic and prognostic biomarker of SKCM.
Prediction model for the pretreatment evaluation of mortality risk in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease
Authors: Gui Xianhua , Li Wangzhong , Yu Yanzhe , Zhao Tingting , Jin Ziyi , Meng Kaifang , Wang Rujia , Shi Shenyun , Yu Min , Ma Miao , Chen Lulu , Luan Wei , Xin Xiaoyan , Qiu Yuying , Qiu Xiaohua , Zhang Yingwei , Cao Min , Cao Mengshu , Dai Jinghong , Cai Hourong , Huang Mei , Xiao Yonglong 
Published: September 2022

BackgroundAnti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (anti-MDA5 DM-ILD) is a disease with high mortality. We sought to develop an effective and convenient prediction tool to estimate mortality risk in patients with anti-MDA5 DM-ILD and inform clinical decision-making early.MethodsThis prognostic study included Asian patients with anti-MDA5 DM-ILD hospitalized at the Nanjing Drum Hospital from December 2016 to December 2020. Candidate laboratory indicators were retrospectively collected. Patients hospitalized from 2016 to 2018 were used as the discovery cohort and applied to identify the optimal predictive features using a least absolute shrinkage and selection operator (LASSO) logistic regression model. A risk score was determined based on these features and used to construct the mortality risk prediction model in combination with clinical characteristics. Results were verified in a temporal validation comprising patients treated between 2019 and 2020. The primary outcome was mortality risk within one year. The secondary outcome was overall survival. The prediction model’s performance was assessed in terms of discrimination, calibration, and clinical usefulness.ResultsThis study included 127 patients, (72 men [56.7%]; median age, 54 years [interquartile range, 48-63 years], split into discovery (n = 87, 70%) and temporal validation (n=37, 30%) cohorts. Five optimal features were selected by LASSO logistic regression in the discovery cohort (n = 87) and used to construct a risk score, including lymphocyte counts, CD3+CD4+ T-cell counts, cytokeratin 19 fragment (CYFRA21-1), oxygenation index, and anti-Ro52 antibody. The retained predictive variables in the final prediction model were age, Heliotrope, fever, and risk score, and the most predictive factor was the risk score. The prediction model showed good discrimination (AUC: 0.915, 95% CI: 0.846–0.957), good calibration (Hosmer–Lemeshow test, P = 0.506; Brier score, 0.12), and fair clinical usefulness in the discovery cohort. The results were verified among patients in the temporal validation cohort (n = 38). We successfully divided patients into three risk groups with very different mortality rates according to the predictive score in both the discovery and validation cohorts (Cochran-Armitage test for trend, P &lt; 0.001).ConclusionsWe developed and validated a mortality risk prediction tool with good discrimination and calibration for Asian patients with anti-MDA5 DM-ILD. This tool can offer individualized mortality risk estimation and inform clinical decision-making.
Construction and validation of nomograms based on the log odds of positive lymph nodes to predict the prognosis of lung neuroendocrine tumors
Authors: Wang Suyu , Wei Juan , Guo Yibin , Xu Qiumeng , Lv Xin , Yu Yue , Liu Meiyun 
Published: September 2022

BackgroundThis research aimed to investigate the predictive performance of log odds of positive lymph nodes (LODDS) for the long-term prognosis of patients with node-positive lung neuroendocrine tumors (LNETs).MethodsWe collected 506 eligible patients with resected N1/N2 classification LNETs from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The study cohort was split into derivation cohort (n=300) and external validation cohort (n=206) based on different geographic regions. Nomograms were constructed based on the derivation cohort and validated using the external validation cohort to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS) of patients with LNETs. The accuracy and clinical practicability of nomograms were tested by Harrell’s concordance index (C-index), integrated discrimination improvement (IDI), net reclassification improvement (NRI), calibration plots, and decision curve analyses.ResultsThe Cox proportional-hazards model showed the high LODDS group (-0.79≤LODDS) had significantly higher mortality compared to those in the low LODDS group (LODDS&lt;-0.79) for both CSS and OS. In addition, age at diagnosis, sex, histotype, type of surgery, radiotherapy, and chemotherapy were also chosen as predictors in Cox regression analyses using stepwise Akaike information criterion method and included in the nomograms. The values of C-index, NRI, and IDI proved that the established nomograms were better than the conventional eighth edition of the TNM staging system. The calibration plots for predictions of the 1-, 3-, and 5-year CSS/OS were in excellent agreement. Decision curve analyses showed that the nomograms had value in terms of clinical application.ConclusionsWe created visualized nomograms for CSS and OS of LNET patients, facilitating clinicians to bring individually tailored risk assessment and therapy.
Target organ expression and biomarker characterization of chemokine CCL21 in systemic sclerosis associated pulmonary arterial hypertension
Authors: Didriksen Henriette , Molberg Øyvind , Mehta Adi , Jordan Suzana , Palchevskiy Vyacheslav , Fretheim Håvard , Gude Einar , Ueland Thor , Brunborg Cathrine , Garen Torhild , Midtvedt Øyvind , Andreassen Arne K. , Lund-Johansen Fridtjof , Distler Oliver , Belperio John , Hoffmann-Vold Anna-Maria 
Published: September 2022

IntroductionSystemic sclerosis (SSc) is a heterogenous disorder that appears to result from interplay between vascular pathologies, tissue fibrosis and immune processes, with evidence for deregulation of chemokines, which normally control immune trafficking. We recently identified altered levels of chemokine CCL21 in SSc associated pulmonary arterial hypertension (PAH). Here, we aimed to define target organ expression and biomarker characteristics of CCL21.Materials and methodsTo investigate target organ expression of CCL21, we performed immunohistochemistry (IHC) on explanted lung tissues from SSc-PAH patients. We assessed serum levels of CCL21 by ELISA and Luminex in two well-characterized SSc cohorts from Oslo (OUH, n=552) and Zurich (n=93) University hospitals and in 168 healthy controls. For detection of anti-CCl21 antibodies, we performed protein array analysis applying serum samples from SSc patients (n=300) and healthy controls. To characterize circulating CCL21 in SSc, we applied immunoprecipitation (IP) with antibodies detecting both full length and tailless and a custom-made antibody detecting only the C-terminal of CCL21. IP products were analyzed by SDS-PAGE/western blot and Mass spectrometry (MS).ResultsBy IHC, we found that CCL21 was mainly expressed in the airway epithelial cells of SSc patients with PAH. In the analysis of serum levels of CCL21 we found weak correlation between Luminex and ELISA (r=0.515, p&lt;0.001). Serum levels of anti-CCL21 antibodies were higher in SSc patients than in healthy controls (p&lt;0.001), but only 5% of the SSc population were positive for anti-CCL21 antibodies in SSc, and we found no correlation between anti-CCl21 and serum levels of CCL21. By MS, we only identified peptides located within amino acid (aa) 23-102 of CCL21, indicating that CCL21 in SSc circulate as a truncated protein without the C-terminal tail.ConclusionThis study demonstrates expression of CCL21 in epithelial lung tissue from SSc patients with PAH, and indicate that CCL21 in SSc circulates as a truncated protein. We extend previous observations indicating biomarker potential of CCL21, but find that Luminex is not suitable as platform for biomarker analyses. Finally, in vivo generated anti-CCL21 antibodies exist in SSc, but do not appear to modify serum CCL21 levels in patients with SSc-PAH.
Basin-scale control on N2O loss rate and emission in the Changjiang River network, China
Authors: Wang Fang , Yu Qibiao , Yan Weijin , Tian Siyu , Zhang Peipei , Wang Jianing 
Published: September 2022

Global riverine N2O emissions have been made by several studies with great uncertainty. However, the regional N2O budgets and patterns in large river networks is still unclear, due to the lacking understanding of in-river N2O emission rate and well-classified river network water areas. Furthermore, the mass ratio of N2O emission against nitrogen(N) load in river networks remains controversial. Here we report N2O emissions from the largest river of China, the Changjiang River network, emphasizing the basin-scale control on riverine N2O loss rate in response to increasing N loads and river size. We find the N2O emission rate is negatively related to Strahler river orders, and positively related to N loading. The velocity (Vf) of N conversion into N2O was 0.131-0.436 m yr-1, and N2O loss rate (ζ) was 0.27-37.64 ×10-4 d-1 and declined exponentially with water discharge. Both the loss rate and the mass ratio of N conversion into N2O varied significantly at basin scale, indicating the diminishing capacity of river ecosystems to convert excess DIN into N2O when N load increased as a direct result of human activities. Our study shows N2O emission was 0.66 Gg N2O-N (1Gg=109g) in 1986 and increased to 10.3 Gg N2O-N in 2014 for the whole Changjiang River network. We identified the headwater streams are hotspots of N2O emission across the headwater stream to the estuary aquatic continuum. N2O emission was about 0.82% - 5.31% of global riverine N2O budget during 2010-2014. Our study suggested that an integrated approach in view of the riverine N loads and river hydrology is needed to improve estimates of riverine N2O emissions.
Dispersion of subsurface lagrangian drifters in the northeastern Gulf of Mexico
Authors: Hancock Cathrine , Speer Kevin , de Souza Joao Marcos Azevedo Correia , Morey Steven L. 
Published: September 2022

The dispersion of subsurface Lagrangian floats by eddies was observed directly in DeSoto Canyon, located in the northeastern Gulf of Mexico. Key elements of dispersion include the capture and release of floats by variations in eddy structure and intensity. Two separate eddy events were revealed through 60-day trajectories from five subsurface drifters deployed at 400 m depth in DeSoto Canyon. A changing background flow in DeSoto Canyon allowed for the contraction and expansion of the eddy’s “trap zone,” resulting in the capture and release of several drifters deployed in the area. To investigate the variability of dispersion due to this capture-and-release effect, virtual particle tracks from a 5-year numerical model simulation of the Gulf of Mexico were used. Large interannual variability was observed in eddy activity over the 5-year simulation. When coupled with a variable background flow, this greatly affected Lagrangian particle transport within the entire eastern Gulf of Mexico. During years of increased eddy activity, more virtual particles were “captured” from the along-slope flow and “released” offshore, increasing dispersion and residence time within the eastern Gulf of Mexico. The opposite was observed during minimal eddy activity, where more virtual particles remained within the along-slope flow and thus were funneled toward two main exit points out of the eastern Gulf of Mexico. Regions such as DeSoto Canyon with strong topographic constraints, a highly variable background flow, and considerable eddy activity are likely to spread tracers such as nutrients and contaminants over a substantial area due to this capture-and-release effect.
Dynamic responses of 500-kV transmission line towers under impact force of rockfall in a mountainous area
Authors: Linping Yue , Feng Jiang , Hong Jiang , Wei Jiang , Zhiyong Wang , Zheng Zhou , Jianping Xiong , Tian Wu 
Published: September 2022

Since most of the UHV/EHV transmission lines pass through mountainous areas, the impact of rocks caused by landslides or collapses may cause partial deformation of the iron tower, or even collapse, seriously threatening the safety operation of transmission lines. To analyze the dynamic response characteristics and influencing factors of the rolling rock impacting the transmission line tower, a simulation model for the 500-kV steel suspension tower impacted by the falling rock was established by finite element analysis software LS-DYNA in this study, and dynamic response characteristics of the rolling rock impacting the steel tower were analyzed under different conditions. Results show that the stress on the tower foundation is closely related to the mass, volume, and initial velocity of the rolling stone. Under the same rolling stone speed, the stress on the tower foundation increases as the mass of the rolling stone increases. The maximum increase in peak stress generated between the two can reach 110%; when rolling stones of the same size collide with different initial velocities, the location and magnitude of the peak stress of the tower foundation are different. When the initial speed of the rolling stones is more remarkable than 15 m/s, the tower foundation of the hit area increased significantly, causing the tower base to be directly destroyed.
Mesenchymal stem cell therapy on top of triple therapy with remdesivir, dexamethasone, and tocilizumab improves PaO2/FiO2 in severe COVID-19 pneumonia
Authors: Chen Chih-Hao , Chang Kuan-Cheng , Lin Yen-Nien , Ho Mao-Wang , Cheng Meng-Yu , Shih Wen-Hsin , Chou Chia-Huei , Lin Po-Chang , Chi Chih-Yu , Lu Min-Chi , Tien Ni , Wu Mei-Yao , Chang Shih-Sheng , Hsu Wu-Huei , Shyu Woei-Cheang , Cho Der-Yang , Jeng Long-Bin 
Published: September 2022

BackgroundDespite patients with severe coronavirus disease (COVID-19) receiving standard triple therapy, including steroids, antiviral agents, and anticytokine therapy, health condition of certain patients continue to deteriorate. In Taiwan, the COVID-19 mortality has been high since the emergence of previous variants of this disease (such as alpha, beta, or delta). We aimed to evaluate whether adjunctive infusion of human umbilical cord mesenchymal stem cells (MSCs) (hUC-MSCs) on top of dexamethasone, remdesivir, and tocilizumab improves pulmonary oxygenation and suppresses inflammatory cytokines in patients with severe COVID-19.MethodsHospitalized patients with severe or critical COVID-19 pneumonia under standard triple therapy were separated into adjuvant hUC-MSC and non-hUC-MSC groups to compare the changes in the arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio and biological variables.ResultsFour out of eight patients with severe or critical COVID-19 received either one (n = 2) or two (n = 2) doses of intravenous infusions of hUC-MSCs using a uniform cell dose of 1.0 × 108. Both high-sensitivity C-reactive protein (hs-CRP) level and monocyte distribution width (MDW) were significantly reduced, with a reduction in the levels of interleukin (IL)-6, IL-13, IL-12p70 and vascular endothelial growth factor following hUC-MSC transplantation. The PaO2/FiO2 ratio increased from 83.68 (64.34–126.75) to 227.50 (185.25–237.50) and then 349.56 (293.03–367.92) within 7 days after hUC-MSC infusion (P &lt; 0.001), while the change of PaO2/FiO2 ratio was insignificant in non-hUC-MSC patients (admission day: 165.00 [102.50–237.61]; day 3: 100.00 [72.00–232.68]; day 7: 250.00 [71.00–251.43], P = 0.923).ConclusionTransplantation of hUC-MSCs as adjunctive therapy improves pulmonary oxygenation in patients with severe or critical COVID-19. The beneficial effects of hUC-MSCs were presumably mediated by the mitigation of inflammatory cytokines, characterized by the reduction in both hs-CRP and MDW.
Genomic profile of SARS-CoV-2 Omicron variant and its correlation with disease severity in Rajasthan
Authors: Sharma Ravi P. , Gautam Swati , Sharma Pratibha , Singh Ruchi , Sharma Himanshu , Parsoya Dinesh , Deeba Farah , Bhomia Neha , Pal Nita , Potdar Varsha , Yadav Pragya D. , Gupta Nivedita , Bhandari Sudhir , Kumar Abhinendra , Joshi Yash , Pandit Priyanka , Malhotra Bharti 
Published: September 2022

BackgroundOmicron, a new variant of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), was first detected in November 2021. This was believed to be highly transmissible and was reported to evade immunity. As a result, an urgent need was felt to screen all positive samples so as to rapidly identify Omicron cases and isolate them to prevent the spread of infection. Genomic surveillance of SARS-CoV-2 was planned to correlate disease severity with the genomic profile.MethodsAll the SARS-CoV-2 positive cases detected in the state of Rajasthan were sent to our Lab. Samples received from 24 November 2021 to 4 January 2022 were selected for Next-Generation Sequencing (NGS). Processing was done as per protocol on the Ion Torrent S5 System for 1,210 samples and bioinformatics analysis was done.ResultsAmong the 1,210 samples tested, 762 (62.9%) were Delta/Delta-like and other lineages, 291 (24%) were Omicron, and 157 (12.9%) were invalid or repeat samples. Within a month, the proportion of Delta and other variants was reversed, 6% Omicron became 81%, and Delta and other variants became 19%, initially all Omicron cases were seen in international travelers and their contacts but soon community transmission was seen. The majority of patients with Omicron were asymptomatic (56.7%) or had mild disease (33%), 9.2% had moderate symptoms, and two (0.7%) had severe disease requiring hospitalization, of which one (0.3%) died and the rest were (99.7%) recovered. History of vaccination was seen in 81.1%, of the previous infection in 43.2% of cases. Among the Omicron cases, BA.1 (62.8%) was the predominant lineage followed by BA.2 (23.7%) and B.1.529 (13.4%), rising trends were seen initially for BA.1 and later for BA.2 also. Although 8.9% of patients with Delta lineage during that period were hospitalized, 7.2% required oxygen, and 0.9% died. To conclude, the community spread of Omicron occurred in a short time and became the predominant circulating variant; BA.1 was the predominant lineage detected. Most of the cases with Omicron were asymptomatic or had mild disease, and the mortality rate was very low as compared to Delta and other lineages.
A nationwide survey on the management of the COVID-19 pandemic and respiratory disease in South Korea
Authors: Ang Lin , Yim Mi Hong , Song Eunhye , Lee Hye Won , Lee Hyangsook , Kim Tae-Hun , Willcox Merlin , Hu Xiao-Yang , Houriet Joelle , Graz Bertrand , Lee Je-Won , Jang Yunho , Kim Jung Tae , Kim Eunsop , Park Yong Hee , Lee Myeong Soo 
Published: September 2022

BackgroundThis study aimed to explore individual prevalence of respiratory symptoms and to describe the Korean population's treatment approaches, preventive health behaviors, and mental health conditions during the pandemic.MethodsWe analyzed responses from an online nationwide survey, conducted between February 2021 to May 2021, about people's experiences during the pandemic. Statistical analysis was also performed to see if there were any significant differences in treatment and prevention strategies between different groups of respondents (between those had respiratory symptoms, compared with those who did not, and between those tested positive for COVID-19, compared with those who did not).ResultsA total of 2,177 survey respondents completed the survey and, of these, only 142 had experienced symptoms. The most frequently reported respiratory infections related symptoms were runny or blocked nose (47.6%), cough (45.5%), fever (44.1%), sore throat (42.0%), and fatigue (30.1%). More than half of the respondents (53.1%) used complementary and alternative medicine (CAM) approaches as means of preventive measures. In terms of preventive behaviors, the more emphasized behaviors were mask-wearing (58.9%) and hand-washing after coming home (42.7%). The majority of the respondents (64.9%) did not show signs of mental health issues.ConclusionIn South Korea, conventional medicine was mainly used for COVID-19 treatment whereas CAM was commonly used as preventive measures. COVID-19 was also found to have less impact on the general population's mental health. The findings of this study may shed light on how the pandemic impacted the general population.