bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upscaling Methane Flux From Plot Level to Eddy Covariance Tower Domains in Five Alaskan Tundra Ecosystems
Authors: Wang Yihui , Yuan Fengming , Arndt Kyle A. , Liu Jianzhao , He Liyuan , Zuo Yunjiang , Zona Donatella , Lipson David A. , Oechel Walter C. , Ricciuto Daniel M. , Wullschleger Stan D. , Thornton Peter E. , Xu Xiaofeng 
Published: July 2022

Spatial heterogeneity in methane (CH4) flux requires a reliable upscaling approach to reach accurate regional CH4 budgets in the Arctic tundra. In this study, we combined the CLM-Microbe model with three footprint algorithms to scale up CH4 flux from a plot level to eddy covariance (EC) tower domains (200 m × 200 m) in the Alaska North Slope, for three sites in Utqiaġvik (US-Beo, US-Bes, and US-Brw), one in Atqasuk (US-Atq) and one in Ivotuk (US-Ivo), for a period of 2013–2015. Three footprint algorithms were the homogenous footprint (HF) that assumes even contribution of all grid cells, the gradient footprint (GF) that assumes gradually declining contribution from center grid cells to edges, and the dynamic footprint (DF) that considers the impacts of wind and heterogeneity of land surface. Simulated annual CH4 flux was highly consistent with the EC measurements at US-Beo and US-Bes. In contrast, flux was overestimated at US-Brw, US-Atq, and US-Ivo due to the higher simulated CH4 flux in early growing seasons. The simulated monthly CH4 flux was consistent with EC measurements but with different accuracies among footprint algorithms. At US-Bes in September 2013, RMSE and NNSE were 0.002 μmol m−2 s−1 and 0.782 using the DF algorithm, but 0.007 μmol m−2 s−1 and 0.758 using HF and 0.007 μmol m−2 s−1 and 0.765 using GF, respectively. DF algorithm performed better than the HF and GF algorithms in capturing the temporal variation in daily CH4 flux each month, while the model accuracy was similar among the three algorithms due to flat landscapes. Temporal variations in CH4 flux during 2013–2015 were predominately explained by air temperature (67–74%), followed by precipitation (22–36%). Spatial heterogeneities in vegetation fraction and elevation dominated the spatial variations in CH4 flux for all five tower domains despite relatively weak differences in simulated CH4 flux among three footprint algorithms. The CLM-Microbe model can simulate CH4 flux at both plot and landscape scales at a high temporal resolution, which should be applied to other landscapes. Integrating land surface models with an appropriate algorithm provides a powerful tool for upscaling CH4 flux in terrestrial ecosystems.
Identification of Ferroptosis-Associated Genes in Prostate Cancer by Bioinformatics Analysis
Authors: Wo Qijun , Liu Zhenghong , Hu Linyi 
Published: July 2022

Background: In order to reveal the functions of ferroptosis in prostate cancer (PCa), a ferroptosis potential index (FPI) was built. This study researched the influence of ferroptosis on gene mutations, various cellular signaling pathways, biochemical recurrence (BCR), and drug resistance in both FPI-high and FPI-low groups.Methods: RNA-seq, somatic mutation data, and clinical data were obtained from The Cancer Genome Atlas (TCGA). FPI values were calculated. All samples were divided into FPI-high and FPI-low groups. The BCR-free survival rate, tumor mutation burden (TMB) value, cellular signaling pathway, differentially expressed genes (DEGs), and drug resistance in the two FPI groups were identified. Human PCa cells, LNCaP, were treated with ferroptosis inducer erastin or inhibitor ferrostatin-1. The expression of hub genes was detected by qRT-PCR and Western blot.Results: A high FPI level was significantly related to poor BCR-free survival. Also, higher TMB value was found in the FPI-high group, and FPI was shown to be associated with gene mutations. Then, genes in both groups were revealed to be enriched in different pathways. A total of 310 DEGs were identified to be involved in muscle system processes and neuroactive ligand–receptor interactions. A total of 101 genes were found to be related to BCR-free survival, and a protein–protein interaction (PPI) network was constructed. Two sub-modules were identified by MCODE, and eight hub genes were screened out, among which SYT4 had higher expression levels and poorer BCR-free survival in the FPI-high group, while the remaining hub genes had lower expression levels and poorer BCR-free survival. Drug sensitivity was revealed to be different in the two groups by study on the IC50 data of different molecules and ferroptosis regulator gene (FRG) expressions. Finally, erastin increased the expression of SYT4 in LNCaP and decreased the expression of the other four genes (ACTC1, ACTA1, ACTN2, and MYH6), while ferrostatin-1 led to the opposite results. The molecular experimental results were consistent with those of bioinformatics analysis, except TNNI1, TNNC2, and NRAP.Conclusion: The current research depicted the ferroptosis level and FRGs in PCa. Ferroptosis was related to TMB value, BCR-free survival, and drug resistance. This study will be beneficial to further research studies on ferroptosis-related molecular mechanisms.
An Immune-Related Gene Signature Can Predict Clinical Outcomes and Immunotherapeutic Response in Oral Squamous Cell Carcinoma
Authors: Zhang Liyuan , Wang Xiaopeng 
Published: July 2022

Objective: Immune landscape is a key feature that affects cancer progression, survival, and treatment response. Herein, this study sought to comprehensively characterize the immune-related genes (IRGs) in oral squamous cell carcinoma (OSCC) and conduct an immune-related risk score (IRS) model for prognosis and therapeutic response prediction.Methods: Transcriptome profiles and follow-up data of OSCC cohorts were curated from TCGA, GSE41613, and IMvigor210 datasets. An IRS model was established through univariate Cox, Random Survival Forest, and multivariate Cox analyses. Prognostic significance was evaluated with Kaplan–Meier curves, ROC, uni- and multivariate Cox, and subgroup analyses. A nomogram was conducted and assessed with C-index, ROC, calibration curves, and decision curve analyses. Immune cell infiltration and immune response were estimated with ESTIMATE and ssGSEA methods.Results: An IRS model was constructed for predicting the overall survival and disease-free survival of OSCC, containing MASP1, HBEGF, CCL22, CTSG, LBP, and PLAU. High-risk patients displayed undesirable prognosis, and the predictive efficacy of this model was more accurate than conventional clinicopathological indicators. Multivariate Cox analyses demonstrated that this model was an independent risk factor. The nomogram combining IRS, stage, and age possessed high clinical application values. The IRS was positively associated with a nonflamed tumor microenvironment. Moreover, this signature enabled to predict immunotherapeutic response and sensitivity to chemotherapeutic agents (methotrexate and paclitaxel).Conclusion: Collectively, our study developed a robust IRS model with machine learning method to stratify OSCC patients into subgroups with distinct prognosis and benefits from immunotherapy, which might assist identify biomarkers and targets for immunotherapeutic schemes.
Study on the Retreatment, Outcome, and Potential Predictors of Recurrence in Patients With Recurrence of Hepatitis B After Functional Cure
Authors: Lin Xiao , Song Aixin , Lu Junfeng , Zheng Sujun , Hu Zhongjie , Ma Lina , Cao Zhenhuan , Li Hong , Zheng Yanhong , Ren Shan , Chen Xinyue 
Published: July 2022

BackgroundStudies about the retreatment and predictors for patients with hepatitis B recurrence after functional cure are rare. This study aimed to evaluate the effect of retreatment, outcome, and potential predictors of recurrence in patients with recurrence after functional cure.MethodsA long-term follow-up was conducted with 32 cumulatively obtained patients who relapsed after cessation of pegylated interferon (Peg-IFN)-based antiviral treatment. The decision of whether to treatment or which therapeutic method to use [Peg-IFN or nucleos(t)ide analogs (NAs)] was based on the patient’s preferences and wishes. The rate of achieving functional cure and the clinical outcomes of different therapeutic methods were analyzed. Hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc) levels were detected in patients with blood samples during follow-up to evaluate the predictive ability of recurrence.ResultsThe follow-up time of 32 recurrence cases was 42–532 weeks after recurrence (median 226 weeks). In the 20 patients who received retreatment (15 received Peg-IFN and 5 received NAs only), the rate of functional cure was 65.0% (13/20); it was 86.7% (13/15) in the patients retreated with Peg-IFN. Three cases experienced recurrence again. Five patients received NA treatment, and no functional cure was achieved. No drug intervention was administered for 12 patients, 2 of them with hepatitis B virus (HBV) DNA spontaneous clearance, and one patient achieved spontaneous hepatitis B surface antigen (HBsAg) clearance during follow-up. Patients who relapsed after functional cure with Peg-IFN treatment did not have liver cirrhosis or hepatocellular carcinoma during the follow-up, regardless of whether they received retreatment. Anti-HBs and anti-HBc levels at the end of therapy were predictors of recurrence (p &lt; 0.001, p = 0.023). The value of combining the above two indicators in predicting recurrence was further improved, the areas under the receiver operating characteristic curves were 0.833, at combining predictors &gt;-0.386, the predictive sensitivity and specificity for recurrence were 86.67% and 90.62%.ConclusionThe functional cure rate was above 80% for patients with recurrence treated by Peg-IFN. During the follow-up, liver cirrhosis and hepatocellular carcinoma were not observed in all recurrence cases. High levels of anti-HBs and anti-HBc at the time of drug discontinuation are less likely to relapse.
Predicting Prognosis and Distinguishing Cold and Hot Tumors in Bladder Urothelial Carcinoma Based on Necroptosis-Associated lncRNAs
Authors: Liu Dongze , Xu Shengxian , Chang Taihao , Ma Shenfei , Wang Kaibin , Sun Guangyu , Chen Shuaiqi , Xu Yong , Zhang Hongtuan 
Published: July 2022

BackgroundIn reference to previous studies, necroptosis played an important role in cancer development. Our team decided to explore the potential prognostic values of long non-coding RNAs (lncRNAs) associated with necroptosis in bladder urothelial carcinoma (BLCA) and their relationship with the tumor microenvironment (TME) and the immunotherapeutic response for accurate dose.MethodsTo obtain the required data, bladder urothelial carcinoma transcriptome data were searched from Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/). We used co-expression analysis, differential expression analysis, and univariate Cox regression to screen out prognostic lncRNAs associated with necroptosis in BLCA. Then the least absolute shrinkage and selection operator (LASSO) was conducted to construct the necroptosis-associated lncRNAs model. Based on this model, we also performed the Kaplan–Meier analysis and time-dependent receiver operating characteristics (ROC) to estimate the prognostic power of risk score. Multivariate and univariate Cox regression analysis were performed to build up a nomogram. Calibration curves, and time-dependent ROC were also conducted to evaluate nomogram. Principal component analysis (PCA) revealed a difference between high- and low-risk groups. In addition, we explored immune analysis, gene set enrichment analyses (GSEA), and evaluation of the half-maximal inhibitory concentration (IC50) in constructed model. Finally, the entire samples were divided into three clusters based on model of necroptosis-associated lncRNAs to further compare immunotherapy in cold and hot tumors.ResultsA model was built up based on necroptosis-associated lncRNAs. The model revealed good consistence between calibration plots and prognostic prediction. The area of 1-, 3-, and 5-year OS under the ROC curve (AUC) were 0.707, 0.679, and 0.675. Risk groups could be helpful for systemic therapy due to the markedly diverse IC50 between risk groups. To our delight, clusters could effectively identify cold and hot tumors, which would be beneficial to accurate mediation. Clusters 2 and 3 were considered the hot tumor, which was more sensitive to immunotherapeutic drugs.ConclusionsThe outcomes of our study suggested that necroptosis-associated lncRNAs could effectively predict patients with BLCA prognosis, which may be helpful for distinguishing the cold and hot tumors and improving individual treatment of BLCA.
Association of IL-4 and IL-10 Polymorphisms With Preterm Birth Susceptibility: A Systematic Review and Meta-Analysis
Authors: Cao Xian-Ling , Zhou Xuan-You , Xu Nai-Xin , Chen Song-Chang , Xu Chen-Ming 
Published: July 2022

ObjectivePreterm birth (PTB) is a typical inflammatory disease with unclear pathogenesis. The studies investigating the relationship between anti-inflammatory factors IL-4 and IL-10 gene polymorphisms and PTB produced conflicting results. This systematic review and meta-analysis aimed to summarize the effects of IL-4 and IL-10 gene polymorphisms and clarify their possible association with PTB.MethodsA systematic literature review was conducted using PubMed, Web of Science, and Cochrane library (up to 02 April 2022). The MeSH terms, related entry terms, and other names in “Gene” database were used to find relevant articles. A fixed- or random-effects model was used to calculate the significance of IL-4 and IL-10 gene polymorphisms, depending on study heterogeneity. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated in the allele, recessive, dominant, co-dominant, and over-dominant models. The Eggers publication bias plot was used to graphically represent the publication bias.ResultsPolymorphisms in two interleukins (IL-4-590C/T (rs2243250) = 5 and IL-10-592A/C (rs1800872), -819T/C (rs1800871) and -1082A/G (rs1800896) = 16) were found in 21 articles. Overall, only the over-dominant gene model AA + GG vs. AG revealed significant association between IL-10-1082A/G (rs1800896) and PTB (OR [95% CI] = 0.87 [0.76, 0.99], p = 0.04). However, in the allele model, recessive model, dominant model, co-dominant model, and over-dominant model, the polymorphisms for IL-4-590C/T (rs2243250), IL-10-592A/C (rs1800872), and IL-10-819T/C (rs1800871) were not found to be associated with the risk of PTB. In gene models, no statistically significant association was found between IL-4-590C/T (rs2243250), IL-10-592A/C (rs1800872), IL-10-819T/C (rs1800871), and IL-10-1082A/G (rs1800896) polymorphisms and PTB in subgroup analyses by racial or control group Hardy-Weinberg Equilibrium (HWE) p-value. Eggers’s publication bias plot and heterogeneity test (I2&lt;50%, p = 0.05) of IL-10-1082A/G (rs1800896) suggested that the funnel asymmetry could be due to publication bias rather than heterogeneity.ConclusionThe current study suggests that the over-dominant gene model AA + GG vs. AG of IL-10-1082A/G (rs1800896) polymorphism may be associated with genetic susceptibility to PTB and may have a protective function against PTB risk. There was unclear association found between IL-4-590C/T (rs2243250), IL-10-592A/C (rs1800872) and IL-10-819T/C (rs1800871) polymorphisms and PTB. Due to the limitations of included studies and the risk of publication bias, additional research is required to confirm our findings.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-4-0044, identifier INPLASY202240044.
Autoimmunity to Sphingosine-1-Phosphate-Receptors in Systemic Sclerosis and Pulmonary Arterial Hypertension
Authors: Gluschke Hans , Siegert Elise , Minich Waldemar B. , Hackler Julian , Riemekasten Gabriela , Kuebler Wolfgang M. , Simmons Szandor , Schomburg Lutz 
Published: July 2022

ContextPulmonary arterial hypertension (PAH) is a frequent extracutaneous manifestation of systemic sclerosis (SSc). PAH is characterized by increased vasomotor tone, progressive remodeling of pulmonary arteries and arterioles, consequentially increased pulmonary vascular resistance, right heart hypertrophy, and eventually right ventricular failure. Autoimmunity against G-protein coupled receptors (GPCRs) has been implicated in the development of SSc-associated PAH. Sphingosine-1-phosphate (S1P) receptors (S1PR) present a potential, yet so far untested antigen for PAH autoimmunity, given the documented role of S1P/S1PR signaling in PAH pathogenesis.ObjectiveWe hypothesized that S1P receptors (S1PR) may constitute autoantigens in human patients, and that the prevalence of autoantibodies (aAb) to S1PR1, S1PR2 and S1PR3 is elevated in SSc patients and associated with PAH.MethodsFor this exploratory study, serum samples from 158 SSc patients, 58 of whom with PAH, along with 333 healthy control subjects were screened for S1PR-aAb. S1PR1-3 were expressed as fusion proteins with luciferase in human embryonic kidney cells and used to establish novel in-vitro assays for detecting and quantifying S1PR-aAb. The fusion proteins were incubated with serum samples, the aAb-S1PR complexes formed were precipitated by protein-A, washed and tested for luciferase activity. Commercial anti-S1PR-antibodies were used to verify specificity of the assays.ResultsAll three assays showed dose-dependent signal intensities when tested with S1PR-subtype specific commercial antibodies. Natural aAb to each S1PR were detected in healthy controls with a prevalence of &lt;10% each, i.e., 2.7% for S1PR1-aAb, 3.6% for S1PR2-aAb, and 8.3% for S1PR3. The respective prevalence was higher in the cohort of SSc patients without PAH, with 17.1% for S1PR1-aAb, 19.0% for S1PR2-aAb, and 21.5% for S1PR3. In the subgroup of SSc patients with PAH, prevalence of aAb to S1PR2 and S1PR3 was further elevated to 25.9% for S1PR2-aAb, and 27.6% for S1PR3. Notably, the majority of patients with positive S1PR2-aAb (60.7%) or S1PR3-aAb (71.9%) displayed interstitial lung disease.ConclusionS1PR1–3 can constitute autoantigens in humans, particularly in SSC patients with PAH. The potential pathophysiological significance for the etiology of the disease is currently unknown, but the elevated prevalence of S1PR2-aAb and S1PR3-aAb in SSC patients with PAH merits further mechanistic investigations.
The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma
Authors: Pang Wendu , Luo Yaxin , Li Junhong , Cheng Danni , Rao Yufang , Mao Minzi , Qiu Ke , Dong Yijun , Liu Jun , Zou Jian , Wang Haiyang , Chen Fei 
Published: July 2022

BackgroundThe current American Joint Committee on Cancer (AJCC) system only considered the importance of the size and laterality of lymph nodes while not the positive lymph node number (PLNN) for hypopharyngeal squamous cell carcinoma (HPSCC).MethodsA total of 973 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects. We applied six Cox regression models to compare the survival prognostic values of PLNN and AJCC systems.ResultsPositive lymph node number showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P &lt; 0.001) in univariate and multivariable analyses. The increased PLNN of HPSCC gave rise to poor OS and CSS. The survival model incorporating a composite of PLNN and TNM classification (C-index for OS:0.682, C-index for CSS:0.702) performed better than other models.ConclusionsA positive lymph node number could serve as a survival predictor for patients with HPSCC and a complement to enhance the prognostic assessment effects of TNM cancer staging systems.
Efficacy and Safety of Mirror Therapy for Post-stroke Dysphagia: A Systematic Review and Meta-Analysis
Authors: He Kelin , Wu Lei , Ni Fengjia , Li Xinyun , Liang Kang , Ma Ruijie 
Published: July 2022

BackgroundPost-stroke dysphagia is a common symptom after stroke and one of the most frequent and severe complications of stroke. Over the recent years, mirror therapy has generated significant research interest as a non-invasive therapeutic and rehabilitative intervention for post-stroke dysphagia and has been investigated in several randomized controlled trials in single center.ObjectiveIn this study, we aimed to evaluate the efficacy and safety of mirror therapy for post-stroke dysphagia.MethodsA total of seven databases were searched comprehensively from inception to the 31 December 2021, including PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Service System (SinoMed), Wan-fang database, and the Chinese Scientific Journals Database (VIP) from inception to 31 December 2021. The primary outcome measure was efficacy, as measured by clinical effectiveness rate. Secondary outcomes included the water swallowing test and the incidence of pneumonia. In addition, we applied the Cochrane Risk of Bias Tool to investigate the risk of bias. Potential publication bias was evaluated by applying Egger's bias indicator test and by assessing the symmetry of data when visualized as funnel plots.ResultsA total of five randomized controlled trials (135 subjects in the experimental group and control group) were found to report the application of mirror therapy for post-stroke dysphagia and were included in this study. No publication bias was detected. Meta-analysis revealed that mirror therapy had a positive effect on the rate of clinical efficacy [odds ratio (OR) = 4.22; 95% confidence interval (CI): 2.3–7.73] and the water swallowing test [mean difference (MD) = −0.76; 95% CI = −1.29 to −0.22]. Moreover, mirror therapy reduced the incidence of pneumonia (OR = 0.13; 95% CI = 0.03–0.49). Subgroup analyses indicated that mirror therapy during the acute phase was robust but was unstable during the convalescent phase. Sensitivity analysis revealed that the results generated by our meta-analysis were robust and stable.ConclusionsAvailable evidence appears to suggest that mirror therapy may have a role in the management of post-stroke dysphagia but has yet to be fully confirmed. Existing evidence from clinical trials suggests that evidence relating to the safety of mirror therapy for patients with post-stroke dysphagia is not yet sufficient.Systematic Review RegistrationIdentifier: CRD42022302733.