bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis of Immune-Related Metabolic Genes in Lung Adenocarcinoma
Authors: Li Fangfang , Huang Chun , Qiu Lingxiao , Li Ping , Shi Jiang , Zhang Guojun 
Published: July 2022

PurposeThe immunotherapy of lung adenocarcinoma (LUAD) has received much attention in recent years and metabolic reprogramming is linked to immune infiltration in the tumor microenvironment. Therefore, it is indispensable to dissect the role of immune-related metabolic genes in lung adenocarcinoma.MethodsIn this study, we screened immune-related genes by Pearson correlation. The function of these genes was explored by gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. The differently expressed immune-related genes were analyzed by Limma. Furthermore, the LUAD patients were clustered based on immune-related genes through consensus clustering. The Unicox was used to identify survival-immune-related metabolic genes. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to optimize the gene sets. A prediction model was constructed and tested. The potential therapeutic target was selected based on two criteria, these immune-related metabolic genes that were highly expressed in tumor tissues and negatively correlated with the survival of patients in LUAD. Quantitative real‐time PCR (qRT‐PCR) was used for in vitro experimental validations.ResultsWe identified 346 immune-related genes, mainly involved in arachidonic acid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling. Moreover, a total of 141 immune-related genes were dysregulated between tumor and normal tissues. We clustered three subtypes of LUAD based on immune-related metabolic genes and these subtypes exhibited different survival and immune status. We found Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) as a potential therapeutic target, which is positively correlated with the cyclin-dependent kinase family of genes.ConclusionWe comprehensively analyzed the immune-related metabolic genes in LUAD. RRM2 was determined as a promising metabolic checkpoint for lung adenocarcinoma.
The Association Between Circulating Trans Fatty Acids and Thyroid Function Measures in U.S. Adults
Authors: Wang Xiaoqian , Jiang Fengjuan , Chen Wenqing , Yuan Hui , Li Yuan 
Published: July 2022

BackgroundThere has been controversial evidence regarding the effect of trans fatty acids (TFAs) on thyroid function in animal studies, and the epidemiological studies are lacking. We aimed to investigate the potential associations between circulating TFAs and thyroid function biomarkers in a U.S. adult population sample.MethodsWe performed a cross-sectional survey with 626 adults aged ≥20 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2009–2010. Multivariable linear regression models were constructed to elucidate the relationships between circulating concentrations of TFAs (palmitelaidic acid, vaccenic acid, elaidic acid, linoelaidic acid and the sum of the four TFAs) and a panel of thyroid function measures.ResultsFor 626 adults, positive associations were found between palmitelaidic acid, elaidic acid and total thyroxine (TT4), between palmitelaidic acid and total triiodothyronine (TT3), and between linolelaidic acid and thyroid stimulating hormone (TSH), while linolelaidic acid was negatively associated with free thyroxine (FT4) (all P&lt;0.05). Besides, the four TFAs and the sum TFAs were positively associated with free triiodothyronine (FT3). Vaccenic acid, elaidic acid, linoelaidic acid and the sum TFAs were positively associated with FT3/FT4, while the four TFAs and the sum TFAs were negatively associated with FT4/TT4 (all P&lt;0.05). In stratified analysis, the associations between thyroid function measures and the ratios remained significant in female. For men, linolelaidic acid was negatively associated with FT4 and elaidic acid and the sum TFAs were positively associated with FT3. Furthermore, the associations between TFAs and FT3/FT4 remained significant.ConclusionOur findings revealed that TFAs exposure was associated with serum biomarkers of thyroid function. More researches are needed to evaluate the long-term health outcomes of these findings.
Runoff Variation and Influencing Factors in the Kuye River Basin of the Middle Yellow River
Authors: He Yi , Mu Xingmin , Jiang Xiaohui , Song Jinxi 
Published: July 2022

In recent decades, due to climate change and human activities, the hydrological processes of many rivers in the world have undergone significant changes. As an important part of the water cycle, it is of great practical significance to identify the causes of runoff change for water resource management and planning. Taking the Kuye River and its tributaries, the Wulanmulun River and Beiniuchuan River as examples, the trend change in runoff was investigated by the Mann-Kendall trend test and mutation analysis, and the contribution of influencing factors of runoff change was quantitatively evaluated by the Budyko framework. The results showed that the annual runoff depth of the Kuye River basin and its tributaries, the Wulanmulun River basin and Beiniuchuan River basin, showed a significant decreasing trend from 1960 to 2014 (p &lt; 0.01), and the decreasing rates were 1.03 mm/a, 1.24 mm/a and 1.50 mm/a, respectively. The abrupt change point of runoff depth in the Kuye River basin and its upstream Beiniuchuan River basin occurred in 1996, while that in the Wulanmulun River basin, another tributary, occurred in 1992. In the Kuye River basin, Beiniuchuan River basin and Wulanmulun River basin, the contributions of underlying surface change to runoff change were 89.03, 89.54, and 95.42%, respectively, followed by the contribution of rainfall, and the contribution of potential evapotranspiration to runoff change was the lowest. The change in the underlying surface (the Grain for Green Project and coal mining) is the main factor causing the decrease in runoff in the Kuye River basin.
Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma
Authors: Yuan Qing , Zuo Fu-Xing , Cai Hong-Qing , Qian Hai-Peng , Wan Jing-Hai 
Published: July 2022

Background: Studies have suggested that glioblastoma (GBM) cells originate from the subventricular zone (SVZ) and that GBM contact with the SVZ correlated with worse prognosis and higher recurrence. However, research on differentially expressed genes (DEGs) between GBM and the SVZ is lacking.Methods: We performed deep RNA sequencing on seven SVZ-involved GBMs and paired tumor-free SVZ tissues. DEGs and enrichment were assessed. We obtained GBM patient expression profiles and clinical data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The least absolute shrinkage and selection operator Cox regression model was utilized to construct a multigene signature in the CGGA cohort. GBM patient data from TCGA cohort were used for validation.Results: We identified 137 (97 up- and 40 down-regulated) DEGs between GBM and healthy SVZ samples. Enrichment analysis revealed that DEGs were mainly enriched in immune-related terms, including humoral immune response regulation, T cell differentiation, and response to tumor necrosis factor, and the MAPK, cAMP, PPAR, PI3K-Akt, and NF-κb signaling pathways. An eight-gene (BCAT1, HPX, NNMT, TBX5, RAB42, TNFRSF19, C16orf86, and TRPC5) signature was constructed. GBM patients were stratified into two risk groups. High-risk patients showed significantly reduced overall survival compared with low-risk patients. Univariate and multivariate regression analyses indicated that the risk score level represented an independent prognostic factor. High risk score of GBM patients negatively correlated with 1p19q codeletion and IDH1 mutation. Immune infiltration analysis further showed that the high risk score was negatively correlated with activated NK cell and monocyte counts, but positively correlated with macrophage and activated dendritic cell counts and higher PD-L1 mRNA expression.Conclusion: Here, a novel gene signature based on DEGs between GBM and healthy SVZ was developed for determining GBM patient prognosis. Targeting these genes may be a therapeutic strategy for GBM.
Clinical Patterns, Survival, Comorbidities, and Treatment Regimens in 149 Patients With Pemphigus in Tuscany (Italy): A 12-Year Hospital-Based Study
Authors: Quintarelli Lavinia , Coi Alessio , Maglie Roberto , Corrà Alberto , Mariotti Elena Biancamaria , Aimo Cristina , Ruffo di Calabria Valentina , Verdelli Alice , Bianchi Beatrice , Del Bianco Elena , Antiga Emiliano , Caproni Marzia 
Published: July 2022

IntroductionPemphigus encompasses a group of muco-cutaneous autoimmune bullous diseases characterized by the loss of adhesion between keratinocytes. The disease is associated with increased morbidity and mortality.Materials and MethodsWe characterized clinical patterns, survival, comorbidities, and drug prescriptions in patients with pemphigus referred to the Section of Dermatology of the University of Florence from January 2010 to December 2021.ResultsA total of 149 patients were identified (female/male sex ratio = 2.0). Median age at diagnosis was 57.7 ± 17.2 years; 108 patients were diagnosed with pemphigus vulgaris (PV) (72.5%) and 35 (23.5%) with pemphigus foliaceus (PF). Paraneoplastic pemphigus (PNP) and IgA-pemphigus accounted for three patients each. The overall survival rate was 86.9%. Accordingly, 14 (9%) patients died during the study period. The average age at death was 77.8 ± 9.3. Age at diagnosis was a risk factor for death in patients with pemphigus. Average concentration of Dsg3-IgG and Dsg1-IgG was 85.6 ± 68.8 and 75.9 ± 68.4, respectively. The most serious comorbid diseases included cerebro- and cardiovascular accidents and malignancies. Regarding the treatment regimen, we found a substantially stable use of systemic steroids in the 2010–2018 period; the prevalence of use of mycophenolic acid increased, whereas that of azathioprine decreased. The use of rituximab showed the highest increase in the 2013–2018 period. Proton-pump inhibitors and antibiotics were the most frequently prescribed non-immunomodulating drugs.ConclusionsIn this large series of the patients, patients with pemphigus showed a high incidence of serious comorbid diseases, highlighting the importance of a multidisciplinary approach for a proper management of the patients. Rituximab was the immunomodulating drug showing the highest increase in use over time, reflecting the growing evidence of its efficacy as a first-line treatment in pemphigus.
Relationship Between Serum Complement C3 Levels and Outcomes Among Patients With Anti-GBM Disease
Authors: Zhu Mengyue , Wang Jingjing , Le Weibo , Xu Feng , Jin Ying , Jiao Chenfeng , Zhang Haitao 
Published: July 2022

BackgroundIgG and complement 3 (C3) are generally found to be deposited along the glomerular basement membrane (GBM) in human anti-GBM disease. The pathogenic role of complement activation in kidney damage of anti-GBM disease has been explored in recent years. Therefore, we investigated the relationship between serum C3 and outcomes among patients with anti-GBM disease in this study.MethodsNinety-four anti-GBM disease patients between January 2004 and December 2020 at the National Clinical Research Center of Kidney Diseases Jinling Hospital were retrospectively analyzed, and were divided into the low C3 group and the normal C3 group according to serum C3 levels at diagnosis. Fifty-six patients had undergone renal biopsy. We analyzed the clinical manifestations, laboratory tests, kidney pathology, treatment, and outcomes between the two groups. The primary endpoint was kidney failure. Cox regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and kidney failure. The outcomes of the two groups were compared by the Kaplan–Meier curve.ResultsA total of 94 patients (aged 43.6 ± 16.2; male patients, 46%) with anti-GBM disease were enrolled. There were 26 patients with low C3 levels and 68 patients with normal C3 levels. Compared with the normal C3 group, patients in the low C3 group have a higher proportion of glomerular sclerosis progressing to kidney failure. Multivariate Cox regression analysis suggested that C3 is associated with kidney outcomes in patients with anti-GBM disease (HR = 0.782, 95% CI = 0.673–0.907,p= 0.001). Smooth curve fitting of generalized additive mixed model analysis indicated that the level of C3 had a linear relationship with the changing trend of kidney failure. The Kaplan–Meier curve showed that there was a statistical difference between the two groups in terms of kidney failure (p= 0.033).ConclusionThe kidney outcomes of anti-GBM disease in the low C3 group were poorer than those in the normal C3 group. The influence of C3 on the kidney outcomes of patients with anti-GBM disease may be of clinical relevance.
Photobiomodulation Improves Serum Cytokine Response in Mild to Moderate COVID-19: The First Randomized, Double-Blind, Placebo Controlled, Pilot Study
Authors: Marashian Seyed Mehran , Hashemian Mohammadreza , Pourabdollah Mihan , Nasseri Mansour , Mahmoudian Saeed , Reinhart Florian , Eslaminejad Alireza 
Published: July 2022

BackgroundBecause the major event in COVID-19 is the release of pre- and inflammatory cytokines, finding a reliable therapeutic strategy to inhibit this release, help patients manage organ damage and avoid ICU admission or severe disease progression is of paramount importance. Photobiomodulation (PBM), based on numerous studies, may help in this regard, and the present study sought to evaluate the effects of said technology on cytokine reduction.MethodsThis study was conducted in the 2nd half of 2021. The current study included 52 mild-to-moderately ill COVID-19, hospitalized patients. They were divided in two groups: a Placebo group and a PBM group, treated with PBM (620-635 nm light via 8 LEDs that provide an energy density of 45.40 J/cm2 and a power density of 0.12 W/cm2), twice daily for three days, along with classical approved treatment. 28 patients were in Placebo group and 24 in PBM group. In both groups, blood samples were taken four times in three days and serum IL-6, IL-8, IL-10, and TNF-α levels were determined.ResultsDuring the study period, in PBM group, there was a significant decrease in serum levels of IL-6 (-82.5% +/- 4, P&lt;0.001), IL-8 (-54.4% ± 8, P&lt;0.001), and TNF-α (-82.4% ± 8, P&lt;0.001), although we did not detect a significant change in IL-10 during the study. The IL-6/IL-10 Ratio also improved in PBM group. The Placebo group showed no decrease or even an increase in these parameters. There were no reported complications or sequelae due to PBM therapy throughout the study.ConclusionThe major cytokines in COVID-19 pathophysiology, including IL-6, IL-8, and TNF-α, responded positively to PBM therapy and opened a new window for inhibiting and managing a cytokine storm within only 3-10 days.
PD-1 Inhibitor Combined With Radiotherapy and GM-CSF (PRaG) in Patients With Metastatic Solid Tumors: An Open-Label Phase II Study
Authors: Kong Yuehong , Zhao Xiangrong , Xu Meiling , Pan Jie , Ma Yifu , Zou Li , Peng Qiliang , Zhang Junjun , Su Cunjin , Xu Zhi , Zhou Wei , Peng Yong , Yang Jiabao , Zhou Chengliang , Li Yujia , Guo Qiuchen , Chen Guangqiang , Wu Hongya , Xing Pengfei , Zhang Liyuan 
Published: July 2022

Patients with metastatic cancer refractory to standard systemic therapies have a poor prognosis and few therapeutic options. Radiotherapy can shape the tumor microenvironment (TME) by inducing immunogenic cell death and promoting tumor recognition by natural killer cells and T lymphocytes. Granulocyte macrophage-colony stimulating factor (GM-CSF) was known to promote dendric cell maturation and function, and might also induce the macrophage polarization with anti-tumor capabilities. A phase II trial (ChiCTR1900026175) was conducted to assess the clinical efficacy and safety of radiotherapy, PD-1 inhibitor and GM-CSF (PRaG regimen). This trial was registered at http://www.chictr.org.cn/index.aspx. A PRaG cycle consisted of 3 fractions of 5 or 8 Gy delivered for one metastatic lesion from day 1, followed by 200 μg subcutaneous injection of GM-CSF once daily for 2 weeks, and intravenous infusion of PD-1 inhibitor once within one week after completion of radiotherapy. The PRaG regimen was repeated every 21 days for at least two cycles. Once the PRaG therapy was completed, the patient continued PD-1 inhibitor monotherapy until confirmed disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). A total of 54 patients were enrolled with a median follow-up time of 16.4 months. The ORR was 16.7%, and the disease control rate was 46.3% in intent-to-treat patients. Median progression-free survival was 4.0 months (95% confidence interval [CI], 3.3 to 4.8), and median overall survival was 10.5 months (95% CI, 8.7 to 12.2). Grade 3 treatment-related adverse events occurred in five patients (10.0%) and grade 4 in one patient (2.0%). Therefore, the PRaG regimen was well tolerated with acceptable toxicity and may represent a promising salvage treatment for patients with chemotherapy-refractory solid tumors. It is likely that PRaG acts via heating upthe TME with radiotherapy and GM-CSF, which was further boosted by PD-1 inhibitors.
Ferroptosis in Intrahepatic Cholangiocarcinoma: IDH1105GGT Single Nucleotide Polymorphism Is Associated With Its Activation and Better Prognosis
Authors: Sarcognato Samantha , Sacchi Diana , Fabris Luca , Zanus Giacomo , Gringeri Enrico , Niero Monia , Gallina Giovanna , Guido Maria 
Published: July 2022

ObjectivesIntrahepatic cholangiocarcinoma (ICC) has a dismal prognosis and often demonstrates an anti-apoptotic landscape, which is a key step to chemotherapy resistance. Isocitrate dehydrogenase 1 or 2 (IDH1-2)-mutated ICCs have been described and associated with better prognosis. Ferroptosis is a regulated iron-mediated cell death induced by glutathione peroxidase 4 (GPX4) inhibition, and may be triggered pharmacologically. GPX4 is overexpressed in aggressive cancers, while its expression is inhibited by IDH1R132C mutation in cell lines. We investigated tissue expression of ferroptosis activation markers in ICC and its correlation with clinical-pathological features and IDH1-2 status.Materials and MethodsWe enrolled 112 patients who underwent hepatic resection or diagnostic liver biopsy for ICC. Immunostaining for transferrin-receptor 1 and GPX4, and Pearls’ stain for iron deposits were performed to evaluate ferroptosis activation. Immunostaining for STAT3 was performed to study pro-inflammatory and anti-apoptotic landscape. Main IDH1-2 mutations were investigated in 90 cases by real-time polymerase chain reaction.ResultsGPX4 overexpression was seen in 79.5% of cases and related to poor histological prognostic factors (grading and perineural and vascular invasion; p &lt; 0.005 for all) and worse prognosis (OS p = 0.03; DFS p = 0.01). STAT3 was expressed in 95.5% of cases, confirming the inflammation-related anti-apoptotic milieu in ICC, and directly related to GPX4 expression (p &lt; 0.0001). A high STAT3 expression correlated to a worse prognosis (OS p = 0.02; DFS p = 0.001). Nearly 12% of cases showed IDH1105GGT single nucleotide polymorphism, which was never described in ICC up to now, and was related to lower tumor grade (p &lt; 0.0001), longer overall survival (p = 0.04), and lower GPX4 levels (p = 0.001).ConclusionOur study demonstrates for the first time that in most inflammatory ICCs ferroptosis is not active, and its triggering is related to IDH1-2 status. This supports the possible therapeutic role of ferroptosis-inducer drugs in ICC patients, especially in drug-resistant cases.
Efficacy of Red Blood Cell Exchange as Adjunctive Treatment for Hypoxemia and Survival Rate of Patients With Severe Coronavirus-2 Disease: An Open-Labeled Phase 2 Randomized Clinical Trial
Authors: Aminianfar Mohammad , Soleiman-Meigooni Saeed , Hamidi-Farahani Ramin , Darvishi Mohammad , Hoseini-Shokouh Seyyed Javad , Asgari Ali , Faraji-Hormozi Syrous , Asli Maryam 
Published: July 2022

BackgroundSevere acute respiratory syndrome (SARS) coronavirus-2 may infect red blood cells (RBCs) and impact oxygenation. We aimed to evaluate the efficacy of RBC exchange as an adjunctive treatment for hypoxemia and the survival rate of patients with severe coronavirus disease 2019 (COVID-19).MethodsIn a randomized clinical trial, we divided sixty patients with severe COVID-19 into two groups. The intervention group received the standard treatment of severe COVID-19 with RBC exchange three to four times in 2 days. The control group only received the standard treatment. Our primary outcomes were improving hypoxemia in 7 days, recovery or discharge, and death in 28 days. We conducted Chi-square test, independent samples t-test, and Fisher’s exact test to analyze the results. The ethical committee of Aja University of Medical Sciences approved the study (IR.AJAUMS.REC.1399.054), and the Iranian clinical trial registration organization registered it (IRCT20160316027081N2).ResultsTwenty-nine men and thirty-one women with a mean age of 67.5 years entered the study. The frequency of hypertension and diabetes mellitus was 86.7 and 68.3%, respectively. The most common symptoms of severe COVID-19 were dyspnea (91.6%), cough (75%), and fever (66.6%). Our results showed that hypoxemia improved in 21 of the 30 patients (70%) in the intervention group and 10 of the 30 patients (33.3%) in the control group (P &lt; 0.004). The recovery and discharge rates were 19 of 30 patients (63.3%) in the intervention group and 2 of 30 patients (6.7%) in the control group (P &lt; 0.001).ConclusionThe RBC exchange improved the oxygenation and survival rate in patients with severe COVID-19.
Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD
Authors: Kim Hyo Jin , Kim Yunmi , Kang Minjung , Kim Seonmi , Park Sue Kyung , Sung Suah , Hyun Young Youl , Jung Ji Yong , Ahn Curie , Oh Kook-Hwan 
Published: July 2022

BackgroundWe aimed to evaluate soluble Klotho and circulating fibroblast growth factor 23 (FGF23) ratio as a risk factor for renal progression, cardiovascular (CV) events, and mortality in chronic kidney disease (CKD).MethodsWe analyzed 2,099 subjects from a CKD cohort whose soluble Klotho and C-terminal FGF23 levels were measured at enrollment. The Klotho to FGF23 ratio was calculated as Klotho values divided by FGF23 values + 1 (hereinafter called the Klotho/FGF23 ratio). Participants were categorized into quartiles according to Klotho/FGF23 ratio. The primary outcome was renal events, defined as the doubling of serum creatinine, 50% reduction of estimated glomerular filtration rate from the baseline values, or development of end-stage kidney disease. The secondary outcomes consisted of CV events and death. Changes in CV parameters at the time of enrollment and during follow-up according to the Klotho/FGF23 ratio were also examined.ResultsDuring the follow-up period of 64.0 ± 28.2 months, 735 (35.1%) and 273 (13.0%) subjects developed renal events and composite outcomes of CV events and death, respectively. After adjustment, the first (HR: 1.36; 95% CI: 1.08–1.72, P = 0.010) and second (HR: 1.45; 95% CI: 1.15–1.83, P = 0.002) quartiles with regard to the Klotho/FGF23 ratio showed elevated risk of renal events as compared to the fourth quartile group. There was no significant association between Klotho/FGF23 ratio and the composite outcome of CV events and death. The prevalence of left ventricular hypertrophy and vascular calcification was higher in the low Klotho/FGF23 ratio quartiles at baseline and at the fourth-year follow-up.ConclusionsLow Klotho/FGF23 ratio was significantly associated with increased renal events in the cohort of Korean predialysis CKD patients.