bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic data analysis coupled with copy number aberrations reveals a blood-based 17-gene signature for diagnosis and prognosis of patients with colorectal cancer
Authors: Kaya Ibrahim H. , Al-Harazi Olfat , Colak Dilek 
Published: January 2023

Background: Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer-associated deaths worldwide. Diagnosing CRC patients reliably at an early and curable stage is of utmost importance to reduce the risk of mortality.Methods: We identified global differentially expressed genes with copy number alterations in patients with CRC. We then identified genes that are also expressed in blood, which resulted in a blood-based gene signature. We validated the gene signature’s diagnostic and prognostic potential using independent datasets of gene expression profiling from over 800 CRC patients with detailed clinical data. Functional enrichment, gene interaction networks and pathway analyses were also performed.Results: The analysis revealed a 17-gene signature that is expressed in blood and demonstrated that it has diagnostic potential. The 17-gene SVM classifier displayed 99 percent accuracy in predicting the patients with CRC. Moreover, we developed a prognostic model and defined a risk-score using 17-gene and validated that high risk score is strongly associated with poor disease outcome. The 17-gene signature predicted disease outcome independent of other clinical factors in the multivariate analysis (HR = 2.7, 95% CI = 1.3–5.3, p = 0.005). In addition, our gene network and pathway analyses revealed alterations in oxidative stress, STAT3, ERK/MAPK, interleukin and cytokine signaling pathways as well as potentially important hub genes, including BCL2, MS4A1, SLC7A11, AURKA, IL6R, TP53, NUPR1, DICER1, DUSP5, SMAD3, and CCND1.Conclusion: Our results revealed alterations in various genes and cancer-related pathways that may be essential for CRC transformation. Moreover, our study highlights diagnostic and prognostic value of our gene signature as well as its potential use as a blood biomarker as a non-invasive diagnostic method. Integrated analysis transcriptomic data coupled with copy number aberrations may provide a reliable method to identify key biological programs associated with CRC and lead to improved diagnosis and therapeutic options.
SLC25A1-associated prognostic signature predicts poor survival in acute myeloid leukemia patients
Authors: Liu Fangshu , Deng Suqi , Li Yue , Du Juan , Zeng Hui 
Published: January 2023

Background: Acute myeloid leukemia (AML) is a heterogeneous malignant disease. SLC25A1, the gene encoding mitochondrial carrier subfamily of solute carrier proteins, was reported to be overexpressed in certain solid tumors. However, its expression and value as prognostic marker has not been assessed in AML.Methods: We retrieved RNA profile and corresponding clinical data of AML patients from the Beat AML, TCGA, and TARGET databases (TARGET_AML). Patients in the TCGA cohort were well-grouped into two group based on SLC25A1 and differentially expressed genes were determined between the SLC25A1 high and low group. The expression of SLC25A1 was validated with clinical samples. The survival and apoptosis of two AML cell lines were analyzed with SLC25A1 inhibitor (CTPI-2) treatment. Cox and the least absolute shrinkage and selection operator (LASSO) regression analyses were applied to Beat AML database to identify SLC25A1-associated genes for the construction of a prognostic risk-scoring model. Survival analysis was performed by Kaplan-Meier and receiver operator characteristic curves.Results: Our analysis revealed that high expressed level of SLC25A1 in AML patients correlates with unfavorable prognosis. Moreover, SLC25A1 expression was positively associated with metabolism activity. We further demonstrated that the inhibition of SLC25A1 could inhibit the proliferation and increase the apoptosis of AML cells. In addition, a panel of SLC25A1-associated genes, was identified to construct a prognostic risk-scoring model. This SLC25A1-associated prognostic signature (SPS) is an independent risk factor with high area under curve (AUC) values of receiver operating characteristic (ROC) curves. A high SPS in leukemia patients is associated with poor survival. A Prognostic nomogram including the SPS and other clinical parameters, was constructed and its predictive efficiency was confirmed.Conclusion: We have successfully established a SPS prognostic model that predict outcome and risk stratification in AML. This risk model can be used as an independent biomarker to assess prognosis of AML.
Increased Myosin light chain 9 expression during Kawasaki disease vasculitis
Authors: Kobayashi Hironobu , Kimura Motoko Y. , Hasegawa Ichita , Suganuma Eisuke , Ikehara Yuzuru , Azuma Kazuhiko , Ito Toshihiro , Ebata Ryota , Kurashima Yosuke , Kawasaki Yohei , Shiko Yuki , Saito Naoki , Iwase Hirotaro , Lee Youngho , Noval Rivas Magali , Arditi Moshe , Zuka Masahiko , Hamada Hiromichi , Nakayama Toshinori 
Published: January 2023

IntroductionKawasaki disease (KD) is an acute systemic vasculitis that predominantly afflicts children. KD development is known to be associated with an aberrant immune response and abnormal platelet activation, however its etiology is still largely unknown. Myosin light chain 9 (Myl9) is known to regulate cellular contractility of both non-muscle and smooth muscle cells, and can be released from platelets, whereas any relations of Myl9 expression to KD vasculitis have not been examined.MethodsPlasma Myl9 concentrations in KD patients and children with febrile illness were measured and associated with KD clinical course and prognosis. Myl9 release from platelets in KD patients was also evaluated in vitro. Myl9 expression was determined in coronary arteries from Lactobacillus casei cell wall extract (LCWE)-injected mice that develop experimental KD vasculitis, as well as in cardiac tissues obtained at autopsy from KD patients.Results and discussionPlasma Myl9 levels were significantly higher in KD patients during the acute phase compared with healthy controls or patients with other febrile illnesses, declined following IVIG therapy in IVIG-responders but not in non-responders. In vitro, platelets from KD patients released Myl9 independently of thrombin stimulation. In the LCWE-injected mice, Myl9 was detected in cardiac tissue at an early stage before inflammatory cell infiltration was observed. In tissues obtained at autopsy from KD patients, the highest Myl9 expression was observed in thrombi during the acute phase and in the intima and adventitia of coronary arteries during the chronic phase. Thus, our studies show that Myl9 expression is significantly increased during KD vasculitis and that Myl9 levels may be a useful biomarker to estimate inflammation and IVIG responsiveness to KD.
National experience with adenosine deaminase deficiency related SCID in Polish children
Authors: Dąbrowska-Leonik Nel , Piątosa Barbara , Słomińska Ewa , Bohynikova Nadezda , Bernat-Sitarz Katarzyna , Bernatowska Ewa , Wolska-Kuśnierz Beata , Kałwak Krzysztof , Kołtan Sylwia , Dąbrowska Anna , Goździk Jolanta , Ussowicz Marek , Pac Małgorzata 
Published: January 2023

IntroductionDeficiency of adenosine deaminase (ADA) manifests as severe combined immunodeficiency (SCID), caused by accumulation of toxic purine degradation by-products. Untreated patients develop immune and non-immune symptoms with fatal clinical course. According to ESID and EBMT recommendations enzyme replacement therapy (ERT) should be implemented as soon as possible to stabilize the patient’s general condition, normalize transaminases, treat pulmonary proteinosis, bone dysplasia, and protect from neurological damage. Hematopoietic stem cell transplantation (HSCT) from a matched related donor (MRD) is a treatment of choice. In absence of such donor, gene therapy (GT) should be considered. HSCT from a matched unrelated donor (MUD) and haploidentical hematopoietic stem cell transplantation (hHSCT) are associated with worse prognosis.Material and methodsWe retrospectively evaluated the clinical course and results of biochemical, immunological and genetic tests of 7 patients diagnosed in Poland with ADA deficiency since 2010 to 2022.ResultsAll patients demonstrated lymphopenia affecting of T, B and NK cells. Diagnosis was made on the basis of ADA activity in red blood cells and/or genetic testing. Patients manifested with various non-immunological symptoms including: lung proteinosis, skeletal dysplasia, liver dysfunction, atypical hemolytic-uremic syndrome, and psychomotor development disorders. Five patients underwent successful HSCT: 3 patients from matched unrelated donor, 2 from matched sibling donor, and 1 haploidentical from a parental donor. In 4 patients HSCT was preceded by enzyme therapy (lasting from 2 to 5 months). One patient with multiple organ failure died shortly after admission, before the diagnosis was confirmed. None of the patients had undergone gene therapy.ConclusionsIt is important to diagnose ADA SCID as early as possible, before irreversible multi-organ failure occurs. In Poland HSCT are performed according to international immunological societies recommendations, while ERT and GT are less accessible. Implementation of Newborn Screening (NBS) for SCID in Poland could enable recognition of SCID, including ADA-SCID.
Identification of the osteoarthritis signature gene PDK1 by machine learning and its regulatory mechanisms on chondrocyte autophagy and apoptosis
Authors: Meng Jinzhi , Du Huawei , Lv Haiyuan , Lu Jinfeng , Li Jia , Yao Jun 
Published: January 2023

BackgroundOsteoarthritis (OA) is a degenerative joint disease frequently diagnosed in the elderly and middle-aged population. However, its specific pathogenesis has not been clarified. This study aimed to identify biomarkers for OA diagnosis and elucidate their potential mechanisms for restoring OA-dysregulated autophagy and inhibiting chondrocyte apoptosis in vitro.Material and methodsTwo publicly available transcriptomic mRNA OA-related datasets (GSE10575 and GSE51588) were explored for biomarker identification by least absolute shrinkage and selection operator (LASSO) regression, weighted gene co-expression network analysis (WGCNA), and support vector machine recursive feature elimination (SVM-RFE). We applied the GSE32317 and GSE55457 cohorts to validate the markers’ efficacy for diagnosis. The connections of markers to chondrocyte autophagy and apoptosis in OA were also comprehensively explored in vitro using molecular biology approaches, including qRT-PCR and Western blot.ResultsWe identified 286 differentially expressed genes (DEGs). These DEGs were enriched in the ECM-receptor interaction and PI3K/AKT signaling pathway. After external cohort validation and protein-protein interaction (PPI) network construction, PDK1 was finally identified as a diagnostic marker for OA. The pharmacological properties of BX795-downregulated PDK1 expression inhibited LPS-induced chondrocyte inflammation and apoptosis and rescued OA-dysregulated autophagy. Additionally, the phosphorylation of the mediators associated with the MAPK and PI3K/AKT pathways was significantly downregulated, indicating the regulatory function of PDK1 in apoptosis and autophagy via MAPK and PI3K/AKT-associated signaling pathways in chondrocytes. A significantly positive association between the PDK1 expression and Neutrophils, Eosinophils, Plasma cells, and activated CD4 memory T cells, as well as an evident negative correlation between T cells follicular helper and CD4 naive T cells, were detected in the immune cell infiltration analysis.ConclusionsPDK1 can be used as a diagnostic marker for OA. Inhibition of its expression can rescue OA-dysregulated autophagy and inhibit apoptosis by reducing the phosphorylation of PI3K/AKT and MAPK signaling pathways.
BNT162b2 COVID-19 vaccination elicited protective robust immune responses in pediatric patients with inborn errors of metabolism
Authors: Zubarioglu Tanyel , Dinc Harika Oyku , Hopurcuoglu Duhan , Gulmez Ruveyda , Uygur Esma , Yilmaz Gizem , Ahmadzada Saffa , Uzunyayla-Inci Gozde , Oge-Enver Ece , Kiykim Ertugrul , Kocazeybek Bekir , Aktuglu-Zeybek Cigdem 
Published: January 2023

IntroductionSARS-CoV-2 infection can lead to a life-threatening acute metabolic decompensation in children with inborn errors of metabolism (IEM), so vaccination is mandatory. However, IEMs can also impair innate or adaptive immunity, and the impact of these immune system alterations on immunogenicity and vaccine efficacy is still unknown. Here, we investigated humoral immune responses to the BNT162b2 mRNA COVID-19 vaccine and clinical outcomes in pediatric IEM patients.MethodsFifteen patients between 12-18 years of age with a confirmed diagnosis of IEM, and received BNT162b2 were enrolled to the study. Patients with an anti-SARS-CoV-2 IgG concentration &gt;50 AU/mL before vaccination were defined as “COVID-19 recovered” whereas patients with undetectable anti-SARS-CoV-2 IgG concentration were defined as “COVID-19 naïve”. Anti-SARS-CoV-2 Immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibody (nAb) titers were measured to assess humoral immune response.ResultsAnti-SARS-CoV-2 IgG titers and nAb IH% increased significantly after the first dose. The increase in antibody titers after first and second vaccination remained significant in COVID-19 naïve patients. Complete anti-SARS-CoV-2 IgG seropositivity and nAb IH% positivity was observed in all patients after the second dose. Vaccination appears to be clinically effective in IEM patients, as none of the patients had COVID-19 infection within six months of the last vaccination.DiscussionHumoral immune response after two doses of BNT162b2 in pediatric IEM patients was adequate and the immune response was not different from that of healthy individuals.
α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS
Authors: Cong Zhukai , Yang Cui , Zeng Zhaojin , Wu Changyi , Zhao Feng , Shen Ziyuan , Xiao Han , Zhu Xi 
Published: January 2023

IntroductionCatecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating adrenergic receptors (ARs). But the role of α1-AR in this process has yet to be elucidated.MethodsIn this study, ARDS mouse model was induced by intratracheal instillation of lipopolysaccharide. After treatment with α1-AR agonist phenylephrine or antagonist prazosin, lung pathological injury, alveolar barrier disruption and inflammation, and haemodynamic changes were evaluated. Cytokine levels and cell viability of alveolar macrophages were measured in vitro. Nuclear factor κB (NF-κB), mitogen-activated protein kinase, and Akt signalling pathways were analysed by western blot.ResultsIt showed that α1-AR activation alleviated lung injuries, including reduced histopathological damage, cytokine expression, and inflammatory cell infiltration, and improved alveolar capillary barrier integrity of ARDS mice without influencing cardiovascular haemodynamics. In vitro experiments suggested that α1-AR stimulation inhibited secretion of TNF-α, IL-6, CXCL2/MIP-2, and promoted IL-10 secretion, but did not affect cell viability. Moreover, α1-AR stimulation inhibited NF-κB and enhanced ERK1/2 activation without significantly influencing p38, JNK, or Akt activation.DiscussionOur studies reveal that α1-AR stimulation could ameliorate lipopolysaccharide-induced lung injury by inhibiting NF-κB and promoting ERK1/2 to suppress excessive inflammatory responses of alveolar macrophages.
Investigating regulatory patterns of NLRP3 Inflammasome features and association with immune microenvironment in Crohn’s disease
Authors: Wu Huihuan , Zeng Ruijie , Qiu Xinqi , Chen Kequan , Zhuo Zewei , Guo Kehang , Xiang Yawen , Yang Qi , Jiang Rui , Leung Felix W. , Lian Qizhou , Sha Weihong , Chen Hao 
Published: January 2023

IntroductionCrohn’s disease is characterized of dysregulated inflammatory and immune reactions. The role of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in Crohn’s disease remains largely unknown.MethodsThe microarray-based transcriptomic data and corresponding clinical information of GSE100833 and GSE16879 were obtained from the Gene Expression Omnibus (GEO) database. Identification of in the NLRP3 inflammasome-related genes and construction of LASSO regression model. Immune landscape analysis was evaluated with ssGSEA. Classification of Crohn’s-disease samples based on NLRP3 inflammasome-related genes with ConsensusClusterPlus. Functional enrichment analysis, gene set variation analysis (GSVA) and drug-gene interaction network.ResultsThe expressions of NLRP3 inflammasome-related genes were increased in diseased tissues, and higher expressions of NLRP3 inflammasome-related genes were correlated with generally enhanced immune cell infiltration, immune-related pathways and human leukocyte antigen (HLA)-gene expressions. The gene-based signature showed well performance in the diagnosis of Crohn’s disease. Moreover, consensus clustering identified two Crohn’s disease clusters based on NLRP3 inflammasome-related genes, and cluster 2 was with higher expressions of the genes. Cluster 2 demonstrated upregulated activities of immune environment in Crohn’s disease. Furthermore, four key hub genes were identified and potential drugs were explored for the treatment of Crohn’s disease.ConclusionsOur findings indicate that NLRP3 inflammasome and its related genes could regulate immune cells and responses, as well as involve in the pathogenesis of Crohn’s disease from transcriptomic aspects. These findings provide in silico insights into the diagnosis and treatment of Crohn’s disease and might assist in the clinical decision-making process.
Spatial variability of dissolved nickel is enhanced by mesoscale dynamics in the Gulf of Mexico
Authors: Félix-Bermúdez Armando , Delgadillo-Hinojosa Francisco , Lares María Lucila , Torres-Delgado Eunise Vanessa , Huerta-Díaz Miguel Angel , Tovar-Sanchez Antonio , Camacho-Ibar Víctor Froylan 
Published: January 2023

The Gulf of Mexico (GoM) is one of the most dynamic marginal seas in the world owing to the intrusion of the Loop Current and the shedding of anticyclonic eddies (LCE) that travel westward across the Gulf. However, the impacts of these mesoscale dynamics on the supply and removal of bioessential trace metals in surface waters remain unclear. We study the impact of mesoscale eddies on the distribution of dissolved nickel (Ni), a biologically active element scarcely studied in the region. The vertical distribution of Ni was determined in the deep-water region of the GoM during summer of 2017, when two anticyclonic LCE (Quantum and Poseidon) were present. Nutrient-like profiles of Ni in the GoM resemble those from the Atlantic Ocean, but they showed high spatial variability within the first 1000 m, which was associated with the impact of mesoscale eddies. Similarly to subtropical gyres, macronutrients were almost depleted in surface waters, while Ni never fell below 1.51 nmol kg-1, suggesting low Ni lability or alternatively, slow biological uptake compared to that of macronutrients. In particular, lowest levels of Ni and macronutrients (PO4 and NO3) were recorded in surface waters of the anticyclonic eddies and the Loop Current area. Anticyclonic LCEs deepened these Ni-poor waters pushing the Ni-rich core of Tropical Atlantic Central Water up to 600 m, whereas its shallowest position (up to 200 m) was recorded under cyclonic conditions in Campeche Bay. This eddy-induced vertical displacement of water masses also affected the integrated Ni and macronutrient concentrations in the upper 350 m but without modifying their stoichiometries. We suggest that a significant decrease in surface inventories of Ni and macronutrient in areas impacted by LCEs is a consequence of the trapping of the water within eddies, the biological uptake of Ni and macronutrients combined with their limited replenishment from below, which likely affects autotrophic groups. In conclusion, the mesoscale dynamic permanently present in the GoM play an important role in modifying the vertical distribution of Ni and macronutrients as well as their availability in the upper water column of this marginal sea.
Biofouling characteristics in Xinghua Bay of Fujian, China
Authors: Lin Heshan , Huang Yaqin , Lin Yingyue , Zhang Shuyi , Yu Shihao , Liu Kun , Mou Jianfeng , Lin Junhui , He Xuebao , Fu Sujing , Xie Weijie , Li Zhongbao 
Published: January 2023

Biofouling is one of the main factors affecting the efficiency and safety of cooling water systems in coastal nuclear power plants. Understanding the population dynamics, succession rules and cumulative effects of major fouling organisms is the basis for targeted prevention and control. A 1-year simulated concrete panel test was conducted from December 2020 to November 2021 in Xinghua Bay, China. A total of 78 species of fouling organisms were recorded by combining the monthly, seasonal, semiannual, annual and monthly cumulative panels, and the community composition was dominated by nearshore warm-water species, making for a typical subtropical inner bay-type community. The fouling organisms had a peak attachment period from June to October. Significantly more attachment was observed during summer (from June to August) than during the other three seasons. The attachment amount in the second half-year (from June to November) was much higher than that in the first half-year (from December to May). The attachment thickness, density, and biomass of the bottom summer panels reached 20 cm, 105,150 ind./m2, and 19,274.50 g/m2, respectively, while those of the bottom annual panels were 40 cm, 27,300 ind./m2, and 17,762.50 g/m2, respectively. The dominant fouling organisms with calcified shells mainly included Amphibalanus reticulatus and Pernaviridis. These species had high attachment amounts,could accumulate attachments for a long time, and even might cause secondary blockage, making them the most detrimental to the safety of a cooling system. Moreover,the seasonal upward growth of hydroids and bryozoans can also significantly reduce the efficiency of cooling water intake. We suggest that targeted prevention and control should be carried out according to the larval attachment period of different dominant groups of fouling organisms during June-October, which can greatly improve the prevention and control efficiency. Strengthening the research on the biological cycle phenomenon of the main species and their main environmental impact factors, and establishing a scientific and effective early-warning model are the governance direction of formulating and implementing scientific pollution prevention and control in the future.