bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics identification and experimental validation of m6A-related diagnostic biomarkers in the subtype classification of blood monocytes from postmenopausal osteoporosis patients
Authors: Zhang Peng , Chen Honglin , Xie Bin , Zhao Wenhua , Shang Qi , He Jiahui , Shen Gengyang , Yu Xiang , Zhang Zhida , Zhu Guangye , Chen Guifeng , Yu Fuyong , Liang De , Tang Jingjing , Cui Jianchao , Liu Zhixiang , Ren Hui , Jiang Xiaobing 
Published: March 2023

BackgroundPostmenopausal osteoporosis (PMOP) is a common bone disorder. Existing study has confirmed the role of exosome in regulating RNA N6-methyladenosine (m6A) methylation as therapies in osteoporosis. However, it still stays unclear on the roles of m6A modulators derived from serum exosome in PMOP. A comprehensive evaluation on the roles of m6A modulators in the diagnostic biomarkers and subtype identification of PMOP on the basis of GSE56815 and GSE2208 datasets was carried out to investigate the molecular mechanisms of m6A modulators in PMOP.MethodsWe carried out a series of bioinformatics analyses including difference analysis to identify significant m6A modulators, m6A model construction of random forest, support vector machine and nomogram, m6A subtype consensus clustering, GO and KEGG enrichment analysis of differentially expressed genes (DEGs) between different m6A patterns, principal component analysis, and single sample gene set enrichment analysis (ssGSEA) for evaluation of immune cell infiltration, experimental validation of significant m6A modulators by real-time quantitative polymerase chain reaction (RT-qPCR), etc.ResultsIn the current study, we authenticated 7 significant m6A modulators via difference analysis between normal and PMOP patients from GSE56815 and GSE2208 datasets. In order to predict the risk of PMOP, we adopted random forest model to identify 7 diagnostic m6A modulators, including FTO, FMR1, YTHDC2, HNRNPC, RBM15, RBM15B and WTAP. Then we selected the 7 diagnostic m6A modulators to construct a nomogram model, which could provide benefit with patients according to our subsequent decision curve analysis. We classified PMOP patients into 2 m6A subtypes (clusterA and clusterB) on the basis of the significant m6A modulators via a consensus clustering approach. In addition, principal component analysis was utilized to evaluate the m6A score of each sample for quantification of the m6A subgroups. The m6A scores of patients in clusterB were higher than those of patients in clusterA. Moreover, we observed that the patients in clusterA had close correlation with immature B cell and gamma delta T cell immunity while clusterB was linked to monocyte, neutrophil, CD56dim natural killer cell, and regulatory T cell immunity, which has close connection with osteoclast differentiation. Notably, m6A modulators detected by RT-qPCR showed generally consistent expression levels with the bioinformatics results.ConclusionIn general, m6A modulators exert integral function in the pathological process of PMOP. Our study of m6A patterns may provide diagnostic biomarkers and immunotherapeutic strategies for future PMOP treatment.
Bayesian feature selection for radiomics using reliability metrics
Authors: Shoemaker Katherine , Ger Rachel , Court Laurence E. , Aerts Hugo , Vannucci Marina , Peterson Christine B. 
Published: March 2023

Introduction: Imaging of tumors is a standard step in diagnosing cancer and making subsequent treatment decisions. The field of radiomics aims to develop imaging based biomarkers using methods rooted in artificial intelligence applied to medical imaging. However, a challenging aspect of developing predictive models for clinical use is that many quantitative features derived from image data exhibit instability or lack of reproducibility across different imaging systems or image-processing pipelines.Methods: To address this challenge, we propose a Bayesian sparse modeling approach for image classification based on radiomic features, where the inclusion of more reliable features is favored via a probit prior formulation.Results: We verify through simulation studies that this approach can improve feature selection and prediction given correct prior information. Finally, we illustrate the method with an application to the classification of head and neck cancer patients by human papillomavirus status, using as our prior information a reliability metric quantifying feature stability across different imaging systems.
Transcriptomic profiles of age-related genes in female trachea and bronchus
Authors: Liu Jia , Lu Haiyan , Hu Silu , Wang Faping , Tang Xiaoju , Wan Huajing , Luo Fengming 
Published: March 2023

Background: Studies demonstrated that age-related cellular and functional changes of airway significantly contribute to the pathogenesis of many airway diseases. However, our understanding on the age-related molecular alterations of human airway remains inadequate.Methods: Airway (trachea and bronchus) brushing specimens were collected from 14 healthy, female non-smokers with ages ranging from 20 to 60 years. Bulk RNA sequencing was performed on all the specimens (n = 28). Airway cell types and their relative proportions were estimated using CIBERSORTx. The cell type proportions were compared between the younger (age 20–40) and elder group (age 40–60) in the trachea and bronchus respectively. The linear association between cell type proportion and age was assessed using the Pearson correlation coefficient. Differentially expressed genes (DEGs) between the two age groups were identified using DESeq2. Three kinds of enrichment analysis of the age-related DEGs were performed, including Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and disease enrichment analysis.Results: Sixteen and thirteen cell types were separately identified in tracheal and bronchial brushings, with the airway epithelial cells (including suprabasal, submucosal gland (SMG) goblet, serous, secretory, multiciliated, cycling.basal, basal cells) accounting for 85.1% in the trachea and 92.5% in the bronchus. The lymphatic cell and NK cells had a higher abundance ratio in the trachea, compared with the bronchus. The proportion of basal cells was negatively related to age both in the trachea and bronchus. Thirty-one and fifty-two age-related DEGs (p &lt; 0.1) were identified in the trachea and bronchus, respectively. Among them, five common DEGs (CXCL2, CXCL8, TCIM, P4HA3, AQP10) were identified. Pathway enrichment analysis showed both tracheal and bronchial age-related DEGs were primarily involved in immune regulatory signaling pathways (TNF, NF-kappa B, IL-17 et al.). Disease enrichment analysis suggested that tracheal age-related DEGs significantly related to asthmatic pulmonary eosinophilia, and chronic airflow obstruction et al., and that bronchial age-related DEGs were enriched in airflow obstruction, bronchiectasis, pulmonary emphysema, and low respiratory tract infection et al.Conclusion: We found the proportion of basal cells decreased with age in both the trachea and bronchus, suggesting a weakening of their self-renew ability with age. We identified transcriptomic signature genes associated with the early aging process of the human trachea and bronchus, and provided evidence to support that changes in their immune regulatory function may play critical roles in age-related airway diseases.
Relevance of TMPRSS2, CD163/CD206, and CD33 in clinical severity stratification of COVID-19
Authors: Martínez-Diz Silvia , Marín-Benesiu Fernando , López-Torres Ginesa , Santiago Olivia , Díaz-Cuéllar José F. , Martín-Esteban Sara , Cortés-Valverde Ana I. , Arenas-Rodríguez Verónica , Cuenca-López Sergio , Porras-Quesada Patricia , Ruiz-Ruiz Carmen , Abadía-Molina Ana C. , Entrala-Bernal Carmen , Martínez-González Luis J. , Álvarez-Cubero Maria Jesus 
Published: March 2023

BackgroundApproximately 13.8% and 6.1% of coronavirus disease 2019 (COVID-19) patients require hospitalization and sometimes intensive care unit (ICU) admission, respectively. There is no biomarker to predict which of these patients will develop an aggressive stage that we could improve their quality of life and healthcare management. Our main goal is to include new markers for the classification of COVID-19 patients.MethodsTwo tubes of peripheral blood were collected from a total of 66 (n = 34 mild and n = 32 severe) samples (mean age 52 years). Cytometry analysis was performed using a 15-parameter panel included in the Maxpar® Human Monocyte/Macrophage Phenotyping Panel Kit. Cytometry by time-of-flight mass spectrometry (CyTOF) panel was performed in combination with genetic analysis using TaqMan® probes for ACE2 (rs2285666), MX1 (rs469390), and TMPRSS2 (rs2070788) variants. GemStone™ and OMIQ software were used for cytometry analysis.ResultsThe frequency of CD163+/CD206- population of transitional monocytes (T-Mo) was decreased in the mild group compared to that of the severe one, while T-Mo CD163-/CD206- were increased in the mild group compared to that of the severe one. In addition, we also found differences in CD11b expression in CD14dim monocytes in the severe group, with decreased levels in the female group (p = 0.0412). When comparing mild and severe disease, we also found that CD45- [p = 0.014; odds ratio (OR) = 0.286, 95% CI 0.104–0.787] and CD14dim/CD33+ (p = 0.014; OR = 0.286, 95% CI 0.104–0.787) monocytes were the best options as biomarkers to discriminate between these patient groups. CD33 was also indicated as a good biomarker for patient stratification by the analysis of GemStone™ software. Among genetic markers, we found that G carriers of TMPRSS2 (rs2070788) have an increased risk (p = 0.02; OR = 3.37, 95% CI 1.18–9.60) of severe COVID-19 compared to those with A/A genotype. This strength is further increased when combined with CD45-, T-Mo CD163+/CD206-, and C14dim/CD33+.ConclusionsHere, we report the interesting role of TMPRSS2, CD45-, CD163/CD206, and CD33 in COVID-19 aggressiveness. This strength is reinforced for aggressiveness biomarkers when TMPRSS2 and CD45-, TMPRSS2 and CD163/CD206, and TMPRSS2 and CD14dim/CD33+ are combined.
Efficacy and safety of Iguratimod as an add-on therapy for refractory lupus nephritis: A preliminary investigational study
Authors: Yan Qingran , Zhang Mei , Du Fang , Kang Yuening , Ye Ping , Li Qianqian , Liu Bei , Dai Min , Bao Chunde 
Published: March 2023

ObjectivesIGU (IGU), a novel immunomodulatory agent for rheumatoid arthritis, has been shown to be effective and safe as monotherapy in a small population with refractory lupus nephritis (LN). The aim of this prospective study was to evaluate the efficacy and safety of IGU as an add-on therapy in patients with refractory LN in the context of clinical practice.MethodsThis is a single-arm observational study. We have enrolled LN patients since 2019 at Renji Hospital. All participants should have recurrent or refractory LN with at least one immunosuppressant (IS) and have a baseline urine protein/creatinine ratio (UPCR) &gt;1.0. After enrollment, we added IGU (25 mg twice daily) to one of their previous immunosuppressants (IS) without increasing the dose of steroids. The primary outcome was the complete renal response (CRR) in the 6th month. UPCR decrease of over 50% was defined as partial response (PR). Extended follow-up was performed after the initial 6 months.ResultsWe enrolled 26 eligible participants. 11/26 patients had chronic kidney disease (CKD) stage 2/3 at the baseline. The IS combined with IGU included mycophenolate mofetil, tacrolimus, and cyclosporin A. No IS change was allowed. 80.7% of patients had baseline steroids less than 0.5mg/kg daily and there was no steroids escalation during the IGU treatment. The CRR rate was 42.3% (11/26) at month 6. With a median follow-up of 52 weeks (range: 23-116 weeks), the CRR rate at the last visit was 50% (13/26) and 73.1% (19/26) of patients had UPCR decrease of over 50%. Six patients withdrew, three for no response and three for renal flare after initial CRR. One patient had an estimated glomerular filtration rate worsening of over 20% and was classified as renal flare. Three mild to moderate adverse events were recorded.ConclusionsOur investigation merits further investigation in IGU as a potentially tolerable component of combination therapy for refractory LN.
Effect of postoperative systemic prednisolone on short-term and long-term outcomes in chronic rhinosinusitis with nasal polyps: A multi-centered randomized clinical trial
Authors: Mueller Sarina K. , Wendler Olaf , Mayr Susanne , Traxdorf Maximilian , Hosemann Werner , Olze Heidi , Steinhart Helmut , Wiegand Susanne , Teymoortash Afshin , Kuehnel Thomas , Hackenberg Stephan , Hummel Thomas , Ambrosch Petra , Fazel Azita , Schick Bernhard , Baenkler Hanns-Wolf , Koch Michael , Buerner Harald , Mantsopoulos Konstantinos , Grundtner Philipp , Nocera Angela , Agaimy Abbas , Bleier Benjamin , Iro Heinrich 
Published: March 2023

IntroductionThe objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures.MethodsThis was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels.Results106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p&gt;0.05 for all). Reported adverse events were similar between the two groups.ConclusionIn conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.
Integrative bioinformatics analysis to identify novel biomarkers associated with non-obstructive azoospermia
Authors: Zhong Yucheng , Zhao Jun , Deng Hao , Wu Yaqin , Zhu Li , Yang Meiqiong , Liu Qianru , Luo Guoqun , Ma Wenmin , Li Huan 
Published: March 2023

AimThis study aimed to identify autophagy-related genes (ARGs) associated with non-obstructive azoospermia and explore the underlying molecular mechanisms.MethodsTwo datasets associated with azoospermia were downloaded from the Gene Expression Omnibus database, and ARGs were obtained from the Human Autophagy-dedicated Database. Autophagy-related differentially expressed genes were identified in the azoospermia and control groups. These genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, protein–protein interaction (PPI) network, and functional similarity analyses. After identifying the hub genes, immune infiltration and hub gene–RNA-binding protein (RBP)–transcription factor (TF)–miRNA–drug interactions were analyzed.ResultsA total 46 differentially expressed ARGs were identified between the azoospermia and control groups. These genes were enriched in autophagy-associated functions and pathways. Eight hub genes were selected from the PPI network. Functional similarity analysis revealed that HSPA5 may play a key role in azoospermia. Immune cell infiltration analysis revealed that activated dendritic cells were significantly decreased in the azoospermia group compared to those in the control groups. Hub genes, especially ATG3, KIAA0652, MAPK1, and EGFR were strongly correlated with immune cell infiltration. Finally, a hub gene–miRNA–TF–RBP–drug network was constructed.ConclusionThe eight hub genes, including EGFR, HSPA5, ATG3, KIAA0652, and MAPK1, may serve as biomarkers for the diagnosis and treatment of azoospermia. The study findings suggest potential targets and mechanisms for the occurrence and development of this disease.
Chronic cold-stress induced histopathological changes, oxidative stress, and alterations in liver functions and nutrient composition of hybrid red tilapia and the potential protection of unsaturated fatty acids
Authors: Refaey Mohamed M. , Mehrim Ahmed I. , El-Komy Magda M. , Zenhom Osama A. , Mansour Abdallah Tageldein 
Published: March 2023

The hybrid red tilapia (♂Oreochromis niloticus × ♀O. mossambicus) is a promising tilapia fish with high growth rate, market acceptability, and the ability to live in a wide range of salinities, but it is sensitive to low water temperature. Therefore, the objective of this experiment was to improve hybrid red tilapia resistance to chronic cold stress by increasing unsaturated fatty acids and evaluating their effects on fish body weight, hepatosomatic index (HSI), body nutrient composition, liver function enzymes, histopathological alterations, and biomarkers of oxidative stress in the gills and liver. For 98 days, fish were fed four diets based on two dietary fat sources: corn oil (a traditional source) and Aquafat-O® (a commercial product rich in high polyunsaturated fatty acids), in different ratios of 3:0 (T0), 2:1 (T1), 1:2 (T2), and 0:3 (T3), respectively. Subsequently, all groups (T0+, T1, T2, and T3) were subjected to water cold stress at 13 °C for 15 days, with half of the control group serving as a negative control (T0-; at a rearing water temperature of 25-26 °C). Chronic old stress caused significant reductions in fish body weight, HSI, aspartate transaminase and alanine transaminase activities, fat and energy contents, and oxidative stress biomarkers in the liver and gills. Red tilapia subjected to low temperatures showed severely altered histopathological conditions in the liver and gills. However, by gradually increasing the Aquafat-O® ratio in the diet, the negative effects of cold stress were mitigated. Thus, it could be concluded that the beneficial use of Aquafat-O® (as a promising fat source) at a percentage of up to 69.60 g kg-1 is necessary to cope with the cold-water stress for sensitive hybrid red tilapia.
Effect of acupuncture on the modulation of functional brain regions in migraine: A meta-analysis of fMRI studies
Authors: Li Mengyuan , Huang Haipeng , Yao Lin , Yang Hongmei , Ma Shiqi , Zheng Haizhu , Zhong Zhen , Yu Shuo , Yu Bin , Wang Hongfeng 
Published: March 2023

BackgroundAcupuncture, a traditional Chinese medicine therapy, is an effective migraine treatment, especially in improving pain. In recent years, many acupuncture brain imaging studies have found significant changes in brain function following acupuncture treatment of migraine, providing a new perspective to elucidate the mechanism of action of acupuncture.ObjectiveTo analyse and summarize the effects of acupuncture on the modulation of specific patterns of brain region activity changes in migraine patients, thus providing a mechanism for treating migraine by acupuncture.MethodsChinese and English articles published up to May 2022 were searched in three English databases (PubMed, Embase and Cochrane) and four Chinese databases (China national knowledge infrastructure, CNKI; Chinese Biomedical Literature database, CBM; the Chongqing VIP database, VIP; and the Wanfang database, WF). A neuroimaging meta-analysis on ALFF, ReHo was performed on the included studies using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software. Subgroup analyses were used to compare differences in brain regions between acupuncture and other groups. Meta-regression was used to explore the effect of demographic information and migraine alterations on brain imaging outcomes. Linear models were drawn using MATLAB 2018a, and visual graphs for quality evaluation were produced using R and RStudio software.ResultsA total of 7 studies comprising 236 patients in the treatment group and 173 in the control group were included in the meta-analysis. The results suggest that acupuncture treatment helps to improve pain symptoms in patients with migraine. The left angular gyrus is hyperactivation, and the left superior frontal gyrus and the right superior frontal gyrus are hypoactivated. The migraine group showed hyperactivation in the corpus callosum compared to healthy controls.ConclusionAcupuncture can significantly regulate changes in brain regions in migraine patients. However, due to the experimental design of neuroimaging standards are not uniform, the results also have some bias. Therefore, to better understand the potential mechanism of acupuncture on migraine, a large sample, multicenter controlled trial is needed for further study. In addition, the application of machine learning methods in neuroimaging studies could help predict the efficacy of acupuncture and screen migraine patients suitable for acupuncture treatment.
Outcome and clinical features in juvenile myasthenia gravis: A systematic review and meta-analysis
Authors: Lin Yangtao , Kuang Qianjin , Li Hongjin , Liang Bo , Lu Jiaxin , Jiang Qilong , Yang Xiaojun 
Published: March 2023

BackgroundJuvenile myasthenia gravis (JMG) is a rare autoimmune disease that has so far only been described in small cohort studies. We defined the clinical characteristics, management, and outcomes of JMG patients over the past 22 years.MethodsA search of PubMed, EMBASE, and web of science (1/2000–2/2022) identified all English language and human studies of JMG. The population was patients diagnosed with JMG. Outcomes included the history of myasthenic crisis, autoimmune comorbidity, mortality, and treatment outcome. Data extraction was performed by independent reviewers. And we performed a pooled reanalysis of all published data in the included studies and compared with other studies of adult cohorts.ResultsWe identified 11 articles describing 1,109 patients diagnosed between 2006 and 2021. JMG occurred in 60.4% of female patients. The mean age at presentation was 7.38 years old, and 60.6% of the patients had ocular symptoms as the first clinical manifestation. The most common initial presentation was ptosis, which occurred in 77.7% patients. AchR-Ab positive accounted for 78.7%. 641 patients received thymus examination, found to have thymic hyperplasia in 64.9% and thymoma in 2.2%. Autoimmune comorbidity was found in 13.6% and the most common one is thyroid disease (61.5%). First-line therapy, including pyridostigmine and steroids, was initiated in 97.8 and 68.6%, respectively. Six patients resolved spontaneously without treatment. Thymectomy was performed in 45.6%. 10.6% of patients had a history of myasthenic crisis. Completely stable remission was achieved in 23.7% and mortality was reported in 2 studies, which reported 8 deaths.ConclusionJMG is a rare disease with a relatively benign course, and differs from adult MG in some clinical features. The treatment regimen guideline for children is still not well-established. There is a need for prospective studies to properly evaluate treatment regimes.