Machine learning-based radiomics strategy for prediction of acquired EGFR T790M mutation following treatment with EGFR-TKI in NSCLC.

The epidermal growth factor receptor (EGFR) Thr790 Met (T790M) mutation is responsible for approximately half of the acquired resistance to EGFR-tyrosine kinase inhibitor (TKI) in non-small-cell lung cancer (NSCLC) patients. Identifying patients at diagnosis who are likely to develop this mutation after first- or second-generation EGFR-TKI treatment is crucial for better treatment outcomes. This study aims to develop and validate a radiomics-based machine learning (ML) approach to predict the T790M mutation in NSCLC patients at diagnosis. We collected retrospective data from 210 positive EGFR mutation NSCLC patients, extracting 1316 radiomics features from CT images. Using the LASSO algorithm, we selected 10 radiomics features and 2 clinical features most relevant to the mutations. We built models with 7 ML approaches and assessed their performance through the receiver operating characteristic (ROC) curve. The radiomics model and combined model, which integrated radiomics features and relevant clinical factors, achieved an area under the curve (AUC) of 0.80 (95% confidence interval [CI] 0.79-0.81) and 0.86 (0.87-0.88), respectively, in predicting the T790M mutation. Our study presents a convenient and noninvasive radiomics-based ML model for predicting this mutation at the time of diagnosis, aiding in targeted treatment planning for NSCLC patients with EGFR mutations.

Association of Self-Leadership With Acute Stress Responses and Acute Stress Disorders in Chinese Medics During the COVID-19 Pandemic: A Cross-Sectional Study.

Background: The outbreak of the highly infectious coronavirus disease 2019 (COVID-19) renders a huge physical and psychological risk to the public, especially to the medics. Additionally, self-leadership has proven to improve self-efficacy and mediate tension, such as nervousness and depression. Therefore, a cross-sectional survey was conducted to explore the association of self-leadership with acute stress responses (ASRs) and acute stress disorders (ASDs) in medics during the COVID-19 epidemic. Methods: Self-reported online questionnaires were administered, and 627 participants were finally included. The data were analyzed using the univariate analysis and the logistical regression model to identify whether self-leadership and sociodemographic and epidemic characteristics were associated with mental health, including ASRs and ASDs. Results: Initially, 790 medics responded. Of these, 627 remained after excluding for invalid questionnaires and those with a substantial amount of missing data. Therefore, the participation validity rate was 79.37%. Frontline medical staff (ß = 0.338; p < 0.001), possibility of infection among people around the medic being mild (ß = 0.141; p < 0.001), subjective estimation of epidemic duration being 3-6 months (ß = 0.074; p < 0.05), self-sets (ß = -0.022; p < 0.001), self-punishment (ß = 0.229; p < 0.001), belief hypothesis and evaluation (ß = -0.147; p < 0.05), and successful foresight (ß = 0.105; p < 0.05) were statistically significant with ASRs. Marital status [adjusted odds ratio (AOR) =1.813; 95% CI (1.141, 2.881); p = 0.012], being a frontline worker [AOR = 25.760; 95% CI (14.220, 46.667); p < 0.001], visiting Hubei in the previous 14 days [AOR = 3.656; 95% CI (1.500, 8.911); p = 0.004], self-punishment [AOR = 1.352; 95% CI (1.180, 1.548); p < 0.001], and self-dialogue [AOR = 1.256; 95% CI (11.063, 1.483); p = 0.007] were the risk factors for ASD. Conversely, having frontline medical staff in one's family [AOR = 0.523; 95% CI (0.297, 0.923); p = 0.025], self-sets [AOR = 0.814; 95% CI (0.715, 0.826); p = 0.002], and belief hypothesis and evaluation [AOR = 0.796; 95% CI (0.672, 0.943); p = 0.038] were the protective factors. Conclusion: The special working environment of the COVID-19 epidemic resulted in ASR and ASD. Notably, findings revealed a positive association between ASR symptoms and frontline medical staff, the subjective estimation of epidemic duration, self-punishment, and successful foresight. Nevertheless, marital status, having visited Hubei in the previous 14 days, and self-dialogue were the risk factors accounting for ASD symptoms. Surprisingly, having frontline medical staff in one's family, self-sets, and belief hypothesis and evaluation had potential benefits for ASD symptoms.

Interleukin­27 ameliorates allergic asthma by alleviating the lung Th2 inflammatory environment.

Interleukin (IL)­27 can inhibit the differentiation of Th2 cells and plays a role in the development of asthma. However, whether the therapeutic administration of IL­27 in a mouse model of asthma can inhibit allergic responses remains a matter of debate. Additionally, the mechanisms through which IL­27 ameliorates inflammatory responses in asthma are not yet fully understood. Thus, the aim of the present study was to examine the effects of IL­27 on asthma using a mouse model and to elucidate the underlying mechanisms. For this purpose, mice received an intranasal administration of IL­27 and the total and differential cell counts, levels of cytokines and type 1 regulatory T (Tr1) cells in the lungs were detected. The protein and mRNA levels of signal transducer and activator of transcription (STAT)1 and STAT3 were analyzed and airway remodeling was assessed. The results indicated that IL­27 did not ameliorate airway inflammation, airway hyperresponsiveness, and airway remolding when administrated therapeutically. Preventatively, the administration of IL­27 decreased the concentrations of Th2 cytokines and increased the number of Tr1 cells. The protein and mRNA levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrate that the prophylactic administration of IL­27 ameliorates asthma by alleviating the lung Th2 inflammatory environment through the restoration of both the STAT1 and STAT3 pathways. IL­27 may thus prove to be useful as a novel agent for the prevention of asthma.

Machine Learning-Based Radiomics for Prediction of Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma.

Identifying an epidermal growth factor receptor (EGFR) mutation is important because EGFR tyrosine kinase inhibitors are the first-line treatment of choice for patients with EGFR mutation-positive lung adenocarcinomas (LUAC). This study is aimed at developing and validating a radiomics-based machine learning (ML) approach to identify EGFR mutations in patients with LUAC. We retrospectively collected data from 201 patients with positive EGFR mutation LUAC (140 in the training cohort and 61 in the validation cohort). We extracted 1316 radiomics features from preprocessed CT images and selected 14 radiomics features and 1 clinical feature which were most relevant to mutations through filter method. Subsequently, we built models using 7 ML approaches and established the receiver operating characteristic (ROC) curve to assess the discriminating performance of these models. In terms of predicting EGFR mutation, the model derived from radiomics features and combined models (radiomics features and relevant clinical factors) had an AUC of 0.79 (95% confidence interval (CI): 0.77-0.82), 0.86 (0.87-0.88), respectively. Our study offers a radiomics-based ML model using filter methods to detect the EGFR mutation in patients with LUAC. This convenient and low-cost method may be of help to noninvasively identify patients before obtaining tumor sample for molecule testing.

Relationship Between Acute Stress Responses and Quality of Life in Chinese Health Care Workers During the COVID-19 Outbreak.

This study aimed to determine the relationship between acute stress and quality of life and explore their influencing factors on health care workers. A descriptive cross-sectional study was conducted, and a sample of 525 health care workers was recruited from 15 hospitals through a convenient sampling method. Participants completed an online self-report questionnaire to assess their acute stress and quality of life. Descriptive and multiple linear regression statistics were used for this analysis. The results regarding acute stress responses varied significantly among the differences in marital status, physical activity, work status, perceived risk of contracting COVID-19, and the expected duration of the pandemic. Moreover, a younger age, lack of physical activity, being a front-line medical staff, and higher acute stress scores indicated a worse quality of life. Healthcare workers' acute stress was negatively correlated with their quality of life. Therefore, the authorities should pay special attention to health care workers' mental health and provide them with timely protection during the pandemic.

MicroRNA expression profiles analysis of apheresis platelets treated with vitamin B2 and ultraviolet-B during storage.

Whether platelet (PLT) microRNA (miRNA) profiles are affected by pathogen reduction technology (PRT) using vitamin B2 and ultraviolet-B (VB2-PRT) remains unclear. Samples from VB2-PRT-treated (experimental group, E_) and untreated (control group, C_) apheresis PLTs were taken on days 1, 3 and 5 of storage, designated as E_1, E_3, E_5, C_1, C_3 and C_5, respectively. The miRNA expression profiles were assessed by DNA Nano Ball (DNB) sequencing technology, and verified by quantitive real-time fluorescence quantitative PCR (qRT-PCR). Compared with the expression profiles of PLT miRNAs, 3895 miRNAs were identified in the E_ groups while 4106 were in the C_ groups. There were 487 significant differentially expressed miRNAs in E_1 vs C_1 group, including 220 upregulated and 287 downregulated, such as miR-146a-5p and let-7b-5p. There were 908 significant differentially expressed miRNAs in E_3 vs C_3 group, including 297 upregulated and 611 downregulated, such as miR-142-5p and miR-7-5p. There were 229 significant differentially expressed miRNAs in E_5 vs C_5 group, including 80 upregulated and 149 downregulated, such as miR-3529-3p and miR-451a. These differentially expressed miRNAs had been suggested to have functional roles in energy homeostasis, cell communication, proliferation, migration and apoptosis. GO analysis showed a significant enrichmen in relevant biological process categories as receptor activity, signal transduction, cell transport, motility and chemotaxis. The significantly enriched KEGG pathway of predicted target genes was Glycosaminoglycan biosynthesis in E_ vs C_ groups. These new observation could provide insights on the understanding of change of miRNA profiles of PLT treated with VB2-PRT.

[Analysis of miRNA-326's action on its target gene BCL-XL].

OBJECTIVE: To analyze the action of miRNA-326 on its target gene BCL-XL and the molecular mechanism of platelet apoptosis regulated by miRNAs. METHODS: Dual-luciferase vectors containing respectively the wild-type and mutant 3'-untranslated region (3'UTR) fragments of the BCL-XL gene were constructed with firefly and renilla luciferases and transfected into 293T cells. Relative fluorescence intensities of the transfected cells were measured. RESULTS: Dual-luciferase reporter gene vectors for PsiCHECK- BCL-XL -3'UTR-WT (wild-type) and PsiCHECK- BCL-XL -3' UTR-MT (variant) were respectively constructed. Relative fluorescence intensities of the 293T cells co-transfected by miRNA-326 and PsiCHECK- BCL-XL -3'UTR-WT plasmid were significantly lower compared with the control group (co-transfected by a miRNA-326 negative sequence and PsiCHECK- BCL-XL -3' UTR-WT plasmid) ( P = 0.034). The relative fluorescence intensity was also significantly reduced in cells co-transfected by miRNA-326 and PsiCHECK- BCL-XL -3' UTR-WT plasmid compared with the mutant control group co-transfected by miRNA-326 and PsiCHECK- BCL-XL -3'UTR-MT plasmid (P = 0.022). CONCLUSION: miRNA-326 may participate in the regulation of platelet apoptosis by acting on the 3'-UTR of the BCL-XL gene.

IL­27 suppresses airway inflammation, hyperresponsiveness and remodeling via the STAT1 and STAT3 pathways in mice with allergic asthma.

Type 2 cytokine­associated immunity may be involved in the pathogenesis of allergic asthma. Although interleukin 27 (IL­27) has been reported as an initiator and suppressor of T­helper 1 (Th1) and T­helper 2 (Th2) responses, respectively, its effects on the development of asthma remain unclear. In the present study, mice were induced and challenged with ovalbumin and received subsequent intranasal administration of IL­27. Total and differential cell counts were determined from Wright­Giemsa­stained cytospins, whereas the cytokine levels were detected using ELISA. In addition, the expression levels of signal transducer and activator of transcription (STAT) 1, STAT3, GATA­binding protein­3 (GATA3) and T­bet (T­box transcription factor) were analyzed in T cells by western blot analysis. Their corresponding mRNA expression levels were determined by quantitative PCR. Airway remodeling was assessed by conventional pathological techniques. The results indicated that intranasal administration of IL­27 ameliorated airway inflammation and hyperresponsiveness in an acute model of asthma. Furthermore, IL­27 prevented airway remodeling in a chronic model of asthma. Following administration of IL­27, the mRNA expression levels of STAT1 and T­bet were upregulated, while those of GATA3 were downregulated. Moreover, the phosphorylation levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrated that intranasal administration of IL­27 ameliorated Th2­related allergic lung inflammation and remodeling in mouse models of asthma by repairing both the STAT1 and STAT3 pathways.

Association of Inflammatory Cytokines With the Symptom Cluster of Pain, Fatigue, Depression, and Sleep Disturbance in Chinese Patients With Cancer.

CONTEXT: Pain, fatigue, depression, and sleep disturbance are common in patients with cancer and usually co-occur as a symptom cluster. However, the mechanism underlying this symptom cluster is unclear. OBJECTIVES: This study aimed to identify subgroups of cluster symptoms, compare demographic and clinical characteristics between subgroups, and examine the associations between inflammatory cytokines and cluster symptoms. METHODS: Participants were 170 Chinese inpatients with cancer from two tertiary hospitals. Inflammatory markers including interleukin-6 (IL-6), interleukin-1 receptor antagonist, and tumor necrosis factor alpha were measured. Intergroup differences and associations of inflammatory cytokines with the cluster symptoms were examined with one-way analyses of variance and logistic regression. RESULTS: Based on cluster analysis, participants were categorized into Subgroup 1 (all low symptoms), Subgroup 2 (low pain and moderate fatigue), or Subgroup 3 (moderate-to-high on all symptoms). The three subgroups differed significantly in Eastern Cooperative Oncology Group (ECOG) performance status, sex, residence, current treatment, education, economic status, and inflammatory cytokines levels (all P < 0.05). Compared with Subgroup 1, Subgroup 3 had a significantly poorer ECOG physical performance status and higher IL-6 levels, were more often treated with combined chemoradiotherapy, and were more likely to be rural residents. IL-6 and ECOG physical performance status were significantly associated with 1.246-fold (95% CI 1.114-1.396) and 31.831-fold (95% CI 6.017-168.385) increased risk of Subgroup 3. CONCLUSION: Our findings suggest that IL-6 levels are associated with cluster symptoms in cancer patients. Clinicians should identify patients at risk for more severe symptoms and formulate novel target interventions to improve symptom management.

Alterations of pulmonary function in patients with inflammatory bowel diseases.

AIM: The aim of this study was to investigate the alterations of pulmonary function tests (PFTs) and their relationship with disease activity in inflammatory bowel diseases (IBDs). METHODS: Sixty-four IBD patients (31 Crohn's disease [CD] and 33 ulcerative colitis [UC]) and thirty healthy individuals (controls) were studied with regard to the following parameters of PFTs: Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio, mid-forced expiratory flow of 25-75% (FEF 25-75), residual volume, total lung capacity, and diffusing capacity of the lung for carbon monoxide (DLCO). The disease activity was calculated using the Crohn's Disease Activity Index for CD and Mayo Clinic Score for UC. Correlation analysis was performed between disease activity and sputum cytology and PFTs. RESULTS: Nineteen of the 31 CD patients (61.29%) and 17 of the 33 UC patients (51.52%) but none of the controls showed at least one abnormal PFTs (P < 0.05). Compared with controls, both CD and UC patients exhibited a significant reduction in FEV1 (P < 0.05), FVC (P < 0.05), FEF 25-75 (P < 0.05), and DLCO (P < 0.05). The majority with decreased measurements of PFTs were in the active phase of diseases (P < 0.05). IBD activity scores correlated negatively with some parameters of PFTs and positively with lymphocytosis and eosinophilia of sputum (P < 0.05). CONCLUSIONS: Pulmonary function disorders are significantly common in IBD patients. The impairment in active disease is significantly greater than in remission.