Replicability in cancer omics data analysis: measures and empirical explorations.

In biomedical research, the replicability of findings across studies is highly desired. In this study, we focus on cancer omics data, for which the examination of replicability has been mostly focused on important omics variables identified in different studies. In published literature, although there have been extensive attention and ad hoc discussions, there is insufficient quantitative research looking into replicability measures and their properties. The goal of this study is to fill this important knowledge gap. In particular, we consider three sensible replicability measures, for which we examine distributional properties and develop a way of making inference. Applying them to three The Cancer Genome Atlas (TCGA) datasets reveals in general low replicability and significant across-data variations. To further comprehend such findings, we resort to simulation, which confirms the validity of the findings with the TCGA data and further informs the dependence of replicability on signal level (or equivalently sample size). Overall, this study can advance our understanding of replicability for cancer omics and other studies that have identification as a key goal.

Exploring the diagnostic value of endothelial cell and angiogenesis-related genes in Hashimoto's thyroiditis based on transcriptomics and single cell RNA sequencing.

(1) BACKGROUND: Hashimoto's thyroiditis (HT) can cause angiogenesis in the thyroid gland. However, the molecular mechanism of endothelial cells and angiogenesis related genes (ARGs) has not been extensively studied in HT. (2) METHODS: The HRA001684, GSE29315 and GSE163203 datasets were included in this study. Using single-cell analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, machine learning algorithms and expression analysis for exploration. And receiver operator characteristic (ROC) curves was draw. Gene set enrichment analysis (GSEA) was utilized to investigate the biological function of the biomarkers. Meanwhile, we investigated into the relationship between biomarkers and different types of immune cells. Additionally, the expression of biomarkers in the TCGA-TC dataset was examined and the mRNA-drug interaction network was constructed. (3) RESULTS: We found 14 cell subtypes were obtained in HT samples after single-cell analysis. A total of 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were derived, and they had excellent diagnostic performance. Then, 27 drugs targeting biomarkers were predicted. The expression analysis showed that CD74 and HLA-B were significantly up-regulated in HT samples. (4) CONCLUSION: In this study, 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were screened and their expressions in endothelial cells was compared to offer a new reference for the recognition and management of HT.

Dietary ferulic acid supplementation improves antioxidant capacity and lipid metabolism in liver of piglets with intrauterine growth retardation.

Intrauterine growth retardation (IUGR) can result in early liver oxidative damage and abnormal lipid metabolism in neonatal piglets. Ferulic acid (FA), a phenolic compound widely found in plants, has many biological functions, such as anti-inflammation and anti-oxidation. Thus, we explored the effects of dietary FA supplementation on antioxidant capacity and lipid metabolism in newborn piglets with IUGR. In the study, 24 7-day-old piglets were divided into three groups: normal birth weight (NBW), IUGR, and IUGR + FA. The NBW and IUGR groups were fed formula milk as a basal diet, while the IUGR + FA group was fed a basal diet supplemented with 100 mg/kg FA. The trial lasted 21 days. The results showed that IUGR decreased absolute liver weight, increased transaminase activity, reduced antioxidant capacity, and disrupted lipid metabolism in piglets. Dietary FA supplementation enhanced absolute liver weight, reduced serum MDA level and ROS concentrations in serum and liver, markedly increased serum and liver GSH-PX and T-SOD activities, decreased serum HDL-C and LDL-C and liver NEFA, and increased TG content and HL activity in the liver. The mRNA expression related to the Nrf2-Keap1 signaling pathway and lipid metabolism in liver were affected by IUGR. Supplementing FA improved the antioxidant capacity of liver by down-regulating Keap1 and up-regulating the mRNA expression of SOD1 and CAT, and regulated lipid metabolism by increasing the mRNA expression level of Fasn, Pparα, LPL, and CD36. In conclusion, the study suggests that FA supplementation can improve antioxidant capacity and alleviate lipid metabolism disorders in IUGR piglets.

Cross-cultural adaptation, validity and reliability of the Chinese Version of Miller Behavioral Style Scale.

BACKGROUND: Health education basing on patients' information-seeking styles can improve the effectiveness of health education and patients' health outcomes. The Miller Behavioral Style Scale (MBSS) is widely used to identify individual's information-seeking styles, but the Chinese version is lacking. The study aim was to translate and culturally adapt the MBSS into Chinese version and test the content validity, construct validity and internal consistency reliability of the Chinese version of MBSS (C-MBSS). METHODS: The forward-back-translation procedure was adopted in the translation of the MBSS. Content validity was assessed in a panel of experts. In a sample of 1343 individuals including patients, patients' caregivers, university students, and medical staff, reliability and construct validity were assessed using Cronbach's alpha coefficient and factor analysis. The measurement invariance across samples was tested using multigroup confirmatory factor analysis (MGCFA). Floor and ceiling effects were checked. RESULTS: The C-MBSS achieved conceptual and semantic equivalence with the original scale. The item-level content validity index (I-CVI) of each item ranged from 0.78 to 1, and the averaging scale-level content validity index (S-CVI/ Ave) was 0.95. The exploratory factor analysis resulted in 2-factor assumption for each hypothetical threat-evoking scenario. Confirmatory factor analysis demonstrated a good fit between theoretical model and data, which provided confirmatory evidence for the second-order factor structure of 2-factor solution (Monitoring and Blunting). The Cronbach's alpha coefficients for the Monitoring and Blunting sub-scales of the C-MBSS were 0.75 and 0.62 respectively. MGCFA results supported the measurement invariance for the Monitoring sub-scale of the C-MBSS across samples. No floor or ceiling effects occurred. CONCLUSIONS: This study indicates that the C-MBSS has good content and construct validity. The Monitoring sub-scale of the C-MBSS had acceptable internal consistency reliability while the Blunting sub-scale had unsatisfactory one, which suggest that the Monitoring sub-scale of the C-MBSS can be used to identify individuals' information-seeking styles in Chinese contexts across different populations.

Perceptions of patients undergoing percutaneous coronary intervention on pre-operative education in China: A qualitative study.

OBJECTIVES: To explore the perceptions of patients undergoing percutaneous coronary intervention (PCI) regarding their pre-operative health education. METHODS: A qualitative study using semi-structured, in-depth interviews was conducted in one cardiology unit in China from July 2019 to December 2019. Purposeful sampling of 17 patients undergoing PCI was interviewed about their perceptions of pre-operative health education. Thematic analysis of the transcribed data was then used to identify the themes. RESULTS: Four themes emerged from the data:(a) triple roles of pre-operative education with the categories of relief (reliving fear); burden (leading to stress); and meaningless (changing nothing); (b) family member involvement with the categories of shared responsibility and family members' duty; (c) facilitators in the process of pre-operative health education with the categories of emotional support, plain language and individualized pre-operative education; (d) inhibitors in the process of pre-operative health education with the categories of contradiction and threatening words. CONCLUSIONS: Pre-operative health education for patients undergoing PCI should be aligned with the individual patients' information-seeking styles and personal differences, emphasizing individualized patient education. Traditional Chinese philosophy should be considered in the practice of pre-operative education for patients undergoing PCI, which emphasizes family member involvement; at the same time, patient empowerment and self-care should also be stressed. In addition, emotional support and plain language from health professionals are important in pre-operative health education for patients undergoing PCI; contradiction should be avoided, and threatening words should be used with caution and with consideration for cultural variations during pre-operative education for patients undergoing PCI.

Baccalaureate nursing students' perspectives on learning about caring in China: a qualitative descriptive study.

BACKGROUND: The need to provide humanistic care in the contemporary healthcare system is more imperative now and the importance of cultivating caring in nursing education is urgent. Caring as the primary work of nursing has been discussed extensively, such as the meaning of caring, and teaching and learning strategies to improve nursing students' caring ability. Yet attempts to understand students' perspectives on learning about caring and to know their learning needs are seldom presented. The aim of this qualitative descriptive study was to explore the baccalaureate nursing students' perspectives on learning about caring in China. METHODS: A qualitative descriptive study using focus group interviews were undertaken in two colleges in Yunnan Province, China from February 2010 to April 2010. Purposeful sampling of 20 baccalaureate nursing students were recruited. Content analysis of the transcribed data was adopted to identify the themes. RESULTS: Four categories with some sub-categories related to students' perspectives on learning about caring were identified from the data: 1) Learning caring by role model; 2) conducive learning environment as the incentive to the learning about caring; 3) lack of directive substantive way of learning as the hindrance to the learning about caring; 4) lack of cultural competency as the barrier to the learning about caring. CONCLUSIONS: Both caring and uncaring experiences can promote the learning about caring in a way of reflective practice. The formal, informal and hidden curricula play an important role in the learning about caring. Cultural awareness, sensitivity and humility are important in the process of learning to care in a multicultural area.

Gallic acid pretreatment mitigates parathyroid ischemia-reperfusion injury through signaling pathway modulation.

Thyroid surgery often results in ischemia-reperfusion injury (IRI) to the parathyroid glands, yet the mechanisms underlying this and how to ameliorate IRI remain incompletely explored. Our study identifies a polyphenolic herbal extract-gallic acid (GA)-with antioxidative properties against IRI. Through flow cytometry and CCK8 assays, we investigate the protective effects of GA pretreatment on a parathyroid IRI model and decode its potential mechanisms via RNA-seq and bioinformatics analysis. Results reveal increased apoptosis, pronounced G1 phase arrest, and significantly reduced cell proliferation in the hypoxia/reoxygenation group compared to the hypoxia group, which GA pretreatment mitigates. RNA-seq and bioinformatics analysis indicate GA's modulation of various signaling pathways, including IL-17, AMPK, MAPK, transient receptor potential channels, cAMP, and Rap1. In summary, GA pretreatment demonstrates potential in protecting parathyroid cells from IRI by influencing various genes and signaling pathways. These findings offer a promising therapeutic strategy for hypoparathyroidism treatment.

Functional magnetic resonance imaging reveals dysfunction of the paraspinal muscles in patients with chronic low back pain: a cross-sectional study.

Background: Patients with chronic low back pain (CLBP) undergo structural changes of the paraspinal muscles; however, it is unclear if functional changes also occur. This study aimed to examine the metabolic and perfusion function changes in the paraspinal muscles of patients with CLBP as indirectly reflected by blood oxygen level-dependent (BOLD) imaging and T2 mapping. Methods: All participants were consecutively enrolled at our local hospital from December 2019 to November 2020. Patients were diagnosed with CLBP in the outpatient clinic, and asymptomatic participants were considered to be those with no CLBP or other diseases. This study was not registered on a clinical trial platform. Participants underwent BOLD imaging and T2 mapping scans at the L4-S1 disc level. The effective transverse relaxation rate (R2* values) and transverse relaxation time (T2 values) of the paraspinal muscles were measured on the central plane of the L4/5 and L5/S1 intervertebral discs. Finally, the independent samples t-test was used to assess the differences in R2* and T2 values between the 2 groups, while Pearson correlation analysis was used to determine their correlation with age. Results: A total of 60 patients with CLBP and 20 asymptomatic participants were enrolled. The paraspinal muscles of the CLBP group had higher total R2* values [46.7±2.9 vs. 44.0±2.9 s-1; 95% confidence interval (CI): 1.2-4.2; P=0.001] and lower total T2 values (45.4±4.2 vs. 47.1±3.7 ms; 95% CI: -3.8 to 0.4; P=0.109) than did the asymptomatic participants. For the different muscles, R2* values for the erector spinae (ES) (L4/5: 45.5±2.6 vs. 43.0±3.0 s-1, 95% CI: 1.1-4.0, P=0.001; L5/S1: 48.5±4.9 vs. 45.9±4.2 s-1; 95% CI: 0.2-5.1; P=0.035) and the R2* values of the multifidus (MF) muscles (L4/5: 46.4±2.9 vs. 43.7±3.5 s-1, 95% CI: 1.1-4.3, P=0.001; L5/S1: 46.3±3.5 vs. 42.5±2.8 s-1, 95% CI: 2.1-5.5, P<0.001) of the CLBP group at both spinal levels were higher than those of the asymptomatic participants. In the patients with CLBP, the R2* values at the L4/5 (45.9±2.1 s-1) were lower than those at the L5/S1 (47.4±3.6 s-1; 95% CI: -2.6 to -0.4; P=0.007). The R2* values were positively correlated with age in both groups (CLBP group: r=0.501, 95% CI: 0.271-0.694, P<0.001; asymptomatic group: r=0.499, 95% CI: -0.047 to 0.771; P=0.025). Conclusions: The R2* values were higher in the paraspinal muscles of patients with CLPB and may suggest metabolic and perfusion dysfunction of the paraspinal muscles in these patients.

Effects of pre-operative education tailored to information-seeking styles on pre-operative anxiety and depression among patients undergoing percutaneous coronary intervention: A randomized controlled trial.

Objective: This study aimed to evaluate the impact of pre-operative education tailored to percutaneous coronary intervention (PCI) patients' information-seeking styles on pre-operative anxiety and depression. Methods: A single-blind randomized control trial was conducted. A total of 114 participants were recruited from the cardiology department in a tertiary hospital in Kunming, Southwest China from April to September 2020 and randomly allocated to the intervention group (n = 57) or control group (n = 57). All patients received oral pre-operative education as well as printed pre-operative education manuals and divided into monitors or blunters by the Chinese Version of the Monitoring Subscale of the Miller Behavioral Style Scale (C-MMBSS). The intervention group received pre-operative education tailored to information-seeking styles, while the control group received routine education. Anxiety and depression were measured at baseline and 1 h before the operation. Satisfaction with pre-operative education and length of stay were assessed at discharge. Results: A total of 104 participants completed the study (52 participants in each group). Pre-operative education tailored to information-seeking styles was beneficial for reducing pre-operative anxiety (P < 0.01), reducing pre-operative depression (P < 0.01), and improving satisfaction with pre-operative education (P < 0.01) compared with routine education. There was no significant difference in length of stay between the intervention and control groups (P = 0.209). Conversely, pre-operative anxiety of patients was increased (P = 0.017) after pre-operative education in the control group. Conclusion: This study confirmed that pre-operative education tailored to information-seeking styles effectively reduces pre-operative anxiety and depression and improves satisfaction with preoperative education.

Pyolysin of Trueperella pyogenes Induces Pyroptosis and IL-1ß Release in Murine Macrophages Through Potassium/NLRP3/Caspase-1/Gasdermin D Pathway.

Trueperella pyogenes (T. pyogenes) is a commensal and an opportunistic pathogen of animals. This organism can cause inflammatory diseases, such as pneumonia, mastitis and endometritis in hosts. However, the molecular basis for the pro-inflammatory properties of this organism is still largely unknown. In the current study, using murine macrophages as model, the ability of T. pyogenes to induce pyroptosis was first determined. Then, pyolysin (PLO), a cholesterol-dependent cytolysin secreted by T. pyogenes, was found to be closely related to T. pyogenes-induced pyroptosis. Next, our work showed that PLO can form pores in the cell membrane, leading to the efflux of potassium (K+), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated caspase-1 activation, and gasdermin D (GSDMD) cleavage. Inhibition of the K+/NLRP3/caspase-1/GSDMD pathway abolished T. pyogenes and PLO-induced IL-1ß release. Taken together, these results indicate T. pyogenes-induced inflammation is related to PLO-induced pyroptosis and IL-1ß release. Our work shed light on the pathogenesis of T. pyogenes and the interaction between T. pyogenes and hosts' immune system.

Eugenol Attenuates Transmissible Gastroenteritis Virus-Induced Oxidative Stress and Apoptosis Via ROS-NRF2-ARE Signaling.

Transmissible gastroenteritis virus (TGEV), a coronavirus that causes severe diarrhea due to oxidative stress in the piglet intestine, is a major cause of economic loss in the livestock industry. However, limited interventions have been shown to be effective in the treatment of TGEV. Here, we demonstrate the therapeutic activity of eugenol in TGEV-induced intestinal oxidative stress and apoptosis. Our data show that eugenol supplementation protects intestine and IPEC-J2 cells from TGEV-induced damage. Mechanistically, eugenol reduces TGEV-induced oxidative stress in intestinal epithelial cells by reducing reactive oxygen species levels. Interestingly, eugenol also inhibits TGEV-induced intestinal cell apoptosis in vitro and in vivo. In conclusion, our data suggest that eugenol prevents TGEV-induced intestinal oxidative stress by reducing ROS-mediated damage to antioxidant signaling pathways. Therefore, eugenol may be a promising therapeutic strategy for TGEV infection.

Evaluation of the Potency of Two Pyolysin-Derived Recombinant Proteins as Vaccine Candidates of Trueperella Pyogenes in a Mouse Model: Pyolysin Oligomerization and Structural Change Affect the Efficacy of Pyolysin-Based Vaccines.

Trueperella pyogenes (T. pyogenes) is an important opportunistic pathogen in livestock and wild animals. However, only one commercial T. pyogenes vaccine is currently available, and its immunoprotective effect is not ideal. Pyolysin (PLO) is one of the important virulence factors expressed by T. pyogenes and one of the targets for the development of new T. pyogenes vaccines. In this study, we constructed two recombinant antigens, tPLOA1 (contains amino acids 1-110 and domain 4 of the PLO molecule) and tPLOA2 (contains amino acids 190-296 and domain 4 of the PLO molecule). Vaccines were prepared by mixing the two recombinant antigens with incomplete Freund's adjuvant or sheep red blood cell membrane and provided partial immune protection to immunized mice against the lethal challenge of T. pyogenes. Analysis of the PLO-specific IgG levels of immunized mice indicated that the antibody-inducing potency and immunoprotective efficacy of PLO-based vaccines are affected by the oligomerization and structural changes of PLO after binding to a cholesterol-containing membrane. In addition, the titer of anti-hemolysis antibodies is not a suitable indicator of the immunoprotective effect of these vaccines in PLO-based vaccine-immunized animals. The results provide new insights into the development of T. pyogenes vaccines.

Determination of the expression of three fimbrial subunit proteins in cultured Trueperella pyogenes.

BACKGROUND: Trueperella pyogenes is a commensal and a significant opportunistic pathogen in animals. A variety of identified or putative virulence factors are considered to significantly contribute to the occurrence of T. pyogenes infection in different species. However, these virulence factors are not fully understood. RESULTS: In the current study, the genes encoding putative fimbrial proteins, i.e. Fim A, Fim C, and Fim E, were cloned. Recombinant Fim A (rFim A), Fim C (rFim C), and Fim E (rFim E) were prepared and used to generate rabbit anti-rFim A, anti-rFim C, and anti-rFim E serum, respectively. Using these sera, we found that only Fim E was constitutively expressed in T. pyogenes. The expression level of Fim E in T. pyogenes peaked within 6-10 h of culture period in pH 7.5. Fim E protein expression was unaffected by anaerobic condition, but was inhibited by the microaerophilic condition. Tube agglutination tests indicated that Fim E was exhibited on the surface of T. pyogenes cells because anti-rFim E serum caused strong agglutination. Additionally, the blots for Fim A detection showed nonspecific reactions. Furthermore, the tube agglutination tests showed that anti-Fim A serum failed to cause agglutination of T. pyogenes cells, which indicated that Fim A was not, or poorly, expressed in cultured T. pyogenes. Anti-rFim C serum caused strong agglutination. However, the blots for Fim C detection showed a strong nonspecific reaction. Thus, the expression of Fim C was difficult to be determined using the current method. CONCLUSIONS: Fim E was expressed in cultured T. pyogenes. However, Fim A was either not or poorly expressed in cultured T. pyogenes. Moreover, Fim C expression was not determined using the current strategy.

The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder.

Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) network or limbic-cortico-striatal-thalamic-cortical (LCSTC) circuits in patients with major depressive disorder (MDD), but few studies have investigated the subcortical structural abnormalities. Therefore, we sought to determine whether focal subcortical grey matter (GM) changes might be present in MDD at an early stage. We recruited 30 first episode, untreated patients with major depressive disorder (MDD) and 26 healthy control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures, respectively. In addition, probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM. Compared to healthy controls, MDD patients had significant volume reductions in the bilateral putamen and left thalamus (FWE-corrected, p < 0.05). Meanwhile, the vertex-based shape analysis showed regionally contracted areas on the dorsolateral and ventromedial aspects of the bilateral putamen, and on the dorsal and ventral aspects of left thalamus in MDD patients (FWE-corrected, p < 0.05). Additionally, a negative correlation was found between local atrophy in the dorsal aspects of the left thalamus and clinical variables representing severity. Furthermore, probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen and left thalamus have connections with the frontal and temporal lobes, which were found to be related to major depression. Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD, which support the role of subcortical structure in the pathophysiology of MDD. Meanwhile, the present study showed that these subcortical structural abnormalities might be the potential trait markers of MDD.