290 results on '"Hui-Chen Hsu"'
Search Results
2. Systemic immune–inflammation index for predicting postoperative atrial fibrillation following cardiac surgery: a meta-analysis
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Yu-Chou Chen, Chien-Cheng Liu, Hui-Chen Hsu, Kuo-Chuan Hung, Ying-Jen Chang, Chun-Ning Ho, Chung-Hsi Hsing, and Ching-Yi Yiu
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postoperative atrial fibrillation ,systemic immune-inflammation index ,cardiac surgery ,inflammation ,cardiopulmonary bypass ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundPostoperative atrial fibrillation (POAF) is a frequent complication that may increase morbidity and mortality risk following cardiac surgery. The systemic immune–inflammation index (SII) is an emerging biomarker that provides an integrated measure of inflammation by incorporating neutrophil, lymphocyte, and platelet counts. Recent studies have reported associations between elevated SII and increased POAF risk; however, significant heterogeneity exists regarding its predictive efficacy. This meta-analysis aimed to assess SII's diagnostic efficacy for predicting POAF risk.MethodsTo synthesize existing evidence on the ability of perioperative SII for predicting POAF in patients undergoing cardiac surgery, a systematic review and meta-analysis was conducted. In August 2023, a comprehensive literature search was performed to identify relevant studies reporting SII cutoff values with corresponding sensitivity and specificity. The primary aim was to evaluate SII's diagnostic utility for predicting POAF, whereas secondary outcomes included the pooled incidence of POAF and the relationship between the SII and POAF.ResultsEight studies published between 2021 and 2023 with 3,245 patients were included. Six studies involved coronary artery bypass grafting (CABG) surgery; one encompassed various cardiac procedures, and another focused solely on mitral valve surgery. The pooled incidence of POAF was 23.6% [95% confidence interval (CI), 18.7%–29.2%]. Elevated SII significantly increased the odds of POAF by 3.24-fold (odds ratio, 3.24; 95% CI, 1.6–6.55; p = 0.001). SII's pooled sensitivity and specificity for predicting POAF were 0.80 (95% CI, 0.68–0.89) and 0.53 (95% CI, 0.23–0.8), respectively. The SII had moderate predictive accuracy based on a hierarchical summary receiver operating characteristic (HSROC) area under the curve of 0.78 (95% CI, 0.74–0.81). Subgroup analyses, whether focusing on CABG alone or CABG with cardiopulmonary bypass (CPB), both indicated an area under the HSROC curve of 0.78 (95% CI, 0.74–0.81).ConclusionElevated SII is significantly correlated with an increased POAF risk following cardiac surgery, highlighting its utility as a predictive biomarker. Considering its moderate diagnostic accuracy, further research is essential for clarifying SII's clinical effectiveness, either as an independent predictor or combined with other risk factors, for stratifying patients at high POAF risk.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier [CRD42023456128]. more...
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- 2024
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3. Diagnostic efficacy of serum presepsin for postoperative infectious complications: a meta-analysis
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Chun-Ying Lu, Chia-Li Kao, Kuo-Chuan Hung, Jheng-Yan Wu, Hui-Chen Hsu, Chia-Hung Yu, Wei-Ting Chang, Ping-Hsun Feng, and I-Wen Chen
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presepsin ,procalcitonin ,C-reactive protein ,postoperative ,infectious complications ,meta-analysis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundPostoperative infectious complications (PICs) are major concerns. Early and accurate diagnosis is critical for timely treatment and improved outcomes. Presepsin is an emerging biomarker for bacterial infections. However, its diagnostic efficacy for PICs across surgical specialties remains unclear.MethodsIn this study, a systematic search on MEDLINE, Embase, Google Scholar, and Cochrane Library was performed on September 30, 2023, to identify studies that evaluated presepsin for diagnosing PICs. PIC is defined as the development of surgical site infection or remote infection. Pooled sensitivity, specificity, and hierarchical summary receiver operating characteristic (HSROC) curves were calculated. The primary outcome was the assessment of the efficacy of presepsin for PIC diagnosis, and the secondary outcome was the investigation of the reliability of procalcitonin or C-reactive protein (CRP) in the diagnosis of PICs.ResultsThis meta-analysis included eight studies (n = 984) and revealed that the pooled sensitivity and specificity of presepsin for PIC diagnosis were 76% (95% confidence interval [CI] 68%–82%) and 83% (95% CI 75%–89%), respectively. The HSROC curve yielded an area under the curve (AUC) of 0.77 (95% CI 0.73–0.81). Analysis of six studies on procalcitonin showed a combined sensitivity of 78% and specificity of 77%, with an AUC of 0.83 derived from the HSROC. Meanwhile, data from five studies on CRP indicated pooled sensitivity of 84% and specificity of 79%, with the HSROC curve yielding an AUC of 0.89.ConclusionPresepsin exhibits moderate diagnostic accuracy for PIC across surgical disciplines. Based on the HSROC-derived AUC, CRP has the highest diagnostic efficacy for PICs, followed by procalcitonin and presepsin. Nonetheless, presepsin demonstrated greater specificity than the other biomarkers. Further study is warranted to validate the utility of and optimize the cutoff values for presepsin.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023468358. more...
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- 2023
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4. The intercorrelation of vitamin D deficiency and SPP1 (Osteopontin) genetic polymorphisms with bone mineral density in middle-aged women: A cross-sectional study
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Ying-Hao Su, Hui-Chen Hsu, Wei-Syu Chen, Jeng-Min Chiou, Keh-Sung Tsai, Yen-Ching Chen, and Jen-Hau Chen
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Diseases of the musculoskeletal system ,RC925-935 - Published
- 2023
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5. Lupus nephritis correlates with B cell interferon-β, anti-Smith, and anti-DNA: a retrospective study
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Fatima Alduraibi, Huma Fatima, Jennie A. Hamilton, W. Winn. Chatham, Hui-Chen Hsu, and John D. Mountz
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Systemic lupus erythematosus ,Lupus nephritis ,B cell interferon beta ,Autoantibodies ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background In systemic lupus erythematosus (SLE), detection of interferon-β (IFNβ) in B cells was found to be most prominent in patients with high anti-Smith (Sm) and renal disease, but a mechanistic connection was not clear. The objective of the present study is to determine the association of IFNβ in peripheral blood naïve B cells with the histopathological features of lupus nephritis (LN). Methods The percentage of IFNβ+ cells in IgD+CD27− naïve CD19+ B cells (B cell IFNβ) among peripheral blood mononuclear cells (PBMCs) from 80 SLE patients were analyzed using flow cytometry. Serological and clinical data were collected. The correlations of B cell IFNβ with LN classification and with histopathological findings (light, electron, and immunofluorescence [IF] microscopic analyses for deposition of IgM, IgG, IgA, C1q, and C3) were determined in 23 available biopsy specimens. Results B cell IFNβ is positively associated with anti-Sm (p = 0.001), anti-DNA (p = 0.013), and LN (p < 0.001) but was negatively associated with oral/nasal ulcer (p = 0.003) and photosensitivity (p = 0.045). B cell IFNβ positively correlated with immune complex (IC) deposit in the glomerular basement membrane (GBM) (p = 0.002) but not in the mesangial (p = 0.107) or tubular region (p = 0.313). Patients with high B cell IFNβ had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B cell IFNβ (p more...
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- 2022
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6. 204 IL-4 as a negative regulator of pathogenic extrafollicular DN2 B cells in SLE
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Min Gao, Winn Chatham, Shanrun Liu, Hui-Chen Hsu, John D Mountz, and Changming Lu
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2022
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7. Safety assessment of the standardized aqueous extract from solid-state cultured Xylaria nigripes (Wuling Shen) in rats
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Ming-Nan Lai, Hui-Chen Hsu, and Lean-Teik Ng
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Xylaria nigripes ,Mushroom ,Toxicity ,Hematology ,Histology ,Rat ,Medicine ,Homeopathy ,RX1-681 - Abstract
Abstract Background Xylaria nigripes (Koltz.) Cooke, also known as Wuling Shen, is a high-value medicinal mushroom. It is a herbal medicine traditionally used for treating insomnia, trauma and depression. However, its toxicity has never been systematically evaluated. This study aimed to evaluate the safety of a standardized aqueous extract (XNE), an ingredient of commercial products, prepared from solid-state cultured X. nigripes in rats. Methods A 90-day subchronic toxicity study was conducted by oral administration of XNE at daily doses of 20, 1000 and 2000 mg/kg body weight to Sprague-Dawley rats of both sexes, and the control group was given distilled water (vehicle). All animals were checked daily for general behavior, body weight changes and signs of toxicity. At the end of the treatment period, hematological analysis, biochemical analysis and histopathological examination of organs were conducted. Results At tested concentrations, oral XNE administration caused no treatment-induced adverse effects on general health, body weight gain, relative organ weights, and hematological and biochemical parameters. Histopathological results also showed no significant structural changes in organs even in high-dose XNE-treated animals. Conclusion This study suggests that treatment with XNE for 90 days does not produce significant toxicity, even up to 100 fold (2000 mg/kg body weight/day) of the recommended daily intakes. Therefore, the use of XNE as herbal medicines is considered to be relatively safe. more...
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- 2021
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8. 510 B-cell interferon-β correlates with lupus nephritis in systemic lupus erythematosus
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Jennie A Hamilton, Hui-Chen Hsu, John D Mountz, Fatima Alduraibi, Huma Fatima, and Walter Winn Chatham
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2021
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9. Surfactin Containing Bacillus licheniformis-Fermented Products Alleviate Dextran Sulfate Sodium-Induced Colitis by Inhibiting Colonic Inflammation and the NLRP3 Inflammasome in Mice
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Wei-Che Tsai, Wei-Ting Wong, Hsien-Ta Hsu, Yeong-Hsiang Cheng, Yu-Hsiang Yu, Wei-Jung Chen, Chen-Lung Ho, Hui-Chen Hsu, and Kuo-Feng Hua
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Bacillus licheniformis ,surfactin ,inflammatory bowel disease ,colitis ,NLRP3 inflammasome ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Inflammatory bowel disease (IBD) is a non-infectious disease characterized by chronic inflammation of the gastrointestinal tract. Currently, management of IBD is still a clinical challenge. The purpose of this study was to investigate the therapeutic potential of surfactin containing Bacillus licheniformis-fermented products (SBLF) and commercial surfactin (CS) on the treatment of dextran sulfate sodium (DSS)-induced colitis in a mouse model. We found that mice that received drinking water containing 3% DSS developed significant colitis symptoms, including increased disease activity index, body weight loss, shortening of the colon length, splenomegaly, colonic inflammation and colonic NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Notably, orally received SBLF, CS or clinical anti-inflammatory drug 5-aminosalicylic acid improved DSS-induced colitis symptoms in mice. These findings show that SBLF can improve IBD in mice by reducing colonic inflammation and inhibiting the NLRP3 inflammasome activation, suggesting that SBLF has the potential to be used as a nutraceutical in humans or a feed additive in economic and companion animals for preventing IBD. more...
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- 2022
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10. Probiotics as a Friendly Antibiotic Alternative: Assessment of Their Effects on the Health and Productive Performance of Poultry
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Rafiq Ahmad, Yu-Hsiang Yu, Felix Shih-Hsiang Hsiao, Andrzej Dybus, Ilyas Ali, Hui-Chen Hsu, and Yeong-Hsiang Cheng
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intestinal morphology ,reproduction ,antibiotic resistance ,probiotics ,poultry ,Fermentation industries. Beverages. Alcohol ,TP500-660 - Abstract
Antibiotics have been used to maintain the overall health of poultry by increasing production efficiency, promoting growth, and improving intestinal function for more than 50 years. However, they have a number of side effects, such as antibiotic resistance, gut dysbiosis, destruction of beneficial bacteria, and the potential to spread diseases to humans. In order to address the aforementioned issues, a lot of effort is put into the development of antibiotic alternatives. One of them is the use of probiotics that can be added to the feed in order to increase poultry performance and avoid the aforementioned problems. Probiotics are live microorganisms consumed as feed additives or supplements. They function in the poultry gastrointestinal tract to benefit the host. Probiotics improve growth performance, bone health, meat and eggshell quality. The addition of probiotics to the diet also positively affects the immune response, intestinal microflora, and disease resistance. Careful selection of probiotic strains is of utmost importance. This review focuses on the significance of probiotics as a potential antibiotic-free alternative and the way in which they can be used as supplements in poultry feed for boosting production and safeguarding health. more...
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- 2022
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11. Antibacterial and Anticancer Activities of Pleurocidin-Amide, a Potent Marine Antimicrobial Peptide Derived from Winter Flounder, Pleuronectes americanus
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Hui-Chen Hsu, Ming-Hsin Chen, Ming-Lung Yeh, and Wei-Jung Chen
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Pleurocidin (Ple) ,antimicrobial peptide (AMP) ,antibacterial ,anticancer ,multidrug resistance (MDR) ,non-small cell lung adenocarcinoma ,Biology (General) ,QH301-705.5 - Abstract
The extensive use of conventional antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. Evidence suggests that cationic antimicrobial peptides (AMPs) have the greatest potential to serve as traditional antibiotic substitutes. Recent studies have also reported that certain AMPs have selective toxicity toward various types of cancer cells. The electrostatic attraction between the negatively charged membrane components and AMPs is believed to play a crucial role in the disruption of bacterial and cancer cell membranes. In the current study, we used a potent AMP called Pleurocidin (Ple) derived from winter flounder Pleuronectes americanus and its C-terminal-amidated derivative Pleurocidin-amide (Ple-a), and evaluated their antibacterial and anticancer activities. Our results indicated that both Ple and Ple-a exhibited significant antibacterial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, especially marine pathogens, with MIC values ranging from 0.25 to 32 μg/mL. These peptides are also potent against several multidrug-resistant (MDR) bacterial strains, with MIC values ranging from 2 to 256 μg/mL. When used in combination with certain antibiotics, they exhibited a synergistic effect against MDR E. coli. Ple and Ple-a also showed notable cytotoxicity toward various cancer cell lines, with IC50 values ranging from 11 to 340 μM, while normal mouse fibroblast 3T3 cells were less susceptible to these peptides. Ple-a was then selected to study its anticancer mechanism toward A549 human lung adenocarcinoma cells. Western blot analysis and confocal microscopy showed that Ple-a could inhibit autophagy of A549 cells, and induce apoptosis 48 h after treatment. Our findings provided support for the future application of Ple-a as potential therapeutic agent for bacterial infections and cancer treatment. more...
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- 2022
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12. Initial clinical radiological findings and staging to predict prognosis of primary hepatic angiosarcoma: A retrospective analysis.
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Wei-Hsin Yuan, Anna Fen-Yau Li, Hui-Chen Hsu, Yong-Sin Hu, and Rheun-Chuan Lee
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Medicine ,Science - Abstract
OBJECTIVE:Primary hepatic angiosarcoma (PHA) is extremely rare and most patients die within 12 months of diagnosis. The object of the study is to determine the association of initial clinical-radiological features and staging with outcomes in patients with PHA. METHODS:The medical records of adult patients with PHA were retrieved from an electronic medical record database and a pathology database and retrospectively reviewed. During 10 years, 22 eligible patients were included. Data extracted focused on the information before the first formal treatment with a pathological proof, including demographic characteristics, medical history, laboratory data, preliminary images, histopathological records, treatment, and follow-up survival period. Two radiologists blindly re-analyzed preliminary images of all 22 patients together and recorded tumor features and imaging stage based on the American Joint Committee on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) Staging System for hepatocellular carcinoma. A radiologist compiled the initial clinical data and preliminary image stage to analyze the association with patients' survival outcome. RESULTS:Higher aspartate aminotransferase (AST), higher total bilirubin (TB), lower albumin (ALB), longer prothrombin time (PT) and lower platelet count of serum relative to the normal reference range were more common in patients who survived ≤ 90 days (all P < 0.05). Overall survival was much better in patients with single PHA than in those with other tumor patterns of multiple PHA (all P < 0.05). Overall survival determined by preliminary imaging showed significant differences between stage I and stage III (P = 0.044), stage I and stage IV (P = 0.011), and stage III and IV (P = 0.047). No patients were at stage II. CONCLUSIONS:Initial serum levels of ALT, TB, ALB, and PT, platelet count, single mass in liver, and preliminary imaging staging could help predict survival outcomes of patients with PHA. more...
- Published
- 2019
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13. Clinical and ultrasonographic features of male breast tumors: A retrospective analysis.
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Wei-Hsin Yuan, Anna Fen-Yau Li, Yi-Hong Chou, Hui-Chen Hsu, and Ying-Yuan Chen
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Medicine ,Science - Abstract
The purpose of this study was to determine clinical and ultrasonographic characteristics of male breast tumors.The medical records of male patients with breast lesions were retrieved from an electronic medical record database and a pathology database and retrospectively reviewed. A total of 112 men (125 breast masses) with preoperative breast ultrasonography (US) were included (median age, 59.50 years; age range, 15-96 years). Data extracted included patient age, if the lesions were bilateral, palpable, and tender, and the presence of nipple discharge. Breast lesion features on static US images were reviewed by three experienced radiologists without knowledge of physical examination or pathology results, original breast US image interpretations, or surgical outcomes. The US features were documented according to the BI-RADS (Breast Imaging-Reporting and Data System) US lexicons. A forth radiologist compiled the data for analysis.Of the 125 breast masses, palpable tender lumps and bilateral synchronous masses were more likely to be benign than malignant (both, 100% vs 0%, P < 0.05). Advanced age and bloody discharge from nipples were common in malignant lesions (P more...
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- 2018
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14. Dysregulated cytokine production by dendritic cells modulates B cell responses in the NZM2410 mouse model of lupus.
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Allison Sang, Ying-Yi Zheng, Yiming Yin, Igor Dozmorov, Hao Li, Hui-Chen Hsu, John D Mountz, and Laurence Morel
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Medicine ,Science - Abstract
The breakdown in tolerance of autoreactive B cells in the lupus-prone NZM2410-derived B6.Sle1.Sle2.Sle3 (TC) mice results in the secretion of autoantibodies. TC dendritic cells (DCs) enhance B cell proliferation and antibody secretion in a cytokine-dependent manner. However, the specific cytokine milieu by which TC DCs activate B cells was not known. In this study, we compared TC and C57BL/6 (B6) control for the distribution of DC subsets and for their production of cytokines affecting B cell responses. We show that TC DCs enhanced B cell proliferation through the production of IL-6 and IFN-γ, while antibody secretion was only dependent on IL-6. Pre-disease TC mice showed an expanded PDCA1(+) cells prior to disease onset that was localized to the marginal zone and further expanded with age. The presence of PDCA1(+) cells in the marginal zone correlated with a Type I Interferon (IFN) signature in marginal zone B cells, and this response was higher in TC than B6 mice. In vivo administration of anti-chromatin immune complexes upregulated IL-6 and IFN-γ production by splenic DCs from TC but not B6 mice. The production of BAFF and APRIL was decreased upon TC DC stimulation both in vitro and in vivo, indicating that these B cell survival factors do not play a role in B cell modulation by TC DCs. Finally, TC B cells were defective at downregulating IL-6 expression in response to anti-inflammatory apoptotic cell exposure. Overall, these results show that the TC autoimmune genetic background induces the production of B cell-modulating inflammatory cytokines by DCs, which are regulated by the microenvironment as well as the interplay between DC. more...
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- 2014
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15. PAGER-CoV-Run: An online interactive analytical platform for COVID-19 functional genomic downstream analysis.
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Zongliang Yue, Nishant Batra, Hui-Chen Hsu, John Mountz, and Jake Y. Chen
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- 2021
16. IL-4-Induced Quiescence of Resting Naive B Cells Is Disrupted in Systemic Lupus Erythematosus
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Min Gao, Shanrun Liu, W. Winn Chatham, John D. Mountz, and Hui-Chen Hsu
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Immunology ,B-Lymphocyte Subsets ,Humans ,Lupus Erythematosus, Systemic ,RNA ,Immunology and Allergy ,Immunoglobulin D ,Interleukin-4 ,Autoantibodies - Abstract
Activated naive (aNAV) B cells have been shown to be the precursor of the CD11c+T-bet+ IgD−CD27− double-negative (DN)2 or atypical memory (aMEM) B cells in systemic lupus erythematosus (SLE). To determine factors that maintain resting naive (rNAV) B cells, the transcriptomic program in naive (IGHD+IGHM+) B cells in human healthy control subjects (HC) and subjects with SLE was analyzed by single-cell RNA-sequencing analysis. In HC, naive B cells expressed IL-4 pathway genes, whereas in SLE, naive B cells expressed type I IFN-stimulated genes (ISGs). In HC, aNAV B cells exhibited upregulation of the gene signature of germinal center and classical memory (cMEM) B cells. In contrast, in SLE, aNAV B cells expressed signature genes of aMEM. In vitro exposure of SLE B cells to IL-4 promoted B cell development into CD27+CD38+ plasmablasts/plasma and IgD−CD27+ cMEM B cells. The same treatment blocked the development of CD11c+Tbet+ aNAV and DN2 B cells and preserved DN B cells as CD11c−Tbet− DN1 B cells. Lower expression of IL-4R and increased intracellular IFN-β in naive B cells was correlated with the accumulation of CD21−IgD− B cells and the development of anti-Smith and anti-DNA autoantibodies in patients with SLE (n = 47). Our results show that IL-4R and type I IFN signaling in naive B cells induce the development of distinct lineages of cMEM versus aMEM B cells, respectively. Furthermore, diminished IL-4R signaling shifted activated B cell development from the DN1 to the DN2 trajectory in patients with SLE. Therapies that enhance IL-4R signaling may be beneficial for ISGhi SLE patients. more...
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- 2022
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17. A 24GHz low-power CMOS receiver design.
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Chen-Yuan Chu, Chien-Cheng Wei, Hui-Chen Hsu, Shu-Hau Feng, and Wu-Shiung Feng
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- 2008
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18. Surfactin Containing
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Wei-Che, Tsai, Wei-Ting, Wong, Hsien-Ta, Hsu, Yeong-Hsiang, Cheng, Yu-Hsiang, Yu, Wei-Jung, Chen, Chen-Lung, Ho, Hui-Chen, Hsu, and Kuo-Feng, Hua
- Abstract
Inflammatory bowel disease (IBD) is a non-infectious disease characterized by chronic inflammation of the gastrointestinal tract. Currently, management of IBD is still a clinical challenge. The purpose of this study was to investigate the therapeutic potential of surfactin containing more...
- Published
- 2022
19. Safety assessment of the standardized aqueous extract from solid-state cultured Xylaria nigripes (Wuling Shen) in rats
- Author
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Hui-Chen Hsu, Lean-Teik Ng, and Ming-Nan Lai
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0106 biological sciences ,Histology ,Solid-state ,01 natural sciences ,Mushroom ,03 medical and health sciences ,Ingredient ,0302 clinical medicine ,Oral administration ,010608 biotechnology ,Diabetes mellitus ,medicine ,Adverse effect ,General Environmental Science ,Aqueous extract ,Traditional medicine ,Toxicity ,business.industry ,RX1-681 ,Hematology ,Homeopathy ,Xylaria nigripes ,medicine.disease ,General Earth and Planetary Sciences ,Rat ,Medicine ,business ,030217 neurology & neurosurgery - Abstract
Background Xylaria nigripes (Koltz.) Cooke, also known as Wuling Shen, is a high-value medicinal mushroom. It is a herbal medicine traditionally used for treating insomnia, trauma and depression. However, its toxicity has never been systematically evaluated. This study aimed to evaluate the safety of a standardized aqueous extract (XNE), an ingredient of commercial products, prepared from solid-state cultured X. nigripes in rats. Methods A 90-day subchronic toxicity study was conducted by oral administration of XNE at daily doses of 20, 1000 and 2000 mg/kg body weight to Sprague-Dawley rats of both sexes, and the control group was given distilled water (vehicle). All animals were checked daily for general behavior, body weight changes and signs of toxicity. At the end of the treatment period, hematological analysis, biochemical analysis and histopathological examination of organs were conducted. Results At tested concentrations, oral XNE administration caused no treatment-induced adverse effects on general health, body weight gain, relative organ weights, and hematological and biochemical parameters. Histopathological results also showed no significant structural changes in organs even in high-dose XNE-treated animals. Conclusion This study suggests that treatment with XNE for 90 days does not produce significant toxicity, even up to 100 fold (2000 mg/kg body weight/day) of the recommended daily intakes. Therefore, the use of XNE as herbal medicines is considered to be relatively safe. more...
- Published
- 2021
20. IL-4 receptor blockade is a global repressor of naïve B cell development and responses in a dupilumab-treated patient
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John D. Mountz, Min Gao, David M. Ponder, Shanrun Liu, Chiao-Wang Sun, Fatima Alduraibi, Kathryn Sullivan, Betty Pat, Louis J. Dell'Italia, and Hui-Chen Hsu
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COVID-19 Vaccines ,Immunology ,Immunology and Allergy ,Antibodies, Monoclonal ,Humans ,RNA ,Receptors, Antigen, B-Cell ,Interleukin-4 ,Antibodies, Monoclonal, Humanized ,Receptors, Interleukin-4 ,COVID-19 Drug Treatment - Abstract
Here, we report a case of atopic dermatitis (AD) in a patient who received biweekly doses of dupilumab, an antibody against the IL-4 receptor α chain (IL-4Rα). Single cell RNA-sequencing showed that naïve B cells expressed the highest levels of IL4R compared to other B cell subpopulations. Compared to controls, the dupilumab-treated patient exhibited diminished percentages of IL4R+IGHD+ naïve B cells and down-regulation of IL4R, FCER2 (CD23), and IGHD. Dupilumab treatment resulted in upregulation of genes associated with apoptosis and inhibition of B cell receptor signaling and down-regulation of class-switch and memory B cell development genes. The dupilumab-treated patient exhibited a rapid decline in COVID-19 anti-spike and anti-receptor binding domain antibodies between 4 and 8 and 11 months post COVID-19 vaccination. Our data suggest that intact and persistent IL-4 signaling is necessary for maintaining robust survival and development of naïve B cells, and maintaining a long term vaccine response. more...
- Published
- 2022
21. IL-23 Promotes a Coordinated B Cell Germinal Center Program for Class-Switch Recombination to IgG2b in BXD2 Mice
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PingAr Yang, Jake Y. Chen, Peter D. Burrows, Shanrun Liu, Huixian Hong, John D. Mountz, Hui-Chen Hsu, Min Gao, Qi Wu, Hao Li, and Daniel J. Cua
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Immunology ,Population ,Plasma cell ,Interleukin-23 ,Article ,Autoimmune Diseases ,Transcriptome ,Interferon-gamma ,Mice ,Downregulation and upregulation ,T-Lymphocyte Subsets ,medicine ,Animals ,Immunology and Allergy ,Cyclin-Dependent Kinase Inhibitor p19 ,education ,B cell ,Mice, Knockout ,B-Lymphocytes ,education.field_of_study ,Chemistry ,Germinal center ,Cell Differentiation ,T helper cell ,Germinal Center ,Immunoglobulin Class Switching ,Molecular biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Immunoglobulin class switching ,Immunoglobulin G ,Th17 Cells - Abstract
IL-23 promotes autoimmune disease, including Th17 CD4 T cell development and autoantibody production. In this study, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19−/−) mouse leads to a shift of the follicular T helper cell program from follicular T helper (Tfh)–IL-17 to Tfh–IFN-γ. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19−/− mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that whereas Ifngr1, Il21r, and Il4r genes exhibited a synchronized expression pattern with Cxcr5 and plasma cell program genes, Il17ra exhibited a synchronized expression pattern with Cxcr4 and GC program genes. Downregulation of Ighg2b in BXD2-p19−/− GC B cells was associated with decreased expression of CSR-related novel base excision repair genes that were otherwise predominantly expressed by Il17ra+ GC B cells in BXD2 mice. Together, these results suggest that although IL-23 is dispensable for GC formation, it is essential to promote a population of Tfh–IL-17 cells. IL-23 acts indirectly on Il17ra+ GC B cells to facilitate CSR-related base excision repair genes during the dark zone phase of GC B cell development. more...
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- 2020
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22. Interrelation of T-cell Cytokines and Autoantibodies in Lupus Nephritis: A Cross-sectional Study
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Fatima Alduraibi, Kathryn Sullivan, W.Winn Chatham, Hui-Chen Hsu, and John D. Mountz
- Abstract
Objective: To determine if circulating autoantibodies (autoAbs) and T-helper cell cytokines correlate with a different class of lupus nephritis (LN), including class III/IV, compared to class V and other manifestations of systemic lupus erythematosus (SLE). Methods: All patients (N=62) met the SLE classification criteria of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) or Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. Demographic, clinical data, and serologic manifestations included anti-DNA, anti-Smith (Anti-Sm), C3, and C4 were included. Plasma levels of interferon gamma (IFNɣ), interleukin 17 (IL-17), interleukin 10 (IL-10) isotype-specific (IgG) anti-DNA, anti-Ro/SSA (SSA), and anti-Sm were measured using enzyme-linked immunosorbent assay (ELISA).Results: The most common manifestations by history were arthritis in 61% (N=38), photosensitivity rash in 53% (N=33), LN in 44% (N=27), and oral/nasal ulcer in 31% (N=19) SLE patients. AutoAbs (anti-DNA, anti-SSA, and anti-Sm), IFNɣ, and IL-17, but not IL-10, were significantly elevated in SLE patients compared to healthy controls. There were elevated plasma levels of anti-DNA (p = 0.0101) and anti-Sm (p = 0.0499) in patients with a history of LN compared to patients without LN. In contrast, plasma levels of anti-Sm were decreased in patients who had a history of acute mucocutaneous manifestations, including photosensitivity rash and/or malar rash (p = 0.0152). Among the three cytokines that were analyzed, IL-10 was significantly elevated in patients with a history of LN compared to patients without LN (p = 0.0216). IL-17 was positively correlated with anti-SSA (p = 0.0130) and was significantly higher in patients with discoid rash (p = 0.0238) and history of class V LN (p = 0.0055). IFNɣ was positively correlated with anti-DNA (p = 0.0355) and anti-SSA (p = 0.0402). Conclusion: This cross-sectional study supports the role of different T-helper cell cytokines that may be associated with the development of different autoAbs in influencing the diversity of SLE clinical manifestations. The results suggests that elevated IFNɣ and IL-17 are more generalized features in SLE patients. In contrast, higher levels of IL-10 were observed in patients with a history of LN. This provide insights into the pathogenic mechanisms of LN that can help guide future diagnosis and therapies. more...
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- 2022
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23. Host genetics but not commensal microbiota determines the initial development of systemic autoimmune disease in BXD2 mice
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Jeremy B. Foote, Hui-Chen Hsu, Trenton R. Schoeb, Charles O. Elson, David Ponder, Huixian Hong, John D. Mountz, Huma Fatima, Casey D. Morrow, Fatima Alduraibi, and Wayne Duck
- Subjects
Programmed Cell Death 1 Receptor ,Immunology ,Autoimmunity ,Biology ,medicine.disease_cause ,Article ,Flow cytometry ,Autoimmune Diseases ,Interferon-gamma ,chemistry.chemical_compound ,Mice ,Rheumatology ,Rheumatic Diseases ,medicine ,Immunology and Allergy ,Animals ,IL-2 receptor ,Autoantibodies ,Genetics ,Systemic lupus erythematosus ,medicine.diagnostic_test ,Ionomycin ,Microbiota ,Interleukin-17 ,Autoantibody ,Germinal center ,FOXP3 ,medicine.disease ,Gastrointestinal Microbiome ,chemistry ,Immunoglobulin G - Abstract
To determine the extent to which the gut microbiome influences systemic autoimmunity in a mouse model of lupus.We generated germ-free (GF) lupus-prone BXD2 mice, which under normal conditions develop spontaneous germinal centers (GCs) and high titers of serum autoantibodies. GF status was confirmed by gut bacterial culture. The autoimmune phenotypes of 6- and 12-month-old gnotobiotic GF BXD2 mice and specific pathogen-free (SPF) BXD2 mice were compared. Serum levels of autoantibodies were measured by enzyme-linked immunosorbent assay. Histologic sections of the mouse kidney and joints were evaluated. Flow cytometry was used to analyze GCs and age-associated B cells. CD4+ T cells were analyzed for PD-1+ICOS+ activated T cells, T follicular regulatory (Tfr) cells (Foxp3+CD25+ PD-1+CXCR5+), and PD-1+ICOS+ T cells expressing interleukin-17A (IL-17A) or interferon-γ (IFNγ) after stimulation with phorbol myristate acetate (PMA)/ionomycin.In 6-month-old mice, GF status did not affect splenomegaly, GC B cells, age-associated B cells, or serum autoantibody levels, except for IgG antihistone. GF BXD2 mice exhibited a significantly higher percentage of Tfr cells compared to their SPF counterparts (P0.05). At 12 months of age, however, GF BXD2 mice had significantly diminished IgG autoantibody levels and a lower percentage of GC B cells and age-associated B cells (P0.05). Following stimulation with PMA/ionomycin, PD-1+ICOS+ CD4+ T cells expressed significantly lower IL-17A, but not IFNγ, levels in GF BXD2 mice compared to SPF BXD2 mice (P0.01). SPF BXD2 mice and GF BXD2 mice developed equivalent renal and joint disease with no significant differences in severity.Our results suggest a model in which genetics plays a dominant role in determining the initial development of autoimmunity. In contrast, gut microbiomes may regulate the persistence of certain aspects of systemic autoimmunity. more...
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- 2022
24. Interrelation of T cell cytokines and autoantibodies in systemic lupus erythematosus: A cross-sectional study
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Fatima K. Alduraibi, Kathryn A. Sullivan, W. Winn Chatham, Hui-Chen Hsu, and John D. Mountz
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Immunology ,Immunology and Allergy - Published
- 2023
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25. A Comparison of Nurse Aides and Nurses Regarding the Work Competence of Nurse Aides in a Skill-Mixed Institution
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Hui-Chen Hsu, Hsiang-Wen Kung, Wen-Jen Chiang, Bih-O Lee, and Ruey-Hsia Wang
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nurse aide ,institutional healthcare ,work competence ,registered nurse ,Leadership and Management ,Health Policy ,Health Informatics ,Article ,InformationSystems_GENERAL ,Health Information Management ,ComputingMilieux_COMPUTERSANDSOCIETY ,Medicine - Abstract
Objective: To compare the differences between the work competencies self-reported by nurse aides’ and those perceived by nurses. Method: A cross-sectional survey was employed. The settings were units implemented a skill mix model institution in Taiwan. The instruments consisted of the participants’ demographic data and a nurse aide work competence scale. Results: The results indicated that the nurse aides had room for improvement in terms of “problem solving” and “activity design”. The nurse aides and nurses differed significantly in terms of the nurse aides’ competence in “activity design”, as the nurse aides reported themselves to be more competent in “activity design” than reported by the nurses. Conclusion: Nurse aides should be incorporated into cross-disciplinary teams. Activity design should be handled by other healthcare providers such as physical therapists or senior social workers. more...
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- 2021
26. Lupus Nephritis Correlates with B-Cell Interferon-β, Anti-Smith, and Anti-DNA: A Retrospective Study
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Jennie A Hamilton, Huma Fatima, John D. Mountz, Hui-Chen Hsu, Fatima Alduraibi, and W. Winn Chatham
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Male ,Anti dna ,business.industry ,Lupus nephritis ,Retrospective cohort study ,Interferon-beta ,medicine.disease ,Lupus Nephritis ,medicine.anatomical_structure ,Interferon β ,Antibodies, Antinuclear ,Immunology ,Leukocytes, Mononuclear ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Female ,Kidney Diseases ,business ,B cell ,Retrospective Studies - Abstract
Background In systemic lupus erythematosus (SLE), detection of interferon-β (IFNβ) in B cells was found to be most prominent in patients with high anti-Smith (Sm) and renal disease, but a mechanistic connection was not clear. The objective of the present study is to determine the association of IFNβ in peripheral blood naïve B cells with the histopathological features of lupus nephritis (LN). Methods The percentage of IFNβ+ cells in IgD+CD27− naïve CD19+ B cells (B cell IFNβ) among peripheral blood mononuclear cells (PBMCs) from 80 SLE patients were analyzed using flow cytometry. Serological and clinical data were collected. The correlations of B cell IFNβ with LN classification and with histopathological findings (light, electron, and immunofluorescence [IF] microscopic analyses for deposition of IgM, IgG, IgA, C1q, and C3) were determined in 23 available biopsy specimens. Results B cell IFNβ is positively associated with anti-Sm (p = 0.001), anti-DNA (p = 0.013), and LN (p < 0.001) but was negatively associated with oral/nasal ulcer (p = 0.003) and photosensitivity (p = 0.045). B cell IFNβ positively correlated with immune complex (IC) deposit in the glomerular basement membrane (GBM) (p = 0.002) but not in the mesangial (p = 0.107) or tubular region (p = 0.313). Patients with high B cell IFNβ had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B cell IFNβ (p p = 0.023), chronic glomerular lesions indicated by segmental sclerosis (p = 0.033), and a membranous pattern of renal damage indicated by spike/holes (p = 0.015). Conclusion B cell IFNβ correlates with history of severe LN, glomerular basement membrane (GBM) IC deposition, and anatomical features of both active and chronic glomerular lesions. more...
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- 2021
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27. 510 B-cell interferon-β correlates with lupus nephritis in systemic lupus erythematosus
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Walter Winn Chatham, Fatima Alduraibi, John D. Mountz, Hui-Chen Hsu, Jennie A Hamilton, and Huma Fatima
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medicine.anatomical_structure ,Interferon β ,business.industry ,Immunology ,medicine ,Lupus nephritis ,Immunologic diseases. Allergy ,RC581-607 ,medicine.disease ,business ,B cell - Published
- 2021
28. Disability, emotional distress and well‐being among patients with lumbar spondylolisthesis
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Hui Chen Hsu, Chih Ju Chang, Tsae Jyy Wang, and Heng Hsin Tung
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Male ,Research design ,Family support ,Anxiety ,Psychological Distress ,Severity of Illness Index ,Disability Evaluation ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Humans ,Medicine ,Outpatient clinic ,030212 general & internal medicine ,General Nursing ,Depression (differential diagnoses) ,Aged ,Lumbar Vertebrae ,030504 nursing ,Depression ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Mental health ,Spondylolisthesis ,Oswestry Disability Index ,Cross-Sectional Studies ,Female ,medicine.symptom ,0305 other medical science ,business ,Clinical psychology - Abstract
Aim and objective To explore the disability, emotional distress and well-being of patients with lumbar spondylolisthesis. Background Few studies have investigated the correlations between disability, emotional distress and well-being of patients with lumbar spondylolisthesis. Design This study used a cross-sectional research design. Methods Participants were 133 patients aged over 50 years who were experiencing lumbar spondylolisthesis. The research instruments included a demographic information questionnaire; the Numeric Rating Scale (NRS); the Charlson Comorbidity Index (CCI); the Chinese versions of the Oswestry Disability Index (ODI), State-Trait Anxiety Inventory-State (STAI-S) and Center for Epidemiological Study-Depression (CES-D); and the Psychological Well-being (PWB) Scale. Emotional distress was measured by the STAI-S and CES-D. Pearson's correlations coefficient, multiple linear regression and a mediating effect model were introduced to explore correlations between the variables and predictors of psychological well-being, and details of the methods are reported in coherence to STROBE criteria. Results Eighty-six participants (64.6%) had moderate and severe anxiety, and 42 (31.6%) experienced depression. Participants reported medium to high levels of well-being; "satisfaction with interpersonal relationships" was rated the highest and "physical and mental health" the lowest. Disability, depression and anxiety had significant negative correlations with well-being. Depression and anxiety mediated the relationship between disability and well-being. Moreover, depression, family support, educational background and anxiety were predictors of well-being, accounting for 39.1% of the total variance. Conclusions Disability and emotional distress among patients with lumbar spondylolisthesis had a negative impact on well-being. Anxiety and depression were closely correlated with and substantially influenced well-being. Relevance to clinical practice Health professionals will enhance the understanding of important factors influencing well-being among patients with lumbar spondylolisthesis. This study suggests the conduct of depression and anxiety evaluations at outpatient clinics and prior to surgery, so that clinicians will be aware of the emotional distress status of patients with lumbar spondylolisthesis and, therefore, enhance their well-being. more...
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- 2019
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29. Evaluate the Differences in CT Features and Serum IgG4 Levels between Lymphoma and Immunoglobulin G4-Related Disease of the Orbit
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Chia-Hung Wu, Wan You Guo, Wei Hsin Yuan, Hui-Chen Hsu, Shu Yi Yu, Ying Yuan Chen, Anna Fen Yau Li, and Jiing Feng Lirng
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medicine.medical_specialty ,genetic structures ,medicine.medical_treatment ,lcsh:Medicine ,Orbital lymphoma ,computed tomography (CT) ,Gastroenterology ,Immunoglobulin G ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Precontrast ,Hounsfield scale ,Internal medicine ,parasitic diseases ,orbital lymphoma (OL) ,medicine ,Hounsfield unit ,immunoglobulin G4-related orbital disease (IgG4-ROD) ,Chemotherapy ,integumentary system ,biology ,business.industry ,fungi ,lcsh:R ,General Medicine ,medicine.disease ,Confidence interval ,Lymphoma ,Radiation therapy ,030221 ophthalmology & optometry ,biology.protein ,sense organs ,business - Abstract
Background: Benign immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD)&mdash, characterized as tumors mimicking malignant orbital lymphoma (OL)&mdash, responds well to steroids, instead of chemotherapy, radiotherapy and/or surgery of OL. The objective of this study was to report the differences in computed tomography (CT) features and- serum IgG4 levels of IgG4-ROD and OL. Methods: This study retrieved records for patients with OL and IgG4-ROD from a pathology database during an eight-year-and-five-month period. We assessed the differences between 16 OL patients with 27 lesions and nine IgG4-ROD patients with 20 lesions according to prebiopsy CT features of lesions and prebiopsy serum IgG4 levels and immunoglobulin G (IgG) levels This study also established the receiver-operating curves (ROC) of precontrast and postcontrast CT Hounsfield unit scales (CTHU), serum IgG4 levels, serum IgG levels and their ratios. Results: Significantly related to IgG4-ROD (all p <, 0.05) were the presence of lesions with regular borders, presence of multiple lesions&mdash, involving both lacrimal glands on CT scans&mdash, higher median values of postcontrast CTHU, postcontrast CTHU/precontrast CTHU ratios, serum IgG4 levels and serum IgG4/IgG level ratios. Compared to postcontrast CTHU, serum IgG4 levels had a larger area under the ROC curve (0.847 [95% confidence interval (CI): 0.674&ndash, 1.000, p = 0.005] vs. 0.766 [95% CI: 0.615&ndash, 0.917, p = 0.002]), higher sensitivity (0.889 [95% CI: 0.518&ndash, 0.997] vs. 0.75 [95% CI: 0.509&ndash, 0.913]), higher specificity (0.813 [95% CI: 0.544&ndash, 0.960] vs. 0.778 [95% CI: 0.578&ndash, 0.914]) and a higher cutoff value (&ge, 132.5 mg/dL [milligrams per deciliter] vs. &ge, 89.5). Conclusions: IgG4-ROD showed distinct CT features and elevated serum IgG4 (&ge, 132.5 mg/dL), which could help distinguish IgG4-ROD from OL. more...
- Published
- 2020
30. Cutting Edge: Intracellular IFN-β and Distinct Type I IFN Expression Patterns in Circulating Systemic Lupus Erythematosus B Cells
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PingAr Yang, Shanrun Liu, Qi Wu, Hui-Chen Hsu, Bao Luo, John D. Mountz, Alexa L. Mattheyses, Jennie A Hamilton, Jun Li, Ignacio Sanz, and W. Winn Chatham
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0301 basic medicine ,Immunology ,B-Lymphocyte Subsets ,Intracellular Space ,Biology ,Article ,Immunophenotyping ,Flow cytometry ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Renal Insufficiency, Chronic ,skin and connective tissue diseases ,Cells, Cultured ,B cell ,Autoantibodies ,B-Lymphocytes ,Lupus erythematosus ,Systemic lupus erythematosus ,medicine.diagnostic_test ,Autoantibody ,Interferon-beta ,Flow Cytometry ,medicine.disease ,United States ,Black or African American ,030104 developmental biology ,medicine.anatomical_structure ,Blood Circulation ,Interferon Type I ,TLR3 ,Female ,Single-Cell Analysis ,030215 immunology - Abstract
In systemic lupus erythematosus (SLE), type I IFNs promote induction of type I IFN–stimulated genes (ISG) and can drive B cells to produce autoantibodies. Little is known about the expression of distinct type I IFNs in lupus, particularly high-affinity IFN-β. Single-cell analyses of transitional B cells isolated from SLE patients revealed distinct B cell subpopulations, including type I IFN producers, IFN responders, and mixed IFN producer/responder clusters. Anti-Ig plus TLR3 stimulation of SLE B cells induced release of bioactive type I IFNs that could stimulate HEK-Blue cells. Increased levels of IFN-β were detected in circulating B cells from SLE patients compared with controls and were significantly higher in African American patients with renal disease and in patients with autoantibodies. Together, the results identify type I IFN–producing and –responding subpopulations within the SLE B cell compartment and suggest that some patients may benefit from specific targeting of IFN-β. more...
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- 2018
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31. Myeloid-Derived Suppressor Cells Impair B Cell Responses in Lung Cancer through IL-7 and STAT5
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Steven R. Duncan, Cara C. Schafer, Selvarangan Ponnazhagan, Sultan Tousif, Hui-Chen Hsu, John F. Kearney, Jessy S. Deshane, Kenneth P. Hough, and Yong Wang
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0301 basic medicine ,Adoptive cell transfer ,Lung Neoplasms ,Stromal cell ,T cell ,Immunology ,Bone Marrow Cells ,Biology ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Transforming Growth Factor beta ,Cell Line, Tumor ,STAT5 Transcription Factor ,Tumor Microenvironment ,medicine ,Animals ,Immunology and Allergy ,Phosphorylation ,B cell ,Cell Proliferation ,B-Lymphocytes ,Cell growth ,Interleukin-7 ,Myeloid-Derived Suppressor Cells ,Cell Differentiation ,Adoptive Transfer ,Coculture Techniques ,Mice, Inbred C57BL ,Editorial Commentary ,030104 developmental biology ,medicine.anatomical_structure ,Tumor progression ,Immunoglobulin G ,Cancer research ,Myeloid-derived Suppressor Cell ,Female ,Tumor Escape ,Signal Transduction ,030215 immunology - Abstract
Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity, affecting amino acid metabolism and T cell function in the tumor microenvironment. However, it is unknown whether MDSCs regulate B cell responses during tumor progression. Using a syngeneic mouse model of lung cancer, we show reduction in percentages and absolute numbers of B cell subsets including pro–, pre–, and mature B cells in the bone marrow (BM) of tumor-bearing mice. The kinetics of this impaired B cell response correlated with the progressive infiltration of MDSCs. We identified that IL-7 and downstream STAT5 signaling that play a critical role in B cell development and differentiation were also impaired during tumor progression. Global impairment of B cell function was indicated by reduced serum IgG levels. Importantly, we show that anti–Gr-1 Ab-mediated depletion of MDSCs not only rescued serum IgG and IL-7 levels but also reduced TGF-β1, a known regulator of stromal IL-7, suggesting MDSC-mediated regulation of B cell responses. Furthermore, blockade of IL-7 resulted in reduced phosphorylation of downstream STAT5 and B cell differentiation in tumor-bearing mice and administration of TGF-β–blocking Ab rescued these IL-7–dependent B cell responses. Adoptive transfer of BM-derived MDSCs from tumor-bearing mice into congenic recipients resulted in significant reductions of B cell subsets in the BM and in circulation. MDSCs also suppressed B cell proliferation in vitro in an arginase-dependent manner that required cell-to-cell contact. Our results indicate that tumor-infiltrating MDSCs may suppress humoral immune responses and promote tumor escape from immune surveillance. more...
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- 2018
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32. Unmasking Fucosylation: from Cell Adhesion to Immune System Regulation and Diseases
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Hui-Chen Hsu, John D. Mountz, Jun Li, and John G. Allen
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0301 basic medicine ,Glycan ,Glycosylation ,Clinical Biochemistry ,Cell ,Anemia, Sickle Cell ,Biochemistry ,Fucose ,Arthritis, Rheumatoid ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immune system ,Polysaccharides ,Neoplasms ,Drug Discovery ,Cell Adhesion ,medicine ,Animals ,Humans ,Cell adhesion ,Molecular Biology ,Fucosylation ,Pharmacology ,Antibody-dependent cell-mediated cytotoxicity ,Immunity, Cellular ,biology ,Cell growth ,Macrophages ,Immunity, Innate ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Selectins ,biology.protein ,Molecular Medicine - Abstract
Fucosylation is a biological process broadly observed in vertebrates, invertebrates, plants, bacteria, and fungi. Fucose moieties on cell-surface glycans are increasingly recognized as critical to many cell-cell interaction and signaling processes. One of the characteristic roles of fucose is its regulation of selectin-dependent leukocyte adhesion that has been well studied over the last two decades. Recent studies of fucose in immune cell development and function regulation have significantly expanded the contemporary understanding of fucosylation. From cellular adhesion to immune regulation, herein we discuss the use of gene knockout studies, competitive inhibitors of fucose-containing glycan, and metabolic inhibitors of fucose biosynthesis to probe fucosylated glycan biosynthesis and signaling and its functional consequences. Promising clinical and preclinical applications in sickle cell disease, rheumatoid arthritis, tumor inhibition, metastasis prevention, antibody-dependent cell-mediated cytotoxicity, chemoresistance reversal, and in improving chemotherapy-related side effects and recovery are reviewed. more...
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- 2018
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33. Cutting Edge: Endogenous IFN-β Regulates Survival and Development of Transitional B Cells
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Shanrun Liu, PingAr Yang, Hui-Chen Hsu, John D. Mountz, Mark R. Walter, Bao Luo, Jennie A Hamilton, Jun Li, Eleanor N. Fish, Qi Wu, and Huixian Hong
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0301 basic medicine ,Cellular differentiation ,Immunology ,Spleen ,TLR7 ,Biology ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,Single-cell analysis ,Downregulation and upregulation ,Gene expression ,medicine ,Immunology and Allergy ,B cell ,030215 immunology - Abstract
The transitional stage of B cell development is a formative stage in the spleen where autoreactive specificities are censored as B cells gain immune competence, but the intrinsic and extrinsic factors regulating survival of transitional stage 1 (T1) B cells are unknown. We report that B cell expression of IFN-β is required for optimal survival and TLR7 responses of transitional B cells in the spleen and was overexpressed in T1 B cells from BXD2 lupus-prone mice. Single-cell gene expression analysis of B6 Ifnb+/+ versus B6 Ifnb–⁄– T1 B cells revealed heterogeneous expression of Ifnb in wild-type B cells and distinct gene expression patterns associated with endogenous IFN-β. Single-cell analysis of BXD2 T1 B cells revealed that Ifnb is expressed in early T1 B cell development with subsequent upregulation of Tlr7 and Ifna1. Together, these data suggest that T1 B cell expression of IFN-β plays a key role in regulating responsiveness to external factors. more...
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- 2017
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34. Autoreactive B Cells in SLE, Villains or Innocent Bystanders?
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Hui-Chen Hsu, John D. Mountz, and Jennie A Hamilton
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0301 basic medicine ,Immunology ,Autoimmunity ,Biology ,medicine.disease_cause ,Article ,03 medical and health sciences ,0302 clinical medicine ,Interferon ,medicine ,Immune Tolerance ,Immunology and Allergy ,Animals ,Humans ,Lupus Erythematosus, Systemic ,Autocrine signalling ,B cell ,Autoantibodies ,B-Lymphocytes ,Systemic lupus erythematosus ,breakpoint cluster region ,Interleukin ,Dendritic Cells ,T-Lymphocytes, Helper-Inducer ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Cytokines ,Interleukin 17 ,030215 immunology ,medicine.drug - Abstract
The current concepts for development of autoreactive B cells in SLE (systemic lupus erythematosus) focus on extrinsic stimuli and factors that provoke B cells into tolerance loss. Traditionally, major tolerance loss pathways are thought to be regulated by factors outside the B cell including autoantigen engagement of the B-cell receptor (BCR) with simultaneous type I interferon (IFN) produced by dendritic cells, especially plasmacytoid dendritic cells (pDCs). Later, in autoreactive follicles, B-cells encounter T-follicular helper cells (Tfh) that produce interleukin (IL)-21, IL-4 and pathogenic cytokines, IL-17 and IFN gamma (IFNɣ). This review discusses these mechanisms and also highlights recent advances pointing to the peripheral transitional B-cell stage as a major juncture where transient autocrine IFNβ expression by developing B-cells imprints a heightened susceptibility to external factors favoring differentiation into autoantibody-producing plasmablasts. Recent studies highlight transitional B-cell heterogeneity as a determinant of intrinsic resistance or susceptibility to tolerance loss through the shaping of B-cell responsiveness to cytokines and other environment factors. more...
- Published
- 2019
35. 192 Disparities of B-cell type I interferon production and responses in SLE
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Hui-Chen Hsu, Shanrun Liu, Bao Luo, Oluwagbemiga Ojo, PingAr Yang, John D. Mountz, Jennie A Hamilton, Qi Wu, W. Winn Chatham, and Alex Essman
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biology ,business.industry ,Autoantibody ,breakpoint cluster region ,TLR9 ,Type I interferon production ,Molecular biology ,Epitope ,Transcriptome ,medicine.anatomical_structure ,biology.protein ,medicine ,Antibody ,business ,B cell - Abstract
Background Dysregulated responses to type I interferons (IFNs) is a hallmark of autoreactive B-cell development in SLE. This study investigated the source of IFN, the major type I IFN responsive B cells, and the disparities associated with B-cell IFN production and type I IFN responses. Methods IFN expression in B, CD4 T and plasmacytoid dendritic cells (pDCs) in PBMCs were analyzed by flow cytometry. Single cell gene expression analysis was carried out using the Fluidigm/BioMark system for targeted expression of low abundance genes, and the 10x Chromium platform for unbiased transcriptome and BCR V(D)J analysis of approximately 2,000 B cells per subject. Autoantigen epitope targets were analyzed using a 4287 high-throughput PEPperPrint Autoimmune Epitope Microarray and a conventional ELISA analysis. Results IFN was analyzed in B cells, CD4 T cells and pDCs in PBMCs of SLE patients and healthy controls (HCs). Endogenous IFN was significantly increased in transitional (Tr), mature naive, and memory B cells of SLE patients compared to HCs. Endogenous IFN in B cells was equivalent to that in pDCs. B-cell endogenous IFN was highly correlated with renal disease, anti-dsDNA, anti-Sm and anti-SSA. Strikingly, the highest correlation of IFN with clinical manifestations was observed in African-American (AA) patients with IgG autoAbs against snRNP323-339, U1snRNP-C97-113. At the single cell transcriptome levels, Tr B cells could be divided into type I IFN expressing (IFN+) or type I IFN stimulated gene (ISG+) subpopulations. TLR7 and TLR3 were mainly expressed by IFN +cells whereas TLR9 was mainly expressed by ISG +B cells. Unbiased single cells analysis of B cells indicated highly expressed ISG gene set in IGHM+, IGHD+, and IGHG +B cells in AA patients with autoantibodies and renal disease. Further, ISG highly expressing SLE B cells exhibited unique heavy- and light-chain repertoires including expression of the autoreactive IGHV4-34 gene, targeted with the 9 G4 anti-idiotype antibody that recognizes DNA- and RBP-autoreactive B cells. Conclusions (i) B cells are an important source of type I IFNs in modulating TLR and BCR responses in SLE; (ii) there are well-orchestrated distinct programs in type I IFN expression and response genes in subsets of B cells, (iii) distinct pathways of autoreactive B cell survival and activation are effected by combined signaling through BCR, TLR, and IFNAR with resultant distinct BCR heavy- and light-chain repertoire. Funding Source(s): R01-AI-071110, R01 AI134023, LRA Distinguished Innovator Award and Novel Research Award, VA Merit Review Award I01B × 004049, Immunology T32 Training Grant 2T32AI007051-39, the LFA Finzi Summer Fellowship. more...
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- 2019
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36. Role of B-cell endogenous interferon beta in lupus nephritis
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Fatima Khalid Alduraibi, Hui-Chen Hsu, Huma Fatima, W. Winn Chatham, and John D Mountz
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Immunology ,Immunology and Allergy - Abstract
Lupus nephritis (LN) is histologically evident yet early diagnosis can be challenging since some patients do not exhibit overt clinical manifestations until advanced stages. The objective of the present study is to determine if B-cell expression of interferon beta (IFNβ) can be a unique systemic lupus erythematosus (SLE) clinical prognostic marker and if specific histopathologic features of LN can be identified in patients with elevated B-cell expression of IFNβ. A total of 80 patients who met the ACR/EULAR classification criteria of SLE were recruited. LN was identified in 41% (N=33). Multivariate regression analysis indicated a significant positive correlation between naïve B-cell IFNβ with race (African American > European American; P=0.006) and LN class (P more...
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- 2021
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37. Two lineages of memory B cell development regulated by type I interferon and IL-4R are perturbed in systemic lupus erythematosus
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Min Gao, Shanrun Liu, Changming Lu, Jake Y Chen, W Winn Chatham, Hui-Chen Hsu, and John D Mountz
- Subjects
Immunology ,Immunology and Allergy - Abstract
Abnormal expansion of type I interferon (IFN) stimulated B cells and T-bet+CD11c+IgD−CD27− DN2 atypical memory B cells are both hallmarks of SLE. To determine how they are interrelated, we have carried out single cell transcriptomics analysis using B cells derived from 3 SLE patients (anti-DNA+ and anti-Smith+) and 3 healthy controls (HCs)(all African Americans). We have identified that elevation of IL4R in pre-switched IGHM+/IGHD+ B cells is the opposing signature of type I IFN stimulated genes (ISGs) and DN2 B cells (TBX21, ITGAX, FCRL3, FCRL5, and ZEB2). In HCs, IGHM+/IGHD+ B cells expressed elevated IL4R. Further, activated naïve B cells (IGHM+IGHD+IGHG+) exhibited upregulation of the germinal center-oriented classical memory B-cell signature genes, CD27, TNFRSF13B (the gene encoding TACI), and GPR183 (the gene encoding EBI2). Flow cytometry analysis confirmed that down-regulation IL-4R and upregulation of intracellular IFN-β in naïve IgD+CD27− B cells correlated with the accumulation of atypical CD21−IgD−CD27−B cells and a reduction in the percentage of classical IgD−CD27+memoryB cells in SLE patients (n=47). In vitro exposure of SLE B cells to IL-4 prior to treatment with anti-Ig+IL-21+IFN-gamma+TLR7+BAFF stimulation significantly enhanced B-cell development into CD27+CD38+ plasmablasts/plasma cells as well as IgD−CD27+memoryB cells but it significantly blocked the development of DN2 B cells. Our results show that upregulation of type I IFN and down-regulation of IL-4R signaling in naïve B cells lead to the accumulation of atypical memory B cells in SLE. Type I IFN and IL-4R signaling in naïve B cells induce the development of distinct lineages of atypical versus classical memory B cells, respectively. more...
- Published
- 2021
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38. IL-17 receptor A signaling on B cells promotes B-cell responses to TLR7 and enhances autoreactive germinal center B-cell development
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Shanrun Liu, Chiao-Wang Sun, Changming Lu, Thomas M Ryan, Hui-Chen Hsu, and John D Mountz
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Immunology ,Immunology and Allergy - Abstract
IL-17 receptor A (IL-17RA) expression has been identified in B cells and macrophages. There was low expression of IL-17RA on T cells. Surprisingly, we previously showed that IL-17RA signaling through NF-κB p65/p50 has a complex effect on both B and T-cell localization and germinal center (GC) architecture, making it difficult to dissect the specific effects of IL-17RA on B cells. To isolate the effects of the absence of IL-17RA specifically on B cells, we have generated a B-cell specific IL-17RA knockout (Il17rafloxed/floxed x Cd19.Cre) BXD2 mice. Flow cytometry confirmed the loss of IL-17RA expression in only CD19+ B cells but not CD3+ T cells or CD11b+ macrophages. There was a 2-fold decreased spontaneous GC B cell population in Il17rafloxed/floxed x Cd19.Cre BXD2, compared to Il17rawt/floxed x Cd19.Cre BXD2 mice. Interestingly, the abnormal activation and expansion of T-follicular helper cell (Tfh) phenotype in BXD2-Il17ra−/− mice was abrogated in Il17rafloxed/floxed x Cd19.Cre BXD2 mice. In the BXD2-Il17ra−/− mice, B cells were anergic to TLR7 stimulation and exhibited a strong stimulus-specific transcription repressor p50/p50 homodimer and a lower NF-κB phospho-p65. To demonstrate that this anergy is due specifically to IL-17RA on B cells but not other cells, we have identified that there was a lower TLR7-induced CD69 in vitro in Il17rafloxed/floxed x Cd19.Cre BXD2 mice. Taken together, our results suggest that IL-17RA signaling directly regulates B cell autoimmune phenotype in the BXD2 mice through an enhancement of B-cell responses stimulated by the NF-κB signaling pathway. A deficiency of such signal enforces B cell anergy and prevents autoreactive GC formation. more...
- Published
- 2021
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39. Chinese Version of Psychometric Evaluation of Self-Reflection and Insight Scale on Taiwanese Nursing Students
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Hui-Chen Hsu, Hui-Mei Chang, Shu-Yueh Chen, Chen-Chun Lai, and Hsiang-Chu Pai
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Adult ,Male ,China ,Psychometrics ,020205 medical informatics ,education ,Taiwan ,Self-concept ,02 engineering and technology ,03 medical and health sciences ,Asian People ,Nursing ,Cronbach's alpha ,Surveys and Questionnaires ,0202 electrical engineering, electronic engineering, information engineering ,Humans ,Nurse education ,General Nursing ,Self-efficacy ,030504 nursing ,Age Factors ,Reproducibility of Results ,General Medicine ,Middle Aged ,Translating ,Self Concept ,Self Efficacy ,Confirmatory factor analysis ,Exploratory factor analysis ,Cross-Sectional Studies ,Convergent validity ,Female ,Students, Nursing ,0305 other medical science ,Psychology - Abstract
Background: Self-reflection (also known as reflection) is an internal process that is difficult to perceive or assess. An instrument that is able to measure self-reflection may serve as a resource for educators to assess the learning process of students and to tailor education approaches to student needs. Purpose: The aim of this study was to translate the Self- Reflection and Insight Scale (SRIS) into Chinese and evaluate its psychometric properties for use with Taiwanese nursing students. Methods: For this cross-sectional study, nursing students were recruited from two nursing schools in southern Taiwan in two phases: Phase 1, which included 361 fourth-year students, and Phase 2, which included 703 fifth-year students. Data were collected in December 2012 and May 2013 using the Chinese version of the SRIS (SRIS-C), Taiwan Critical Thinking Disposition Inventory, and the Perceived Identity as a Nurse Questionnaire, which was developed by the author. In Phase 1, exploratory factor analysis was used to explore the factor structure of the SRIS-C in the fourth-year student participants. In Phase 2, confirmatory factor analysis was used to determine the fitness of the model for the fifth-year student participants. Results: Eight items were deleted from the original SRIS to create the SRIS-C. Thus, the Chinese-version measure had 12 items and two factors (self-reflection and insight) that fit the data well. The Cronbach's alpha coefficients for the total scale and its two subscales were .79, .87, and .83, respectively. The 3-week test-retest reliability was .74. SRIS-C scores correlated significantly with scores on the Taiwan Critical Thinking Disposition Inventory and the Perceived Identity as a Nurse Questionnaire, indicating good convergent validity for the SRIS-C. Conclusions: The current study showed that the SRIS-C has sound psychometric properties. This instrument provides nurse educators with information that may be used to evaluate the self-reflection and insight of students and to develop interventions to effectively improve these skills in Chinese-language-based nursing education. more...
- Published
- 2016
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40. Tamoxifen metabolite endoxifen interferes with the polyamine pathway in breast cancer
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Ping Ar Yang, Tuomo A. Keinänen, Thresia Thomas, Hui-Chen Hsu, Shali John, Thekkumkat Thomas, and Mervi T. Hyvönen
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0301 basic medicine ,medicine.medical_specialty ,Spermine oxidase ,Clinical Biochemistry ,Estrogen receptor ,Breast Neoplasms ,Biology ,Pharmacology ,Biochemistry ,Ornithine decarboxylase ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,skin and connective tissue diseases ,APAO ,Estradiol ,Biogenic Polyamines ,Organic Chemistry ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Spermidine ,Tamoxifen ,030104 developmental biology ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Female ,Polyamine ,Polyamine oxidase ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Tamoxifen is the most widely used drug to treat women with estrogen receptor α (ERα)-positive breast cancer. Endoxifen is recognized as the active metabolite of tamoxifen in humans. We studied endoxifen effects on ERα-positive MCF-7 breast cancer cells. Estradiol increased the proliferation of MCF-7 cells by two- to threefold and endoxifen suppressed its effects. Endoxifen suppressed c-myc, c-fos and Tff1 oncogene expression, as revealed by RT-PCR. Estradiol increased the activity of ornithine decarboxylase (ODC) and adenosyl methioninedecarboxylase (AdoMetDC), whereas endoxifen suppressed these enzyme activities. Endoxifen increased activities of spermine oxidase (SMO) and acetyl polyamine oxidase (APAO) significantly, and reduced the levels of putrescine and spermidine. These data suggest a possible mechanism for the antiestrogenic effects of tamoxifen/endoxifen, involving the stimulation of polyamine oxidase enzymes. Therefore, SMO and APAO stimulation might be useful biomarkers for the efficacy of endoxifen treatment of breast cancer. more...
- Published
- 2016
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41. IL-4 synergizes with low-dose IL-2 to restore systemic lupus erythematosus B cells at the resting naive status
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Hui-Chen Hsu, Shanrun Liu, Min Gao, Qi Wu, PingAr Yang, W. Winn Chatham, and John D. Mountz
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Immunology ,Immunology and Allergy - Abstract
We have recently identified that down-regulation of interleukin-4 receptor (IL-4R) is a novel hallmark of B-cell dysregulation in SLE patients. Single cell transcriptomics analysis revealed that elevation of IL4R in pre-switched B cells is the opposing signature of increased type I interferon stimulated genes (ISGs) and double negative B cells (TBX21, ITGAX, FCRL3, FCRL5, and ZEB2). Flow cytometry analysis further confirmed that down-regulation IL-4R and upregulation of intracellular IFN-β correlated with the loss of CD21+IgD+CD27− resting naïve (rNVA) B cells and accumulation of CD21−IgD+CD27− activated naïve (aNAV) and double negative CD21−IgD+CD27− B cells in SLE patients (n=47). Interestingly, exposure of SLE B cells to IL-4 prior to treatment with low-dose IL-2 (0.2 ng/mL) blocks the anti-Ig, IL-21, IFN-gamma, TLR7 and BAFF-stimulated development of T-bet+CD11c+IgD−CD27− DN2 B cells and CD27+CD38+ plasmablasts (PBs) and preserves B cells in the rNAV state. Such effect was diminished in the absence of IL-4 or when low-dose of IL-2 was substituted with high-dose of IL-2 (20 ng/mL). Stimulation of B cells with IL-4 promoted the induction of CD25 (IL-2RA) on B cells. Together, our results suggest a mechanism of action underlying the synergism between IL-4 and low-dose IL-2. Specifically, the IL-4R signaling pathways upregulate CD25 on B cells, thereby promoting formation of the high affinity IL-2R complexes required for low-dose IL-2 signaling that induces a regulatory signal that restores SLE B cells to the rNAV stage. Our results suggest that the process of development of autoreactive B cells in SLE can be directly measured in a clinical lab, and can be directly abrogated using cytokine therapy available for clinical use. more...
- Published
- 2020
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42. Dysregulation of type I IFN and IL-4R signaling regulates the development of BCR VH and VL repertoire encoding anti-Sm autoantibodies in SLE
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John D. Mountz, Min Gao, Shanrun Liu, Zechen Chong, Qi Wu, PingAr Yang, W. Winn Chatham, and Hui-Chen Hsu
- Subjects
Immunology ,Immunology and Allergy - Abstract
The most specific predictor for systemic lupus erythematosus (SLE) and lupus nephritis (LN) is the presence of anti-Smith (Sm) autoAb. Mechanisms leading to selection bias for anti-Sm development is unclear. We found that anti-Sm levels in SLE correlated with increased endogenous IFN-β and interferon-stimulated genes (ISGs) in combination with low (IL-4R) network genes. Using flow cytometry analysis of 47 SLE patients, we found that anti-Sm+ patients exhibited an increased ratio of IFN-β+ activated naive (aNAV) B cells and a decrease in IL-4R+ resting naive (rNAV) B cells. Using a combined 10X single-cell transcriptomics and BCR usage analysis, anti-Sm+LN+ISGhiIL4Rlopatients (Sm+) were compared with anti-Sm−LN− ISGloIL4Rhi patients (Sm−). BCR heavy chain analysis showed that while B cells from Sm+ patients exhibit greater usage of IGHV1-2, IGHV4-34, and IGHV4-39 genes, Sm− SLE patients exhibit greater usage of IGHV3-30, IGHV3-33, and IGHV4-31 genes. Preferential Ig light chain usage for ISGhi B cells was IGLV1-51, IGLV3-21, IGLV6-57, IGKV1-5, IGKV3-15 and IGKV 6-21. Dominant heavy-light chain pair usages for the Sm+ patients were IGHV4/IGKV1 and IGHV4/IGKV3. IGHV4-34, which is intrinsically autoreactive and the target of the 9G4 anti-idiotype Ab, was found to be expressed by the ISGhiIL4Rlo B cells derived from the same Sm+ patients. The results indicated that increased levels of ISGs and decreased levels of IL-4R pathway genes are the two dominant signatures and the underlying mechanisms leading to selection and activation of anti-Sm+ B cells. Verification that the B-cell IFN-β and IL-4R phenotypes are associated with race (AA vs. EA), repertoire (anti-Sm+) and disease (LN+) would lay the basis for targeted rational therapies. more...
- Published
- 2020
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43. Genetics but not intestinal microbiota determines the onset of systemic autoimmune disease in BXD2 mice
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Huixian Hong, Qi Wu, PingAr Yang, Wayne Duck, Casey D. Morrow, Jeremy B. Foote, Trenton R. Schoeb, Charles O. Elson, Hui-Chen Hsu, and John D. Mountz
- Subjects
Immunology ,Immunology and Allergy - Abstract
The onset and severity of autoimmunity can be attributed to both genetic predisposition and environmental triggers including intestinal microbiota dysbiosis. To determine if development of spontaneous autoimmunity is dependent on gut microbiota, we generated germ-free (GF) BXD2 lupus mice which otherwise develop spontaneous germinal centers (GCs) and high titers of serum autoantibodies. The microbiome and immune phenotypes in specific pathogen free (SPF) and GF BXD2 and normal B6 strains of mice were analyzed. The GF status was confirmed by gut bacterial culture. Surprisingly, the GF status did not affect disease onset and severity in 6-mo-old mice. There were comparable serum levels of IgG or IgM autoantibodies against lupus autoantigens (DNA, histone, and RNP) in SPF versus GF BXD2 mice. Flow cytometry analysis showed that the frequency and absolute numbers of GC B cells, CD4+ T cells, follicular T-helper (Tfh) cells in the spleen were also indistinguishable between SPF and GF BXD2 mice although GF BXD2 mice exhibited a higher number of CD19+ B cells and Tregs, compared to the SPF counterpart. Histologic examination of kidney and lung also showed similar disease scores between SPF and GF BXD2 mice. At older age (12-mo-old), however, there were diminished GC B cells and serum levels of autoantibodies in GF BXD2 mice compared to SPF mice. The results suggest a model in which genetic factors play a dominant role in determining the onset and susceptibility of autoimmunity and that endogenous self-antigens are the primary driver of autoreactive T and B cells leading to spontaneous GCs in BXD2 mice. In contrast, environmental factors such as gut microbiomes may play a modifying role in regulating the persistence of systemic autoimmunity. more...
- Published
- 2020
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44. Gene Therapy and Immunosenescence
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Hui-Chen Hsu, Jian Chen, and John D. Mountz
- Published
- 2019
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45. Dysregulation of T Follicular Helper Cells in Lupus
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Hui-Chen Hsu, André Ballesteros-Tato, and John D. Mountz
- Subjects
Immunology ,Plasma Cells ,Article ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Immunopathology ,Follicular phase ,medicine ,Immunology and Allergy ,Animals ,Humans ,Lupus Erythematosus, Systemic ,In patient ,skin and connective tissue diseases ,Autoantibodies ,Systemic lupus erythematosus ,Lupus erythematosus ,business.industry ,Disease progression ,Autoantibody ,Germinal center ,T-Lymphocytes, Helper-Inducer ,medicine.disease ,Germinal Center ,business ,030215 immunology - Abstract
Although multiple and overlapping mechanisms are ultimately responsible for the immunopathology observed in patients with systemic lupus erythematosus, autoreactive Abs secreted by autoreactive plasma cells (PCs) are considered to play a critical role in disease progression and immunopathology. Given that PCs derive from the germinal centers (GC), long-term dysregulated GC reactions are often associated with the development of spontaneous autoantibody responses and immunopathology in systemic lupus erythematosus patients. In this review, we summarize the emerging evidence concerning the roles of T follicular helper cells in regulating pathogenic GC and autoreactive PC responses in lupus. more...
- Published
- 2018
46. II-05 B cells from SLE patients have increased endogenous production of IFNβ which is stimulated by BCR signaling and is required for survival of autoreactive B cells
- Author
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PingAr Yang, William A Essman, John D. Mountz, Hui-Chen Hsu, Jun Li, W. Winn Chatham, Qi Wu, Bao Luo, Jennie A Hamilton, Shanrun Liu, and Ojo Oluwagbemiga A
- Subjects
medicine.diagnostic_test ,business.industry ,HEK 293 cells ,Cell ,breakpoint cluster region ,TLR9 ,Molecular biology ,Flow cytometry ,Transcriptome ,medicine.anatomical_structure ,Interferon ,medicine ,business ,B cell ,medicine.drug - Abstract
Background Increased type I interferon (IFN) has been shown to affect survival and activation of B cells in SLE. This study investigated novel mechanisms of endogenous production and autocrine activity of IFNβ in SLE B cells at the single-cell level. Methods IFNβ in B cells from SLE patients was analyzed using t-SNE platform based high dimensional flow cytometry. Intracellular IFNβ expression was visualized and analyzed by super-resolution confocal imaging and ImageStream analysis. Single cell gene expression analysis was carried out using the Fluidigm/BioMark system for targeted expression of low abundance genes, and the 10x Chromium platform for unbiased transcriptome analysis of up to 4,000 B cells per subject. Functional production of type I IFNs by B cells was analyzed using a human type I IFNs SEAP reporter HEK293 cell line. Results High dimension flow cytometry analysis identified intracellular IFNβ expression in pDCs, B cells, and CD4 T cells. B-cell endogenous IFNβ was required for optimal in vitro BCR and TLR7-induced activation and survival of B cells. Using a Fluidigm targeted-gene approach, B cells could be divided into type I IFN expressing (IFN+) or type I IFN stimulated gene (ISG+) subpopulations, suggesting B cells not only respond to type I IFNs but also express type I IFNs including IFNB and different IFNA genes. TLR7 and TLR3 were mainly expressed by IFN +cells whereas TLR9 was mainly expressed by ISG +B cells. The production of functional IFNβ and IFNα protein by single B cells from SLE subjects and was verified using a novel alkaline phosphatase live staining of HEK-blue reporter cells. There was enhanced IFNAR signaling by reporter cells in direct contact with SLE B cells which was blocked by anti-IFNβ and anti-IFNα. Interesting, anti-Ig crosslinking was required for optimal B-cell endogenous type I IFNs to stimulate responder cells. Unbiased single cells transcriptome analysis of SLE B cells using the 5’ 10X Chromium platform and Loupe V(D)J Browser indicated that gene clusters in type I IFN expressing or responding SLE B cells exhibited unique heavy- and light-chain gene expression repertoires. Conclusion (i) B cells are an important source of type I IFNs in modulating TLR and BCR responses in SLE; (ii) well-orchestrated and distinct programs in type I expression and responses genes in subsets of B cells, and (iii) distinct pathways of B cell survival and activation based on combined signaling through BCR, TLR, and IFNAR with a distinct BCR heavy- and light-chain repertoire. Acknowledgements This work was supported by grants from R01-AI-071110, R01 AI134023, Lupus Research Alliance Distinguished Innovator Award, I01B × 004049, and 1I01B × 000600 to J.D.M, 2T32AI007051–39 Immunology T32 Training Grant and the LFA Finzi Summer Fellowship to J.A.H, and the LRA Novel Research Award to H.-C.H. more...
- Published
- 2018
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47. AA-05 B cell intrinsic IFNβ is associated with autoantibodies and active renal disease in SLE
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Jennie A Hamilton, John D. Mountz, PingAr Yang, Qi Wu, Bao Luo, Shanrun Liu, Iñaki Sanz, W. Winn Chatham, Hui-Chen Hsu, and Jun Li
- Subjects
Systemic lupus erythematosus ,biology ,business.industry ,Autoantibody ,Plasma cell ,medicine.disease ,Immunoglobulin D ,Peripheral blood mononuclear cell ,medicine.anatomical_structure ,Interferon ,Immunology ,biology.protein ,medicine ,Antibody ,business ,B cell ,medicine.drug - Abstract
Background Dysregulated responses to type I interferons (IFNs) is a hallmark of autoreactive B cell development in SLE patients. High sera levels of type I IFN protein were recently shown to occur in the absence of increased circulating pDCs and in the absence of increased pDC IFNs, suggesting the likelihood of other important sources of type I IFN that may act on B cells. The present study determined the cellular source of IFNβ and its association with disease activities in SLE. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from 31 SLE patients meeting ACR 1997 revised criteria for SLE and 9 healthy controls. Intracellular IFNβ was determined using flow cytometry with FITC-anti-IFNβ mAb. Comprehensive clinical data was recorded for each SLE subject and the clinical data and laboratory analysis of B-cell intracellular IFNβ expression were collected in a double-blind fashion. Results IFNβ was detected in various cell types including CD4 T cells, B cells and pDCs in PBMCs of SLE patients. Endogenous IFNβ in B cells was significantly higher than endogenous IFNβ in CD4 T cells and were equivalent to that seen in pDCs. Within B cells, there was a significant increase in endogenous IFNβ in all B cell subpopulations of SLE patients compared to healthy controls. The most significant increase was found in the CD27+IgD– memory subpopulation. B-cell endogenous IFNβ was not a result of B-cell uptake of exogenous IFNβ as coculture of SLE B cells with HEK293 reporter cells resulted in induction of interferon stimulatory genes as determined by the secreted alkaline phosphatase assay. This was further blocked by an anti-IFNβ neutralization antibody. Interestingly B-cell endogenous IFNβ was highly correlated with clinical disease including renal disease and autoantibodies including anti-dsDNA, anti-Sm and anti-SSA. Strikingly, the highest correlation of IFNβ with clinical manifestations was observed in African-American patients. B-cell IFNβ expression was significantly correlated with CD19loCD38hiCD27+ plasma cell formation. Conclusion Intracellular IFNβ production by B cells is a novel and important B-cell intrinsic factor that may be essential for B-cell development into autoantibody producing B cells. The present work suggests a need for future human lupus studies into type I IFN dysregulation that pioneer beyond the view of pDC produced IFNα. These results also provided a mechanistic basis for development of more effective therapies to target the high-affinity IFNβ or the enhanceosome components that promote its induction in a subgroup of lupus patients. Acknowledgements This work was supported by grants from R01-AI-071110, R01 AI134023, Lupus Research Alliance Distinguished Innovator Award, I01B × 004049, and 1I01B × 000600 to J.D.M, 2T32AI007051–39 Immunology T32 Training Grant and the LFA Finzi Summer Fellowship to J.A.H, and the LRA Novel Research Award to H.-C.H. more...
- Published
- 2018
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48. Role of production of type I interferons by B cells in the mechanisms and pathogenesis of systemic lupus erythematosus
- Author
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Jennie A, Hamilton, Hui-Chen, Hsu, and John D, Mountz
- Subjects
Autocrine Communication ,Interferon Type I ,Paracrine Communication ,Plasma Cells ,Animals ,Humans ,Lupus Erythematosus, Systemic ,Dendritic Cells ,Signal Transduction - Abstract
Type I interferons (IFNs) have a prominent role in many aspects of normal innate and adaptive immunity and autoimmunity. However, cell-type specific information about type I IFN expression and autocrine/paracrine signaling is sparse and mostly focused on non-lymphocyte and non-immune cell populations. A major function of B cells is cytokine production, but surprisingly, type I IFN production by B cells in systemic lupus erythematosus (SLE) has not been thoroughly investigated. This is due, in part, to the established view that plasmacytoid dendritic cells (pDCs) are the primary source of pathogenic type I IFN in lupus. Recent studies, however, have provided evidence to challenge this paradigm. Here, we discuss data supporting a new concept that the production of type I IFN, especially IFNβ, by early stage transitional B cells may be an important source of type I IFN to support autoreactive B cell development in lupus. These findings, if confirmed, may provide a new paradigm in designing and developing more effective therapies for preventing the formation of autoreactive B cells. more...
- Published
- 2018
49. Developing a reading comprehension intervention: Translating cognitive theory to educational practice
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Pyung Gang Jung, Elizabeth A. Lam, Bonita Janda, Kristen L. McMaster, Amy Bethel Leinen, Viveca Pinto, Martin Van Boekel, Paul van den Broek, Hui Chen Hsu, and Christine A. Espin
- Subjects
Online and offline ,Recall ,media_common.quotation_subject ,Narrative text ,Cognition ,Education ,Developmental psychology ,Comprehension ,Reading comprehension ,Intervention (counseling) ,Reading (process) ,Developmental and Educational Psychology ,Psychology ,Cognitive psychology ,media_common - Abstract
The purpose of this study was to translate cognitive models of reading comprehension to educational practice to develop an intervention that is theoretically sound, effective, and feasible for classroom use. Specifically, the effects of questioning type (Causal versus General) and timing (Online versus Offline) on struggling readers’ comprehension were compared. Sixty-two fourth-graders identified as struggling comprehenders were placed in groups of 3–5 students; groups were assigned randomly to Causal or General questioning conditions. All groups received both Online and Offline questioning in counterbalanced order. Tutors delivered intervention for 20–30 min, 3 times per week, for 18 sessions. Dependent measures included students’ recall and oral reading of narrative text. Theoretical, empirical, and practical perspectives were triangulated to select the combination of question type and timing that appeared most promising. Findings are discussed with particular emphasis on challenges associated with translating cognitive theory to practice in classroom-based settings. more...
- Published
- 2015
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50. Gene Therapy and Immunosenescence
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Jian Chen, John D. Mountz, and Hui-Chen Hsu
- Subjects
business.industry ,Genetic enhancement ,Immunology ,Medicine ,Immunosenescence ,business - Published
- 2017
- Full Text
- View/download PDF
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