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Article ; Online: Increased risk of major depressive disorder in sleep apnea patients in Taiwan

Chia-Min Chen / Chia-Yu Kuo / Meng-Ni Wu / Jen-Yu Hung / Chung-Yao Hsu / Ming-Ju Tsai

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 10

Abstract: Abstract The association between sleep apnea (SA) and depression had been reported in a few previous studies. However, whether SA increases the risk of major depressive disorder (MDD) has not been studied comprehensively in a large-scale study. We ... ...

Abstract	Abstract The association between sleep apnea (SA) and depression had been reported in a few previous studies. However, whether SA increases the risk of major depressive disorder (MDD) has not been studied comprehensively in a large-scale study. We performed this population-based cohort study to assess the association between SA and MDD. We identified adult patients having SA from the Taiwan National Health Insurance Research Database and excluded those having MDD before SA diagnosis. Thirty control subjects were randomly selected to match to each SA patient by age and sex. Totally, 10,259 SA patients were matched to 102,590 control subjects. The incidence rate and cumulative incidence of MDD were significantly higher in SA patients than in the control subjects (both p < 0.0001). Multivariable Cox regression analysis showed that SA remained an independent risk factor for incident MDD after adjusting for age, sex, residency, income level, and comorbidities (hazard ratio = 2.9 [95% CI 2.8–3.1], p < 0.0001). In summary, SA patients have an increased risk to develop MDD. Physicians caring for SA patients must pay attention to their psychosocial health status.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ambient Cumulative PM2.5 Exposure and the Risk of Lung Cancer Incidence and Mortality

Hung-Ling Huang / Yung-Hsin Chuang / Tzu-Hsuan Lin / Changqing Lin / Yen-Hsu Chen / Jen-Yu Hung / Ta-Chien Chan

International Journal of Environmental Research and Public Health, Vol 18, Iss 12400, p

A Retrospective Cohort Study

2021 Volume 12400

Abstract: Smoking, sex, air pollution, lifestyle, and diet may act independently or in concert with each other to contribute to the different outcomes of lung cancer (LC). This study aims to explore their associations with the carcinogenesis of LC, which will be ... ...

Abstract	Smoking, sex, air pollution, lifestyle, and diet may act independently or in concert with each other to contribute to the different outcomes of lung cancer (LC). This study aims to explore their associations with the carcinogenesis of LC, which will be useful for formulating further preventive strategies. This retrospective, longitudinal follow-up cohort study was carried out by connecting to the MJ Health Database, Taiwan Cancer Registry database, and Taiwan cause of death database from 2000 to 2015. The studied subjects were persons attending the health check-ups, distributed throughout the main island of Taiwan. Cox proportional hazards regression models were used to investigate the risk factors associated with LC development and mortality after stratifying by smoking status, with a special emphasis on ambient two-year average PM 2.5 exposure, using a satellite-based spatiotemporal model at a resolution of 1 km 2 , and on dietary habit including consumption of fruits and vegetables. After a median follow-up of 12.3 years, 736 people developed LC, and 401 people died of LC-related causes. For never smokers, the risk of developing LC (aHR: 1.32, 95%CI: 1.12–1.56) and dying from LC-related causes (aHR: 1.28, 95%CI: 1.01–1.63) rises significantly with every 10 μg/m 3 increment of PM 2.5 exposure, but not for ever smokers. Daily consumption of more than two servings of vegetables and fruits is associated with lowering LC risk in ever smokers (aHR: 0.68, 95%CI: 0.47–0.97), and preventing PM 2.5 exposure is associated with lowering LC risk for never smokers.
Keywords	fine particulate matter ; lung cancer ; health behaviors ; diet ; Medicine ; R
Subject code	333
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cysteinyl Leukotriene Pathway and Cancer

Ming-Ju Tsai / Wei-An Chang / Cheng-Hao Chuang / Kuan-Li Wu / Chih-Hung Cheng / Chau-Chyun Sheu / Ya-Ling Hsu / Jen-Yu Hung

International Journal of Molecular Sciences, Vol 23, Iss 120, p

2022 Volume 120

Abstract: Cancer remains a leading cause of death worldwide, despite many advances being made in recent decades. Changes in the tumor microenvironment, including dysregulated immunity, may contribute to carcinogenesis and cancer progression. The cysteinyl ... ...

Abstract	Cancer remains a leading cause of death worldwide, despite many advances being made in recent decades. Changes in the tumor microenvironment, including dysregulated immunity, may contribute to carcinogenesis and cancer progression. The cysteinyl leukotriene (CysLT) pathway is involved in several signal pathways, having various functions in different tissues. We summarized major findings of studies about the roles of the CysLT pathway in cancer. Many in vitro studies suggested the roles of CysLTs in cell survival/proliferation via CysLT 1 receptor (CysLT 1 R). CysLT 1 R antagonism decreased cell vitality and induced cell death in several types of cancer cells, such as colorectal, urological, breast, lung and neurological malignancies. CysLTs were also associated with multidrug resistance of cancer, and CysLT 1 R antagonism might reverse chemoresistance. Some animal studies demonstrated the beneficial effects of CysLT 1 R antagonist in inhibiting tumorigenesis and progression of some cancer types, particularly colorectal cancer and lung cancer. The expression of CysLT 1 R was shown in various cancer tissues, particularly colorectal cancer and urological malignancies, and higher expression was associated with a poorer prognosis. The chemo-preventive effects of CysLT 1 R antagonists were demonstrated in two large retrospective cohort studies. In summary, the roles of the CysLT pathway in cancer have been delineated, whereas further studies are still warranted.
Keywords	leukotriene ; montelukast ; zafirlukast ; chemoprevention ; cell death ; apoptosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 616
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparing survival and subsequent treatment of first-line tyrosine kinase inhibitors in patients of advanced lung adenocarcinoma with epidermal growth factor receptor mutation

Ming-Yi Huang / Kun-Pin Hsieh / Ru-Yu Huang / Jen-Yu Hung / Li-Tzong Chen / Ming-Ju Tsai / Yi-Hsin Yang

Journal of the Formosan Medical Association, Vol 121, Iss 1, Pp 170-

2022 Volume 180

Abstract: Background/purpose: Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR mutation. However, studies comparing efficacy or effectiveness of ... ...

Abstract	Background/purpose: Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR mutation. However, studies comparing efficacy or effectiveness of these EGFR TKIs came out with inconclusive results. Methods: In this real-world data analysis with a nationwide retrospective cohort design, adult patients with newly diagnosed advanced lung adenocarcinoma with EGFR mutation between 2011 and 2016, who received a first-line EGFR TKI, were included. Overall survival (OS) and time to next treatment (TTNT) were compared between patients receiving different EGFR TKIs after overlap weighting. Results: We enrolled 10,431 patients, including 6,230, 2,359, and 1842 in gefitinib, erlotinib, and afatinib groups, respectively. The median (95% confidence interval [CI]) OS were 24.2 (22.9–26.2), 25.7 (24.0–27.9), and 29.1 (25.8–32.1) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p = 0.001). The hazard ratios (95% CI) for the afatinib group were 0.85 (0.74–0.98) and 0.91 (0.79–1.05) comparing with the gefitinib and erlotinib groups, respectively. The median (95% CI) TTNT were 10.9 (10.4–11.2), 11.7 (11.3–12.1), 13.4 (12.5–14.3) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p < 0.001). The hazard ratios (95% CI) for the afatinib group were 0.79 (0.70–0.88) and 0.89 (0.79–1.00) comparing with the gefitinib and erlotinib groups, respectively. There were 6111 (59%) patients receiving subsequent therapies, and the majority of them received a second-line chemotherapy, particularly platinum-based chemotherapy. Conclusion: Afatinib, compared with gefitinib, might provide better effectiveness as the first-line targeted therapy for patients of advanced lung adenocarcinoma with EGFR mutation.
Keywords	Targeted therapy ; Effectiveness ; Gefitinib ; Erlotinib ; afatinib ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming

Kuan-Li Wu / Yung-Chi Huang / Yu-Yuan Wu / Chao-Yuan Chang / Yung-Yun Chang / Hung-Hsing Chiang / Lian-Xiu Liu / Ying-Ming Tsai / Jen-Yu Hung

Biology, Vol 11, Iss 975, p

2022 Volume 975

Abstract: Lung adenocarcinoma (LUAD) is a common type of lung cancer. Although the diagnosis and treatment of LUAD have significantly improved in recent decades, the survival for advanced LUAD is still poor. It is necessary to identify more targets for developing ... ...

Abstract	Lung adenocarcinoma (LUAD) is a common type of lung cancer. Although the diagnosis and treatment of LUAD have significantly improved in recent decades, the survival for advanced LUAD is still poor. It is necessary to identify more targets for developing potential agents against LUAD. This study explored the dysregulation of translation initiation factors, specifically eukaryotic initiation factors 4A1 ( EIF4A1 ) and EIF4A2 , in developing LUAD, as well as their underlying mechanisms. We found that the expression of EIF4A1 , but not EIF4A2 , was higher in tumor tissue and associated with poor clinical outcomes in LUAD patients. Elevated expression of EIF4H with poor prognosis may potentiate the oncogenic role of EIF4A1 . Functional enrichment analysis revealed that upregulation of EIF4A1 was related to cell cycle regulation and DNA repair. The oncogenic effect of EIF4A1 was further elucidated by Gene Set Variation Analysis (GSVA). The GSVA score of the gene set positively correlated with EIF4A1 was higher in tumors and significantly associated with worse survival. In the meantime, gene set enrichment analysis (GSEA) also indicated that elevated EIF4A1 expression in LUAD patients was associated with a decreased infiltration score for immune cells by reducing anticancer immune cell types and recruiting immunosuppressive cells. Consistent with the results, the GSVA score of genes whose expression was negatively correlated with EIF4A1 was lower in the tumor tissue of LUAD cases with worse clinical outcomes and was strongly associated with the disequilibrium of anti-cancer immunity by recruiting anticancer immune cells. Based on the results from the present study, we hypothesize that the dysregulation of EIF4A1 might be involved in the pathophysiology of LUAD development by promoting cancer growth and changing the tumor immune microenvironment. This can be used to develop potential diagnostic biomarkers or therapeutic targets for LUAD.
Keywords	cell cycle ; DNA repair ; EIF4A1 ; LUAD ; tumor immune microenvironment ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Novel mechanical ventilator weaning predictive model

Wei‐Chan Chung / Chau‐Chyun Sheu / Jen‐Yu Hung / Tuan‐Jung Hsu / Ssu‐Han Yang / Jong‐Rung Tsai

Kaohsiung Journal of Medical Sciences, Vol 36, Iss 10, Pp 841-

2020 Volume 849

Abstract: Abstract Mechanical ventilation (MV) is a common life support system in intensive care units. Accurate identification of patients who are capable of being extubated can shorten the MV duration and potentially reduce MV‐related complications. Therefore, ... ...

Abstract	Abstract Mechanical ventilation (MV) is a common life support system in intensive care units. Accurate identification of patients who are capable of being extubated can shorten the MV duration and potentially reduce MV‐related complications. Therefore, prediction of patients who can successfully be weaned from the mechanical ventilator is an important issue. The electronic medical record system (EMRs) has been applied and developed in respiratory therapy in recent years. It can increase the quality of critical care. However, there is no perfect index available that can be used to determine successful MV weaning. Our purpose was to establish a novel model that can predict successful weaning from MV. Patients' information was collected from the Kaohsiung Medical University Hospital respiratory therapy EMRs. In this retrospective study, we collected basic information, classic weaning index, and respiratory parameters during spontaneous breathing trials of patients eligible for extubation. According to the results of extubation, patients were divided into successful extubation and extubation failure groups. This retrospective cohort study included 169 patients. Statistical analysis revealed successful extubation predictors, including sex; height; oxygen saturation; Glasgow Coma Scale; Acute Physiology and Chronic Health Evaluation II score; pulmonary disease history; and the first, 30th, 60th, and 90th minute respiratory parameters. We built a predictive model based on these predictors. The area under the curve of this model was 0.889. We established a model for predicting the successful extubation. This model was novel to combine with serial weaning parameters and thus can help intensivists to make extubation decisions easily.
Keywords	critical care ; mechanical ventilation ; weaning ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Corrigendum to “Novel mechanical ventilator weaning predictive model”[Kaohsiung J Med Sci. 2020;36(10):841‐849]

Wei‐Chan Chung / Chau‐Chyun Sheu / Jen‐Yu Hung / Tuan‐Jung Hsu / Ssu‐Han Yang / Jong‐Rung Tsai

Kaohsiung Journal of Medical Sciences, Vol 36, Iss 11, Pp n/a-n/a (2020)

2020

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Downregulated ADAMTS1 Incorporating A2M Contributes to Tumorigenesis and Alters Tumor Immune Microenvironment in Lung Adenocarcinoma

Hsiao-Chen Lee / Chao-Yuan Chang / Yung-Chi Huang / Kuan-Li Wu / Hung-Hsing Chiang / Yung-Yun Chang / Lian-Xiu Liu / Jen-Yu Hung / Ya-Ling Hsu / Yu-Yuan Wu / Ying-Ming Tsai

Biology, Vol 11, Iss 760, p

2022 Volume 760

Abstract: Lung adenocarcinoma (LUAD) still holds the most dreadful clinical outcomes worldwide. Despite advanced treatment strategies, there are still some unmet needs. Next-generation sequencing of large-scale cancer genomics discovery projects combined with ... ...

Abstract	Lung adenocarcinoma (LUAD) still holds the most dreadful clinical outcomes worldwide. Despite advanced treatment strategies, there are still some unmet needs. Next-generation sequencing of large-scale cancer genomics discovery projects combined with bioinformatics provides the opportunity to take a step forward in meeting clinical conditions. Based on in-house and The Cancer Genome Atlas (TCGA) cohorts, the results showed decreased levels of ADAMTS1 conferred poor survival compared with normal parts. Gene set enrichment analyses (GSEA) indicated the negative correlation between ADAMTS1 and the potential roles of epithelial–mesenchymal transition (EMT), metastasis, and poor prognosis in LUAD patients. With the knockdown of ADAMTS1, A549 lung cancer cells exhibited more aggressive behaviors such as EMT and increased migration, resulting in cancer metastasis in a mouse model. The pathway interaction network disclosed the linkage of downregulated α2-macroglobulin (A2M), which regulates EMT and metastasis. Furthermore, immune components analysis indicated a positive relationship between ADAMTS1 and the infiltrating levels of multiple immune cells, especially anticancer CD4 + T cells in LUAD. Notably, ADAMTS1 expression was also inversely correlated with the accumulation of immunosuppressive myeloid-derived suppressor cells and regulatory T cells, implying the downregulated ADAMTS1 mediated immune adjustment to fit the tumor survival disadvantages in LUAD patients. In conclusion, our study indicates that ADAMTS1 interacts with A2M in regulating EMT and metastasis in LUAD. Additionally, ADAMTS1 contributes to poor prognosis and immune infiltration in LUAD patients
Keywords	A2M ; ADAMTS1 ; EMT ; immunity ; LUAD ; metastasis ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy

Hsiao-Chen Lee / Chao-Yuan Chang / Kuan-Li Wu / Hung-Hsing Chiang / Yung-Yun Chang / Lian-Xiu Liu / Yung-Chi Huang / Jen-Yu Hung / Ya-Ling Hsu / Yu-Yuan Wu / Ying-Ming Tsai

Journal of Personalized Medicine, Vol 12, Iss 902, p

2022 Volume 902

Abstract: Lung cancer is well known for its high mortality worldwide. The treatment for advanced lung cancer needs more attention to improve its survival time. A disintegrin and metallopeptidase with thrombospondin motifs 8 (ADAMTS8) has been linked to several ... ...

Abstract	Lung cancer is well known for its high mortality worldwide. The treatment for advanced lung cancer needs more attention to improve its survival time. A disintegrin and metallopeptidase with thrombospondin motifs 8 (ADAMTS8) has been linked to several cancer types. However, its role in lung cancer is worthy of deep investigation to promote novel drug development. This study took advantage of RNA-seq and bioinformatics to verify the role that ADAMTS8 plays in lung cancer. The functional assays suggested that ADAMTS8 mediates invasion and metastasis when expressed at a low level, contributing to poor overall survival (OS). The expression of ADAMTS8 was under the regulation of GATA Binding Protein 1 (GATA1) and executed its pathologic role through Thrombospondin Type 1 Domain Containing 1 (THSD1) and ADAMTS Like 2 (ADAMTSL2). To define the impact of ADAMTS8 in the lung cancer treatment strategy, this study further grouped lung cancer patients in the TCGA database into mutated epidermal growth factor receptor (EGFR)/wild-type EGFR and programmed death ligand 1 (PD-L1) high/low groups. Importantly, the expression of ADAMTS8 was correlated positively with the recruitment of anticancer NKT cells and negatively with the infiltration of immunosuppressive Treg and exhausted T cells. The results indicated that lung cancer patients with higher ADAMTS8 levels among wild-type EGFR or low PD-L1 groups survive longer than those with lower levels do. This study indicates that ADAMTS8 might be a treatment option for patients with lung adenocarcinoma who lack efficient targeted or immunotherapies.
Keywords	ADAMTS8 ; EGFR ; GATA1 ; NKT ; lung cancer ; Treg ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Factors Predicting Concordant Epidermal Growth Factor Receptor (EGFR) Mutation Detected in Liquid/Tissue Biopsy and the Related Clinical Outcomes in Patients of Advanced Lung Adenocarcinoma with EGFR Mutations

Chia-Yu Kuo / Mei-Hsuan Lee / Ming-Ju Tsai / Chih-Jen Yang / Jen-Yu Hung / Inn-Wen Chong

Journal of Clinical Medicine, Vol 8, Iss 11, p

2019 Volume 1758

Abstract: Liquid biopsy to identify epidermal growth factor receptor ( EGFR ) gene mutations from circulating tumor DNA (ctDNA) for lung adenocarcinoma is less invasive than traditional tissue biopsy. Most patients have concordant results in liquid/tissue biopsy, ... ...

Abstract	Liquid biopsy to identify epidermal growth factor receptor ( EGFR ) gene mutations from circulating tumor DNA (ctDNA) for lung adenocarcinoma is less invasive than traditional tissue biopsy. Most patients have concordant results in liquid/tissue biopsy, while the clinical significance of concordant results remains unclear. Our study aimed to evaluate the predicting factors and clinical outcomes associated with concordant results in liquid/tissue biopsy in newly diagnosed lung adenocarcinoma patients with EGFR mutations. In the 80 patients of stage III or IV lung adenocarcinoma, 51 patients had EGFR mutations detected in tissue samples, while 33 (65%) of them had concordant results shown in liquid biopsy. Multivariable regression analysis showed that lymph node involvement (adjusted odds ratio (95% CI): 8.71 (1.88−40.35), p = 0.0057) and bone metastasis (adjusted odds ratio (95% CI): 9.65 (1.72−54.05), p = 0.0099) were the independent predicting factors for concordant results. Forty of these 51 patients were stage IV and were treated with EGFR tyrosine kinase inhibitors (TKIs). The concordant results in liquid/tissue samples were associated with significantly poorer progression-free survival (PFS) in univariate analysis. However, multivariable analysis showed that lymph node involvement was the only independent predicting factor for poorer PFS, while concordant results in liquid/tissue samples were excluded during variable selection. The concordant results in liquid/tissue samples might indicate a larger tumor burden, which actually contributes to poorer PFS.
Keywords	lung cancer ; adenocarcinoma ; egfr ; liquid biopsy ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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