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Yi-Cheng Li,1,2 Yia-Ling Chang,3 Fang-Yih Liaw,2,4 Chih-Chia Wang,2,4 Yaw-Wen Chang2,4 1Department of Family Medicine, Hualien Armed Forces General Hospital, Hualien, Taiwan, Republic of China; 2School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Department of Nursing, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Penghu, Taiwan, Republic of China; 4Department of Family and Community Medicine, Tri-Service General Hospital, Taipei, Taiwan, Republic of ChinaCorrespondence: Yaw-Wen Chang, School of Medicine, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Road, Neihu District, Taipei City, 11490, Taiwan, Republic of China, Email yawwenc@office365.ndmctsgh.edu.twBackground: The Discharge Planning Curriculum (DPC) is a 4-hour course for penultimate-year medical students at a tertiary teaching hospital in Taiwan. The course begins with a 30-minute introduction, followed by the students shadowing discharge planning case managers as they visit patients on the wards. After patient visits, the students engaged in a 1-hour case discussion. Our research assessed the effectiveness of the DPC for medical students.Methods: This mixed methods study recruited medical students participating in family medicine rotations between October 2017 and May 2018. To determine the impact of the DPC, we quantitatively analyzed questionnaire responses to measure changes in self-efficacy, attitude toward discharge planning, and course satisfaction before and after completing the DPC. Additionally, we conducted qualitative focus group interviews to gain insight into the students’ learning experiences and applied thematic analysis to the interview data.Results: Our study found two quantitative results: 1) The DPC significantly improved self-efficacy and attitude toward discharge planning (p < 0.001). 2) The medical students acquired knowledge about home care, assistive device application, long-term care facility referral, home rehabilitation, and home care services, and more than 95% of the students reported being satisfied with the course. In addition, the focus group interviews revealed that medical students learned several aspects of discharge planning through the curriculum, including an understanding of various aspects of discharge planning through the curriculum, the importance of early discharge planning, the roles of doctors and case managers, and the challenges faced in the process.Conclusion: The DPC helped medical students understand different team members’ roles in discharge planning and appreciate the challenges that case managers face in this process. The DPC improved medical students’ attitudes toward discharge planning. The curriculum can be a valuable tool in training future healthcare providers in effective transitional care.Keywords: continuity of patient care, curriculum evaluation, interdisciplinary training, patient discharge, undergraduate medical education

Chuanchuan Sun,1 Heng Shi,1 Xinhai Zhao,2 Yu-Ling Chang,2 Xianghong Wang,3 Shiping Zhu,2 Shengyun Sun1 1Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Endocrinology and Metabolism, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of ChinaCorrespondence: Shengyun Sun, Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510630, People’s Republic of China, Email shengyunsun2020@163.comAbstract: The activation of the cGAS-STING pathway is associated with many sterile inflammatory and inflammatory conditions, including acute kidney injury. As a cytoplasmic DNA sensor, sensitization of the cGAS-STING pathway can ignite the innate immune response in vivo and trigger a series of biological effects. In recent years, there is increasing evidence showing that the cGAS-STING pathway plays a vital role in acute kidney injury, a non-inflammatory disease induced by activation of innate immune cells, and closely related to intracellular reactive oxygen species, mitochondrial DNA, and the cGAS-STING pathway. This review provides a prospect of the cGAS-STING pathway and its relationship to acute kidney injury.Keywords: mitochondrial DNA, innate immunity, reactive oxygen species, mitochondrial dysfunction, acute kidney injury

Mohsen Saffari,1,2,&ast; I-Hua Chen,3,&ast; Po-Ching Huang,4 Kerry S O’Brien,5 Yi-Ping Hsieh,6 Ji-Kang Chen,7 Yun-Hsuan Chang,8– 11 Xingyong Jiang,12 Nadia Bevan,5 Yen-Ling Chang,13 Jung-Sheng Chen,14 Ching-Chung Tsai,15,16 Mark D Griffiths,17 Chung-Ying Lin4,18– 20 1Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran; 2Health Education Department, Faculty of Health, Baqiyatallah University of Medical Sciences, Tehran, Iran; 3Chinese Academy of Education Big Data, Qufu Normal University, Qufu, People’s Republic of China; 4Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5School of Social Sciences, Monash University, Melbourne, Australia; 6Department of Social Work, College of Nursing and Professional Disciplines, University of North Dakota, Grand Forks, ND, USA; 7Department of Social Work, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; 8Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 10Department of Psychology, National Cheng Kung University, Tainan, Taiwan; 11Institute of Genomics and Bioinformatics, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; 12Yangan Primary School of Qionglai City, Qionglai, People’s Republic of China; 13Department of Family Medicine, Cardinal Tien Hospital, New Taipei, Taiwan; 14Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; 15Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; 16School of Medicine, I-Shou University, Kaohsiung, Taiwan; 17International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 18Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 19Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 20Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chung-Ying Lin, Institute of Allied Health Sciences, Department of Occupational Therapy, Department of Public Health, Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701401, Taiwan, Tel +886 6 2353535 ext. 5106, Fax +886 6 2367981, Email cylin36933@gmail.com Ching-Chung Tsai, Department of Pediatrics, E-Da Hospital, School of Medicine, I-Shou University, 1 Yi-Da Road, Kaohsiung, 824005, Taiwan, Email u101130@gmail.comIntroduction: Preventative factors in young people’s physical inactivity require further understanding, including related psychosocial factors (eg, body image and weight stigma). The Tendency to Avoid Physical Activity and Sport Scale (TAPAS) is a recently developed instrument to address this issue and the present study examined its psychometric properties among Chinese university students particularly in relation to patterns across sex, physical activity (PA) level, and weight status.Methods: Using a convenience sample of 3142 students (mean age = 19.8 years; 56% female) in mainland China, data were collected using an online survey between August and October 2022. Psychometric instruments including the Weight Bias Internalization Scale, 21-item Depression, Anxiety and Stress Scale, and International Physical Activity Questionnaire Short Form were administered along with the TAPAS to assess convergent and discriminant validity. Multi-group confirmatory factor analysis (CFA) assessed the measurement invariance across specific groups.Results: The unidimensional structure of the scale was confirmed through CFA (CFI=0.995; RMSEA=0.046). All configural, metric and scalar models of invariance indicated that the scale was invariant across sex, PA level, and weight status. Acceptable convergent and discriminant validity for the scale were found.Conclusion: The TAPAS is a suitable instrument to assess body image and weight stigma concerns for avoiding physical activity and sport among Chinese university students.Keywords: confirmatory factor analysis, factor structure, psychometrics, weight stigma, young adults, China

Yi-Ju Liao,1 Tzu-Hung Hsiao,2– 4 Ching-Heng Lin,2,3,5,6 Chun-Sheng Hsu,7– 10 Yen-Lin Chang,1,8 Yu-Wei Chen,11 Chiann-Yi Hsu,2,12 Yi-Ming Chen,2,10,13– 15,&ast; Ming-Fen Wu1,&ast; 1Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Public Health, Fu Jen Catholic University, New Taipei City, Taiwan; 4Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan; 5Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; 6Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan; 7Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung, Taiwan; 8Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan; 9School of Medicine, National Defense Medical Center, Taipei, Taiwan; 10Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 11Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan; 12Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan; 13Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 14Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 15School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yi-Ming ChenDivision of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Xitun Dist., Taichung, 407, Taiwan, Tel +886-4-2359-2525 ext. 4400, Fax +886-4-2359-2705, Email ymchen1@vghtc.gov.twPurpose: Clopidogrel is widely used in coronary artery, peripheral arterial, and cerebrovascular disease. We aimed to study the association of the CYP2C19 phenotype with cardiovascular outcomes and interventional procedures in a hospital-based population.Patients and Methods: This cross-sectional, retrospective study enrolled patients with prior exposure to clopidogrel at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI). Data on the CYP2C19 phenotype, drug-prescription profile, comorbidities, vascular intervention procedures, and hospitalization due to acute myocardial infarction (AMI) or stroke of clopidogrel users were analyzed.Results: From the 32,728 patients in the TCVGH-TPMI cohort, we selected 2687 clopidogrel users. A total of 400 (14.9%) clopidogrel poor metabolizers (PMs), 1235 (46.0%) intermediate metabolizers (IMs), and 1052 (39.2%) extensive metabolizers (EMs) were identified. The predominant loss-of-function allele is &ast;2. In 2687 patients with clopidogrel exposure, the CYP2C19 PM phenotype was unassociated with hospitalization due to AMI or stroke after adjusting for comorbidities and carotid angiographies. Among the 1554 clopidogrel users who underwent cardiovascular intervention, 193 (12.4%) received two or more types of interventional procedures. Compared with non-PMs, patients with the PM phenotype had a higher risk of multiple carotid interventions (OR: 3.13, 95% CI: 1.19– 8.22).Conclusion: In this hospital-wide cohort, 8.2% were clopidogrel users, of which 14.9% were CYP2C19 PMs. The result of this study does not support universal genotyping of CYP2C19 in all clopidogrel users to identify risks for stroke and AMI. CYP2C19 PMs are more likely to undergo multiple carotid interventions than non-PMs. Prospective studies to investigate the association of the CYP2C19 genotype and carotid interventions and outcomes are needed to validate our results.Keywords: pharmacogenomics, clopidogrel, CYP2C19, Taiwan precision medicine initiative, TPMI, carotid intervention

Yenlin Huang,1,2 Chieh Lin,3 Huang-Kai Kao,2,4 Shao-Yu Hung,4 Hung-Ju Ko,2 Yu-Chen Huang,5 Yu-Liang Chang,5 Kai-Ping Chang2,6 1Department of Anatomic Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Department of Oral & Maxillofacial Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Kai-Ping ChangDepartment of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, No. 5, Fu-Hsing Street, Kwei-Shan, Taoyuan 333005, TaiwanTel +886-3-3281200 ext 3972Fax +886-3-3979361Email dr.kpchang@gmail.comPurpose: The presence of CD8+ tumor-infiltrating lymphocytes (TILs) has been reported to be associated with treatment outcomes in many types of solid tumors. However, the results vary due to the various methods of visual estimation and subjective interpretation. The current study is the first to use digital image analyses to evaluate the density of CD8+/CD3+ TILs in tongue squamous cell carcinoma (TSCC).Patients and Methods: From 2005 to 2015, a cohort of 258 TSCC patients were consecutively enrolled in this study. After immunohistochemistry on representative sections, the density of CD8+/CD3+ TILs at tumor invasive margins was evaluated by digital image analysis. The subjects were stratified by the median values of CD3+ cell density, CD8+ cell density, CD8/CD3, and scores (0, 1, and 2) to demonstrate the association with various clinicopathological manifestations.Results: Low CD8+ TIL counts were associated with advanced tumor stages (p=0.034), and low CD8/CD3 ratios were associated with perineural invasion (p=0.043). Both parameters were also associated with increased tumor depths (p=0.034 and 0.004, respectively). Univariate analyses revealed that advanced tumor stages, perineural invasion, extranodal extension, tumor depth, lower CD8 counts, and lower scores (score 0 vs 2) were associated with poorer overall survival, and multivariate analysis further indicated that extranodal extension and low scores (score 0 vs 2) were both independent factors for overall survival (p < 0.0001 and p = 0.0369, respectively).Conclusion: The use of digital image analysis to assess CD8+ TILs at the invasive margins provides an objective indicator of prognoses including overall survival.Keywords: oral cavity, squamous cell carcinoma, oral cancer, SCC, tumor-infiltrating lymphocyte, TIL

Vincent Yi-Fong Su,1–3 Han-Fang Liao,4 Diahn-Warng Perng,3,5 Yueh-Ching Chou,4,6,7 Chia-Chen Hsu,6 Chia-Lin Chou,4,6 Yuh-Lih Chang,4,6 Jiin-Cherng Yen,4 Tzeng-Ji Chen,3,8,9 Ting-Chun Chou4,6 1Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan; 2Institute of Clinical Medicine, 3Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 4Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; 5Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 6Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan; 7School of Pharmacy, Taipei Medical University, Taipei, Taiwan; 8Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 9Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan Objective: The effect of antacid therapy for patients with COPD and gastroesophageal reflux disease (GERD) remains unclear.Patients and methods: This nationwide population-based study was conducted using data from Taiwan’s National Health Insurance Research Database, and enrolled COPD patients with or without GERD. Patients with COPD who were not prescribed COPD medications were excluded. Patients with GERD who underwent upper gastrointestinal endoscopy or 24-hour pH monitoring and received at least 1 antacid were enrolled as symptomatic GERD group. The primary endpoint was acute exacerbation and mortality.Results: This study included 3,485 patients with COPD and symptomatic GERD, and 13,938 patients with COPD alone and covered 12,806.57 and 56,809.78 person-years, respectively, from 2000 to 2011. After multivariate adjustment, symptomatic GERD was associated with acute exacerbation (adjusted hazard ratio [HR]: 1.35, 95% CI: 1.23–1.48, p

Bih-Ru Wang,1,2,* Yuh-Lih Chang,1,2,* Tzeng-Ji Chen,3,4 Jen-Hwey Chiu,5,6 Jing Chong Wu,7 Min-Shan Wu,1 Chia-Lin Chou,1 Yueh-Ching Chou1,2,81Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; 3Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan; 5Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; 6Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Traditional Medicine Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 8College of Pharmacy, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workBackground: Many female breast cancer (FBC) patients take Chinese herbal medicine (CHM) and Western medication (WM) concurrently in Taiwan. Despite the possibility of interactions between the CHM and WM mentioned in previous studies, the pattern of these coprescriptions in FBC patients remains unclear. Hence, the aim of the present study is to investigate the utilization of coprescriptions of CHM and WM among the FBC patients in Taiwan.Methods: The study was a cross-sectional survey using the sampled cohort in 2009 obtained from the National Health Insurance Research Database in Taiwan. There were 3,507 FBC patients identified from the registry for catastrophic illness patients. Ambulatory visit records, corresponding prescriptions, and the data of beneficiaries belonging to the FBC patients were further extracted. A total of 1,086 FBC patients used CHM at least once. CHM and WM prescribed within any overlapping duration were defined as coprescriptions.Results: There were 868 (80.0%) patients simultaneously receiving CHM and WM. A total of 4,927 CHM prescriptions and 6,358 WM prescriptions were prescribed concurrently. Among these coprescriptions, the most frequently used CHM was jia-wei-xiao-yao-san (21.2%), and the most frequently coprescribed WM was acetaminophen (38.9%), followed by tamoxifen (25.5%). There were 346 patients using systemic adjuvant therapy and CHM concurrently. The most commonly coprescribed CHM with chemotherapy, endocrine therapy, and trastuzumab was xiang-sha-liu-jun-zi-tang, jia-wei-xiao-yao-san, and zhi-gan-cao-tang, respectively.Conclusion: The combined use of CHM with WM is prevalent. The main purpose of combining CHM with systemic cancer treatment is to alleviate the treatment-related adverse effects. However, the combination may result in the potential risk of drug–herb interactions. Further clinical studies are needed to evaluate the efficacy and safety of the CHM and WM coprescriptions for FBC patients.Keywords: drug utilization patterns, complementary and alternative medicine, pharmacoep-idemiology

Galactic PeV cosmic-ray accelerators (PeVatrons) are Galactic sources theorized to accelerate cosmic rays up to PeV in energy. The accelerated cosmic rays are expected to interact hadronically with nearby ambient gas or the interstellar medium, resulting in γ-rays and neutrinos. Recently, the Large High Altitude Air Shower Observatory (LHAASO) identified 12 γ-ray sources with emissions above 100 TeV, making them candidates for PeVatrons. While at these high energies the Klein-Nishina effect exponentially suppresses leptonic emission from Galactic sources, evidence for neutrino emission would unequivocally confirm hadronic acceleration. Here, we present the results of a search for neutrinos from these γ-ray sources and stacking searches testing for excess neutrino emission from all 12 sources as well as their subcatalogs of supernova remnants and pulsar wind nebulae with 11 yr of track events from the IceCube Neutrino Observatory. No significant emissions were found. Based on the resulting limits, we place constraints on the fraction of γ-ray flux originating from the hadronic processes in the Crab Nebula and LHAASO J2226+6057.

The U.S. welfare reform of 1996 brought about highly decentralized Welfare-to-Work (WTW) programs, granting discretion to states and local governments to implement policies. Previous research has emphasized racial disparities in WTW sanction rates, by focusing on state/county characteristics or frontline-workers' biases. There is a dearth of research focusing on different understandings of equity or equality and corresponding practices embedded within WTW programs at the state and local levels. This knowledge is important to better understand how race disparities in WTW may be shaped. Our case is California's comparatively generous and highly devolved WTW program and its implementation in two most different counties. Descriptive analysis of administrative data reveals racial disparities in WTW sanctions and exemptions at the state-level and contrasting racial disparity patterns across two counties. Drawing on an equity framework, critical discourse analysis (CDA) of policy documents and interviews at the state level reveals conflicting discourses and practices around equity and equality, leaving room for interpretation at local agencies. CDA of county-level documents and interviews with county administrators showcases contrasting discourses and practices: while one county operates on an equality discourse that does not challenge existing disparities, the other county adopts an equity-related discourse of providing better treatment towards some historically disadvantaged groups. The observed discourses and practices help to understand the different racial disparity patterns. We conclude that in the absence of a clear equity framework at the state level, decentralization in WTW complicates the manner in which equity discourses and practices play out at the local level.

Drawing from Critical Race Theory (CRT), and a structural intersectionality framework, we examine intersecting structural inequalities embedded in county welfare-to-work (WTW) service delivery in California. Using a mixed-method analytic approach, our results reveal that second-order-devolution revolution (SODR) shapes intersecting gender, racial, class, and spatial inequalities, and reproduces white supremacy. We find that counties with multiple privileged socioeconomic characteristics operate employment- or training-oriented WTW systems, whereas counties with multiple disadvantaged socioeconomic characteristics operate sanction- or education-oriented WTW systems. We discuss policy solutions to address the disparities in WTW service delivery systems.

Although research has paid substantial attention to the impact of the Great Recession on the economic well-being of working households and the uneven economic recovery among different sociodemographic groups, limited research is available on the association between state-level unemployment insurance (UI) protection and household-level economic recovery during the postrecessionary years. Using nationally representative panel data from the 2008 survey of income and program participation, this study examined the relationship between state UI modernization and the growth trajectory of economic security among American working households. After controlling for state-level and household-level covariates, the results of the multilevel growth modeling showed that, on average, the state enactment of UI modernization provisions was associated with a faster improvement rate of household economic security over a five-and-a-half-year period. The findings have implications for future studies concerning UI provisions and household economic security.

Although social work research has paid substantial attention to employment patterns among low-income single mothers after welfare reform, little is known about their work-hour trajectories over time. This study uses group-based trajectory modeling to analyze the work-hour trajectories among low-income single mothers in the United States (N = 870). Only approximately two-fifths (41.9 percent) of participants in the sample had stable employment. About 18 percent did not work throughout the study period. Yet several groups experienced changes in working patterns over time: Increasing hours (20.7 percent), decreasing then increasing hours (11.3 percent), and decreasing hours (8.4 percent). This study uses a generalized linear mixed model to determine the factors associated with change in work hours over time. Significant factors include marital status, high school completion, race, citizenship, homeownership, child care arrangement, income support program participation, work disability, age of youngest child, age of the mother, state unemployment rate, and state minimum wage. These findings have important policy implications for targeting supports to diverse needs of low-income single-mother families to promote employment stability and economic improvement.

Despite the increased attention paid to federal-state unemployment insurance (UI) schemes after the Great Recession (2007-2009), research examining the policy characteristics and the underlying logic shaping the social protection provided by a federal-state UI system is limited. Integrating the perspectives of policy design theory, comparative welfare politics, and fiscal welfare, this paper examines the unequal social protection under the American UI system during and after the Great Recession. By using model-based cluster analysis and fixed-effect panel regression models, this paper identifies three distinct UI approaches, i.e. the limited social protection approach, the unbalanced social protection approach, and the balanced social protection approach. The policy choices made by those states that follow the three approaches reflect different mixtures of policy logic, including social protection, economic stabilization, work disincentives, and interstate competition. The overall downward trend in social protection signals that the American UI system is under-prepared for the next economic recession, thereby exposing unemployed workers to the risk of economic insecurity. These findings provide implications for future policy designs aiming to strengthen the social protection of the federal-state UI system.

This paper addresses a gap in welfare reform literature by investigating the social constructions of poor people in state policymaking within the context of diminishing General Assistance (GA) after the Great Recession. Using social construction and policy design theory and thematic content analysis of Washington State’s legislative archives, I found that the negative constructions of GA recipients as deviants with undesired psychological and behavioral problems were associated with the reform direction toward a regulated, punitive model. These constructions, intersecting with the ideologies of personal responsibility and work ethic, contribute to the dismantling of the social safety net for Washington’s poorest residents.

Rationale: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T-cell immunity in tumor-bearing hosts. Their clinical relevance remains unclear.Objectives: To identify subtypes of myeloid-derived suppressor cells in patients with non-small cell lung cancer (NSCLC) and their clinical relevance.Methods: CD11b(+)CD14(-) and CD11b(+)CD14(+) cells, determined and phenotyped by fluorescence-activated cell sorter analysis, in the peripheral blood mononuclear cells (PBMCs) of treatment-naive patients with advanced NSCLC were correlated with clinical data. T-cell activation in response to CD3/CD28 costimulation was determined by carboxy-fluorescein diacetate succinimidyl ester (CFSE) staining and ELISA analysis of IFN-γ. The percentage of CD11b(+)CD14(+)S100A9(+) cells in PBMCs was correlated with and tested as a predictor for treatment response in a cohort of patients prospectively receiving first-line cisplatin-based chemotherapy.Measurements and Main Results: Patients with NSCLC had a significantly higher ratio of CD11b(+)CD14(+) cells than healthy subjects, which was correlated with poor performance status and poor response to chemotherapy. The depletion of these cells in the PBMC reversed the suppression of CD8(+) and CD4(+) T cells. Isolated CD11b(+)CD14(+) cells suppressed CD8(+) T-cell proliferation and IFN-γ production, and the former effect was attenuated by the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine hydrochloride, arginase inhibitor N-hydroxy-nor-l-arginine (nor-NOHA), and blocking antibodies for IL-4Rα(+) and IL-10. CD11b(+)CD14(+) cells were monocyte-like, expressing CD33(+), CD15(-/low), IL-4Rα(+), and S100A9(+) and producing iNOS, arginase, and several cytokines. The ratio of S100A9(+) cells positively correlated with the suppressive ability of the CD11b(+)CD14(+) cells, was associated with poor response to chemotherapy, and predicted shorter progression-free survival.Conclusions: CD14(+)S100A9(+) inflammatory monocytes in patients with NSCLC are a distinct subset of MDSCs, which suppress T cells by arginase, iNOS, and the IL-13/IL-4Rα axis. The amount of these inflammatory monocytes is associated with poor response to chemotherapy. Clinical trial registered with www.clinicaltrials.gov (NCT 01204307). [ABSTRACT FROM AUTHOR]

Purpose: Wogonin, a plant flavonoid, has antitumor activity in various cancers. Dysregulation of GSK-3β has been implicated in tumorigenesis and cancer progression. In this study, we investigated the antitumor activity and the mechanistic action of wogonin in human nasopharyngeal carcinoma (NPC) cells. Methods: The effects of wogonin on the cell survival and apoptosis in NPC cells were investigated by MTS assay, flow cytometry, and PARP cleavage assays. Pharmacological inhibitors (BIO, LiCl, and OA), or small interfering RNA (siRNA) were used to address the expression status of GSK-3β and the anticancer effect of ΔNp63 in NPC cells. Results: Wogonin was shown to induce dose-dependent cell apoptosis due to the induction of sub-G1-phase cells, PARP cleavage, and downregulation of ΔNp63, a survival factor in NPC cells. Strikingly, the apoptotic effect of wogonin involved GSK-3β inactivation via prominent inhibition of phosphorylation at Tyr216 and slightly increment of phosphorylation at Ser9, while there is no change in total GSK-3β proteins. Dysregulation of GSK-3β caused cell apoptosis was confirmed by pharmacological inhibitors (lithium chloroid, LiCl, and 6-bro-moindirubin-3-oxime, BIO). Administration of okadaic acid (OA, a protein phosphatase inhibitor) that significantly inactivated GSK-3β also induced ΔNp63 downregulation and apoptosis. Targeted silencing of ΔNp63 repressed the phosphorylation of GSK-3β at Tyr216 and sensitized NPC cells to wogonin-induced apoptosis. Furthermore, GSK-3β or PP2A inhibitors enhanced wogonin-induced apoptosis via activation of caspase 3/7. Conclusion: These results indicate that GSK-3β, as well as ΔNp63, are novel targets for wogonin action and suggest that wogonin might provide a potential therapeutic option in NPC. Further in vitro and in vivo studies will help to clarify the therapeutic role of wogonin in NPC. [ABSTRACT FROM AUTHOR]