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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7 ( 2023-04-04), p. 1048-1061
    Abstract: Hepatitis B virus (HBV) infection is a major driver of hepatocarcinogenesis. Ferroptosis is a type of iron-mediated cell death that can suppress liver transformation. Previous studies have linked HBV to ferroptosis in liver fibrosis and acute liver failure. However, whether ferroptosis is involved in HBV-mediated liver cancer is poorly understood. Here, we identified heat shock protein family A member 8 (HSPA8) as a crucial host factor that modulates HBV replication and ferroptosis in liver cancer. Hepatitis B X protein (HBx) upregulated HSPA8 by coactivating the transcription factor heat shock factor 1 (HSF1) in cells. HSPA8 enhanced HBV replication by recruiting hepatitis B core protein (HBc) to the HBV covalently closed circular DNA (cccDNA) minichromosome, forming a positive feedback loop. Moreover, HSPA8 suppressed ferroptosis in liver cancer cells by upregulating the expression of SLC7A11/GPX4 and decreasing erastin-mediated reactive oxygen species and Fe2+ accumulation in cells in vitro and in vivo. Inhibition of HSPA8 reduced the growth of HBV-positive liver tumors and increased sensitivity to erastin. In conclusion, HBx-elevated HSPA8 regulates both HBV replication and ferroptosis in liver cancer. Targeting HSPA8 could be a promising strategy for controlling HBV and hepatocarcinogenesis. Significance: HBV-induced upregulation of HSPA8 promotes hepatocarcinogenesis by suppressing ferroptosis and stimulating HBV replication, identifying HSPA8 as a potential therapeutic target in liver cancer.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    In: Movement Disorders, Wiley, Vol. 38, No. 6 ( 2023-06), p. 1099-1104
    Abstract: Recently, homozygous variants in PTPA were identified as the disease cause for two pedigrees with early‐onset parkinsonism and intellectual disability. Although the initial link between PTPA and parkinsonism has been established, further replication was still necessary. Objectives To evaluate the genetic role of PTPA in Parkinson's disease (PD). Methods We analyzed rare variants of PTPA in cohorts of Asian and European ancestries (N case  = 2743, N control  = 8177) with whole‐exome sequencing, and further explored the functional effect of the target variant. Results One patient with early‐onset PD from a consanguineous family carried the homozygous variant p.Met329Val, while her parents and elder sister with heterozygous p.Met329Val were healthy. This patient developed minor cognitive decline within 1 year, with a Montreal Cognitive Assessment (MoCA) score dropping from 28 to 25. Functional exploration with overexpression studies suggested that this variant was associated with decreased protein phosphatase 2A (PTPA) protein level by affecting protein stability, but not mRNA expression. Conclusions These results have broadened the mutation spectrum of PTPA , and paved the way for further research into the role of PTPA in PD. © 2023 International Parkinson and Movement Disorder Society.
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2041249-6
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  • 3
    In: International Journal of Cancer, Wiley, Vol. 151, No. 12 ( 2022-12-15), p. 2095-2106
    Abstract: State‐specific information on lost earnings due to smoking‐attributable cancer deaths to inform and advocate for tobacco control policies is lacking. We estimated person‐years of life lost (PYLL) and lost earnings due to cigarette smoking‐attributable cancer deaths in the United States nationally and by state. Proportions and numbers of cigarette smoking‐attributable cancer deaths and associated PYLL among individuals aged 25 to 79 years in 2019 were calculated and combined with annual median earnings to estimate lost earnings attributable to cigarette smoking. In 2019, estimated total PYLL and lost earnings associated with cigarette smoking‐attributable cancer deaths in ages 25 to 79 years in the United States were 2 188 195 (95% CI, 2 148 707‐2 231 538) PYLL and $20.9 billion ($20.0 billion‐$21.7 billion), respectively. States with the highest overall age‐standardized PYLL and lost earning rates generally were in the South and Midwest. The estimated rate per 100 000 population ranged from 352 (339‐366) in Utah to 1337 (1310‐1367) in West Virginia for PYLL and from $4.3 million ($3.5 million‐$5.2 million) in Idaho to $14.8 million ($10.6 million‐$20.7 million) in Missouri for lost earnings. If age‐specific PYLL and lost earning rates in Utah had been achieved by all states, 58.2% (57.0%‐59.5%) of the estimated total PYLL (1 274 178; 1 242 218‐1 306 685 PYLL) and 50.5% (34.2%‐62.4%) of lost earnings ($10.5 billion; $7.1 billion‐$13.1 billion) in 2019 nationally would have been avoided. Lost earnings due to smoking‐attributable cancer deaths are substantial in the United States and are highest in states with weaker tobacco control policies.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 218257-9
    detail.hit.zdb_id: 1474822-8
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  • 4
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 112, No. 7 ( 2020-07-01), p. 671-687
    Abstract: Lack of health insurance coverage is associated with poor access and receipt of cancer care and survival in the United States. Disruptions in coverage are common among low-income populations, but little is known about associations of disruptions with cancer care, including prevention, screening, and treatment, as well as outcomes of stage at diagnosis and survival. Methods We conducted a systematic review of studies of health insurance coverage disruptions and cancer care and outcomes published between 1980 and 2019. We used the PubMed, EMBASE, Scopus, and CINAHL databases and identified 29 observational studies. Study characteristics and key findings were abstracted and synthesized qualitatively. Results Studies evaluated associations between coverage disruptions and prevention or screening (31.0%), treatment (13.8%), end-of-life care (10.3%), stage at diagnosis (44.8%), and survival (20.7%). Coverage disruptions ranged from 4.3% to 32.8% of patients age-eligible for breast, cervical, or colorectal cancer screening. Between 22.1% and 59.5% of patients with Medicaid gained coverage only at or after cancer diagnosis. Coverage disruptions were consistently statistically significantly associated with lower receipt of prevention, screening, and treatment. Among patients with cancer, those with Medicaid disruptions were statistically significantly more likely to have advanced stage (odds ratios = 1.2-3.8) and worse survival (hazard ratios = 1.28-2.43) than patients without disruptions. Conclusions Health insurance coverage disruptions are common and adversely associated with receipt of cancer care and survival. Improved data infrastructure and quasi-experimental study designs will be important for evaluating the associations of federal and state policies on coverage disruptions and care and outcomes.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 5
    In: Alcohol and Alcoholism, Oxford University Press (OUP), ( 2022-08-03)
    Abstract: This study evaluated the possible protective impact of different vintages of Hongqu rice wines on metabolic syndrome (MetS) in rats induced by high-fat/high-fructose diet (HFFD). Methods Rats were randomly divided into six groups and treated with (a) basal diet (13.9 kJ/g); (b) HFFD (20.0% w/w lard and 18.0% fructose, 18.9 kJ/g) and (c–f) HFFD with 3-, 5-, 8- and 15-year-aged Hongqu rice wines (9.96 ml/kg body weight), respectively, at an oral route for 20 weeks. Results Hongqu rice wines could alleviate HFFD-induced augment of body weight gain and fat accumulation, and the release of pro-inflammatory cytokines. Glycolipid metabolic abnormalities caused by HFFD were ameliorated after Hongqu rice wines consumption by lowering levels of fasting insulin, GSP, HOMA-IR, AUC of OGTT and ITT, and lipid deposition (reduced contents of TG, TC, FFA and LDL-C, and elevated HDL-C level) in the serum and liver, probably via regulating expressions of genes involving in IRS1/PI3K/AKT pathway, LDL-C uptake, fatty acid β-oxidation, and lipolysis, export and synthesis of TG. In addition, concentrations of MDA and blood pressure markers (ANG-II and ET-1) declined, and activities of antioxidant enzymes (SOD and CAT) were improved in conditions of Hongqu rice wines compared to those in the HFFD group. Eight-year-aged Hongqu rice wine produced a more effective effect on alleviating HFFD-caused MetS among different vintages of Hongqu rice wines. Conclusion To sum up, Hongqu rice wines exhibited ameliorative effects on HFFD-induced MetS in rats based on antiobesity, antihyperlipidemic, antihyperglycemic, antioxidant, anti-inflammatory and potential antihypertensive properties.
    Type of Medium: Online Resource
    ISSN: 0735-0414 , 1464-3502
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1483492-3
    SSG: 15,3
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  • 6
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 113, No. 12 ( 2021-11-29), p. 1670-1682
    Abstract: The American Cancer Society, National Cancer Institute, Centers for Disease Control and Prevention, and North American Association of Central Cancer Registries provide annual information about cancer occurrence and trends in the United States. Part 1 of this annual report focuses on national cancer statistics. This study is part 2, which quantifies patient economic burden associated with cancer care. Methods We used complementary data sources, linked Surveillance, Epidemiology, and End Results-Medicare, and the Medical Expenditure Panel Survey to develop comprehensive estimates of patient economic burden, including out-of-pocket and patient time costs, associated with cancer care. The 2000-2013 Surveillance, Epidemiology, and End Results-Medicare data were used to estimate net patient out-of-pocket costs among adults aged 65 years and older for the initial, continuing, and end-of-life phases of care for all cancer sites combined and separately for the 21 most common cancer sites. The 2008-2017 Medical Expenditure Panel Survey data were used to calculate out-of-pocket costs and time costs associated with cancer among adults aged 18-64 years and 65 years and older. Results Across all cancer sites, annualized net out-of-pocket costs for medical services and prescriptions drugs covered through a pharmacy benefit among adults aged 65 years and older were highest in the initial ($2200 and $243, respectively) and end-of-life phases ($3823 and $448, respectively) and lowest in the continuing phase ($466 and $127, respectively), with substantial variation by cancer site. Out-of-pocket costs were generally higher for patients diagnosed with later-stage disease. Net annual time costs associated with cancer were $304.3 (95% confidence interval = $257.9 to $350.9) and $279.1 (95% confidence interval = $215.1 to $343.3) for adults aged 18-64 years and ≥65 years, respectively, with higher time costs among more recently diagnosed survivors. National patient economic burden, including out-of-pocket and time costs, associated with cancer care was projected to be $21.1 billion in 2019. Conclusions This comprehensive study found that the patient economic burden associated with cancer care is substantial in the United States at the national and patient levels.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  JNCI: Journal of the National Cancer Institute Vol. 114, No. 6 ( 2022-06-13), p. 863-870
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 114, No. 6 ( 2022-06-13), p. 863-870
    Abstract: Cancer survivors frequently experience medical financial hardship in the United States. Little is known, however, about long-term health consequences. This study examines the associations of financial hardship and mortality in a large nationally representative sample of cancer survivors. Methods We identified cancer survivors aged 18-64 years (n = 14 917) and 65-79 years (n = 10 391) from the 1997-2014 National Health Interview Survey and its linked mortality files with vital status through December 31, 2015. Medical financial hardship was measured as problems affording care or delaying or forgoing any care because of cost in the past 12 months. Risk of mortality was estimated with separate weighted Cox proportional hazards models by age group with age as the timescale, controlling for the effects of sociodemographic characteristics. Health insurance coverage was added sequentially to multivariable models. Results Among cancer survivors aged 18-64 years and 65-79 years, 29.6% and 11.0%, respectively, reported financial hardship in the past 12 months. Survivors with hardship had higher adjusted mortality risk than their counterparts in both age groups: 18-64 years (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.04 to 1.30) and 65-79 years (HR = 1.14, 95% CI = 1.02 to 1.28). Further adjustment for health insurance reduced the magnitude of association of hardship and mortality among survivors aged 18-64 years (HR = 1.09, 95% CI = 0.97 to 1.24). Adjustment for supplemental Medicare coverage had little effect among survivors aged 65-79 years (HR = 1.15, 95% CI = 1.02 to 1.29). Conclusion Medical financial hardship was associated with mortality risk among cancer survivors in the United States.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 8
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  JNCI: Journal of the National Cancer Institute Vol. 114, No. 8 ( 2022-08-08), p. 1176-1185
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 114, No. 8 ( 2022-08-08), p. 1176-1185
    Abstract: Medicaid expansion under the Affordable Care Act (ACA) is associated with increased insurance coverage among patients with cancer. Whether these gains translate to improved survival is largely unknown. This study examines changes in 2-year survival among patients newly diagnosed with cancer following the ACA Medicaid expansion. Methods Patients aged 18-62 years from 42 states’ population-based cancer registries diagnosed pre (2010-2012) and post (2014-2016) ACA Medicaid expansion were followed through September 30, 2013, and December 31, 2017, respectively. Difference-in-differences (DD) analysis of 2-year overall survival was stratified by sex, race and ethnicity, census tract–level poverty, and rurality. Results A total of 2 555 302 patients diagnosed with cancer were included from Medicaid expansion (n = 1 523 585) and nonexpansion (n = 1 031 717) states. The 2-year overall survival increased from 80.58% pre-ACA to 82.23% post-ACA in expansion states and from 78.71% to 80.04% in nonexpansion states, resulting in a net increase of 0.44 percentage points (ppt) (95% confidence interval [CI] = 0.24ppt to 0.64ppt) in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer (DD = 0.90ppt, 95% CI = 0.19ppt to 1.60ppt), lung cancer (DD = 1.29ppt, 95% CI = 0.50ppt to 2.08ppt), non-Hodgkin lymphoma (DD = 1.07ppt, 95% CI = 0.14ppt to 1.99ppt), pancreatic cancer (DD = 1.80ppt, 95% CI = 0.40ppt to 3.21ppt), and liver cancer (DD = 2.57ppt, 95% CI = 1.00ppt to 4.15ppt). The improvement in 2-year overall survival was larger among non-Hispanic Black patients (DD = 0.72ppt, 95% CI = 0.12ppt to 1.31ppt) and patients residing in rural areas (DD = 1.48ppt, 95% CI= -0.26ppt to 3.23ppt), leading to narrowing survival disparities by race and rurality. Conclusions Medicaid expansion was associated with greater increase in 2-year overall survival, and the increase was prominent among non-Hispanic Blacks and in rural areas, highlighting the role of Medicaid expansion in reducing health disparities. Future studies should monitor changes in longer-term health outcomes following the ACA.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 9
    In: Journal of Affective Disorders, Elsevier BV, Vol. 283 ( 2021-03), p. 147-155
    Type of Medium: Online Resource
    ISSN: 0165-0327
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1500487-9
    SSG: 12
    SSG: 5,2
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. e18920-e18920
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e18920-e18920
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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