Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy ...preferentially recruits and degrades the oncogenic microRNA (miR)‐224 to prevent HCC. Therefore, in the present study, we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development. We found that increased autophagic activity leads to cyclin D1 ubiquitination and selective recruitment to the autophagosome (AP) mediated by a specific receptor, sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation. Autophagy‐selective degradation of ubiquitinated cyclin D1 through SQSTM1 was confirmed using cyclin D1/ubiquitin binding site (K33‐238R) and phosphorylation site (T286A) mutants, lentivirus‐mediated silencing autophagy‐related 5 (ATG5), autophagy‐related 7 (ATG7), and Sqstm1 knockout cells. Functional studies revealed that autophagy‐selective degradation of cyclin D1 plays suppressive roles in cell proliferation, colony, and liver tumor formation. Notably, an increase of autophagic activity by pharmacological inducers (amiodarone and rapamycin) significantly suppressed tumor growth in both the orthotopic liver tumor and subcutaneous tumor xenograft models. Our findings provide evidence of the underlying mechanism involved in the regulation of cyclin D1 by selective autophagy to prevent tumor formation. Conclusion: Taken together, our data demonstrate that autophagic degradation machinery and the cell‐cycle regulator, cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of value in the development of alternative therapeutics for HCC patients. (Hepatology 2018;68:141‐154).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In the United States, COVID-19 was the third leading cause of death, after heart disease and cancer, during 2020, according to the provisional mortality data report released by the National Center ...for Health Statistics (NCHS) on March 31, 2021,1'2 By contrast, COVID-19 was the leading cause of death, followed by dementia and Alzheimer's disease, ischemic heart disease, stroke, and lung cancer, in England and Wales in February 2021, according to the provisional mortality analysis released by the Office for National Statistics on March 18, 2021.3 One month later, COVID-19 became the third leading cause of death.4 Some people might wonder why the names of the categories used for rankings in the United States (e.g., cancer or heart disease) differed from those used in England and Wales (e.g., lung cancer or ischemic heart disease). That is, the countries did not use the same list in ranking the leading causes of death.
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CEKLJ, DOBA, FSPLJ, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
We examined mortality trends of hepatitis C virus (HCV) infection in the United States in 1999‐2018 according to the following definitions: HCV as the underlying cause of death (UCOD), HCV mentioned ...anywhere on the death certificate (mentioned), and HCV recorded in Part 1 of the death certificate. By using entity axis information in mortality multiple‐cause files, we ascertained the position of HCV on the death certificate. Joinpoint regression analysis was used to evaluate changes in HCV mortality rates according to the definitions. The age‐standardized HCV mortality rates (deaths per 100,000 people) in terms of UCOD, mentioned, and Part 1 were, respectively, 1.36, 2.87 and 1.94, in 1999; increased to 1.90, 5.09 and 2.96 in 2013; and declined to 0.98, 3.77 and 2.29 in 2018. The mentioned/UCOD mortality ratio was 2.11 in 1999 and increased to 3.86 in 2018. The mentioned/Part 1 ratio was almost identical (ie 1.48 in 1999 and 1.65 in 2018). The extent of decline from 2014 to 2018 differed according to the definitions; the annual per cent changes for UCOD, mentioned, and Part 1 were −14.6%, −7.1% and −9.8%, respectively. For the same age group, the baby boomer subcohort 1950‐1954 had the highest mortality rates among the subcohorts (1945‐1949, 1955‐1959 and 1960‐1964). HCV mortality according to HCV in Part 1 of the death certificate—the explicit opinion of a certifying physician that HCV played a substantial role and directly caused death—differed from that according to HCV as UCOD and HCV mentioned.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
This paper reports a multi-valve module with high chemical inertness and embedded flow heating for microscale gas chromatography (µGC) systems. The multi-valve module incorporates a monolithically ...microfabricated die stack, polyimide valve membranes, and solenoid actuators. The design incorporates three valves within a single module of volume 30.2 cm
, which is suitable for the small form factor of µGC systems. The die stack uses fused silica wafers and polyimide valve membranes that enhance chemical inertness. The monolithic die stack requires only three lithographic masks to pattern fluidic microchannels, valve seats, and thin-film metal heaters and thermistors. The performance of fabricated multi-valve modules is compared to a commercial valve in tests using multiple volatile organic compounds, including alkanes, alcohols, ketones, aromatic hydrocarbons, and phosphonates. The valves show almost no distortion of chromatographic peaks. The experimentally measured ratio of flow conductance is 3.46 × 10
, with 4.15 sccm/kPa in the open state and 0.0012 sccm/kPa in the closed state. The response time is <120 ms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The ranking lists used by most countries for leading causes of death (CODs) comprise broad category such as cancer, heart disease, and accidents. To provide more specific information, the World ...Health Organization (WHO) and the Institute of Health Metrics and Evaluation (IHME) proposed lists that splitting broad categories into specific categories. We examined the changes in rankings of leading CODs according to different lists in Japan, Korea, and Taiwan from 1998 to 2018.
We obtained the number of deaths for three countries from the WHO mortality database for 1998, 2008, and 2018. Age-standardized death rates were calculated for rankings 10 leading CODs using WHO 2000 age structure as standard.
The first leading COD was cancer in Japan, Korea, and Taiwan from 1998 to 2018 based on government list; nevertheless, became stroke based on WHO list, and was stroke and ischemic heart disease based on IHME list. In the WHO and IHME lists, cancer is categorized based on cancer site. The number of cancer sites included in the 10 leading CODs in 2018 was 4, 4, and 3 in Japan, Korea, and Taiwan, respectively according to the WHO list and was 4, 4, and 2, respectively according to IHME list. The only difference was the rank of liver cancer in Taiwan, which was 6th according to WHO list and was 18th according to IHME list. The ranking and number of deaths for some CODs differed greatly between the WHO and IHME lists due to the reallocation of "garbage codes" into relevant specific COD in IHME list.
Through the use of WHO and the IHME lists, the relative importance of several specific and avoidable causes could be revealed in 10 leading CODs, which could not be discerned if the government lists were used. The information is more relevant for health policy decision making.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
People with dermatomyositis (DM) or polymyositis (PM) often die from cancer, pulmonary, cardiac complications, or infections. In such cases, DM or PM might not be designated as the underlying cause ...of death (UCD) for mortality tabulation. In this study, we investigated DM/PM mortality trends in the USA from 1981 to 2020 with respect to UCD and multiple causes of death (MCD) data.
We used the MCD data to identify all deaths with DM or PM mentioned anywhere on the death certificate and as the UCD in the USA from 1981-1982 to 2019-2020. We calculated age-adjusted mortality rates (AAMRs) and annual percentage changes (APCs) based on joinpoint regression analysis.
We identified 12,249 (3985 with DM and 7097 with PM) and 23,608 (8264 with DM and 15,344 with PM) people who died between 1981 and 2020 according to the UCD and MCD data, respectively. For DM, the APC was - 6.7% (from 1981-1982 to 1985-1986), - 0.1% (from 1985-1986 to 2003-2004), and - 1.9% (from 2003-2004 to 2019-2020) according UCD and was - 1.2% (from 1981-1982 to 2003-2004), - 2.5% (from 2003-2004 to 2015-2016), and 2.8% (from 2015-2016 to 2019-2020) according MCD. For PM, the APC was 1.9% (from 1981-1982 to 1989-1990), - 2.3% (from 1989-1990 to 2005-2006), and - 5.2% (from 2005-2006 to 2019-2020) according UCD and was 1.3% (from 1981-1982 to 1991-1992) and - 4.1% (from 1991-1992 to 2019-2020) according MCD.
We identified two times as many DM/PM deaths using the MCD as those identified using the UCD. Similar downward DM/PM mortality trends were noted according to UCD and MCD. However, the year of significant decline in PM mortality was about 10 years earlier according to MCD than those according to UCD.
Background
Malignant mesothelioma (MM) is rare and fatal; survival in most cases is only about one year. Mortality rate is, therefore, a good proxy measure of incidence rate. However, the specific ...International Classification of Diseases (ICD) code for MM was not available until the Tenth Revision ICD (ICD‐10). Little is known on which Ninth Revision ICD (ICD‐9) codes were assigned for MM in the ICD‐9 era.
Methods
We used a 1996 double‐coded mortality file compiled by the National Center for Health Statistics to calculate the detection rate (DR) and confirmation rate (CR) of selected ICD‐9 codes.
Results
Of 2386 decedents whose underlying cause of death was MM (ICD‐10 code C45), the DR (deaths) of corresponding ICD‐9 code was 57% (1365) for code 199 “malignant neoplasm without specification of site;” 19% (448) for code 162.9 “malignant neoplasm of trachea, bronchus, and lung, unspecified;” 13% (310) for code 163 “malignant neoplasm of pleura;” and 11% (271) for other codes. The CR (deaths) for the aforementioned three ICD‐9 codes were 4.0% (1365/33,942), 0.3% (448/150,342), and 70.8% (310/438), respectively.
Conclusions
The three ICD‐9 codes (199, 162.9, and 163) were the most commonly used codes for MM and composed nine‐tenths of all MM deaths in the years before the ICD‐10 was introduced. Using only ICD‐9 code 163, the code most often used as the surrogate measure of MM in mortality studies in the ICD‐9 era, capture may have been only 13% of all MM deaths in the US, and the estimated number of MM deaths missed in 1996 would be 2086.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
To examine the age differences in secular trends in black–white disparities in mortality from systemic lupus erythematosus (SLE) among women in the United States from 1988 to 2017.
Methods
...We used mortality data to calculate age-specific SLE and all-causes (as reference) mortality rates and black/white mortality rates ratios among women from 1988 to 2017. Annual percent change was estimated using joinpoint regression analysis.
Results
We identified 10,793 and 4,165,613 black women and 19,455 and 31,129,528 white women who died between 1988 and 2017 from SLE and all-causes, respectively. The black/white SLE mortality rate ratio according joinpoint regression model was 6.6, 7.2, 4.4, and 1.4 for decedents aged 0–24, 25–44, 45–64, and 65+ years in 1988 and was 7.2, 5.9, 4.1, and 1.9, respectively in 2017. No significant decline trend was noted and the annual percent change was 0.3%, –0.7%, –0.2%, and 1.0%, respectively. On the contrast, the black/white all-causes mortality rate ratio was 2.0, 2.5, 1.8, and 1.0, respectively in 1988 and was 1.7, 1.3, 1.5, and 0.9, respectively in 2017, a significant decline trend was noted in each age group.
Conclusions
Black adults, youths and adolescents had four to seven times higher SLE mortality rates than their white counterparts and the black–white disparities persisted during the past three decades. On the contrast, black women had less than two times higher all-causes mortality rates than their white counterparts and black–white disparities significantly diminish during the past three decades.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In 1997–1998 a widespread economic crisis hit the economies of many East/Southeast Asian countries; its impact on suicide rates across the region has not been systematically documented. We ...investigated the impact of the Asian economic crisis (1997–1998) on suicide in Japan, Hong Kong, South Korea, Taiwan, Singapore and Thailand. Suicide and population data for the period 1985–2006 were extracted from the World Health Organisation's mortality database and Taiwanese mortality statistics. Sex-specific age-standardised suicide rates for people aged 15
years or above were analysed using joinpoint regression. Trends in divorce, marriage, unemployment, gross domestic product (GDP) per capita and alcohol consumption were compared with trends in suicide rates graphically and using time-series analysis. Suicide mortality decreased in the late 1980s and early 1990s but subsequently increased markedly in all countries except Singapore, which had steadily declining suicide rates throughout the study period. Compared to 1997, male rates in 1998 rose by 39% in Japan, 44% in Hong Kong and 45% in Korea; rises in female rates were less marked. Male rates also rose in Thailand, but accurate data were incomplete. The economic crisis was associated with 10,400 more suicides in 1998 compared to 1997 in Japan, Hong Kong and Korea. Similar increases in suicide rates were not seen in Taiwan and Singapore, the two countries where the economic crisis had a smaller impact on GDP and unemployment. Time-series analyses indicated that some of the crisis's impact on male suicides was attributable to increases in unemployment. These findings suggest an association of the Asian economic crisis with a sharp increase in suicide mortality in some, but not all, East/Southeast Asian countries, and that these increases were most closely associated with rises in unemployment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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