Taipei Medical University

Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., et. al.

ABSTRACT In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Fitzmaurice C., Abate D., Abbasi N., Abbastabar H., Abd-Allah F., Abdel-Rahman O., Abdelalim A., Abdoli A., Abdollahpour I., Abdulle A.S., Abebe N.D., Abraha H.N., Abu-Raddad L.J., Abualhasan A., Adedeji I.A., et. al.

Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

Kocarnik J.M., Compton K., Dean F.E., Fu W., Gaw B.L., Harvey J.D., Henrikson H.J., Lu D., Pennini A., Xu R., Ababneh E., Abbasi-Kangevari M., Abbastabar H., Abd-Elsalam S.M., Abdoli A., et. al.

The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Botvinik-Nezer R., Holzmeister F., Camerer C.F., Dreber A., Huber J., Johannesson M., Kirchler M., Iwanir R., Mumford J.A., Adcock R.A., Avesani P., Baczkowski B.M., Bajracharya A., Bakst L., Ball S., et. al.

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2–5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

Lai C., Liu Y.H., Wang C., Wang Y., Hsueh S., Yen M., Ko W., Hsueh P.

Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.

Huang L., Chao S., Hu C.

Alzheimer disease (AD) accounts for 60–70% of dementia cases. Given the seriousness of the disease and continual increase in patient numbers, developing effective therapies to treat AD has become urgent. Presently, the drugs available for AD treatment, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate receptor, can only inhibit dementia symptoms for a limited period of time but cannot stop or reverse disease progression. On the basis of the amyloid hypothesis, many global drug companies have conducted many clinical trials on amyloid clearing therapy but without success. Thus, the amyloid hypothesis may not be completely feasible. The number of anti-amyloid trials decreased in 2019, which might be a turning point. An in-depth and comprehensive understanding of the contribution of amyloid beta and other factors of AD is crucial for developing novel pharmacotherapies.In ongoing clinical trials, researchers have developed and are testing several possible interventions aimed at various targets, including anti-amyloid and anti-tau interventions, neurotransmitter modification, anti-neuroinflammation and neuroprotection interventions, and cognitive enhancement, and interventions to relieve behavioral psychological symptoms. In this article, we present the current state of clinical trials for AD at clinicaltrials.gov. We reviewed the underlying mechanisms of these trials, tried to understand the reason why prior clinical trials failed, and analyzed the future trend of AD clinical trials.

Nguyen H.C., Nguyen M.H., Do B.N., Tran C.Q., Nguyen T.T., Pham K.M., Pham L.V., Tran K.V., Duong T.T., Tran T.V., Duong T.H., Nguyen T.T., Nguyen Q.H., Hoang T.M., Nguyen K.T., et. al.

The coronavirus disease 2019 (COVID-19) epidemic affects people’s health and health-related quality of life (HRQoL), especially in those who have suspected COVID-19 symptoms (S-COVID-19-S). We examined the effect of modifications of health literacy (HL) on depression and HRQoL. A cross-sectional study was conducted from 14 February to 2 March 2020. 3947 participants were recruited from outpatient departments of nine hospitals and health centers across Vietnam. The interviews were conducted using printed questionnaires including participants’ characteristics, clinical parameters, health behaviors, HL, depression, and HRQoL. People with S-COVID-19-S had a higher depression likelihood (OR, 2.88; p < 0.001), lower HRQoL-score (B, −7.92; p < 0.001). In comparison to people without S-COVID-19-S and low HL, those with S-COVID-19-S and low HL had 9.70 times higher depression likelihood (p < 0.001), 20.62 lower HRQoL-score (p < 0.001), for the people without S-COVID-19-S, 1 score increment of HL resulted in 5% lower depression likelihood (p < 0.001) and 0.45 higher HRQoL-score (p < 0.001), while for those people with S-COVID-19-S, 1 score increment of HL resulted in a 4% lower depression likelihood (p = 0.004) and 0.43 higher HRQoL-score (p < 0.001). People with S-COVID-19-S had a higher depression likelihood and lower HRQoL than those without. HL shows a protective effect on depression and HRQoL during the epidemic.

Chen R., Sun C., Chen J., Jen H., Kang X.L., Kao C., Chou K.

A large-scale survey study was conducted to assess trauma, burnout, posttraumatic growth, and associated factors for nurses in the COVID-19 pandemic. The Trauma Screening Questionnaire, Maslach Burnout Inventory, and Posttraumatic Growth Inventory-Short Form were utilized. Factors associated with trauma, burnout, and posttraumatic growth were analysed using logistic and multiple regressions. In total, 12 596 completed the survey, and 52.3% worked in COVID-19 designated hospitals. At the survey’s conclusion in April, 13.3% reported trauma (Trauma ≥ 6), there were moderate degrees of emotional exhaustion, and 4,949 (39.3%) experienced posttraumatic growth. Traumatic response and emotional exhaustion were greater among (i) women (odds ratio [OR]: 1.48, 95% CI 1.12–1.97 P = 0.006; emotional exhaustion OR: 1.30, 95% CI 1.09–1.54, P = 0.003), (ii) critical care units (OR: 1.20, 95% CI 1.06–1.35, P = 0.004; emotional exhaustion OR: 1.23, 95% CI 1.12–1.33, P < 0.001) (iii) COVID-19 designated hospital (OR: 1.24, 95% CI 1.11–1.38; P < 0.001; emotional exhaustion OR: 1.26, 95% CI 1.17–1.36; P < 0.001) and (iv) COVID-19-related departments (OR: 1.16, 95% CI 1.04–1.29, P = 0.006, emotional exhaustion only). To date, this is the first large-scale study to report the rates of trauma and burnout for nurses during the COVID-19 pandemic. The study indicates that nurses who identified as women, working in ICUs, COVID-19 designated hospitals, and departments involved with treating COVID-19 patients had higher scores in mental health outcomes. Future research can focus on the factors the study has identified that could lead to more effective prevention and treatment strategies for adverse health outcomes and better use of resources to promote positive outcomes.

Zhou D., Duyvesteyn H.M., Chen C., Huang C., Chen T., Shih S., Lin Y., Cheng C., Cheng S., Huang Y., Lin T., Ma C., Huo J., Carrique L., Malinauskas T., et. al.

The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD–EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19. EY6A, a neutralizing antibody isolated from a patient convalescing from COVID-19, binds the receptor binding domain of the SARS-CoV-2 spike glycoprotein with high affinity, at a location away from the binding site for the ACE2 receptor, similar to the one recognized by CR3022.

Lai C., Wang C., Wang Y., Hsueh S., Ko W., Hsueh P.

• As of 29 Feb. 2020, COVID-19 has affected 85 403 patients in 57 countries/territories and caused 2924 deaths in 9 countries. • The incidence (per 1 000 000 people) ranged from 61.4 in Republic of Korea to 0.0002 in India. • Daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between first reported case and 29 Feb. 2020) was greatest in China (1320.85). • High DCIs were also seen in the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). • The incidence and mortality were correlated with the DCI. It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. So far, COVID-19 has affected 85 403 patients in 57 countries/territories and has caused 2924 deaths in 9 countries. However, epidemiological data differ between countries. Although China had higher morbidity and mortality than other sites, the number of new daily cases in China has been lower than outside of China since 26 February 2020. The incidence ranged from 61.44 per 1 000 000 people in the Republic of Korea to 0.0002 per 1 000 000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and 29 February 2020) was greatest in China (1320.85), followed by the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). However, the DCIs in other countries/territories were