Summary Background Information about the distribution of causes of and time trends for child mortality should be periodically updated. We report the latest estimates of causes of child mortality in ...2010 with time trends since 2000. Methods Updated total numbers of deaths in children aged 0–27 days and 1–59 months were applied to the corresponding country-specific distribution of deaths by cause. We did the following to derive the number of deaths in children aged 1–59 months: we used vital registration data for countries with an adequate vital registration system; we applied a multinomial logistic regression model to vital registration data for low-mortality countries without adequate vital registration; we used a similar multinomial logistic regression with verbal autopsy data for high-mortality countries; for India and China, we developed national models. We aggregated country results to generate regional and global estimates. Findings Of 7·6 million deaths in children younger than 5 years in 2010, 64·0% (4·879 million) were attributable to infectious causes and 40·3% (3·072 million) occurred in neonates. Preterm birth complications (14·1%; 1·078 million, uncertainty range UR 0·916–1·325), intrapartum-related complications (9·4%; 0·717 million, 0·610–0·876), and sepsis or meningitis (5·2%; 0·393 million, 0·252–0·552) were the leading causes of neonatal death. In older children, pneumonia (14·1%; 1·071 million, 0·977–1·176), diarrhoea (9·9%; 0·751 million, 0·538–1·031), and malaria (7·4%; 0·564 million, 0·432–0·709) claimed the most lives. Despite tremendous efforts to identify relevant data, the causes of only 2·7% (0·205 million) of deaths in children younger than 5 years were medically certified in 2010. Between 2000 and 2010, the global burden of deaths in children younger than 5 years decreased by 2 million, of which pneumonia, measles, and diarrhoea contributed the most to the overall reduction (0·451 million 0·339–0·547, 0·363 million 0·283–0·419, and 0·359 million 0·215–0·476, respectively). However, only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4. Interpretation Child survival strategies should direct resources toward the leading causes of child mortality, with attention focusing on infectious and neonatal causes. More rapid decreases from 2010–15 will need accelerated reduction for the most common causes of death, notably pneumonia and preterm birth complications. Continued efforts to gather high-quality data and enhance estimation methods are essential for the improvement of future estimates. Funding The Bill & Melinda Gates Foundation.
To appraise effective predictors for COVID-19 mortality in a retrospective cohort study.
A total of 1270 COVID-19 patients, including 984 admitted in Sino French New City Branch (training and ...internal validation sets randomly split at 7:3 ratio) and 286 admitted in Optical Valley Branch (external validation set) of Wuhan Tongji hospital, were included in this study. Forty-eight clinical and laboratory features were screened with LASSO method. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed death risk prediction model with simple-tree XGBoost model. Performances of models were evaluated by AUC, prediction accuracy, precision, and F1 scores.
Six features, including disease severity, age, levels of high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), ferritin, and interleukin-10 (IL-10), were selected as predictors for COVID-19 mortality. Simple-tree XGBoost model conducted by these features can predict death risk accurately with >90% precision and >85% sensitivity, as well as F1 scores >0.90 in training and validation sets.
We proposed the disease severity, age, serum levels of hs-CRP, LDH, ferritin, and IL-10 as significant predictors for death risk of COVID-19, which may help to identify the high-risk COVID-19 cases.
KEY MESSAGES
A machine learning method is used to build death risk model for COVID-19 patients.
Disease severity, age, hs-CRP, LDH, ferritin, and IL-10 are death risk factors.
These findings may help to identify the high-risk COVID-19 cases.
The outbreak of coronavirus named COVID-19, initially identified in Wuhan, China in December 2019, has spread rapidly at the global scale. Most countries have rapidly stopped almost all activities ...including industry, services and transportation of goods and people, thus decreasing air pollution in an unprecedented way, and providing a unique opportunity to study air pollutants. While satellite data have provided visual evidence for the global reduction in air pollution such as nitrogen dioxide (NO
2
) worldwide, precise and quantitative information is missing at the local scale. Here we studied changes in particulate matter (PM
2.5
, PM
10
), carbon monoxide (CO), NO
2
, sulfur dioxide (SO
2
) and ozone (O
3
) at 10 urban sites in Hangzhou, a city of 7.03 million inhabitants, and at 1 rural site, before city lockdown, January 1–23, during city lockdown, January 24-February 15, and during resumption, February 16–28, in 2020. Results show that city lockdown induced a sharp decrease in PM
2.5
, PM
10
, CO, and NO
2
concentrations at both urban and rural sites. The NO
2
decrease is explained by reduction in traffic emissions in the urban areas, and by lower regional transport in rural areas during lockdown, as expected. SO
2
concentrations decreased from 6.3 to 5.3 μg m
−3
in the city, but increased surprisingly from 4.7 to 5.8 μg m
−3
at the rural site: this increase is attributed both to higher coal consumption for heating and emissions from traditional fireworks of the Spring Eve and Lantern Festivals during lockdown. Unexpectedly, O
3
concentrations increased by 145% from 24.6 to 60.6 μg m
−3
in the urban area, and from 42.0 to 62.9 μg m
−3
in the rural area during the lockdown. This finding is explained by the weakening of chemical titration of O
3
by NO due to reductions of NO
x
fresh emissions during the non-photochemical reaction period from 20:00 PM to 9:00 AM (local time). During the lockdown, compared to the same period in 2019, the daily average concentrations in the city decreased by 42.7% for PM
2.5
, 47.9% for PM
10
, 28.6% for SO
2
, 22.3% for CO and 58.4% for NO
2
, which is obviously explained by the absence of city activities. Overall, we observed not only the expected reduction in some atmospheric pollutants (PM, SO
2
, CO, NO
2
), but also unexpected increases in SO
2
in the rural areas and of ozone (O
3
) in both urban and rural areas, the latter being paradoxically due to the reduction in nitrogen oxide levels. In other words, the city lockdown has improved air quality by reducing PM
2.5
, PM
10
, CO, and NO
2
, but has also decreased air quality by augmenting O
3
and SO
2
.
Wuhan was the epicenter of the Coronavirus Disease 2019 (COVID-19), outbreak in China. We aimed at surveying the general public in China to better understand their levels of psychological state and ...its influencing factors after the Wuhan shutdown on January 23.
The cross-sectional survey was conducted online and 4,701 respondents participated in this survey. Of them, 3,803 respondents were considered for final analysis. Data on subjective indicators of daily life changes were collected, and individual scores on changes in anxiety, depression, and stress were tested by 8-item, 11-item, and 6-item questionnaires, respectively.
Multivariable regression analyses showed that living in the rural areas, living in the other regions except Hubei, and higher education were independent correlates of less negative emotions. Besides, the level of attention, self-assessed infection risk, impact on the daily life and mental health help-seeking tended to be positively associated with the scores of anxiety, depression, and stress.
City of residence, education, marital status, monthly income, level of attention, self-assessed infection risk, impact on daily life and mental health help-seeking were important correlates of anxiety, depression, and stress scores.
Abstract
Systemic immune-inflammation index (SII) emerged as a biomarker of chronic inflammation and an independent prognostic factor for many cancers. We aimed to investigate the associations of SII ...level with total and cause-specific mortality risks in the general populations, and the potential modification effects of lifestyle-related factors on the above associations. In this study, we included 30,521 subjects from the Dongfeng-Tongji (DFTJ) cohort and 25,761 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999–2014. Cox proportional hazards regression models were used to estimate the associations of SII with mortality from all-cause, cardiovascular diseases (CVD), cancer and other causes. In the DFTJ cohort, compared to subjects in the low SII subgroup, those within the middle and high SII subgroups had increased risks of total mortality hazard ratio, HR (95% confidence interval, CI) = 1.12 (1.03–1.22) and 1.26 (1.16–1.36), respectively) and CVD mortality HR (95%CI) = 1.36 (1.19–1.55) and 1.50 (1.32–1.71), respectively; those within the high SII subgroup had a higher risk of other causes mortality HR (95%CI) = 1.28 (1.09–1.49). In the NHANES 1999–2014, subjects in the high SII subgroup had higher risks of total, CVD, cancer and other causes mortality HR (95%CI) = 1.38 (1.27–1.49), 1.33 (1.11–1.59), 1.22 (1.04–1.45) and 1.47 (1.32–1.63), respectively. For subjects with a high level of SII, physical activity could attenuate a separate 30% and 32% risk of total and CVD mortality in the DFTJ cohort, and a separate 41% and 59% risk of total and CVD mortality in the NHANES 1999–2014. Our study suggested high SII level may increase total and CVD mortality in the general populations and physical activity exerted a beneficial effect on the above associations.
Snail is a master inducer of epithelial-mesenchymal transition (EMT) and metastasis, however, Snail protein is labile and is quickly degraded through the predominate ubiquitination-mediated ...proteasome pathway. Deubiquitinases (DUBs) can counteract the Snail degradation process to maintain high level of Snail protein in cancer cells. In this study, we screened a cDNA library containing 79 DUBs, and discovered that a panel of DUBs consisting of USP13, USP28, USP29, USP37, OTUD6A, and DUB3 can markedly stabilize Snail protein, with USP29 displaying the strongest activity to prevent Snail degradation. Mechanistically, USP29 enhances the interaction of Snail and SCP1, resulting in simultaneous dephosphorylation and deubiquitination of Snail and thereafter cooperative prevention of Snail degradation. Biologically, ectopic expression of USP29 promotes gastric cancer cell migration, and depletion of Snail abolishes USP29-mediated cell migration; and USP29 can be induced by major EMT and metastatic inducing factors such as TGFβ, TNFα, and hypoxia. More importantly, high expression levels of Snail, USP29, and SCP1 are associated with poor survival and prognosis. Collectively, these data indicate that Snail is a crucial substrate for USP29 to promote cell migration and USP29/SCP1 complex may be new therapeutic targets to treat metastatic cancer.
To evaluate health-related quality of life (HRQoL) of middle-aged and elderly people with hypertension in Enshi, China, and to explore the important correlates defining HRQoL.
From April through July ...2018, a self-monitoring intervention program for hypertension control was implemented in a remote area of central China. Participants completed a cross-sectional survey which included demographic characteristics, the Health-related Quality of Life Survey, and the Pittsburgh Sleep Quality Index Survey. Univariate analysis was performed by analysis of variance, and multiple linear regression analysis was used to analyze the influencing factors of HRQoL in middle-aged and elderly hypertensive patients. In the multivariate analysis, the variables with P≤0.05 in the single factor analysis were combined with the professional significance to establish a multiple linear regression model.
Information from 500 participants was available for analysis. Among them, the scores of PCS and MCS was 31.66 ± 9.50 and 41.38 ± 10.69, respectively. Multivariable regression analyses showed that higher education and sleep quality, and moderate physical activity (30 minutes for at least five days a week) had a positive influence on PCS scores. Higher monthly family income (3,000-5,000 ¥) and sleep quality, regular tea-drinking, having 30 minutes of moderate physical activity at least five days a week were positively associated with MCS scores.
The overall HRQoL for rural middle-aged and elderly hypertensive patients in Xuan'en county of Hubei province was poor. Effective relevant measures for the above factors were urgently needed to improve the quality of life for the elderly in rural areas. Awareness of these relevant factors could help health care professionals provide better supportive care.
SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD
)-dependent histone deacetylase. It is involved in the regulation of various pathophysiological processes, including cell ...proliferation, survival, differentiation, autophagy, and oxidative stress. Therapeutic activation of SIRT1 protects the heart and cardiomyocytes from pathology-related stress, particularly myocardial ischemia/reperfusion (I/R). Autophagy is an important metabolic pathway for cell survival during energy or nutrient deficiency, hypoxia, or oxidative stress. Autophagy is a double-edged sword in myocardial I/R injury. The activation of autophagy during the ischemic phase removes excess metabolic waste and helps ensure cardiomyocyte survival, whereas excessive autophagy during reperfusion depletes the cellular components and leads to autophagic cell death. Increasing research on I/R injury has indicated that SIRT1 is involved in the process of autophagy and regulates myocardial I/R. SIRT1 regulates autophagy through various pathways, such as the deacetylation of FOXOs, ATGs, and LC3. Recent studies have confirmed that SIRT1-mediated autophagy plays different roles at different stages of myocardial I/R injury. By targeting the mechanism of SIRT1-mediated autophagy at different stages of I/R injury, new small-molecule drugs, miRNA activators, or blockers can be developed. For example, resveratrol, sevoflurane, quercetin, and melatonin in the ischemic stage, coptisine, curcumin, berberine, and some miRNAs during reperfusion, were involved in regulating the SIRT1-autophagy axis, exerting a cardioprotective effect. Here, we summarize the possible mechanisms of autophagy regulation by SIRT1 in myocardial I/R injury and the related molecular drug applications to identify strategies for treating myocardial I/R injury.
Epigenetic modifications affect the differentiation of T cell subsets and the pathogenesis of autoimmune diseases, but many mechanisms of epigenetic regulation of T cell differentiation are unclear. ...Here we show reduced expression of the transcription factor RFX1 in CD4
T cells from patients with systemic lupus erythematosus, which leads to IL-17A overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 tri-methylation. Conditional deletion of Rfx1 in mice exacerbates experimental autoimmune encephalomyelitis and pristane-induced lupus-like syndrome and increases induction of Th17 cells. In vitro, Rfx1 deficiency increases the differentiation of naive CD4
T cells into Th17 cells, but this effect can be reversed by forced expression of Rfx1. Importantly, RFX1 functions downstream of STAT3 and phosphorylated STAT3 can inhibit RFX1 expression, highlighting a non-canonical pathway that regulates differentiation of Th17 cells. Collectively, our findings identify a unique role for RFX1 in Th17-related autoimmune diseases.
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