Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for ...asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.
Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were ...showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations.
We analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them.
During a median follow-up period of 7.1 years (interquartile range: 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.02 per 1mg/L increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mg/L (false-discovery rate adjust (FDR-adjusted) P
< 0.001 and FDR-adjusted P
< 0.001). For site-specific cancer, we observed positive linear associations for cancers of esophagus and stomach (FDR-adjusted P
< 0.050 and FDR-adjusted P
> 0.050). In addition, we also observed three different patterns of non-linear associations, including "fast-to-low increase" (head and neck, colorectal, liver, lung, kidney cancer, and non-Hodgkin lymphoma), "increase-to-decrease" (breast cancer), and "decrease-to-platform" (chronic lymphocytic leukemia). Furthermore, the inflection points of non-linear association patterns were consistently at around 3mg/L. By contrast, there was no evidence for linear or non-linear associations between genetically predicted CRP and risks of overall cancer or site-specific cancers.
Our results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks.
N6-Methyladenosine (m6A) is an RNA modification that interacts with numerous coding and non-coding RNAs and plays important roles in the development of cancers. Nonetheless, the clinical impacts of ...m6A interactive genes on these cancers largely remain unclear since most studies focus only on a single cancer type. We comprehensively evaluated m6A modification patterns, including 23 m6A regulators and 83 interactive coding and non-coding RNAs among 9,804 pan-cancer samples. We used clustering analysis to identify m6A subtypes and constructed the m6A signature based on an unsupervised approach. We used the signatures to identify potential m6A modification targets across the genome. The prognostic value of one target was further validated in 3,444 samples from six external datasets. We developed three distinct m6A modification subtypes with different tumor microenvironment cell infiltration degrees: immunological, intermediate, and tumor proliferative. They were significantly associated with overall survival in 24 of 27 cancer types. Our constructed individual-level m6A signature was associated with survival, tumor mutation burden, and classical pathways. With the signature, we identified 114 novel genes as potential m6A targets. The gene shared most commonly between cancer types, BCL9L, is an oncogene and interacts with m6A patterns in the Wnt signaling pathway. In conclusion, m6A regulators and their interactive genes impact the outcome of various cancers. Evaluating the m6A subtype and the signature of individual tumors may inform the design of adjuvant treatments.
Background: Chronic kidney disease (CKD) is an important contributor to morbidity and mortality from noncommunicable diseases. We aimed to examine the longitudinal trajectories in risk factors, ...estimate their impact on CKD burden in China from 1991 to 2011, and project trends in the next 20 years.Methods: We used data from a cohort of the China Health and Nutrition Survey and applied the comparative risk assessment method to estimate the number of CKD events attributable to all non-optimal levels of each risk factors.Results: In 2011, current smoking was the leading individual attributable factor for CKD burden in China responsible for 7.9 (95% confidence interval CI, 7.5–8.3) million CKD cases with a population-attributable fraction of 8.7% (95% CI, 6.0–11.6), while the rates of smoking have reduced and may have mitigated the increase in CKD. High triglyceride (TG) and high systolic blood pressure (SBP) were the leading metabolic risk factors responsible for 6.8 (95% CI, 6.4–7.1) million and 5.8 (95% CI, 5.5–6.1) million CKD-attributable cases, respectively. Additionally, the number of CKD cases associated with high body mass index (BMI), high diastolic blood pressure (DBP), high plasma glucose, and low high-density lipoprotein cholesterol (HDL-C) was 5.4 (95% CI, 5.1–5.6), 3.9 (95% CI, 3.7–4.1), 3.0 (95% CI, 2.8–3.1) and 2.6 (95% CI, 2.5–2.8) million, respectively.Conclusion: Current smoking, high TG, and high SBP were the top three risk factors that contributed to CKD burden in China. Increased BMI, DBP, plasma glucose, and decreased HDL-C were also associated with the increase in CKD burden.
The early detection of hepatocellular carcinoma (HCC) presents a challenge because of the lack of specific biomarkers. Serum/plasma microRNAs (miRNAs) can discriminate HCC patients from controls. We ...aimed to identify and evaluate HCC‐associated plasma miRNAs originating from the liver as early biomarkers for detecting HCC. In this multicenter three‐phase study, we first performed screening using both plasma (HCC before and after liver transplantation or liver hepatectomy) and tissue samples (HCC, para‐carcinoma and cirrhotic tissues). Then, we evaluated the diagnostic potential of the miRNAs in two case–control studies (training and validation sets). Finally, we used two prospective cohorts to test the potential of the identified miRNAs for the early detection of HCC. During the screening phase, we identified ten miRNAs, eight of which (miR‐20a‐5p, miR‐25‐3p, miR‐30a‐5p, miR‐92a‐3p, miR‐132‐3p, miR‐185‐5p, miR‐320a and miR‐324‐3p) were significantly overexpressed in the HBV‐positive HCC patients compared with the HBV‐positive cancer‐free controls in both the training and validation sets, with a sensitivity of 0.866 and specificity of 0.646. Furthermore, we assessed the potential for early HCC detection of these eight newly identified miRNAs and three previously reported miRNAs (miR‐192‐5p, miR‐21‐5p and miR‐375) in two prospective cohorts. Our meta‐analysis revealed that four miRNAs (miR‐20a‐5p, miR‐320a, miR‐324‐3p and miR‐375) could be used as preclinical biomarkers (pmeta < 0.05) for HCC. The expression profile of the eight‐miRNA panel can be used to discriminate HCC patients from cancer‐free controls, and the four‐miRNA panel (alone or combined with AFP) could be a blood‐based early detection biomarker for HCC screening.
What's new?
Half of all deaths from hepatocellular carcinoma (HCC) occur in China. But while early detection of the disease could improve survival, preclinical diagnostic biomarkers are lacking. Using tissue and plasma samples from HCC patients and plasma samples from prospective cohorts, the authors of this study evaluated the diagnostic and predictive potential of miRNAs. A panel of eight miRNAs dysregulated during HCC development successfully distinguished HCC patients from controls, while a panel of four miRNAs was found to have preclinical potential. The newly described miRNA panels could aid in the detection of HCC before the disease is otherwise clinically apparent.
Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed ...to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk.
In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10−4 p=5 × 10−5 p=5 × 10−6 p=5 × 10−7, and p=5 × 10−8) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low quintile 1 of the polygenic risk score, intermediate quintile 2–4 of the polygenic risk score, and high quintile 5 of the polygenic risk score). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor.
The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10−5) showed the strongest association with gastric cancer risk (p=7·56 × 10−10). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (ptrend<0·0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio HR 1·54 95% CI 1·22–1·94, p=2·67 × 10−4) and a high genetic risk (2·08 1·61–2·69, p<0·0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (ptrend<0·0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2·03 1·46–2·83, p<0·0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0·53 0·29–0·99, p=0·048), with an absolute risk reduction of 1·12% (95% CI 0·62–1·56).
Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer.
National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.
For any given phenotype, there were a large number of underlying genetic loci, each exhibiting only small effect, but in combination, they could explain a significant proportion of the variance of ...phenotypes in the general population. ...by aggregating the effects of relevant genetic loci into a single indicator, polygenic scores (PGSs) (also referred to polygenic risk scores PRSs, or genetic or genomic risk scores GRSs for diseases) have emerged as a quantitative measure to predict an individual's genetic predisposition to a phenotype. 12 By comparing germline de novo mutations between offspring in families conceived spontaneously and assisted reproductive technology (ART) based on whole-genome sequencing trios, Wang et al13 demonstrated that the increased mutations in offspring conceived by ART were primarily originated from fathers. ...a trio approach enables accurate phasing and the assignment of the parental origin of alleles to show parent-of-origin effects. ...there may be potential unintended consequences of ESPS, such as selecting for adverse traits as a result of pleiotropy. ...ESPS is not ready for clinical uses, although disease risk for individuals with extreme PRSs equivalent to monogenic mutations makes meaningful contribution to genetic risk prediction and aforementioned medical applications. ...to address the clinical validity of PGSs, evaluations are required in the clinical or public health context, such as prospective cohorts considering other non-genetic factors for absolute risk estimation, randomized trials with clinically meaningful outcomes, and health economic evaluations or feasibility studies.
Recent findings that human serum contains stably expressed microRNA (miRNA) have revealed a great potential of serum miRNA signature as disease fingerprints to predict survival. We used genome-wide ...serum miRNA expression analysis to investigate the role of serum miRNA in predicting prognosis of non-small-cell lung cancer (NSCLC).
To control disease heterogeneity, we used patients with stages I to IIIa lung adenocarcinoma and squamous cell carcinoma, who were treated with both operation and adjuvant chemotherapies. In the discovery stage, Solexa sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 30 patients with longer survival (alive and mean survival time, 49.54 months) and 30 patients with shorter survival matched by age, sex, and stage (dead and mean survival time, 9.54 months). The detected serum miRNAs then were validated in 243 patients (randomly classified into two subgroups: n = 120 for the training set, and n = 123 for the testing set).
Eleven serum miRNAs were found to be altered more than five-fold by Solexa sequencing between longer-survival and shorter-survival groups, and levels of four miRNAs (ie, miR-486, miR-30d, miR-1 and miR-499) were significantly associated with overall survival. The four-miRNA signature also was consistently an independent predictor of overall survival for both training and testing samples.
The four-miRNA signature from the serum may serve as a noninvasive predictor for the overall survival of NSCLC.
Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide ...association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (P
ranging from 2.79 × 10
to 4.79 × 10
). By incorporating the PRS into EBV-serology-based NPC screening, the test's positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
Aims/hypothesis
We aimed to investigate the associations between maternal diabetes before or during pregnancy and the risk of high refractive error (RE) in offspring until the age of 25 years.
...Methods
This nationwide register-based cohort study comprised 2,470,580 individuals born in 1977–2016. The exposure was maternal diabetes during or before pregnancy (type 1 diabetes, type 2 diabetes and gestational diabetes). Cox regression was used to examine the association between maternal diabetes and the risk of high RE in offspring from birth until the age of 25 years, adjusting for multiple potential confounders.
Results
During up to 25 years of follow-up, 553 offspring of mothers with diabetes and 19,695 offspring of mothers without diabetes were diagnosed with high RE. Prenatal exposure to maternal diabetes was associated with a 39% increased risk of high RE: HR 1.39 (95% CI 1.28, 1.51),
p
< 0.001; standardised cumulative incidence in unexposed offspring at 25 years of age 1.18% (95% CI 1.16%, 1.19%); cumulative incidence difference 0.72% (95% CI 0.51%, 0.94%). The elevated risks were observed for hypermetropia (HR 1.37 95% CI 1.24, 1.51,
p
< 0.001), myopia (HR 1.34 95% CI 1.08, 1.66,
p
= 0.007) and astigmatism (HR 1.58 95% CI 1.29, 1.92,
p
< 0.001). The increased risks were more pronounced among offspring of mothers with diabetic complications (HR 2.05 95% CI 1.60, 2.64,
p
< 0.001), compared with those of mothers with diabetes but no diabetic complications (HR 1.18 95% CI 1.02, 1.37,
p
= 0.030).
Conclusions/interpretation
Our findings suggest that maternal diabetes during pregnancy is associated with an increased risk of high RE in offspring, in particular among those of mothers with diabetic complications. Early ophthalmological screening should be recommended in offspring of mothers with diabetes diagnosed before or during pregnancy.
Graphical abstract
PDF
