Air pollution, greenness and risk of overweight among middle-aged and older adults: A cohort study in China.

BACKGROUND: Exposure to air pollution may increase the risk of obesity, but living in greener space may reduce this risk. Epidemiological evidence, however, is inconsistent. METHODS: Using data from the China Health and Retirement Longitudinal Study (2011-2015), we conducted a nationwide cohort study of 7424 adults. We measured overweight/obesity according to body mass index. We used annual average ground-level air pollutants, including ozone (O3), nitrogen dioxide (NO2), and particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5), to demonstrate air pollution levels. We used the Normalized difference vegetation index (NDVI) to measure greenness exposure. We used time-varying Cox proportional hazard regression models to analyze the connections among air pollution, greenness, and the development of overweight/obesity in middle-aged and older adults in China. We also conducted mediation analyses to examine the mediating effects of air pollution. RESULTS: We found that lower risk of overweight/obesity was associated with more greenness exposure and lower levels of air pollution. We identified that an interquartile increment in NDVI was correlated with a lower hazard ratio (HR) of becoming overweight or obese (HR = 0.806, 95% confidence interval [CI]: 0.754-0.862). Although a 10 µg/m3 increase in PM2.5 and NO2 was correlated with higher risks (HR = 1.049, 95% CI = 1.022-1.075, HR = 1.376, 95% CI = 1.264-1.499). Effects of PM2.5 on being overweight or obese were stronger in men than in women. According to the mediation analysis, PM2.5 and NO2 mediated 8.85% and 19.22% of the association between greenness and being overweight or obese. CONCLUSIONS: An increased risk of being overweight or obese in middle-aged and older adults in China was associated with long-term exposure to higher levels of PM2.5 and NO2. This risk was reduced through NDVI exposure, and the associations were partially mediated by air pollutants. To verify these findings, fine-scale studies are needed.

Associations between greenness and blood pressure and hypertension in Chinese middle-aged and elderly population: A longitudinal study.

BACKGROUND: Greenness is an emerging modifiable environmental factor of high blood pressure and hypertension. However, current evidence is inconsistent, and high-quality studies are urgently needed, especially in developing country with high disease burden of hypertension. METHODS: A longitudinal study was designed and 9,649 participants (aged ≥45 years) with 22,854 number of visits among three waves between 2011 and 2015 were included based on the China Health and Retirement Longitudinal Study. Long term greenness exposure was assessed by annual normalized difference vegetation index (NDVI). Linear and generalized linear mixed effect models were used to estimate the associations between greenness and blood exposure level and hypertension risk, respectively. RESULTS: The median NDVI level was 0.51, with a range from 0.09 to 0.74. An interquartile range (0.15) increase in NDVI was related to 1.05 mmHg reduction (95% CI: -1.65, -0.45) of systolic blood pressure, 0.72 mmHg reduction (95% CI: -1.06, -0.37) of diastolic blood pressure, and 12% (95% CI: 1%, 22%) lower odds of hypertension risk. The association of greenness and blood pressure was significantly stronger in the younger (<60 years) than in the older (≥60 years), and partially mediated by body mass index. CONCLUSIONS: These findings highlight the protective effect of greenness on blood pressure and hypertension in Chines middle-aged and elderly population, especially in the younger (<60 years), and suggest policy makers to take greenness level into special consideration in the process of urbanization.

The establishment of Air Quality Health Index in China: A comparative analysis of methodological approaches.

BACKGROUND: The Air Quality Index (AQI) has been criticized because it does not adequately account for the health effect of multi-pollutants. Although the developed Air Quality Health Index (AQHI) is a more effective communication tool, little is known about the best method to construct AQHI on long time and large spatial scales. OBJECTIVES: To further evaluate the validity of existing approaches to the establishment of AQHI on both long time and larger spatial scales. METHODS: By introducing 3 approaches addressing multi-pollutant exposures: cumulative risk index (CRI), supervised principal component analysis (SPCA), and Bayesian multi-pollutants weighted model (BMP), we constructed CRI-AQHI, SPCA-AQHI, BMP-AQHI and standard-AQHI on cardiovascular mortality in China from 2015 to 2019 at both the national and geographic regional levels. We further assessed the performance of the four methods in estimating the joint effect of multi-pollutants by simulations under various scenarios of pollution effect. RESULTS: The results of national China showed that the BMP-AQHI improved the goodness of fit of the standard-AQHI by 108.24%, followed by CRI-AQHI (5.02%), and all AQHIs performed better than AQI, consistent with 6 geographic regional results. In addition, the simulation result showed that the BMP method provided stable and relatively accurate estimations of the short-term combined effect of exposure to multi-pollutants. CONCLUSIONS: AQHI based on BMP could communicate the air pollution risk to the public more effectively than the current AQHI and AQI.

The construction of the air quality health index (AQHI) and a validity comparison based on three different methods.

The most common currently used air quality risk communication tool, the Air Quality Index (AQI), has been criticized. As a result, Canada proposed the Air Quality Health Index (AQHI) to communicate the health risks of multiple pollutants. However, the AQHI is calculated by directly summing the excess risks from single-pollutant models, which may overestimate the effects of the pollutants. To solve this problem, we introduced two methods for estimating the joint effects of multiple pollutants: the cumulative risk index (CRI) and supervised principal component analysis (SPCA). Based on three methods, i.e., the standard, CRI and SPCA methods, we constructed three types of AQHIs and compared their validity to select the best communication tool. Our results showed that compared with the AQI, all three AQHIs had a linear relationship with mortality. In addition, the CRI-AQHI had the best goodness of fit and captured the overall health risk of pollution mixtures most robustly among various cause-specific mortalities when identifying health risks. Our study indicated that the CRI-AQHI may have the potential to be a better alternative to the standard AQHI in communicating air pollution-related health risks to the public.

The burden of sulfur dioxide pollution on years of life lost from chronic obstructive pulmonary disease: A nationwide analysis in China.

BACKGROUND: Sulfur dioxide (SO2) is one of the major gaseous pollutants in China and other developing countries. Few multicity studies have been done to examine the short-term effect of SO2 on cause-specific years of life lost (YLL). This study was designed to investigate the burden of chronic obstructive pulmonary disease (COPD) associated with SO2 exposure. METHODS: A 5-year time-series study was conducted in 48 Chinese cities from 2013 to 2017. Generalized additive models were first used to estimate the city-specific relationship. Then, random-effects meta-analyses were applied to pool the estimates. Furthermore, the roles of potential modifiers and the related economic loss estimated by the method of value per statistical life year were also evaluated. RESULTS: The annual mean concentration of SO2 was 27.1 µg/m3. A 10 µg/m3 increase in 4-day moving average (lag03) of SO2 concentration was associated with 0.83% (95% CI: 0.13%, 1.53%) relative increment in YLL from COPD, and relevant percent change of mortality was 0.78% (95% CI: 0.16%, 1.41%). Moreover, a significantly higher effect was observed in the warm season, particularly in the south region. SO2 exposure was estimated to account for 1.89% of the total economic loss due to YLL from COPD. CONCLUSIONS: Our findings showed a positive association between short-term exposure to SO2 and YLL from COPD and highlighted the importance of continuous control of SO2 pollution to reduce corresponding attributable disease burden.

Characteristics and prognostic significance of profiling the peripheral blood T-cell receptor repertoire in patients with advanced lung cancer.

Lung cancer is one of the greatest threats to human health, and is initially detected and attacked by the immune system through tumor-reactive T cells. The aim of this study was to determine the basic characteristics and clinical significance of the peripheral blood T-cell receptor (TCR) repertoire in patients with advanced lung cancer. To comprehensively profile the TCR repertoire, high-throughput sequencing was used to identify hypervariable rearrangements of complementarity determining region 3 (CDR3) of the TCR ß chain in peripheral blood samples from 64 advanced lung cancer patients and 31 healthy controls. We found that the TCR repertoire differed substantially between lung cancer patients and healthy controls in terms of CDR3 clonotype, diversity, V/J segment usage, and sequence. Specifically, baseline diversity correlated with several clinical characteristics, and high diversity reflected a better immune status. Dynamic detection of the TCR repertoire during anticancer treatment was useful for prognosis. Both increased diversity and high overlap rate between the pre- and post-treatment TCR repertoires indicated clinical benefit. Combination of the diversity and overlap rate was used to categorize patients into immune improved or immune worsened groups and demonstrated enhanced prognostic significance. In conclusion, TCR repertoire analysis served as a useful indicator of disease development and prognosis in advanced lung cancer and may be utilized to direct future immunotherapy.

Estimation of hepatitis B-positive rates in Chinese blood donors by combining predonation and postdonation screening results.

BACKGROUND: Chinese blood centers use Hepatitis B surface antigen (HBsAg) rapid test (RT) in pre-donation and two rounds of screening with different enzyme-linked immunosorbent assays in post-donation. Nucleic acid testing (NAT) on screening non-reactive (SC-) donations has been gradually implemented since 2010. Yet RT+ and SC-/NAT+ donors are seldom included in hepatitis B virus (HBV) positive rate estimates in Chinese blood donors. METHODS: We performed HBsAg neutralization test (NT) on whole blood (WB) with pre-donation RT+ results and post-donation screening reactive (SC+) samples from Mianyang and Chongqing in 2015. The annual totals of pre- and post-donation NT+ donors were combined with the annual totals of SC-/NAT+ donors to derive the estimated HBV positive rates. RESULT: In Mianyang and Chongqing, 59.4% and 68.2% of RT+ donors in Jan-Aug 2015 contributed for NT, 95.5% and 97.2% of which were NT+ respectively. In 2015, 422 and 667 donors from Mianyang and Chongqing respectively were HBsAg RT+, yielding estimated 403 and 648 pre-donation RT+/NT+ deferrals. 411 and 668 post-donation SC+ samples were NT tested from Mianyang and Chongqing, of which 249 and 323 were NT+ respectively. An estimated 63 donors in Mianyang and 88 donors in Chongqing were SC-/NAT+. The estimated HBV confirmed positive rate in blood donors are 1.59% in Mianyang and 1.01% in Chongqing. CONCLUSION: Pre-donation HBsAg RT effectively intercepts donations from HBV infected donors. Using NT confirmatory results from RT+, SC+ and SC-/NAT+ donors, this study provides a model for more accurate estimation for HBV positive rates in China.

An Adaptive Learning Based Network Selection Approach for 5G Dynamic Environments.

Networks will continue to become increasingly heterogeneous as we move toward 5G. Meanwhile, the intelligent programming of the core network makes the available radio resource be more changeable rather than static. In such a dynamic and heterogeneous network environment, how to help terminal users select optimal networks to access is challenging. Prior implementations of network selection are usually applicable for the environment with static radio resources, while they cannot handle the unpredictable dynamics in 5G network environments. To this end, this paper considers both the fluctuation of radio resources and the variation of user demand. We model the access network selection scenario as a multiagent coordination problem, in which a bunch of rationally terminal users compete to maximize their benefits with incomplete information about the environment (no prior knowledge of network resource and other users' choices). Then, an adaptive learning based strategy is proposed, which enables users to adaptively adjust their selections in response to the gradually or abruptly changing environment. The system is experimentally shown to converge to Nash equilibrium, which also turns out to be both Pareto optimal and socially optimal. Extensive simulation results show that our approach achieves significantly better performance compared with two learning and non-learning based approaches in terms of load balancing, user payoff and the overall bandwidth utilization efficiency. In addition, the system has a good robustness performance under the condition with non-compliant terminal users.

Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers.

PURPOSE: Fragile X CGG repeat alleles often contain one or more AGG interruptions that influence allele stability and risk of a full mutation transmission from parent to child. We have examined transmissions of maternal and paternal alleles with 45-90 repeats to quantify the effect of AGG interruptions on fragile X repeat instability. METHODS: A novel FMR1 polymerase chain reaction assay was used to determine CGG repeat length and AGG interruptions for 1,040 alleles from 705 families. RESULTS: We grouped transmissions into nine categories of five repeats by parental size and found that in every size category, alleles with no AGGs had the greatest risk for instability. For maternal alleles <75 repeats, 89% (24/27) that expanded to a full mutation had no AGGs. Two contractions in maternal transmission were accompanied by loss of AGGs, suggesting a mechanism for generating alleles that lack AGG interruptions. Maternal age was examined as a factor in full mutation expansions using prenatal samples to minimize ascertainment bias, and a possible effect was observed though it was not statistically significant (P = 0.06). CONCLUSION: These results strengthen the association of AGG repeats with CGG repeat stability and provide more accurate risk estimates of full mutation expansions for women with 45-90 repeat alleles.

CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles.

BACKGROUND: Greater than 200 CGG repeats in the 5'UTR of the FMR1 gene lead to epigenetic silencing and lack of the FMR1 protein, causing fragile X Syndrome. Individual carriers of a premutation (PM) allele with 55-200 CGG repeats are typically unmethylated and can present with clinical features defined as FMR1-associated conditions. METHODS: Blood samples from 17 male PM carriers were assessed clinically and molecularly by Southern blot, western blot, PCR and QRT-PCR. Blood and brain tissue from an additional 18 PM males were also similarly examined. Continuous outcomes were modelled using linear regression and binary outcomes were modelled using logistic regression. RESULTS: Methylated alleles were detected in different fractions of blood cells in all PM cases (n=17). CGG repeat numbers correlated with percent of methylation and mRNA levels and, especially in the upper PM range, with greater number of clinical involvements. Inter-tissue/intra-tissue somatic instability and differences in percent methylation were observed between blood and fibroblasts (n=4) and also observed between blood and different brain regions in three of the 18 PM cases examined. CGG repeat lengths in lymphocytes remained unchanged over a period of time ranging from 2 to 6 years, three cases for whom multiple samples were available. CONCLUSIONS: In addition to CGG size instability, individuals with a PM expanded allele can exhibit methylation and display more clinical features likely due to RNA toxicity and/or FMR1 silencing. The observed association between CGG repeat length and percent of methylation with the severity of the clinical phenotypes underscores the potential value of methylation in affected PM to further understand penetrance, inform diagnosis and expand treatment options.

Emerging chemotherapy-based treatments in anaplastic thyroid cancer: an updated analysis of prospective studies.

Background: For patients with anaplastic thyroid cancer (ATC) without mutational driver genes, chemotherapy is suggested to be the first-line treatment option. However, the benefits of chemotherapy in treating ATC are limited. In this analysis, we collected the prospective data reported since 2010 to analyze the emerging chemotherapy-based treatments in ATC comprehensively. Methods: For this updated analysis, we searched PubMed (MEDLINE), Web of Science, Embase, and Cochrane CENTRAL databases from 1 January 2010 to 7 February 2024 for prospective clinical studies that contained chemotherapy-based treatments. This analysis was done to pool overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), disease control rates (DCRs), and grade 3 or worse treatment-related adverse events (TRAEs). Results: Six prospective clinical trials with 232 patients were included. Chemotherapy was commonly combined with targeted therapy or radiotherapy. The pooled median OS was 6.0 months (95% CI 4.1-9.7), and the median PFS was 3.2 months (95% CI 1.9-6.0) in patients with ATC who received chemotherapy-based strategies. The integrated ORR and DCR were 21% (95% CI 15%-27%) and 64% (95% CI 55%-72%), respectively. Regarding the grade 3 or worse TRAE, the pooled incidence was 68% (95% CI 47%-86%). Conclusion: Although the emerging chemotherapy-based treatments showed antitumor activity in patients with ATC, these strategies failed to prolong the survival time substantially. More practical, safe, and novel therapeutic regimens for patients with ATC warrant further investigations.

The efficacy and safety of antiangiogenesis tyrosine kinase inhibitors in patients with advanced anaplastic thyroid cancer: A meta-analysis of prospective studies.

BACKGROUND: The poor prognosis of anaplastic thyroid cancer (ATC) patients is associated with limited effective therapeutic strategies. Multiple antiangiogenesis tyrosine kinase inhibitors (TKIs) have been applied in later-line treatment of ATC; however, the results reported in clinical trials were controversial. In this study, we reconstructed the patient-level data to pooled-analyze the survival data, responses, and adverse events. METHODS: Online databases (PubMed, Web of Science, Embase, and Cochrane CENTRAL) were searched on September 03, 2023. R software combined with the "metaSurvival" and "meta" packages were used to reconstruct the survival curves and summarize the response rates. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were survival rate, objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. RESULTS: Six prospective clinical trials involving 140 ATC patients were enrolled. Four types of TKIs (imatinib, pazopanib, sorafenib, and lenvatinib) were included. When advanced ATC patients were treated with the TKIs, the median OS was 4.8 months and the median PFS was 2.6 months. The pooled ORR and DCR were 9% and 53%. Hypertension, decreased appetite, rash, and lymphopenia were the most common grade ≥ 3 treatment-related adverse events. CONCLUSION: Mono-anitangiogenesis TKI therapy showed limited improvements in treating advanced ATC patients. Combining antiangiogenesis TKI therapy with chemotherapy, radiotherapy, or immunotherapy could be the direction of future studies.

Tyrosine kinase inhibitors in patients with advanced anaplastic thyroid cancer: an effective analysis based on real-world retrospective studies.

Background: Tyrosine kinase inhibitors (TKIs) contribute to the treatment of patients with anaplastic thyroid cancer (ATC). Although prospective clinical studies of TKIs exhibit limited efficacy, whether ATC patients benefit from TKI treatment in real-world clinical practice may enlighten future explorations. Therefore, we conducted this effective analysis based on real-world retrospective studies to illustrate the efficacy of TKI treatment in ATC patients. Methods: We systematically searched the online databases on September 03, 2023. Survival curves were collected and reconstructed to summarize the pooled curves. Responses were analyzed by using the "meta" package. The primary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: 12 studies involving 227 patients were enrolled in the study. Therapeutic strategies included: anlotinib, lenvatinib, dabrafenib plus trametinib, vemurafenib, pembrolizumab plus dabrafenib and trametinib, pembrolizumab plus lenvatinib, pembrolizumab plus trametinib, and sorafenib. The pooled median OS and PFS were 6.37 months (95% CI 4.19-10.33) and 5.50 months (95% CI 2.17-12.03). The integrated ORR and DCR were 32% (95% CI 23%-41%) and 40% (95% CI 12%-74%). Conclusion: In real-world clinical practice, ATC patients could benefit from TKI therapy. In future studies, more basic experiments and clinical explorations are needed to enhance the effects of TKIs in the treatment of patients with ATC.

The persistence of hepatitis C virus transmission risk in China despite serologic screening of blood donations.

BACKGROUND: A total of 2%-2.9% of the population in China is infected with hepatitis C virus (HCV). This study estimated the prevalence and incidence of HCV among Chinese blood donors. STUDY DESIGN AND METHODS: We examined whole blood and apheresis platelet donations at five Chinese blood centers in 2008 to 2010. All donations were screened using two rounds of testing for alanine aminotransferase, antibody to human immunodeficiency virus Types 1 and 2, hepatitis B surface antigen, anti-HCV, and syphilis. Screening reactivity is defined by a reactive result in one or both rounds of screening tests. Confirmatory tests (Ortho third-generation HCV enzyme immunoassay, Johnson & Johnson) were performed on anti-HCV screening-reactive samples. Confirmatory positive rates among first-time donors (prevalence) and repeat donors (incidence) were calculated by blood center and demographic categories. Donor characteristics associated with HCV confirmatory status among first-time donors were examined using trend test and multivariable logistic regression analysis. RESULTS: Among 821,314 donations, 40% came from repeat donors. The overall anti-HCV screening-reactive rate was 0.48%. Estimated HCV prevalence was 235 per 100,000 first-time donors; incidence was 10 per 100,000 person-years in repeat donors. In multivariable logistic regression analysis, first-time donors older than 25 years displayed higher HCV prevalence than the younger donors. Less education is associated with higher HCV prevalence. Donors 26 to 35 years old and those above 45 years displayed the highest incidence rate. CONCLUSION: High prevalence and incidence in donors indicate high residual risks for transfusion-transmitted HCV in Chinese patients. Implementation of minipool nucleic acid testing in routine donation screening may prevent a substantial number of transfusion-transmitted HCV infections.

Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes.

Imprinted genes are clustered in domains, and their allelic repression is mediated by imprinting control regions. These imprinting control regions are marked by DNA methylation, which is essential to maintain imprinting in the embryo. To explore how imprinting is regulated in placenta, we studied the Kcnq1 domain on mouse distal chromosome 7. This large domain is controlled by an intronic imprinting control region and comprises multiple genes that are imprinted in placenta, without the involvement of promoter DNA methylation. We found that the paternal repression along the domain involves acquisition of trimethylation at Lys27 and dimethylation at Lys9 of histone H3. Eed-Ezh2 Polycomb complexes are recruited to the paternal chromosome and potentially regulate its repressive histone methylation. Studies on embryonic stem cells and early embryos support our proposal that chromatin repression is established early in development and is maintained in the placenta. In the embryo, however, imprinting is stably maintained only at genes that have promoter DNA methylation. These data underscore the importance of histone methylation in placental imprinting and identify mechanistic similarities with X-chromosome inactivation in extraembryonic tissues, suggesting that the two epigenetic mechanisms are evolutionarily linked.

Long-Term Apparent Temperature, Extreme Temperature Exposure, and Depressive Symptoms: A Longitudinal Study in China.

Temperature is increasingly understood to impact mental health. However, evidence of the long-term effect of temperature exposure on the risk of depressive symptoms is still scarce. Based on the China Health and Retirement Longitudinal Study (CHARLS), this study estimated associations between long-term apparent temperature, extreme temperature, and depressive symptoms in middle-aged and older adults. Results showed that a 1 °C increase or decrease from optimum apparent temperature (12.72 °C) was associated with a 2.7% (95% CI: 1.3%, 4.1%) and 2.3% (95% CI: 1.1%, 3.5%) increased risk of depressive symptoms, respectively. This study also found that each percent increase in annual change in ice days, cool nights, cool days, cold spell durations, and tropical nights was associated with higher risk of depressive symptoms, with HRs (95%CI) of 1.289 (1.114-1.491), 2.064 (1.507-2.825), 1.315 (1.061-1.631), 1.645 (1.306-2.072), and 1.344 (1.127-1.602), respectively. The results also indicated that people living in northern China have attenuated risk of low apparent temperature. Older people were also observed at higher risk relating to more cool nights. Middle-aged people, rural residents, and people with lower household income might have higher related risk of depressive symptoms due to increased tropical nights. Given the dual effect of climate change and global aging, these findings have great significance for policy making and adaptive strategies for long-term temperature and extreme temperature exposure.

Artificial light at night, MRI-based measures of brain iron deposition and incidence of multiple mental disorders.

BACKGROUND: Epidemiologic evidence on whether iron accumulation in brain modified the association between artificial light at night (ALAN) and incident mental disorders is lacking. The authors aims to investigate modification of brain iron deposition on the associations of ALAN with multiple mental disorders in the middle-aged and older adults. METHODS: This prospective study used data from the UK Biobank. ALAN was drawn from satellite datasets. Susceptibility-weighted magnetic resonance imaging was used to ascertain iron content of each brain region. T2* signal loss was used as indices of iron deposition. The main outcomes are impacts of ALAN exposure on onset of wide spectrum of physician-diagnosed mental disorders, which was estimated by time-varying Cox proportional hazard model. The authors further conducted stratified analyses by levels of iron brain deposition to examine the potential modifying effects. RESULTS: Among 298,283 participants followed for a median of 10.91 years, higher ALAN exposure was associated with increased risk of mental disorders. An IQR (11.37 nW/cm2/sr) increase in annual levels of ALAN was associated with an HR of 1.050 (95 % CI: 1.034,1.066) for any mental disorder, 1.076 (95 % CI: 1.053,1.099) for substance use disorder, and 1.036 (95 % CI: 1.004,1.069) for depression disorder in fully adjusted models. The exposure-response curves showed steeper trends at lower ALAN levels and a plateau at higher exposures. The associations were stronger in participants with high iron deposition in left hippocampus, left accumbens and left pallidum. CONCLUSIONS: ALAN was associated with multiple mental disorders in the middle-aged and older adults, and the findings indicated stricter standards of ALAN is needed and targeted preventive measures are warranted, especially with high brain iron deposition.

Contrived Materials and a Data Set for the Evaluation of Liquid Biopsy Tests: A Blood Profiling Atlas in Cancer (BLOODPAC) Community Study.

The Blood Profiling Atlas in Cancer (BLOODPAC) Consortium is a collaborative effort involving stakeholders from the public, industry, academia, and regulatory agencies focused on developing shared best practices on liquid biopsy. This report describes the results from the JFDI (Just Freaking Do It) study, a BLOODPAC initiative to develop standards on the use of contrived materials mimicking cell-free circulating tumor DNA, to comparatively evaluate clinical laboratory testing procedures. Nine independent laboratories tested the concordance, sensitivity, and specificity of commercially available contrived materials with known variant-allele frequencies (VAFs) ranging from 0.1% to 5.0%. Each participating laboratory utilized its own proprietary evaluation procedures. The results demonstrated high levels of concordance and sensitivity at VAFs of >0.1%, but reduced concordance and sensitivity at a VAF of 0.1%; these findings were similar to those from previous studies, suggesting that commercially available contrived materials can support the evaluation of testing procedures across multiple technologies. Such materials may enable more objective comparisons of results on materials formulated in-house at each center in multicenter trials. A unique goal of the collaborative effort was to develop a data resource, the BLOODPAC Data Commons, now available to the liquid-biopsy community for further study. This resource can be used to support independent evaluations of results, data extension through data integration and new studies, and retrospective evaluation of data collection.

Electrochemical and electronic properties of LiCoO2 cathode investigated by galvanostatic cycling and EIS.

The processes of extraction and insertion of lithium ions in LiCoO(2) cathode are investigated by galvanostatic cycling and electrochemical impedance spectroscopy (EIS) at different potentials during the first charge/discharge cycle and at different temperatures after 10 charge/discharge cycles. The spectra exhibit three semicircles and a slightly inclined line that appear successively as the frequency decreases. An appropriate equivalent circuit is proposed to fit the experimental EIS data. Based on detailed analysis of the change in kinetic parameters obtained from simulating the experimental EIS data as functions of potential and temperature, the high-frequency, the middle-frequency, and the low-frequency semicircles can be attributed to the migration of the lithium ions through the SEI film, the electronic properties of the material and the charge transfer step, respectively. The slightly inclined line arises from the solid state diffusion process. The electrical conductivity of the layered LiCoO(2) changes dramatically at early delithiation as a result of a polaron-to-metal transition. In an electrolyte solution of 1 mol L(-1) LiPF(6)-EC (ethylene carbonate) :DMC (dimethyl carbonate), the activation energy of the ion jump (which is related to the migration of the lithium ions through the SEI film), the thermal activation energy of the electrical conductivity and the activation energy of the intercalation/deintercalation reaction are 37.7, 39.1 and 69.0 kJ mol(-1), respectively.

Genome-wide uH2A localization analysis highlights Bmi1-dependent deposition of the mark at repressed genes.

Polycomb group (PcG) proteins control organism development by regulating the expression of developmental genes. Transcriptional regulation by PcG proteins is achieved, at least partly, through the PRC2-mediated methylation on lysine 27 of histone H3 (H3K27) and PRC1-mediated ubiquitylation on lysine 119 of histone H2A (uH2A). As an integral component of PRC1, Bmi1 has been demonstrated to be critical for H2A ubiquitylation. Although recent studies have revealed the genome-wide binding patterns of some of the PRC1 and PRC2 components, as well as the H3K27me3 mark, there have been no reports describing genome-wide localization of uH2A. Using the recently developed ChIP-Seq technology, here, we report genome-wide localization of the Bmi1-dependent uH2A mark in MEF cells. Gene promoter averaging analysis indicates a peak of uH2A just inside the transcription start site (TSS) of well-annotated genes. This peak is enriched at promoters containing the H3K27me3 mark and represents the least expressed genes in WT MEF cells. In addition, peak finding reveals regions of local uH2A enrichment throughout the mouse genome, including almost 700 gene promoters. Genes with promoter peaks of uH2A exhibit lower-level expression when compared to genes that do not contain promoter peaks of uH2A. Moreover, we demonstrate that genes with uH2A peaks have increased expression upon Bmi1 knockout. Importantly, local enrichment of uH2A is not limited to regions containing the H3K27me3 mark. We describe the enrichment of H2A ubiquitylation at high-density CpG promoters and provide evidence to suggest that DNA methylation may be linked to uH2A at these regions. Thus, our work not only reveals Bmi1-dependent H2A ubiquitylation, but also suggests that uH2A targeting in differentiated cells may employ a different mechanism from that in ES cells.