We introduce the antibody landscape, a method for the quantitative analysis of antibodymediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among ...pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon ...number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100 TeV. As a result, we observed 24 photonlike events with E>100 TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100 TeV from an astrophysical source.
Summary
Background
Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects ...survival after HCC diagnosis.
Methods
This was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.
Results
Approximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).
Conclusions
Anti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.
Purpose
Circulating microRNAs (miRNAs) are potential diagnostic biomarkers for breast cancer (BC). The application of miRNA panels could improve the performance of screening tests. Here, we ...integrated bioinformatic tools and meta-analyses to select circulating miRNAs with high diagnostic accuracy and combined these markers to develop diagnostic panels for BC.
Methods
Analyses across databases were performed to identify potential BC-related circulating miRNAs. Next, a comprehensive meta-analysis was conducted for each miRNA following the PRISMA guidelines. An electronic and manual search for relevant literature was carried out by two reviewers through PubMed, ScienceDirect, Biomed Central, and Google Scholar. The quality of the included studies was assessed using the QUADAS-2, and the statistical analyses were performed using R software 4.1.1. Finally, the accurate biomarkers confirmed through meta-analyses were combined into diagnostic models for BC.
Results
Twenty-seven circulating miRNAs were identified as BC-related by bioinformatic tools. After screening, only 10 miRNAs presented in 45 studies were eligible for meta-analyses. By assessing pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, 8 miRNAs (miR-21, miR-30b, miR-125b, miR-145, miR221 miR-222, and miR-335) were revealed as promising BC diagnostic biomarkers. Two panels constructed from these miRNAs showed excellent diagnostic accuracy for BC, with areas under the SROC curve of 0.917 and 0.944.
Conclusion
We identified 8 potential circulating miRNAs and 2 diagnostic models that are useful for diagnosing BC. However, the established miRNA panels have not been tested in any experimental studies and thus should be validated in large case–control studies for clinical use.
Protected Areas and Effective Biodiversity Conservation Le Saout, Soizic; Hoffmann, Michael; Shi, Yichuan ...
Science (American Association for the Advancement of Science),
11/2013, Letnik:
342, Številka:
6160
Journal Article
Recenzirano
Although protected areas (PAs) cover 13% of Earth's land (1), substantial gaps remain in their coverage of global biodiversity (2). Thus, there has been emphasis on strategic expansion of the global ...PA network (3-5). However, because PAs are often understaffed, underfunded, and beleaguered in the face of external threats (6, 7), efforts to expand PA coverage should be complemented by appropriate management of existing PAs. Previous calls for enhancing PA management have focused on improving operational effectiveness of each PA e.g., staffing and budgets (6). Little guidance has been offered on how to improve collective effectiveness for meeting global biodiversity conservation goals (3). We provide guidance for strategically allocating management efforts among and within existing PAs to strengthen their collective contribution toward preventing global species extinctions.
Objective To determine women’s satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour.Design Multicentre randomised ...controlled equivalence trial.Setting 15 hospitals in the Netherlands. Participants Women with an intermediate to high obstetric risk with an intention to deliver vaginally. To exclude a clinically relevant difference in satisfaction with pain relief of more than 10%, we needed to include 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation to correct for missing data.Intervention Before the onset of active labour consenting women were randomised to a pain relief strategy with patient controlled remifentanil or epidural analgesia if they requested pain relief during labour.Main outcome measures Primary outcome was satisfaction with pain relief, measured hourly on a visual analogue scale and expressed as area under the curve (AUC), thus providing a time weighted measure of total satisfaction with pain relief. A higher AUC represents higher satisfaction with pain relief. Secondary outcomes were pain intensity scores, mode of delivery, and maternal and neonatal outcomes. Analysis was done by intention to treat. The study was defined as an equivalence study for the primary outcome.Results 1414 women were randomised, of whom 709 were allocated to patient controlled remifentanil and 705 to epidural analgesia. Baseline characteristics were comparable. Pain relief was ultimately used in 65% (447/687) in the remifentanil group and 52% (347/671) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48). Cross over occurred in 7% (45/687) and 8% (51/671) of women, respectively. Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The area under the curve for total satisfaction with pain relief was 30.9 in the remifentanil group versus 33.7 in the epidural analgesia group (mean difference −2.8, 95% confidence interval −6.9 to 1.3). For who actually received pain relief the area under the curve for satisfaction with pain relief after the start of pain relief was 25.6 in the remifentanil group versus 36.1 in the epidural analgesia group (mean difference −10.4, −13.9 to −7.0). The rate of caesarean section was 15% in both groups. Oxygen saturation was significantly lower (SpO2 <92%) in women who used remifentanil (relative risk 1.5, 1.4 to 1.7). Maternal and neonatal outcomes were comparable between both groups.Conclusion In women in labour, patient controlled analgesia with remifentanil is not equivalent to epidural analgesia with respect to scores on satisfaction with pain relief. Satisfaction with pain relief was significantly higher in women who were allocated to and received epidural analgesia.Trial registration Netherlands Trial Register NTR2551.
In the absence of a firm link between individual meteorites and their asteroidal parent bodies, asteroids are typically characterized only by their light reflection properties, and grouped ...accordingly into classes. On 6 October 2008, a small asteroid was discovered with a flat reflectance spectrum in the 554-995nm wavelength range, and designated 2008 TC3 (refs 4-6). It subsequently hit the Earth. Because it exploded at 37km altitude, no macroscopic fragments were expected to survive. Here we report that a dedicated search along the approach trajectory recovered 47 meteorites, fragments of a single body named Almahata Sitta, with a total mass of 3.95kg. Analysis of one of these meteorites shows it to be an achondrite, a polymict ureilite, anomalous in its class: ultra-fine-grained and porous, with large carbonaceous grains. The combined asteroid and meteorite reflectance spectra identify the asteroid as F class, now firmly linked to dark carbon-rich anomalous ureilites, a material so fragile it was not previously represented in meteorite collections.
Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed ...cooperatively.
We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others.
The specification of SBML Level 1 is freely available from http://www.sbml.org/
Abstract Aim of the study A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as ...‘epigenetic clock’, has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. Methods Here, we profiled DNA methylation changes in a nested case–control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. Results We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007–1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007–1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020–1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03–1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. Conclusion Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility.
Poor hygiene of housing induces a systemic inflammatory response. Because inflammation and oxidative stress are processes that can sustain each other, the ways pigs are able to activate their ...antioxidant defenses are critical for production performance and health during periods when the immune system is solicited. Selection for production performance can also influence reactive oxygen species (ROS) production and expression levels of genes involved in cellular response to oxidative stress in different tissues. To establish the extent by which poor hygiene and selection for feed efficiency affected redox status, pigs divergently selected for residual feed intake (RFI) were housed in poor or good hygiene during 6 weeks. At the end, blood was collected in all pigs, and half of them were killed for tissue sampling. The remaining pigs were reared in good hygiene conditions during a recovery period of 7-8 weeks.
At week 6, poor hygiene was associated with a lower total antioxidant capacity assessed by plasma ferric reducing ability in all pigs, and with greater plasma levels of hydrogen peroxides in the high RFI pigs (less efficient). Adipose tissue of high RFI pigs exhibited higher activities of catalase and glutathione reductase, and greater thiobarbituric acid reactive substances (TBARS) concentrations when compared with the low RFI pigs (more efficient). Poor hygiene conditions activated the antioxidant enzymes activities (glutathione reductase, superoxide dismutase and catalase) in adipose tissue of both lines, but led to higher ROS production by mature adipocytes isolated from the high RFI pigs only. In liver and muscle, there were only minor changes in antioxidant molecules due to genetics and hygiene conditions. After the resilience period, adipose tissue of pigs previously challenged by poor hygiene maintained higher antioxidant enzyme activities, and for the high RFI line, displayed higher TBARS concentrations.
Pigs selected for improved feed efficiency showed a lower susceptibility to oxidative stress induced by poor hygiene conditions. This could led to a lower inflammatory response and less impaired growth when these pigs are facing sanitary challenges during the production period.
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