Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) ...aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas.
A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world.
MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance.
In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.
•MCDBT-1 had a sensitivity of 69.1% and a specificity of 98.9% in detecting six cancers.•In the real world, MCDBT-1 decreased late-stage incidence by 38.7%-46.4% and increased 5-year survival rate by 33.1%-40.4%.•In parallel, MCDBT-2 was set at a lower specificity but a higher sensitivity than MCDBT-1 and had an ideal performance.
We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of ...the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (∼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (∼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.
Background
Chronic sinusitis (CRS) is a common otorhinolaryngologic disease that is frequently encountered in everyday practice, but there is a lack of precise data regarding the prevalence of CRS in ...developing countries. We performed a national investigation in China to determine the prevalence and associated factors of CRS.
Methods
We conducted a cross‐sectional investigation in 2012. A stratified four‐stage sampling method was used to select participants randomly from seven cities in mainland China. All participants were interviewed face‐to‐face via a standardized questionnaire. Unconditional logistic regression analyses were conducted to examine the association between smoking and sinusitis after adjusting for socio‐demographic factors.
Results
This study included a total of 10 636 respondents from seven cities. The overall prevalence of CRS was 8.0% and ranged from 4.8% to 9.7% in seven centres. Chronic sinusitis affected approximately 107 million people in mainland China. Chronic sinusitis was particularly prevalent among people with specific medical conditions, including allergic rhinitis, asthma, chronic obstructive pulmonary disease and gout. The prevalence was slightly higher among males (8.79%) than females (7.28%) (P = 0.004), and the prevalence varied by age group, ethnicity and marital status and education (P < 0.05), but not by household per capita income or living space (P > 0.05). Both second‐hand tobacco smoke and active smoking were independent risk factors for CRS (P = 0.001).
Conclusions
Chronic sinusitis is an important public health problem in China. Our study provides important information for the assessment of the economic burden of CRS and the development and promotion of public health policies associated with CRS particularly in developing countries.
The entorhinal cortex (EC) is one of the most vulnerable brain regions that is attacked during the early stage of Alzheimer's disease (AD). Here, we report that the synaptic terminals of pyramidal ...neurons in the EC layer II (ECII
) directly innervate CA1 parvalbumin (PV) neurons (CA1
) and are selectively degenerated in AD mice, which exhibit amyloid-β plaques similar to those observed in AD patients. A loss of ECII
-CA1
synapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECII
using a theta burst paradigm rescues ECII
-CA1
synaptic defects and intercepts the decline in spatial learning and memory. These data reveal a novel mechanism of memory loss in AD mice via the selective degeneration of the ECII
-CA1
pathway.
Previous studies have established the link between aberrant microRNA (miRNA) expression and hypoxia in various neoplasms. However, how these hypoxia-related miRNAs modulate tumor progression is still ...unclear. Therefore, the patterns of miRNA in colorectal carcinoma cell lines in response to hypoxia or not were first screened and the hypoxia-induced repression of the miR-15-16 cluster was confirmed. Then, this repression was found to be associated with high tumor stage and poor prognosis in colorectal carcinoma and is shown to promote tumor angiogenesis and metastasis by the loss of restriction of its target gene, fibroblast growth factor-2 (FGF2). Moreover, the general and alterative promoters of the miR-15-16 host (deleted in lymphocytic leukemia 2, DLEU2) were mapped, and three c-Myc/Max binding sites in response to the hypoxia-induced repression of miR-15-16 were further identified. Finally, an enhanced stability of c-Myc/Max heterodimer promoted by increased hypoxia-inducible factor-2α (HIF-2α) was validated, and we also verified that the enhancement contributed to the hypoxia-induced repression of miR-15-16. In brief, the c-Myc-mediated transcriptional repression of miR-15-16 in hypoxia is induced by increased HIF-2α and promoted tumor angiogenesis and hematogenous metastasis by the further loss of post-transcriptional inhibition of FGF2. Our study provides a better understanding of the coping mechanisms in response to tumor hypoxia and may be helpful in developing an effective prognostic marker or treatment target against solid tumors.
Display omitted
Anion exchange membranes (AEMs) are a crucial constituent for alkaline fuel cells. As the core component of fuel cells, the low performance AEMs restrict the development and ...application of the fuel cells. Herein, the trade-off between the OH– conductivity and dimensional stability was solved by constructing AEMs with adequate OH– conductivity and satisfactory alkali resistance using Tröger’s base (TB) poly (crown ether)s (PCEs) as the main chain, the embedded quaternary ammonium (QA) and Na+-functionalized crown ether units as the cationic group. Crown ether is an electron donator, and can capture Na+ to form Na+-functionalized crown ether units to conveniently transfer OH– and significantly promote the alkaline stability of the AEMs. The influence of the Na+-functionalized crown ether units on the performance of AEMs was studied in detail. The PCEs based AEMs show an obvious hydrophobic-hydrophilic microphase separation. These features make them ideal platforms for the OH– conduction applications. As expected, the as-prepared PCEs-QA-100% (100% is the degree of cross-linking) AEM with an ionic exchange capacity (IEC) of 2.07 meq g−1 has a high OH– conductivity of 159 mS cm−1 at 80 °C. Furthermore, the membrane electrode assemblies fabricated using the PCEs-QA-100% AEM possess a maximum power density of 291 mW cm−2 under the current density of 500 mA cm−2.
Abstract We report the first detection of polarization angle orthogonal jumps, a phenomenon previously only observed from radio pulsars, from a fast radio burst (FRB) source FRB 20201124A. We find ...three cases of orthogonal jumps in over 2000 bursts, all resembling those observed in pulsar single pulses. We propose that the jumps are due to the superposition of two orthogonal emission modes that could only be produced in a highly magnetized plasma, and they are caused by the line of sight sweeping across a rotating magnetosphere. The shortest jump timescale is of the order of 1 millisecond, which hints that the emission modes come from regions smaller than the light cylinder of most pulsars or magnetars. This discovery provides convincing evidence that FRB emission originates from the complex magnetosphere of a magnetar, suggesting an FRB emission mechanism that is analogous to radio pulsars despite a huge luminosity difference between two types of objects.
Summary
The relationship between mycoplasma and ureaplasma infection and male infertility has been studied widely; however, results remain controversial. This meta‐analysis investigated the ...association between genital ureaplasmas (Ureaplasma urealyticum, Ureaplasma parvum) and mycoplasmas (Mycoplasma hominis, Mycoplasma genitalium), and risk of male infertility. Differences in prevalence of ureaplasma and mycoplasma infection between China and the rest of the world were also compared. Study data were collected from PubMed, Embase and the China National Knowledge Infrastructure. Summary odds ratio (OR) with 95% confidence interval (CI) was applied to assess the relationship. Heterogeneity testing and publication bias testing were also performed. A total of 14 studies were used: five case–control studies with 611 infertile cases and 506 controls featuring U. urealyticum infection, and nine case–control studies with 2410 cases and 1223 controls concerning M. hominis infection. Two other infection (U. parvum and M. genitalium) were featured in five and three studies, respectively. The meta‐analysis results indicated that U. parvum and M. genitalium are not associated with male infertility. However, a significant relationship existed between U. urealyticum and M. hominis and male infertility. Comparing the global average with China, a significantly higher positive rate of U. urealyticum, but a significantly lower positive rate of M. hominis, was observed in both the infertile and control groups in China.
Here, in an analysis of a 2.92 fb–1 data sample taken at 3.773 GeV with the BESIII detector operated at the BEPCII collider, we measure the absolute decay branching fractions to be B(D0 → K–e+νe) = ...(3.505 ± 0.014 ± 0.033)% and B(D0 → π–e+νe) = (0.295 ± 0.004 ± 0.003)%. From a study of the differential decay rates we obtain the products of hadronic form factor and the magnitude of the CKM matrix element $f$ $^{K}_{+}$(0)|Vcs| = 0.7172 ± 0.0025 ± 0.0035 and $f$ $^{π}_{+}$(0)|Vcd| = 0.1435 ± 0.0018 ± 0.0009.
Background
The aim of this study was to assess the role of lipolysis of epicardial adipose tissue (EAT) in cardiac function after myocardial infarction (MI).
Methods
We used a rat model of MI with or ...without EAT removal to study the effects of EAT lipolysis on cardiovascular function. Echocardiography and cardiac catheterization were used to determine cardiac function, and infarct size and histopathology specimens were analyzed in postmortem sections. Inflammatory responses were evaluated via flow cytometry and Elisa analyses.
Results
We found that the lipolysis of EAT increased significantly after MI. Removal of the EAT after MI (MI-EAT) improved cardiac function by nearly 10% and decreased the infarct area by 6% when compared with rats retaining EAT after MI (MI+EAT). Furthermore, the removal of EAT reduced the number of CD45-positive leukocytes (50 vs. 34.8%) and increased the ratio of macrophage/leukocytes (56 vs. 75%) in the infarcted heart. Compared with the MI+EAT group, the concentration of tumor necrosis factor-alpha and interleukin 1‑beta were reduced in the MI-EAT group.
Conclusion
Lipolysis of EAT increased significantly after MI. Removal of EAT improved cardiac function, in part, by weakening the inflammatory response.
PDF
