High-β_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the ...Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-β_{θe} regime.
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.
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.
Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and ...field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.
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•Stereo-seq enables large field-of-view spatial transcriptomics at cellular resolution•Stereo-seq reveals the spatial cell-type heterogeneity of mouse embryonic tissues•Stereo-seq maps the spatiotemporal transcriptomic dynamics during mouse organogenesis•Stereo-seq defines the spatiotemporal window of developmental disease vulnerability
Stereo-seq combines DNA nanoball-patterned arrays and tissue RNA capture to achieve large field-of-view spatial transcriptomics at cellular resolution, enabling the dissection of spatial cell-type heterogeneity of mouse embryonic tissues.
Successful closure of wall defects is the key procedure following endoscopic full-thickness resection (EFTR). In this report we describe a new method similar to interrupted suture to repair gastric ...defects by means of endoloops and metallic clips.
We retrospectively analyzed 20 patients who presented at our institute between March 2011 and February 2012 with gastric submucosal tumors and who consequently underwent EFTR, with the resulting large gastric defects being closed using endoloops and metallic clips. Tumor characteristics, en bloc resection rates, and postoperative complications were evaluated in all the patients.
The median age of the 20 patients was 47 years. The mean maximum size of lesions was 1.47 ± 0.72 cm (range 0.4 - 3 cm). All lesions were diagnosed by endoscopic ultrasound as tumors in the muscularis propria layer. The en bloc resection rate was 100 %. Five patients developed fever and complained of slight abdominal pain in the first day after treatment. No patient had severe complications such as peritonitis or abdominal abscess. In all cases, wounds healed after 1 month. We observed the persistence of the clips for over 3 months in 6 out of 19 cases without any clinical manifestations or large injury to the intestine.
Our study provides evidence that the use of metallic clips and endoloops is a relatively safe, easy, and feasible method for repairing gastric defects resulting from EFTR.
Summary
Our study demonstrated a high incidence of recollapse of the augmented vertebrae after PVP treatment for OVCFs. A risk score based on all significant factors can predict the rate of ...recollapse and gain clinical benefits to prevent recollapse in patients at high risk.
Background
Recollapse of the augmented vertebrae after percutaneous vertebroplasty (PVP) treatment for osteoporotic vertebral compression fractures (OVCFs) has obtained much attention. However, little is known about risk factors and score for recollapse of the augmented vertebrae.
Objective
To determine risk factors and furthermore develop a risk score related to recollapse of the augmented vertebrae after PVP treatment for OVCFs.
Methods
Patients who were treated with PVP for single OVCFs and met this study’s inclusion criteria were retrospectively reviewed. The follow-up period was at least 2 years. Associations of recollapse with co-variates (age, gender, bone mass density BMD with a T-score, fracture level, intravertebral cleft IVC, fracture type, cement volume, cement leakage, leakage into a disc, cement distribution pattern, Non-PMMA-endplate-contact NPEC, preoperative fracture severity, reduction rate RR, reduction angle RA) were analyzed and a risk score for recollapse was further developed to predict recollapse.
Results
A total of 152 patients were included. Recollapse group was found in 42 (27.6%) patients. Preoperative IVC, solid lump cement distribution pattern, more RR (a cutoff value of 7%) and larger RA (a cutoff value of 3°) was significantly associated with increased risk for recollapse of the augmented vertebrae. A risk score was developed based on the number of risk factors present in each patient. Patients with a score of 4 had an approximately ninefold increased risk of developing recollapse over patients with a score of 0. The receiver operating characteristic curve of the risk score generated an area under the curve of 0.899 (95% CI 0.642–0.836,
P
= 0.000).
Conclusion
A risk score based on preoperative IVC, cement distribution pattern, reduction rate, and reduction angle predicts the rate of recollapse. Additional studies should aim to validate this score and inspect clinical benefits of recollapse prophylaxis in patients at high risk.
Recurrence/persistence of symptoms occurs in approximately 20 % of patients after Heller myotomy for achalasia. Controversy exists regarding the therapy for patients in whom Heller myotomy has ...failed. The aim of the current study was to evaluate the efficacy and feasibility of peroral endoscopic myotomy (POEM), a new endoscopic myotomy technique, for patients with failed Heller myotomy.
A total of 12 patients with recurrence/persistence of symptoms after Heller myotomy, as diagnosed by established methods and an Eckardt score of ≥ 4, were prospectively included. The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤ 3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM.
All 12 patients underwent successful POEM after a mean of 11.9 years (range 2 - 38 years) from the time of the primary Heller myotomy. No serious complications related to POEM were encountered. During a mean follow-up period of 10.4 months (range 5 - 14 months), treatment success was achieved in 11/12 patients (91.7 %; mean score pre- vs. post-treatment 9.2 vs. 1.3; P < 0.001). Mean LES pressure was 29.4 mmHg pre-treatment and 13.5 mmHg post-treatment (P < 0.001). One patient developed mild reflux symptoms and required intermittent medication with proton pump inhibitors.
POEM seems to be a promising new treatment for failed Heller myotomy resulting in short-term symptom relief in > 90 % of cases. Previous Heller myotomy may make subsequent endoscopic remyotomy more challenging, but does not prevent successful POEM.
A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines ...from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)<|Δm(41)(2) |< 0.3 eV(2) range. The relative spectral distortion due to the disappearance of electron antineutrinos was found to be consistent with that of the three-flavor oscillation model. The derived limits on sin(2) 2θ(14) cover the 10(-3) eV(2) ≲ |Δm(41)(2)| ≲ 0.1 eV(2) region, which was largely unexplored.
Emerging evidence has shown that cancer stem cells (CSCs) are the cellular determinants to promote cancer invasion and metastasis. However, the mechanism underlying CSC invasion remains unknown. ...MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression, and their expressions are often dysregulated in cancers. In the present study, we demonstrated that two functionally related microRNAs, miR-20a and -106a (miR-20a/106a), were capable of enhancing the invasiveness of CD133(+) glioma stem cells (GSCs) isolated from both glioblastoma cell line U87 and primary human glioma specimens. We found that the level of miR-20a/106a in GSCs was significantly higher than that in the committed CD133(-) glioma cells, and correlated with the invasive capability of GSCs. By bioinformatic analysis, we identified tissue inhibitor of metalloproteinases-2 (TIMP-2) as one of the miR-20a/106a-targeted genes. TIMP-2 level correlated inversely with miR-20/106 expression. Directly targeting by miR-20a/106a on 3'-untranslation region (3'-UTR) of TIMP-2 mRNA was confirmed by 3'-UTR dual-luciferase reporter assay. Knockdown of miR-20a/106a in GSCs increased endogenous TIMP-2 protein abundance, thereby inhibiting GSC invasion. We also found that Nordy, a synthetic lipoxygenase inhibitor, inhibited GSC invasiveness by elevating the expression of TIMP-2 via downregulation of miR-20a/106a. Our results indicate that miR-20a/106a has a key role in GSC invasion and may serve as targets for treatment of glioblastoma.
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