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BackgroundPrevious studies have shown that leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine, is associated with obesity and non-alcoholic fatty liver disease (NAFLD). It is well known that hepatokines play important roles in mediating interactions among bone, adipose tissue, and liver. We sought to examine serum LECT2 levels in subjects with osteoporosis (OP) to confirm its association with OP.MethodsFrom March 2019 to March 2020, a total of 96 adult subjects (52 OP patients and 44 controls) visiting the 2nd Spine Department of the Affiliated Hospital of School of Medicine of Ningbo University were recruited. The bone mineral density (BMD) of all subjects were assessed by dual-energy X-ray (DXA). Blood samples were collected for measurements of high-sensitivity C-reactive protein (hs-CRP), plasma glucose (PG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), creatinine and uric acid. Serum LECT2 levels of total 96 participants were measured by enzyme linked immunesorbent assay (ELISA). The relationships between serum LECT2 levels and biomedical parameters were analyzed using the Spearman correlation coefficient.ResultsSerum LECT2 levels in OP patients were significantly higher than that of healthy controls (29.57 ng/mL VS 19.82 ng/mL, P < 0.01). To confirm the role LECT2 played in OP, we found a significantly negative correlation in all subjects between serum levels of LECT2 and lumbar BMD, as well as femoralneck BMD. A significantly positive correlation in all was observed between serum levels of LECT2 and TC, whereas there was a significantly negative correlation between serum levels of LECT2 and creatinine. Meanwhile, serum LECT2 levels were measured to diagnose OP patient by plotting receiver-operating characteristic (ROC) curve, the area under the ROC curve was 0.729(P < 0.01). The optimal cutoff point for LECT2 concentration to diagnose OP patient was 16.44 ng/mL.ConclusionsWe showed that serum LECT2 levels were significantly up-regulated in OP patients, and LECT2 levels were significant positively associated with total cholesterol and negatively associated with creatinine. It could be a potential biomarker for OP diagnosis.

Nanotechnology is associated with the development of particles in the nano-size range that can be used in a wide range of applications in the medical field. It has gained more importance in the pharmaceutical research field particularly in drug delivery, as it results in enhanced therapeutic drug performance, improved drug solubility, targeted drug delivery to the specific sites, minimized side effects, and prolonged drug retention time in the targeted site. To date, the application of nanotechnology continues to offer several benefits in the treatment of various chronic diseases and results in remarkable improvements in treatment outcomes. The use of nano-based delivery systems such as liposomes, micelles, and nanoparticles in pulmonary drug delivery have shown to be a promising strategy in achieving drug deposition and maintained controlled drug release in the lungs. They have been widely used to minimize the risks of drug toxicity in vivo. In this review, recent advances in the application of nano- and micro-based delivery systems in pulmonary drug delivery for the treatment of various pulmonary diseases, such as lung cancer, asthma, and chronic obstructive pulmonary disease, are highlighted. Limitations in the application of these drug delivery systems and some key strategies in improving their formulation properties to overcome challenges encountered in drug delivery are also discussed.

Beyond generating long and topic-coherent paragraphs in traditional captioning tasks, the medical image report composition task poses more task-oriented challenges by requiring both the highly-accurate medical term diagnosis and multiple heterogeneous forms of information including impression and findings. Current methods often generate the most common sentences due to dataset bias for individual case, regardless of whether the sentences properly capture key entities and relationships. Such limitations severely hinder their applicability and generalization capability in medical report composition where the most critical sentences lie in the descriptions of abnormal diseases that are relatively rare. Moreover, some medical terms appearing in one report are often entangled with each other and co-occurred, e.g. symptoms associated with a specific disease. To enforce the semantic consistency of medical terms to be incorporated into the final reports and encourage the sentence generation for rare abnormal descriptions, we propose a novel framework that unifies template retrieval and sentence generation to handle both common and rare abnormality while ensuring the semantic-coherency among the detected medical terms. Specifically, our approach exploits hybrid-knowledge co-reasoning: i) explicit relationships among all abnormal medical terms to induce the visual attention learning and topic representation encoding for better topic-oriented symptoms descriptions; ii) adaptive generation mode that changes between the template retrieval and sentence generation according to a contextual topic encoder. Experimental results on two medical report benchmarks demonstrate the superiority of the proposed framework in terms of both human and metrics evaluation., To appear in IEEE Transactions on Cybernetics 2021. We attempt to resolve the challenging medical report composition task by i) enforcing the semantic consistency of medical terms to be incorporated into the final reports; and ii) encouraging the sentence generation for rare abnormal descriptions

Person re-identification (re-ID) aims at matching a person-of-interest across various non-overlap cameras with distinguished visual appearance variances. Pre-existing research methods mainly employ deep neural models to train large-scale person re-ID datasets, achieving good performance. However, these methods are primarily deployed only on visual data, which can be easily influenced by the environment variances (e.g., viewpoints, poses, and illuminations). In this paper, we propose an adaptive multi-task learning (MTL) scheme for cross domain and modal person re-ID. It can effectively utilize the visual and language information from multiple datasets for improving learning performance. Comprehensive experiments are also conducted on the widely-used person re-ID datasets, i.e., Market-1501 and DukeMTMC-reID, validating the effectiveness of the proposed method. It can model the domain difference and the relationship between the vision and language modalities and achieve state-of-the-art performance. The source code of our proposed method will be available at (https://github.com/emdata-ailab/Multitask_Learning_ReID).

Background Video-assisted thoracic surgery (VATS) has been widely used in the surgical treatment of thoracic diseases, and it suggested surgical and oncological advantages compared with open surgery. However, reports on the application of VATS in surgery of small cell lung cancer (SCLC) are scarce. This study aimed to explore the advantages and disadvantages of different surgical approaches in the treatment of pathological stage T1(pT1) SCLC in terms of safety, clinical outcomes, and lymph node dissection. Patients and Methods Patients who underwent lobectomy for pT1 SCLC between January 2014 and September 2017 were identified from the National Collaborative Lung Cancer Database (LinkDoc Database). The patients were stratified based on the surgery approach (VATS or open lobectomy). Perioperative outcomes and long-term survival were analyzed using SPSS software. Results A total of 169 patients with pT1 SCLC met the criteria and were enrolled for this study, including 110 cases of VATS lobectomies and 59 cases of open lobectomies. VATS lobectomy was associated with less blood loss than open surgery (168.1 ± 237.4 vs. 340.0 ± 509.8 mL, P = .002). Open lobectomy harvested more N2 LNs (11.8 ± 8.2 vs. 8.4 ± 5.8, P = .048) and identified more metastasis positive LNs (3.1 ± 6.0 vs. 1.4 ± 3.0, P = .050). Open lobectomy associated with longer overall survival (OS) but has no statistical difference (23.4 ± 13.2 vs. 20.2 ± 10.9, P = .070). Conclusion Open lobectomy had better lymph node dissection results, and comparable postoperative complications, postoperative hospital stay, and OS to VATS lobectomy. Further studies may still be needed to confirm the recommendation of thoracoscopic approach as a routine surgical procedure for operable SCLC, and until then, open surgery should still be considered.

Background The present study aimed to evaluate the elimination of three common pollutants (dimethoate, benzo(a)pyrene (BaP) and bisphenol A (BPA) by different physical exercises and to assess the possible factors which could affect the pollutants elimination. Methods A total of 200 individuals who chose different kinds of exercises in accordance to their own wish were recruited. The levels of urinary pollutants were measured using β-glucuronidase hydrolysis followed by a high-performance liquid chromatography tandem mass spectrometry-based method. Results Totally, the levels of dimethoate, BaP and BPA were reduced after physical exercises. However, the elimination of BaP in male was higher than that in female but the elimination of BPA in female was higher than that in male. Multivariate logistic regression showed that the degree of heart rate (HR) change was a protective factor affecting the improvement effect of dimethoate, BaP and BPA while BMI (body mass index) was a risk factor. Nevertheless, sex was a risk factor affecting the improvement of dimethoate and BaP but had a lower efficacy on BPA improvement. Conclusion The present findings indicate that physical exercises can be considered as a novel approach to eliminate pollutants level in human body and can also give suggestions for choosing specific physical exercises to male and female individuals. Moreover, those who are with higher BMI need to lose weight before eliminating pollutant level through physical exercises.

The analytic approaches for feedforward neural network, e.g., Radial Basis Function (RBF), have some attractive characteristics, such as superior theoretical properties and faster numerical implementations. However, they still have several drawbacks. The primary defect is that their generation performance and computational complexity are susceptible to the influence of irrelevant hidden variables. Thus, how to alleviate this influence has become a crucial issue for the feedforward neural network. In this paper, we propose an Orthogonal Super Greedy learning (OSGL) method for hidden neurons selection. The OSGL selects more than one hidden neurons from a given network structure in a greedy strategy until an adequate sparse network has been constructed. Theoretical analyses show it can reach the optimal learning rate. Extensive empirical results demonstrate the superiority that the proposed method can produce an excellent generalization performance with a sparse and compact feature representation within feedforward networks.

Surgical resection remains the preferred approach for some patients with glioblastoma (GBM), and eradication of the residual tumour niche after surgical resection is very helpful for prolonging patient survival. However, complete surgical resection of invasive GBM is difficult because of its ambiguous boundary. Herein, a novel targeting material, c(RGDyk)-poloxamer-188, was synthesized by modifying carboxyl-terminated poloxamer-188 with a glioma-targeting cyclopeptide, c(RGDyk). Quantum dots (QDs) as fluorescent probe were encapsulated into the self-assembled c(RGDyk)-poloxamer-188 polymer nanoparticles (NPs) to construct glioma-targeted QDs-c(RGDyk)NP for imaging-guided surgical resection of GBM. QDs-c(RGDyk)NP exhibited a moderate hydrodynamic diameter of 212.4 nm, a negative zeta potential of –10.1 mV and good stability. QDs-c(RGDyk)NP exhibited significantly lower toxicity against PC12 and C6 cells and HUVECs than free QDs. Moreover, in vitro cellular uptake experiments demonstrated that QDs-c(RGDyk)NP specifically targeted C6 cells, making them display strong fluorescence. Combined with ultrasound-targeted microbubble destruction (UTMD), QDs-c(RGDyk)NP specifically accumulated in glioma tissue in orthotropic tumour rats after intravenous administration, evidenced by ex vivo NIR fluorescence imaging of bulk brain and glioma tissue sections. Furthermore, fluorescence imaging with QDs-c(RGDyk)NP guided accurate surgical resection of glioma. Finally, the safety of QDs-c(RGDyk)NP was verified using pathological HE staining. In conclusion, QDs-c(RGDyk)NP may be a potential imaging probe for imaging-guided surgery.

The development of the Internet of Things (IoT) plays an important role in smart health. The combination of IoT and ultrasound has great potential applications in telemedicine. The medical information in the echocardiogram stimulates the image analysis of ultrasound IoT devices. Medical image segmentation is a fundamental step in medical image analysis for providing help to the subsequent tasks. However, accurate left ventricular (LV) segmentation in echocardiography is a challenging task due to the cross-vendor and cross-center, multiview ultrasound image characteristics. We introduce an intermediate supervision deep neural networks method in this article, named as deep atrous pyramid intermediate supervision (DAPIS). The SAD block is used as a fixed feature extractor, pyramid pooling module is used to extract context semantic information, global attention upsampling is used for feature fusion module, and intermediate supervision is used to learn a better semantic representation. The performance of the model is evaluated using two echocardiographic data: 1) public data set (CAMUS) and 2) self-made data set (total 18906 images from 160 patients). Sufficient experiments show that DAPIS is prominent generalization and robustness, surpassing other state-of-the-art methods. The correlation graph and Bland–Altman analysis show good clinical correlation, proving the clinical potential of the model.

This study aimed to investigate left atrium (LA) strain components in the assessment of cardiac function and its clinical correlates in pre-eclampsia (PE). With the use of speckle tracking echocardiography, phasic LA strain and (LASr)/(E/e'), the surrogate of LA compliance, were compared between healthy pregnant women (n = 70) and those with PE (n = 146) and among different diastolic dysfunction (DD) grades in PE. Receiver operating characteristic curves and logistic regression analysis were used to identify the role of strain components in distinguishing DD grades and predicting cardiac complications. LA reservoir strain, conduit strain and LA compliance reduced significantly in PE (p0.01). LASr/(E/e') gradually decreased with worsening DD and LASr/(E/e')3.40 was the independent risk factor for cardiac events in PE (p0.01). This study observed significantly decreased LA strain and compliance in PE. Notably, LA compliance decreased progressively with the severity of DD, and LASr/(E/e')3.40 is the independent risk factor for cardiac complications during PE pregnancy.

Arrays of notched holes were fabricated with shapes that serve to initiate and guide crack formation during electrochemical delithiation of RuO2 films. It is demonstrated that these structures caus...

The mechanistic target of rapamycin complex 1 (mTORC1) acts as a central regulator of metabolic pathways that drive cellular growth. Abnormal activation of mTORC1 occurs at high frequency in human and mouse hepatocellular carcinoma (HCC). DEP domain-containing protein 5 (DEPDC5), a component of GATOR1 complex, is a repressor of amino acid-sensing branch of the mTORC1 pathway. In the current study, we found that persistent activation of hepatic mTORC1 signaling caused by Depdc5 ablation was sufficient to induce a pathological program of liver damage, inflammation and fibrosis that triggers spontaneous HCC development. Take advantage of the combinatory treatment with a single dose of diethylnitrosamine (DEN) and chronic feeding with high-fat diet (HFD), we demonstrated that hepatic depdc5 deletion did not aggravate DEN&HFD induced liver tumorigenesis, probably due to its protective effects on diet-induced liver steatosis. In addition, we further showed that chronic rapamycin treatment did not have any apparent tumor-suppressing effects on DEN&HFD treated control mice, whereas it dramatically reduced the tumor burden in mice with hepatic Depdc5 ablation. This study provides the novel in vivo evidence for Depdc5 deletion mediated mTORC1 hyperactivation in liver tumorigenesis caused by aging or DEN&HFD treatment. Moreover, our findings also propose that pharmacological inhibition of mTORC1 signaling maybe a promising strategy to treat HCC patients with mutations in DEPDC5 gene.

Background Tracheal tumors are rare. The aim of this case series was to investigate airway selection during radical surgery for patients with tracheal tumors. Methods Here, we performed a retrospective case review of patients with tracheal tumors who underwent tracheal surgery in our center. A total of 37 cases, including 26 patients with primary tracheal tumors and 11 cases with advanced thyroid cancer, were enrolled into the study. Baseline characteristics and differential prognosis of included patients were estimated. We summarize the strategies for intraoperative airway selection and analyze the risk factors associated with delayed extubation. Results There is a trend for primary tracheal tumors to appear toward the upper (9 of 26) and middle third (9 of 26) of the trachea, followed by the lower third airway (8 of 26). Advanced thyroid cancers occur most frequently in the upper trachea (7 of 11) and then the middle trachea (4 of 11). All primary and secondary patients underwent R0 resection. Minor histological subtypes were found to correlate with a poor prognosis. Extracorporeal support and tracheotomy intubation were applied in high‐risk cases, and a total of 32 patients achieved intrathoracic intubation during the surgical process. Intensive care unit (ICU) delay (>1 day) was observed among 25 patients, which were not enriched in cases who underwent cross‐field endotracheal intubation. Additionally, temporal suboptimal oxygenation (SpO2, We reviewed 37 patients with tracheal tumors in our center and summarized the tumoral features, anesthetic considerations, and airway management during tracheal surgery. This study indicated a favorable curative effect of tracheal tumors is achievable and suggests the safety of personalized intraoperative intubation.

Presently Si-based field-effect transistors (FETs) are approaching their physical limit, and further scaling their gate length down to the sub-10 nm region is becoming extremely difficult. Benefitting from the atomic-scale thickness and dangling-bond-free flat surface, two-dimensional semiconductors (2DSCs) have good electrostatics and carrier transportability. The FETs based on the 2DSC channel have the potential to scale the FETs’ gate length down to the sub-10 nm region while avoiding apparent degradation of the device performance. In this review, we introduce the recent experimental and ab initio quantum transport simulation progress in the 2D FETs with a gate length less than 10 nm. Remarkably, in the extremely optimistic condition, many 2D FETs (i.e phosphorene, silicane, arsenene, tellurene, WSe2, InSe, Bi2O2Se, GeSe, etc.) show excellent device performance for the high performance and/or low power applications and indeed can extend Moore’s law down to 1 ∼ 2-nm gate length in terms of the ab initio quantum transport simulation. The sub-10 nm 2D tunneling FETs are predicted to generally have smaller energy-delay products compared with the 2D metal–oxide–semiconductor FETs and appear more competitive for the low power application. The carrier effective mass plays a key role in determining the device performance. Via negative capacitance techniques, the device performance can be further improved. Finally, we outline the challenges and outlook on the future development directions in the sub-10 nm 2D FETs.

This paper presents an efficient hybrid method consisting of Lorentz reciprocity theorem, finite-difference-time-domain (FDTD) method, thin wire model, transmission line (TL) equations and transfer impedance model, which can be utilized to analyze the system-level transient responses of the microstrip antenna system with antenna, metallic enclosures, braided shielded cable, and lumped element, when illuminated by an external electromagnetic pulse (EMP). In order to avoid over-fine mesh generation and repeated modeling of the antenna in multiple simulations, Lorentz reciprocity theorem is employed to extract an equivalent source model of antenna coupling, thereby improving the computational efficiency. Then, the transfer impedance model and thin wire model are incorporated into the FDTD-TL method efficiently to deal with the back-door coupling through the shielding layer of feeding coaxial cable. Finally, the hybrid FDTD method combined with the extracted equivalent source of antenna coupling is utilized to solve the coupling responses of the whole antenna system. The results of numerical simulation are verified by comparing with the simulation results of CST CS. Then, considering the influence of different incident conditions of external EMP, the characteristics of the coupling response of the system are analyzed. The obtained coupling response information demonstrate that the proposed method is available for further designing electromagnetic protection of the inner circuits of the microstrip antenna system against the impact of external EMP.

Rationale: Both genetic and environmental factors contribute to lung cancer, but the degree to which air pollution modifies the impact of genetic susceptibility on lung cancer remains unknown. Objectives: To investigate whether air pollution and genetic factors jointly contribute to incident lung cancer. Methods: We analyzed data from 455,974 participants (53% women) without previous cancer at baseline in the UK Biobank. The concentrations of particulate matter (PM) (PM ⩽2.5 μm in aerodynamic diameter [PM2.5], coarse PM between 2.5 μm and 10 μm in aerodynamic diameter [PMcoarse], and PM ⩽10 μm in aerodynamic diameter [PM10]), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated by using land-use regression models, and the association between air pollutants and incident lung cancer was investigated by using a Cox proportional hazard model. Furthermore, we constructed a polygenic risk score and evaluated whether air pollutants modified the effect of genetic susceptibility on the development of lung cancer. Measurements and Main Results: The results showed significant associations between the risk of lung cancer and PM2.5 (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.33-2.01; per 5 μg/m3), PM10 (HR, 1.53; 95% CI, 1.20-1.96; per 10 μg/m3), NO2 (HR, 1.10; 95% CI, 1.05-1.15; per 10 μg/m3), and NOx (HR, 1.13; 95% CI, 1.07-1.18; per 20 μg/m3). There were additive interactions between air pollutants and the genetic risk. Compared with participants with low genetic risk and low air pollution exposure, those with high air pollution exposure and high genetic risk had the highest risk of lung cancer (PM2.5: HR, 1.71; 95% CI, 1.45-2.02; PM10: HR, 1.77; 95% CI, 1.50-2.10; NO2: HR, 1.77; 95% CI, 1.42-2.22; NOx: HR, 1.67; 95% CI, 1.43-1.95). Conclusions: Long-term exposure to air pollution may increase the risk of lung cancer, especially in those with high genetic risk.

Cong Wang,1,&ast; Wen-lin Xu,1,&ast; Guan-wu Li,2 Cong Fu,1 Jin-jin Li,1 Jing Wang,1 Xin-yu Chen,3 Zhen Liu,1 Yun-fei Chen1 1Department of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Radiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Acupuncture and Tuina Academy, Beijing University of Chinese Medicine Dongfang College, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun-fei Chen; Zhen LiuDepartment of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of ChinaTel/Fax +86-21-65162628Email icyf1968@163.com; liuzhen8918@163.comStudy Objectives: To evaluate the efficacy and safety of acupuncture at HT 7 (Shenmen) and KI 7 (Fuliu) on sleep and comorbid symptoms for chronic insomnia.Methods and Design: A randomized, single-blind, parallel and sham-controlled trial consisted of an acupuncture group (n = 41) and a sham acupuncture group (n = 41). Setting: a tertiary hospital of integrated Chinese and Western medicine. Participants: 82 subjects with chronic insomnia based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Interventions: a 10-session acupuncture treatment at bilateral HT 7 and KI 7 or sham acupoints with shallow needling was performed over 3 weeks. Measurements: the Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI) were evaluated at baseline, posttreatment, and at two follow-ups as the primary outcome measures. Polysomnography (PSG) on two consecutive nights, the Beck anxiety inventory (BAI), the Beck depression inventory (BDI) fatigue severity scale (FSS) and the Epworth sleepiness scale (ESS) were evaluated at baseline and posttreatment as the secondary outcome measures.Results: After the treatments, PSQI scores decreased by 5.04 in the acupuncture group and 2.92 in the sham acupuncture group. ISI scores decreased by 7.65 in the acupuncture group and 5.05 in the sham acupuncture group. The between-group differences in the primary outcome measures posttreatment were statistically significant. However, no differences were found between the two groups during the two follow-ups. Regarding the PSG data, there were significantly lower levels of sleep onset latency (SOL), a lower percentage of sleep stage N1 and a higher percentage of sleep stage N3 in the acupuncture group than in the sham acupuncture group. After treatment, there were lower levels of comorbid symptoms (BAI, BDI, FSS and ESS) in both groups. However, no significant differences were observed between the groups.Conclusion: Acupuncture at HT 7 and KI 7 is an effective and safe nonpharmacologic intervention option for chronic insomnia.Clinical Trial Registration: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR1900023787, China.Keywords: acupuncture, chronic insomnia, sleep and comorbid symptoms, randomized clinical trial

A coal mine in Datong is an integrated mine. At present, there is goaf in the upper and lower part of the mining coal seam. There is a lot of ponding in the goaf, which has great potential safety hazards for production. In order to find out the scope and location of ponding in goaf, the comprehensive geophysical exploration method combining transient electromagnetic method and high-density resistivity method is used to carry out the research. Firstly, the time-base, turn-off time, receiving delay, current, superposition times, and other parameters of the instrument are tested on the surface of known goaf to obtain the best instrument parameters, and the parameters are used to verify the feasibility of the research scheme; then, the transient electromagnetic method is used for large-area exploration on the surface of the mine, the suspected goaf ponding area is found through comprehensive analysis, and the high-density resistivity exploration is arranged in the suspected goaf ponding area. According to the obtained results, the scope and location of the goaf ponding area are accurately located through comprehensive analysis. The results show that there are two goaf ponding areas in the exploration area, which are located above the 8# coal seam currently mined; the range and location of goaf ponding area can be accurately obtained by using the comprehensive geophysical method of high-density electrical method and transient electromagnetic method. This method can provide reference for mine water prevention and control in Datong area and has great practical significance to ensure coal mine safety production.

Chronic inflammation has been associated with the development of lung cancer. In this study, we examined the association between C-reactive protein (CRP) and lung cancer in a prospective cohort study and used Mendelian randomization (MR) to clarify the causality. We included 420 977 participants from the UK Biobank (UKB) in the analyses; 1892 thereof were diagnosed with lung cancer during the follow-up. Hazards ratios (HRs) of CRP concentrations were estimated by Cox proportional hazard models and two approaches of MR analysis were performed. Besides, we added CRP concentrations to epidemiological model of lung cancer to evaluate its prediagnostic role through time-dependent receiver operating characteristic curve analysis. Elevated CRP levels were associated with a 22% increased lung cancer risk per 1 SD increase (HR = 1.22, 95% confidence interval [CI] = 1.18-1.26). Positive associations were observed in small cell lung cancer (HR = 1.21, 95% CI = 1.10-1.33), lung adenocarcinoma (HR = 1.17, 95% CI = 1.11-1.23) and lung squamous cell carcinoma (HR = 1.22, 95% CI = 1.14-1.31). No genetical association of circulating CRP levels and lung cancer risk was observed in MR analysis. When added to a risk model of lung cancer, CRP improved the performance of model as long as 8 years among current smokers (basic model: C-statistic = 0.78 [95% CI = 0.75-0.80]; CRP model: C-statistic = 0.79 [95% CI = 0.76-0.81]; Pnonadjusted = .003, Padjusted = .014). Our results did not support the causal association of circulating CRP with lung cancer risk. However, circulating CRP could be a prediagnostic marker of lung cancer as long as 8 years in advance for current smokers.

To derive and validate a prediction score for cardiovascular disease (CVD) risk in hemodialysis patients in China. Three hundred and eighty-eight patients with regular hemodialysis for more than 3 months were recruited from January 1, 2015 to September 30, 2019 and followed up till May 31, 2020. We derived a prediction score using all participants as a training data set and validated using a bootstrap validation data set. Discriminatory ability of the prediction score was assessed by the area under the receiver operating characteristic curve (AUC). Of 388 patients without CVD at baseline, 132 developed first CVD events during an average follow-up of 3.27 (inter-quartile range = 3.08) years. Of 26 clinical parameters, age, hypertension, diabetes and abnormal white blood cell (WBC) count were identified as significant predictors and included in the prediction model. Compared to those without any of these risk factors, those with one, two, and three to four points showed increased risks of CVD, with the adjusted hazards ratio and 95% confidence interval (CI) being 3.29 (1.17–9.26), 7.42 (2.68–20.51) and 15.43 (5.44–43.75), respectively. The score showed satisfactory discriminatory ability in both training and validation data set (AUC = 0.7025, 95% CI 0.6520–0.7530, and 0.6876, 95% CI 0.6553–0.7200, respectively). We derived and validated a prediction score for CVD risk in hemodialysis patients in China. Given there is a rapid increase in the number of hemodialysis patients, this simple point score can be used to identify high-risk individuals in clinical practice for more precise and efficient personalized treatment.

Dysbiosis of the gastric microbiome is involved in the development of gastric cancer (GC). A number of studies have demonstrated an increase in the relative abundance of Lactobacillus in GC. In this review, we present data that support the overgrowth of Lactobacillus in GC from studies on molecular and bacterial culture of the gastric microbiome, discuss the heterogenic effects of Lactobacillus on the health of human stomach, and explore the potential roles of the overgrowth of Lactobacillus in gastric carcinogenesis. Further studies are required to examine the association between Lactobacillus and GC at strain and species levels, which would facilitate to elucidate its role in the carcinogenic process.

Summary Background Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. Methods In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18–70 years, had histopathogically confirmed stage II–IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov , NCT02448797 . Findings Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6–36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4–not reached) in the icotinib group and 22·1 months (16·8–30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24–0·55]; p Interpretation Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Funding Betta Pharmaceuticals Translation For the Chinese translation of the abstract see Supplementary Materials section.

Different from the condition rating system for bridges, the criticality and vulnerability rating system for long-span suspension bridges is used to determine the time intervals for routine general ...

The aim of this paper is to develop 10-year cardiovascular disease (CVD) risk prediction models for the contemporary Chinese populations based on the Guangzhou Biobank Cohort Study (GBCS) and to compare its performance with models based on Framingham’s general cardiovascular risk profile and the Prediction for Atherosclerotic CVD Risk in China (China-PAR) project. Subjects were randomly classified into the training (n = 15,000) and validation (n = 12,721) sets. During an average of 12.0 years’ follow-up, 3,732 CVD events occurred. A 10-year sex-specific CVD risk prediction model including age, systolic blood pressure, use of antihypertensive medication, smoking, and diabetes was developed. Compared with the Framingham and China-PAR models, the GBCS model had a better discrimination in both women (c-statistic 0.72, 95% CI 0.71–0.73) and men (c-statistic 0.68, 95% CI 0.67–0.70), and the risk predicted was closer to the actual risk. This prediction model would be useful for identifying individuals at higher risks of CVD in contemporary Chinese populations.

Deep learning (DL) has been applied for automatic left ventricle (LV) ejection fraction (EF) measurement, but the diagnostic performance was rarely evaluated for various phenotypes of heart disease. This study aims to evaluate a new DL algorithm for automated LVEF measurement using two-dimensional echocardiography (2DE) images collected from three centers. The impact of three ultrasound machines and three phenotypes of heart diseases on the automatic LVEF measurement was evaluated. Using 36890 frames of 2DE from 340 patients, we developed a DL algorithm based on U-Net (DPS-Net) and the biplane Simpson's method was applied for LVEF calculation. Results showed a high performance in LV segmentation and LVEF measurement across phenotypes and echo systems by using DPS-Net. Good performance was obtained for LV segmentation when DPS-Net was tested on the CAMUS data set (Dice coefficient of 0.932 and 0.928 for ED and ES). Better performance of LV segmentation in study-wise evaluation was observed by comparing the DPS-Net v2 to the EchoNet-dynamic algorithm (

Whether fish consumption is associated with all-cause, cardiovascular (CVD), ischemic heart disease (IHD) and stroke mortality remains inconclusive. We examined the association of fish consumption with all-cause, cardiovascular (CVD), ischemic heart disease (IHD) and stroke mortality in older men and women in south China. A total of 18,215 participants including men and women without CVD at baseline (2003–2006) from Guangzhou Biobank Cohort Study (GBCS) were included and followed up till December 2017. Deaths were identified through record linkage with the Death Registry. Information on fish consumption was obtained using a food frequency questionnaire. During an average follow-up of 11.4 (standard deviation = 2.1) years, 2,697 deaths occurred, including 917 total CVD, 397 IHD and 374 stroke deaths. After adjusting for potential confounders, compared with fish consumption of 0–3 servings/week (i.e., 0–21 g/day, one serving = 50 g), consumption of 4–6 servings/week (29–43 g/day) showed significantly lower risks of all-cause and CVD mortality (hazards ratio (HR) and 95% confidence interval (CI): 0.85 (0.76, 0.95) and 0.77 (0.64, 0.93), respectively), but the reduced risk of IHD mortality (HR (95% CI): 0.80 (0.60, 1.07)) was not significant. Consumption of 7–10 servings/week or higher showed no association with all-cause, CVD, IHD, and stroke mortality. Moderate fish consumption of 4–6 servings/week (29–43 g/day) was associated with lower all-cause and CVD mortality risk. Our findings support the current general advice on regular fish consumption also in middle-aged and older adults.

Single-walled carbon nanotubes (CNTs) have been considered as a promising semiconductor to construct transistors and integrated circuits in the future owing to their ultrathin channel thickness and ultrahigh injection velocity. Although a 5 nm gate-length CNT field-effect transistor (FET) has already been experimentally fabricated and demonstrates excellent device performance, the potential or constraint factors on performance have not been explored or revealed. Based on the benchmark of the device performance between the experimental and simulated 5 nm gate-length CNT FETs, we use the first-principles quantum transport approach to explore the performance limit of CNT FETs based on the gate-all-around (GAA) device geometry for the first time. It is found that the GAA CNT FETs can fulfill the ITRS 2028 high-performance target in the 2 nm gate-length node in terms of the on-state current, delay time, and power consumption. We also find that the energy-delay product of the CNT FETs is superior to those of the high-performance 2D materials and Si Fin FETs at the sub-5 nm gate length due to its unique electrical property. Though theoretically the gate length of CNT FETs can be potentially scaled to 2 nm, considering the tradeoff between the performance and power consumption, 5 nm is the ultimate scaled limit.

A design approach is presented based on insights into power division among modes for a dual‐band filtering power divider using a single multimode resonator. The relationship between the energy of the input port under different modes and the corresponding external quality factor (Qe) is analysed. Then, the power distribution among the in‐band modes and between output ports can be all expressed by Qe. Therefore, the synthesis of a coupling matrix to achieve independent power distribution in the two bands is simplified. For further verification, a quad‐mode dielectric resonator with independently controllable modes is designed. Based on this, dual‐band filtering power dividers with equal and unequal power split ratios (1:1 in the lower band and 2:1 in the higher band) are simulated and implemented. The simulation and measurement agree, proving the correctness of the approach.

Coal gasification, recognized as one of the most effective coal utilization technologies, will produce a certain amount of fine ash during the high-temperature reaction process. The wettability of gasification fine ash is a critical parameter to characterize the degree of high-temperature reaction and determine the separation efficiency of purification process. In the present work, the effect of physicochemical properties on the wetting behavior of different gasification fine ash is studied. The difference in wettability between particle size and types can be explained by the unique properties of particles (i.e. pore structure, mineral composition, and chemical structure). The results show that with the decrease in particle size, the surface morphology transforms from an irregular shape with a rough surface to a spherical shape with a smooth surface. The pore structure, characterized by fractal surface dimension Ds, presents positive correlations with the contact angle for a single type of fine ash. The mineral composition can just qualitatively assess the hydrophilicity of particles. Only the ratio of hydrophilic chemical structure can be used as a generic parameter to describe the wetting performance. Meanwhile, the wettability of hydrophilic particles can be enhanced by increasing moisture content, but there is no significant effect of moisture content on the wettability of hydrophobic particles.

Background /Objective: In recent years, prostheses have been widely used for limb reconstruction after pelvic tumour resection. However, prostheses are associated with problems leading to tumour recurrence, poor implant matching, defects after tumour resection, and easy implant looseness or failure. To achieve a precise preoperative design, complete tumour resection, and better anatomical structure matching and prosthesis stability, this study used three-dimensionally (3D)-printed osteotomy guides and personalised prostheses for reconstruction after pelvic tumour resection. This study aimed to explore the early clinical efficacy of 3D printed personalised prostheses for the reconstruction of bone defects after pelvic tumour resection. Methods A total of 20 patients (12 males, 8 females) with pelvic tumours surgically treated at our hospital between October 2014 and October 2019 were selected. There were 10 cases each of giant cell bone tumours and osteochondrosarcomas. According to Enneking zoning, there were 11 and 9 cases with tumours located in zones I and II, respectively. All cases were equally divided into conventional and 3D printing groups. For repair and reconstruction, a nail rod system or a steel plate was used in the conventional group while individualised 3D-printed prostheses were used in the 3D printing group. The surgical incision, duration of surgery, intraoperative blood loss, and the negative rate of resection margins in postoperative tumour specimens were examined. The follow-up focused on tumour recurrence, complications, and the Musculoskeletal Tumor Society (MSTS) score. Results All cases were followed-up for 6–24 months. The average incision length, duration of surgery, amount of intraoperative blood loss, and MSTS score of the 3D printing group were 10.0 ± 3.1 cm, 115.2 ± 25.3 min, 213.2 ± 104.6 mL, 23.8 ± 1.3, respectively, and those of the conventional group were 19.8 ± 8.4 cm, 156.8 ± 61.4 min, 361.4 ± 164.2 mL, and 18.3 ± 1.4, respectively. Histological tumour specimen examination showed nine and three cases with negative resection margins in the 3D printing group and the conventional group, respectively. The abovementioned indicators were significantly different between both groups (P Conclusion Applying 3D printed surgical guides and personalised prostheses for pelvic tumour resection, repair, and reconstruction, as well as preoperative planning and design, enables more accurate tumour resections and better prosthesis-patient matchings, possibly reducing surgical trauma, shortening the duration of surgery, and promoting the functional recovery of patients postoperatively. The Translation Potential of this Article Contrary to existing studies on 3D printed personalised prostheses, this study reports the clinical efficacy of the aforementioned technology in treating bone defects in a series of patients who underwent pelvic tumour resection. Moreover, it presents a comprehensive comparison of this technology with conventional procedures, thus strengthening its importance in treatment regimens for reconstructing bone defects.

Background Despite recent improvements in treatment technologies, such as surgical resection and chemoradiotherapy, the prognosis of patients with esophagogastric junction adenocarcinoma (EJA) remains poor due to early lymph node metastasis. Since few studies have investigated genes associated with lymph node metastasis in EJA, we aimed to screen lymph node metastasis‐associated genes and clarify their expression status and prognostic significance in EJA. Methods The differential frequency of mutations between carcinoma and para‐carcinoma tissues from 199 cases with EJA was detected using targeted next‐generation sequencing (tNGS). Following a stratified analysis to determine that gender has no effect on the frequency of gene mutations, lymph node metastasis‐related genes, including CDK6, MET, NOTCH1, and LRP1B, were screened, and CDK6 and LRP1B were selected for further study as they displayed significant differences in mutation rates. Differences in their expression status were verified using immunohistochemical (IHC) staining in 18 CDK6‐ and 17 LRP1B‐mutated samples and a randomly matched control group. Results tNGS revealed that CDK6 and LRP1B mutation frequencies were significantly different between EJA cases with (N ≥ 1) or without (N = 0) lymph node metastasis. In particular, CDK6 mutation frequency was expected less, whereas that of LRP1B was remarkably higher in cases with stage N0 than in those with stage N ≥ 1. IHC staining confirmed significant differences in CDK6 and LRP1B expression status between the study and control cohorts. Chi‐square tests revealed that a high CDK6 expression status correlated significantly with smoking history (p = 0.044), T stage (p = 0.035), N stage (p = 0.000), and advanced TNM stage (p = 0.001) in EJA, whereas a high LRP1B expression status only correlated with BMI (p = 0.013) and N stage (p = 0.000). Furthermore, as confirmed by survival status investigation, a high LRP1B expression status predicted good prognosis, and a high CDK6 expression status was an independent predictor of poor prognosis in patients with EJA. Conclusions Taken together, the findings of this study demonstrate that a high CDK6 and LRP1B expression status promotes and inhibits lymph node metastasis in patients with EJA, respectively, suggesting that both CDK6 and LRP1B are significantly potential predictors of lymph node metastasis and prognosis in EJA., Screening of lymph node metastasis‐related genes by targeted next‐generation sequencing in of esophagogastric junction adenocarcinoma. CDK6 and LRP1B were selected for further study to clarify their expression and prognostic significance in AEG.

The development of next-generation wireless communication technology requires integrated radiofrequency devices capable of operating at frequencies greater than 90 GHz. Carbon nanotube field-effect transistors are promising for such applications, but key performance metrics, including operating frequency, at present fall below theoretical predictions. Here we report radiofrequency transistors based on high-purity carbon nanotube arrays that are fabricated using a double-dispersion sorting and binary liquid interface aligning process. The nanotube arrays exhibit a density of approximately 120 nanotubes per micrometre, a maximum carrier mobility of 1,580 cm2 V−1 s−1 and a saturation velocity of up to 3.0 × 107 cm s−1. The resulting field-effect transistors offer high d.c. performance (on-state current of 1.92 mA µm−1 and peak transconductance of 1.40 mS μm−1 at a bias of −0.9 V) for operation at millimetre-wave and terahertz frequencies. Transistors with a 50 nm gate length show current-gain and power-gain cutoff frequencies of up to 540 and 306 GHz, respectively, and radiofrequency amplifiers can exhibit a high power gain (23.2 dB) and inherent linearity (31.2 dBm output power of the third-order intercept point) in the K-band (18 GHz). Transistors based on arrays of aligned carbon nanotubes can exhibit cutoff frequencies of up to 540 GHz, and could be further scaled for operation at millimetre-wave and terahertz frequencies.

Following a decision to require label warnings for concurrent use of opioids and benzodiazepines and increased risk of respiratory depression and death, the US Food and Drug Administratioin (FDA) recognized that other sedative psychotropic drugs may be substituted for benzodiazepines and be used concurrently with opioids. In some cases, data on the ability of these alternatives to depress respiration alone or in conjunction with an opioid are lacking. A nonclinical in vivo model was developed that could detect worsening respiratory depression when a benzodiazepine (diazepam) was used in combination with an opioid (oxycodone) compared to the opioid alone based on an increased arterial partial pressure of carbon dioxide (pCO2). The current study used that model to assess the impact on respiration of non‐benzodiazepine sedative psychotropic drugs representative of different drug classes (clozapine, quetiapine, risperidone, zolpidem, trazodone, carisoprodol, cyclobenzaprine, mirtazapine, topiramate, paroxetine, duloxetine, ramelteon, and suvorexant) administered alone and with oxycodone. At clinically relevant exposures, paroxetine, trazodone, and quetiapine given with oxycodone significantly increased pCO2 above the oxycodone effect. Analyses indicated that most pCO2 interaction effects were due to pharmacokinetic interactions resulting in increased oxycodone exposure. Increased pCO2 recorded with oxycodone‐paroxetine co‐administration exceeded expected effects from only drug exposure suggesting another mechanism for the increased pharmacodynamic response. This study identified drug‐drug interaction effects depressing respiration in an animal model when quetiapine or paroxetine were co‐administered with oxycodone. Clinical pharmacodynamic drug interaction studies are being conducted with these drugs to assess translatability of these findings.

Introduction Surgical treatment for hepatic cystic ehinococcosis (CE) is not standardized in Kashi Prefecture. Previous evidence identified effectiveness of a clinical pathway in the field of liver surgery. However, proof of a clinical pathway program, especially for CE patients, is lacking. This study aimed to assess the validity of a clinical pathway for hepatic CE surgery performed on patients from Kashi Prefecture. Methods A clinical pathway was developed and implemented by a multidisciplinary team for patients undergoing hepatic CE surgery. Two groups were formed from patients undergoing hepatic CE surgery during a defined period before and after implementing a clinical pathway. Additionally, a propensity score matching analysis was performed. Results In the overall analysis (n = 258) as well as the matched analysis (n = 166), after implementing the clinical pathway, hospital stay was significantly reduced from 13 to 10 days and from 14 to 10 days, respectively (P

Summary Background & aims Sarcopenia is characterized by loss of skeletal muscle mass and associated with poor postoperative outcomes. This study aimed to investigate the prognostic value of preoperative albumin-globulin score (AGS), skeletal muscle index (SMI) as well as their combination in patients with intrahepatic cholangiocarcinoma (ICC) treated with surgical resection. Methods A total of 613 newly diagnosed ICC patients from two centers were retrospectively analyzed (460 in discovery cohort and 153 in validation cohort). The plain computed tomography images were used to measure SMI. The effect of AGS, SMI and CAS grade on clinicopathological characteristics and long-term outcomes of patients with ICC were analyzed. Results The SMI was significantly greater in males than in females. Patients with decreased AGS, increased SMI were associated with improved overall survival (OS) and recurrence-free survival (RFS). Stratefied by CAS grade, 68 (14.8%) patients in grade 1 were associated with increased body mass index (BMI) and best postoperative prognosis, whereas 194 (42.1%) patients in grade 3 were linked to worst OS and RFS. The CAS grade showed a promising accuracy in predicting OS and RFS of ICC patients (area under curves [AUCs] were 0.732 and 0.768). Multiple tumors, MVI and elevated CAS grades were identified as independent risk factors for OS and RFS of ICC patients. These results were confirmed by validation cohort. Conclusion The present study provided compelling evidence that a novel index based on combination of preoperative AGS and SMI was closely related to postoperative long-term outcomes for surgically treated ICC patients. Preoperative evaluation of CAS grade may be useful for risk classification and clinical therapeutic decision-making for ICC patients.

Background This study aimed to investigate the prognostic impact of parenchyma-sparing hepatectomy (PSH) on solitary small intrahepatic cholangiocarcinoma (ICC). Methods A total of 184 patients with solitary small ICC (≤ 5 cm) from 2009 to 2017 were included. Short- and long-term outcomes were compared between PSH and Non-PSH approach. Results 95 (51.6%) patients underwent PSH and 89 (48.4%) patients underwent Non-PSH for solitary small ICC. PSH was associated with less intraoperative blood loss (212.9 mL versus 363.5 mL, P=0.038), lower transfusion rate (7.4% versus 16.9%, P=0.048), without increasing the frequency of tumor recurrence (60.0% versus 58.4%). No significant differences were observed in overall survival (OS), recurrence-free survival (RFS) and liver RFS (P = 0.627, 0.769 and 0.538, respectively). 109 (59.2%) patients experienced recurrence, of these, 67 (36.4%) were intrahepatic recurrence. Subgroup analysis of patients with liver-only recurrence demonstrated an increased likelihood of repeat hepatectomy for PSH compared to Non-PSH (21.2% versus 2.9%, P = 0.031), thus resulting in improved liver OS (P = 0.016). Conclusion PSH was associated with improved perioperative outcomes but it did not increase liver recurrence rates. PSH offered an increased rate of salvage hepatectomy for recurrent tumor, thus improving long-term survival in cases in which liver recurrence occurred.

Interdigital electrochemical energy storage (EES) device features small size, high integration, and efficient ion transport, which is an ideal candidate for powering integrated microelectronic systems. However, traditional manufacturing techniques have limited capability in fabricating the microdevices with complex microstructure. Three-dimensional (3D) printing, as an emerging advanced manufacturing technology in rapid prototyping of 3D microstructures, can fabricate interdigital EES devices with highly controllable structure. The integration of 3D printing and interdigital devices provides great advantages in electrochemical energy storage. In this review, we discuss the common 3D printing techniques for interdigital EES devices fabrication, then the corresponding material requirements are also introduced. Recent significant research progress made in 3D-printed interdigital electrodes of batteries and supercapacitors are highlighted. Finally, to facilitate further development of 3D-printed interdigital EES devices, relevant challenges are summarized and some prospects are also proposed.

Objectives Friedreich ataxia (FRDA) is a rare disorder with progressive neurodegeneration and cardiomyopathy. Luvadaxistat (also known as TAK‐831; NBI‐1065844), an inhibitor of the enzyme d‐amino acid oxidase, has demonstrated beneficial effects in preclinical models relevant to FRDA. This phase 2, randomized, double‐blind, placebo‐controlled, parallel‐arm study evaluated the efficacy and safety of oral luvadaxistat in adults with FRDA. Methods Adult patients with FRDA were randomized 2:1:2 to placebo, luvadaxistat 75 mg twice daily (BID), or luvadaxistat 300 mg BID for 12 weeks. The primary endpoint changed from baseline at week 12 on the inverse of the time to complete the nine‐hole peg test (9‐HPT−1), a performance‐based measure of the function of the upper extremities and manual dexterity. Comparisons between luvadaxistat and placebo were made using a mixed model for repeated measures. Results Of 67 randomized patients, 63 (94%) completed the study. For the primary endpoint, there was no statistically significant difference in change from baseline on the 9‐HPT−1 (seconds−1) at week 12 between placebo (0.00029) and luvadaxistat 75 mg BID (−0.00031) or luvadaxistat 300 mg BID (−0.00059); least squares mean differences versus placebo (standard error) were −0.00054 (0.000746) for the 75 mg dose and −0.00069 (0.000616) for the 300 mg dose. Luvadaxistat was safe and well tolerated; the majority of reported adverse events were mild in intensity. Interpretation Luvadaxistat was safe and well tolerated in this cohort of adults with FRDA; however, it did not demonstrate efficacy as a treatment for this condition.

Acute graft-versus-host disease (aGVHD) is the most severe complication and the major cause of morbidity and mortality in patients who have received hematopoietic stem cell transplantation. Inflammation mediated by donor T cells and neighboring recipient cells is considered to be responsible for intestinal aGVHD. Interleukin (IL)-17A-producing γδT (γδT17) cells have been investigated as key players in cancer, immunity, and inflammatory responses because of their phenotypic plasticity, memory-like activity, and unique migratory features. However, the precise roles and underlying mechanisms of γδT17 cells in aGVHD immunopathogenesis remain elusive. Here, we found that γδT17 cells constituted the major resident γδT population in the intestinal lamina propria of aGVHD mice. Adoptive infusion of induced γδT17 cells markedly attenuated murine aGVHD and increased infiltration of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) into the inflammatory intestine, and did not affect graft-versus-leukemia(GVL) effect. Further experiments indicated that γδT17 cells enhanced both migration ability and immunosuppressive activity of MDSCs. γδT17 cell-mediated protection in aGVHD was blunted by depletion of IL-17A or MDSCs. Our study clarifies an immune pathway where γδT17 cells play a protective role in murine aGVHD by recruiting MDSCs to the inflammatory intestine.

Long noncoding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) has been proved to contribute to the development of cancers. However, the mechanism behind the action of CASC2 in thyroid cancer is not quite clear. We demonstrated that CASC2 was downregulated in thyroid cancer. We noted that CASC2 overexpression restrained the growth, migration, and invasion of thyroid cancer cells, whereas CASC2 depletion caused opposite trends. Bioinformatics analysis predicted that hypoxia inducible factor 1 subunit alpha inhibitor (FIH‐1) was potentially targeted by miR‐18a‐5p, which was confirmed by luciferase reporter assay. Upregulation of FIH‐1 abrogated the promotive effect of miR‐18a‐5p on the growth and invasion of thyroid cancer cells. In addition, CASC2 serves as a competing endogenous RNA (ceRNA) and a ''sponge'' for miR‐18a‐5p, thereby regulating the expression of FIH‐1. These data elucidated the CASC2/miR‐18a‐5p ceRNA network in thyroid cancer pathogenesis.

Summary Background & aims Plasma ceramides have been identified as novel risk factors for metabolic and cardiovascular diseases. We aimed to evaluate the effects of dietary anthocyanins on plasma ceramides and to disentangle whether the alterations in ceramides could be related with those in other cardiometabolic risk factors in the dyslipidemia. Methods In a randomized double-blinded placebo-controlled trial, 176 eligible dyslipidemia subjects were randomly assigned into four groups receiving placebo, 40, 80, or 320 mg/day anthocyanins, respectively for 12 weeks. Results A total of 169 subjects completed the study. After 12-week intervention, dietary anthocyanins dose-dependently reduced plasma concentrations of all six ceramide species in the dyslipidemia subjects (all Ptrend values Conclusions Reductions in plasma Cer 16:0 and Cer 18:0 after 12-week anthocyanin intervention were dose-dependently associated with improvements in plasma lipids and cholesterol efflux capacity in the dyslipidemia. Clinical trial registration The study was registered at ClinicalTrials.gov with the identifier No. NCT03415503.

Cardiorespiratory interaction (CRI) has been intensively studied in adult sleep, yet not in preterm infants, in particular across different sleep states including wake (W), active sleep (AS), and quiet sleep (QS). The aim of this study was to quantify the interaction between cardiac and respiratory activities in different sleep states of preterm infants. The postmenstrual age (PMA) of preterm infants was also taken into consideration. The CRI during sleep was analyzed using a visibility graph (VG) method, enabling the nonlinear analysis of CRI in a complex network. For each sleep state, parameters quantifying various aspects of the CRI characteristics from constructed VG network including mean degree (Dm) and its variability (Dsd), clustering coefficient (CCm) and its variability (CCsd), assortativity coefficient (AC) and complexity (DSE) were extracted from the CRI networks. The interaction effect of sleep state and PMA was found to be statistically significant on all CRI parameters but AC and DSE. The main effect between sleep state and CRI parameters was statistically significant except for CCm, and that between PMA and CRI parameters was statistically significant but DSE. In conclusion, the CRI of preterm infants is associated with sleep states and PMA in general. For preterm infants with a larger PMA, CRI has a more clustered pattern during different sleep states, where QS shows a more regular, stratified, and stronger CRI than other states. In the future, these parameters can be potentially used to separate sleep states in preterm infants.

Background The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC. Methods We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status. Results During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26). Conclusions This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12–16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.

Inspired by the recent achievements of the two-dimensional (2D) sub-5 nm MoS2 field effect transistors (FETs), we use the ab initio quantum-transport methods to simulate the transport properties of...

We demonstrate an 80 nm bandwidth (extending from 1529 to 1609 nm), dual-stage, diode-pumped, lumped Raman amplifier using a relatively short total length (2 km) of highly nonlinear fiber. The impact of Rayleigh back scattering is mitigated and the build-up of thermally generated wavelength dependent noise is controlled by suitably adjusting the spectral gain profile in the two amplifier stages. In this way a high overall gain of 27 dB with 2.6 dB gain flatness and an average noise figure of 5.8 dB with

Obesity has caused wide concerns due to its high prevalence in patients with severe coronavirus disease 2019 (COVID-19). Coexistence of diabetes and obesity could cause an even higher risk of severe outcomes due to immunity dysfunction. We conducted a retrospective study in 1,637 adult patients who were admitted into an acute hospital in Wuhan, China. Propensity score–matched logistic regression was used to estimate the risks of severe pneumonia and requiring in-hospital oxygen therapy associated with obesity. After adjustment for age, sex, and comorbidities, obesity was significantly associated with higher odds of severe pneumonia (odds ratio [OR] 1.47 [95% CI 1.15–1.88]; P = 0.002) and oxygen therapy (OR 1.40 [95% CI 1.10–1.79]; P = 0.007). Higher ORs of severe pneumonia due to obesity were observed in men, older adults, and those with diabetes. Among patients with diabetes, overweight increased the odds of requiring in-hospital oxygen therapy by 0.68 times (P = 0.014) and obesity increased the odds by 1.06 times (P = 0.028). A linear dose-response curve between BMI and severe outcomes was observed in all patients, whereas a U-shaped curve was observed in those with diabetes. Our findings provide important evidence to support obesity as an independent risk factor for severe outcomes of COVID-19 infection in the early phase of the ongoing pandemic.