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An innovative and flexible approach is introduced to address the challenge of self-organizing a group of mobile robots into cubic-spline based patterns without any requirement of control points. Besides the self-organization of mobile robots, the approach incorporates a potential field-based control for obstacle/collision avoidance. This will offer more flexibility to swarm robots to efficiently dealing with many practical situations including smoothly avoiding obstacles during movement, or exploring and covering areas with complex curved patterns. Essentially, this challenge is approached by proposing a formation control model basing on a Smoothed Particle Hydrodynamic estimation technique, which uses special cubic-spline kernel functions applied here to interpolate the density of each robot in the swarm. The moving information is used to weight the distances to the robot’s neighbours available in its field of view. Then an artificial physics mesh is finally built among each robot and its three available neighbours having the smallest weighted distances. Significant results toward emerging cubic-spline patterns are shown with a swarm of foot-bot mobile robots simulated in the ARGoS platform. Analysis results with different metrics are also conducted to assess the performance of the model with different swarm sizes and in the presence of sensory noise as well in the presence of partially faulty robots.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment and have detrimental effects on human health. Embryos are particularly susceptible to environmental insults such as PAHs. We examined the association between prenatal exposure to PAHs and the risk for fetal neural tube defects (NTDs). A case-control study was conducted with 119 NTD cases and 119 controls. A total of 16 PAHs in umbilical cord tissue, determined with gas chromatography–mass spectrometry, were used as in utero exposure markers. Logistic regression and Bayesian kernel machine regression (BKMR) were performed to evaluate the individual and overall effects of PAH exposure on the risk for NTDs, respectively. Median concentrations of 10 PAHs were significantly higher in cases than in controls. In logistic regression, concentrations of four PAHs above the median of all participants were significantly associated with an increased NTD risk, even when potential covariates were adjusted for: phenanthrene, 2.35-fold (95% confidence interval [CI] 1.04–5.34); fluoranthene, 2.37-fold (95% CI 1.02–5.48); pyrene, 2.41-fold (95% CI 1.04–5.62); and benzo(b)fluoranthene, 2.95-fold (95% CI 1.27–6.86). In BKMR, the risk for NTDs increased when PAH concentrations were all above their 65th percentile compared to their median, while no statistical association between a single compound and NTD risk was observed when the remaining nine PAHs were taken into consideration simultaneously. Together these results show that prenatal PAH exposure is a risk factor for NTDs in offspring.

Techniques to reduce the energy burden of an industrial ecosystem often require solving a multiobjective optimization problem. However, collecting experimental data can often be either expensive or time-consuming. In such cases, statistical methods can be helpful. This article proposes Pareto Front (PF) and Pareto Set (PS) estimation methods using Bayesian Additive Regression Trees (BART), which is a non-parametric model whose assumptions are typically less restrictive than popular alternatives, such as Gaussian Processes (GPs). These less restrictive assumptions allow BART to handle scenarios (e.g. high-dimensional input spaces, nonsmooth responses, large datasets) that GPs find difficult. The performance of our BART-based method is compared to a GP-based method using analytic test functions, demonstrating convincing advantages. Finally, our BART-based methodology is applied to a motivating engineering problem. Supplementary materials, which include a theorem proof, algorithms, and R code, for this article are available online., Comment: 27 pages, 8 figures, submitted to Industry 4.0 special issue of Technometrics journal

PURPOSE Urinary stone disease (USD) has been associated with an increased risk of chronic kidney disease (CKD) and end-stage renal disease in Western populations. However, the metabolic disorders associated with unilateral and bilateral renal stones and the association of these types of stones with CKD and kidney tubular injury markers, such as urine N-acetyl-s-D-glucosaminidase (NAG) and alpha-1-microglobulin (α1-MG), have not been fully examined. MATERIALS AND METHODS We performed a cross-sectional study of 10,281 participants in rural China in 2014. All the subjects underwent renal ultrasound to detect USD; stone formers were divided into groups with unilateral or bilateral renal stones by ultrasound examinations. CKD was defined as a decreased estimated glomerular filtration rate (eGFR

Study objective To study the bacteria and fungi causing vulvovaginitis in prepubertal girls. Design Swabs from vaginal introitus were collected from patients with vulvovaginitis in 2018, and cultured for the identification of microorganisms with standard microbiological techniques. Setting A children's hospital in Hangzhou, East China. Participants A total of 1235 Chinese prepubertal girls diagnosed with vulvovaginitis. Main Outcome Measure Bacteria or fungi in pure cultures or as the predominant organism were defined as pathogens. Results A total of 1235 cases were diagnosed as vulvovaginitis, and 515 isolates were identified from 494 patients (40%, 494/1235). The most common pathogen was Streptococcus pyogenes (27.6%,142/515), followed by Haemophilus influenzae (27.2%,140/515), Candida albicans (22.3%,115/515), Staphylococcus aureus (5.8%, 30/515) and Escherichia coli (4.7%,24/515). All S pyogenes isolates were sensitive to penicillin, whereas 53.7% (73/136) of H influenzae isolates were sensitive to ampicillin, and 70.4% (19/27) of S aureus isolates were sensitive to oxacillin. Conclusion S pyogenes and H influenzae were the 2 most commonly identified pathogenic bacteria found in prepubertal girls with vulvovaginitis. Vulvovaginitis in prepubertal girls caused by C albicans may be more common in older children.

Context Metabolic disorders and cardiovascular disease (CVD) threaten human health. Many studies have assessed the phenomenon of metabolic disorders and CVD in patients with diabetes. However, in euglycemic individuals, the relationships between glucose regulation, metabolism, and CVD remain unclear. Objective This work aimed to explore the associations between postprandial glucose dips, metabolic disorders, and CVD risk. Methods We analyzed data from the Thyroid disorders, Iodine status and Diabetes Epidemiological survey (TIDE study), which included 38 878 euglycemic individuals from all 31 provinces of mainland China. The prevalence of metabolic disorders and their related components and CVD risk were calculated according to postprandial glucose dips. Logistic regression models of quartiles of postprandial glucose dips were used to further explore whether the prevalence of these disorders was associated with postprandial glucose dips. Results Odds ratios for the fourth vs the first quartile of glucose dips were 0.59 (95% CI, 0.55-0.63) (P Conclusion Postprandial glucose dips are associated with metabolic disorders, MetS and its related component diseases, and CVD risk. Glucose dips may be a marker of underlying metabolic abnormalities.

Well-designed second near-infrared (NIR-II) fluorophores are promising in optical diagnosis and therapy of tumors. In this work, we synthesized a donor-acceptor-donor (D-A-D) NIR-II fluorophore named BBTD-BET with dithienylethene as an electron donor and benzobisthiadiazole as an electron acceptor. To the best of our knowledge, this is the first report of using dithienylethene, a typical photochromic molecule, as a building block for NIR-II fluorophores. We studied the geometrical configuration, electronic state, and optical properties of BBTD-BET by both theoretical and experimental means. BBTD-BET had absorption and emission in the NIR-I and NIR-II spectral ranges, respectively. Using PEGylated BBTD-BET as a theranostic agent, we achieved NIR-II fluorescence/photoacoustic (PA) dual-modal imaging and attained high imaging resolution, desired signal-to-noise ratio, and excellent photothermal therapy (PTT) efficacy. After one PTT treatment, the tumors established in mice were eradicated. This work provides a novel organic conjugated molecule integrating NIR-II/PA dual-modal imaging and PTT functionalities that is very promising in the theranostic of tumors.

Over the past decade, artificial intelligence (AI) has contributed substantially to the resolution of various medical problems, including cancer. Deep learning (DL), a subfield of AI, is characterized by its ability to perform automated feature extraction and has great power in the assimilation and evaluation of large amounts of complicated data. On the basis of a large quantity of medical data and novel computational technologies, AI, especially DL, has been applied in various aspects of oncology research and has the potential to enhance cancer diagnosis and treatment. These applications range from early cancer detection, diagnosis, classification and grading, molecular characterization of tumors, prediction of patient outcomes and treatment responses, personalized treatment, automatic radiotherapy workflows, novel anti‐cancer drug discovery, and clinical trials. In this review, we introduced the general principle of AI, summarized major areas of its application for cancer diagnosis and treatment, and discussed its future directions and remaining challenges. As the adoption of AI in clinical use is increasing, we anticipate the arrival of AI‐powered cancer care., This review introduced the general principle of AI, summarize major areas of its application for cancer diagnosis, treatment, and precision medicine and discuss its future directions and remaining challenges.

Electrocatalytic N2 reduction under ambient-condition is considered to be the most appealing strategy to the conventional Haber-Bosch process for synthetic ammonia to alleviate greenhouse emissions and reduce environmental pollution, mainly powered by renewable energy. Recent years, rapid advances have been gained in this attractive research field, and numerous electrocatalysts have been exploited. However, its conversion efficiency is still far behind the requirement of industrial applications owing to the breakage of the N≡N triple bond, which is an energetically challenging kinetically complex multistep reaction and the strong competing reaction of hydrogen evolution reaction. Recently, main group metal-based catalysts have been demonstrated promising application prospect for ammonia production, significantly boosting their further application in this field. However, a comprehensive review of main group metal-based catalysts towards electrochemical ammonia production applications is still lacking. In this review, the fundamentals of N2 reduction, such as the reaction pathways, the reaction potential and the challenges of N2 reduction have been comprehensively discussed. And then, the role, mechanism, and effect of each main group element-based catalysts used for N2 reduction (Li, K, Al, Ga, Sn, Sb, Bi, and their compounds) are systematically summarized. Finally, several state-of-the-art strategies to promote their NRR catalytic performance, as well as the existing problems and prospects are put forward. This review is expected to guide the design and establishment of more efficient electrocatalytic N2 reduction systems based on main group metal elements in the future.

Symmetric cryptography is expected to be quantum safe when long‐term security is needed. Kuwakado and Morii gave a 3‐round quantum distinguisher of the Feistel cipher based on Simon's algorithm. However, the quantum distinguisher without considering the specific structure of the round function is not accurate enough. A new quantum cryptanalysis method for Feistel structure is studied here. It can make full use of the specific structure of the round function. The properties of Camellia round function and its linear transformation P are taken into account, and a 5‐round quantum distinguisher is proposed. Then, the authors follow a key‐recovery attack framework by Leander and May, that is, Grover‐meet‐Simon algorithm, and give a quantum key‐recovery attack on 7‐round Camellia in Q2 model with the time complexity of 224. It is the very first time that the specific structure of the round function is used to improve quantum attack on Camellia.

This study was to explore the application value of chest computed tomography (CT) images processed by artificial intelligence (AI) algorithms in the diagnosis of neonatal bronchial pneumonia (NBP). The AI adaptive statistical iterative reconstruction (ASiR) algorithm was adopted to reconstruct the chest CT image to compare and analyze the effect of the reconstruction of CT image under the ASiR algorithm under different preweight and postweight values based on the objective measurement and subjective evaluation. 85 neonates with pneumonia treated in hospital from September 1, 2015, to July 1, 2020, were selected as the research objects to analyze their CT imaging characteristics. Subsequently, the peripheral blood of healthy neonates during the same period was collected, and the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were detected. The efficiency of CT examination, CRP, ESR, and combined examination in the diagnosis of NBP was analyzed. The results showed that the subjective quality score, lung window subjective score, and mediastinal window subjective score were the highest after CT image reconstruction when the preweight value of the ASiR algorithm was 50%. After treatment, 79 NBP cases (92.9%) showed ground-glass features in CT images. Compared with the healthy neonates, the levels of CRP and ESR in the peripheral blood of neonates with bronchial pneumonia were much lower ( P < 0.05 ). The accuracy rates of CT examination, CRP examination, ESR examination, CRP + ESR examination, and CRP + ESR + CT examination for the diagnosis of NBP were 80.7%, 75.3%, 75.1%, 80.3%, and 98.6%, respectively. CT technology based on AI algorithm showed high clinical application value in the feature analysis of NBP.

In this article, a single‐stage bridgeless LLC resonant converter with a constant frequency control method is proposed for a high‐brightness light‐emitting diode (LED) driver. LED strings require drivers with high power density and high efficiency. This article presents a novel LED driver circuit topology based on switch integration and the switching controlled capacitor (SCC) technique. By combining the merits of a totem‐pole bridgeless boost PFC unit and a high frequency SCC‐LLC half‐bridge resonant converter, the proposed topology can achieve high efficiency. Due to the SCC‐LLC circuit topology structure, constant frequency control of the LLC resonant converter is achieved by the regulation of the equivalent resonant capacitance. The proposed novel LED driver topology can automatically achieve soft‐switching characteristics and a high power factor. The operating principle of different operation modes and the characteristics of the proposed LED driver are analysed in detail. Finally, to demonstrate the feature of the proposed topology, a 100 W/70 V laboratory prototype is built. The satisfactory experimental results correspond with the theoretical analysis and parameter design.

Objective To identify the role of fatty acid binding protein 3 (FABP3) in vascular fibrosis in Takayasu’s arteritis (TAK) and to explore the underlying molecular mechanism. Methods The expression of FABP3 and extracellular matrix proteins (ECMs) were detected in aorta tissues from TAK patients (n = 12) and healthy controls (n = 8) by immunohistochemistry. The concentration of serum proteins was determined by ELISA. CCK8 and Ki67 staining were used to measure aorta adventitial fibroblast (AAF) proliferation. Widely targeted lipidomic profiling was used to screen for associated metabolic pathways. Changes in ECMs and fatty acid oxidation (FAO)-related enzymes were determined by RT-qPCR and Western blot. The interactions between FABP3 and these enzymes were explored with a co-immunoprecipitation (Co-IP) assay. Results The expression of FABP3 was increased in the thickened adventitia of TAK patients and was positively correlated with the serum expression of ECMs. FABP3 knockdown inhibited AAF proliferation and ECM production, whereas FABP3 overexpression enhanced these processes. Further analysis revealed that FABP3 upregulation promoted carnitine palmitoyltransferase 1A and carnitine/acylcarnitine carrier protein (CACT) expression, two key enzymes in FAO, as well as adenosine triphosphate (ATP) levels. FABP3 and CACT were co-localized in the adventitia and bound to each other in AAFs. Etomoxir reversed the enhanced FAO, ATP production, AAF proliferation and ECM production mediated by FABP3 upregulation. Treatment with 60 g/day curcumin granules for 3 months reduced the level of serum FABP3. Curcumin also inhibited vascular fibrosis by reducing FABP3-enhanced FAO in AAFs. Conclusion Elevated FABP3 expression accelerated vascular fibrosis in TAK, which was likely mediated by promoting FAO in AAFs.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.

Rapid development of Internet of Things technology makes the Internet interact and communicate with objects in the real world. The diversity of Internet of Things’ system architectures and the diversity of networks determine the complexity of their security issues. A key step in building an Internet of Things’ security system is to build a model and evaluate threats of security. First, this paper studies the distribution of key security about mobile ad hoc networks and analyzed the characteristics of the scene. To promote the certification of the key exchange strategy of both sides, it supports key exchange between the core node and multiple nodes for existing problems that management scheme of random key preallocation is limited by the storage space of the node through combination of key matrix elements which has less information to generate a large number of keys, and each sensor node only needs to store related parameters and key matrix. It saves the memory space of node greatly. The results of simulation show that the program has a strong security; it can fight against the common attacks of wireless sensor networks, such as node forgery attacks, message replay attacks, and denial of service attacks. At the same time, it is superior to traditional solutions in terms of network connectivity and nondestructibility, which can apply clustered wireless sensor network massively.

Presently, Supervisory Control and Data Acquisition (SCADA) systems are broadly adopted in remote monitoring large-scale production systems and modern power grids. However, SCADA systems are continuously exposed to various heterogeneous cyberattacks, making the detection task using the conventional intrusion detection systems (IDSs) very challenging. Furthermore, conventional security solutions, such as firewalls, and antivirus software, are not appropriate for fully protecting SCADA systems because they have distinct specifications. Thus, accurately detecting cyber-attacks in critical SCADA systems is undoubtedly indispensable to enhance their resilience, ensure safe operations, and avoid costly maintenance. The overarching goal of this paper is to detect malicious intrusions that already detoured traditional IDS and firewalls. In this paper, a stacked deep learning method is introduced to identify malicious attacks targeting SCADA systems. Specifically, we investigate the feasibility of a deep learning approach for intrusion detection in SCADA systems. Real data sets from two laboratory-scale SCADA systems, a two-line three-bus power transmission system and a gas pipeline are used to evaluate the proposed method’s performance. The results of this investigation show the satisfying detection performance of the proposed stacked deep learning approach. This study also showed that the proposed approach outperformed the standalone deep learning models and the state-of-the-art algorithms, including Nearest neighbor, Random forests, Naive Bayes, Adaboost, Support Vector Machine, and oneR. Besides detecting the malicious attacks, we also investigate the feature importance of the cyber-attacks detection process using the Random Forest procedure, which helps design more parsimonious models.

The aim is to explore the impact of the Kasai procedure (KP) and the length of native liver survival time (NLST) on outcomes of liver transplantation (LT). Patients with biliary atresia (BA), who underwent LT in Beijing Friendship Hospital from January 2017 to December 2019, were enrolled and divided into non-KP (N-KP) and post-KP (P-KP) groups. The patients in the P-KP group were further divided into early failure (KP-EF) defined by NLST 5years) subgroups. Clinical data at baseline and during follow-up were collected. The inverse probability of treatment weighting method was used to evaluate the independent effect of KP and the length of NLST on clinical outcomes. Among 197 patients with BA, the N-KP group accounted for 43 (21.8%), KP-EF 71 (46.1%), KP-MF 59 (38.3%), and KP-LF 24 (15.6%) cases, respectively. The N-KP and KP-EF groups had significantly longer hospitalization and intensive care unit stays after LT. Graft and overall survival rates were 93.0% in the N-KP group and 97.4% in P-KP group, respectively. The mortality rate in the P-KP group were significantly lower compared with that of the N-KP group with a hazard ratio (HR) of 0.2 (P=0.02). The risks of biliary and vascular complications and cytomegalovirus (CMV) infection after LT were significantly higher in KP-EF group than those in the KP-MF and KP-LF groups (HRs = 0.09, 0.2, and 0.3, respectively; all P&nbsp

Background The fat‐to‐muscle mass ratio (FMR) might be an indicator to assess type 2 diabetes risk independent of general obesity. However, no longitudinal studies have explored the extent to which total and regional FMRs may confer risks. We aimed to measure the sex‐specific associations between FMRs of the arm, leg, trunk and whole body and incident type 2 diabetes. Methods A total of 464 817 participants (207 286 men and 257 531 women, mean age 56.5 ± 8.2 and 56.2 ± 8.0 years old, respectively) free of diabetes at baseline were included in this prospective cohort study with UK Biobank data. Fat mass and muscle mass were estimated using a bioelectrical impedance assessment device (Tanita BC 418MA). FMR was calculated as fat mass divided by muscle mass in corresponding body parts (total body, arm, leg and trunk). Cox proportional hazard models were used to estimate the aforementioned associations among men and women. Interaction analyses were performed between FMRs and body mass index (BMI) categories (BMI

Comorbid chronic pain and depression are increasingly becoming a concerning public problem, but the underlying mechanisms remain unclear. Here, we demonstrate that pain-related depression-like behaviors are induced in a rat model of chronic constriction injury (CCI). Using this model, we found that chronic neuropathic pain decreased the activity and expression of sirtuin 1 (SIRT1, an NAD+-dependent deacetylase) in the central nucleus of the amygdala (CeA). In addition, the pharmacologic activation of SIRT1 in the CeA could alleviate the depression-like behaviors associated with chronic pain while relieving sensory pain. Accordingly, adeno-associated virus (AAV)-mediated SIRT1 overexpression in the CeA produced a positive effect on the easement of chronic pain and comorbid depression. Taken together, these findings highlight the role of SIRT1 in the CeA in chronic pain and depression states and reveal that the upregulation of SIRT1 may be a potential therapy for the treatment of pain-depression comorbidities.

Machine Learning (ML) for swarm motion prediction is a relatively unexplored area that could help sustain and monitor daily swarm robotics collective tasks. This paper focuses on a specific application of swarm robotics which is pattern formation, to demonstrate the ability of Ensemble Learning (EL) approaches to predict the motion speed of swarm robots. Specifically, the boosted trees (BST) and bagged trees (BT) algorithms are introduced to predict the motion speed of a swarm of miniature two-wheels differential driver mobile robots performing a circle-formation via the viscoelastic control model. This choice’s motivation is due to EL-based models’ ability to improve the performance of ML models by combining multiple learners versus single regressors. Both BST and BT algorithms’ performances are compared to ten commonly known prediction models based on Support Vector Regressors (SVRs) and Gaussian Process Regressors (GPRs) with different kernel functions. Using simulated measurements recorded every 0.1 second from the robots’ sensors, we demonstrate the effectiveness of the developed methods over conventional ML models (SVR and GPR) in a free/non-free obstacles environment. Results showed that the BST and BT regression models reached the highest prediction performance with fully and partially connected swarms and even when involving different swarm sizes.

The localized surface plasmon resonance (LSPR) absorption peaks of semiconductor nanocrystals are mainly concentrated in the infrared band, and the absorption characteristics can be controlled by the amount of element doping. The coupling of upconversion nanocrystals (UCNPs) and semiconductor nanocrystals can improve the upconversion luminescence (UCL) of rare-earth ions. Here, the LSPR absorption and morphology of the semiconductor nanocrystalline TiO2: W were adjusted by using ammonium fluoride during synthesis. Significant absorption enhancement of TiO2: W in the near-infrared region was obtained to enhance the UCL of NaYF4: Yb3+, Er3+. The Glass/NaYF4: Yb3+, Er3+/TiO2: W@SiO2 layered structure films were fabricated through spin coating. Compared with Glass/NaYF4: Yb3+, Er3+, the green and red lights of the Glass/NaYF4: Yb3+, Er3+/TiO2: W@SiO2 films were enhanced by 15.9 and 17.8 times, respectively. The UCL enhancement of Glass/NaYF4: Yb3+, Er3+/TiO2: W@SiO2 was derived from the LSPR property of TiO2: W through the enhancement of the excitation. The present work is important for possible applications of these layered structures as biomarkers, photocatalysts, flexible materials, and photoluminescence display panels.

BACKGROUND Chronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent way. Combining adult stress in offspring will increase this sensitivity. Based on the evidence implicating estrogen in exacerbating visceral hypersensitivity in female rodents in preclinical models, we predicted that chronic prenatal stress (CPS) + chronic adult stress (CAS) will maximize visceral hyperalgesia; and that estrogen plays an important role in colonic hyperalgesia. AIM The aim was to illuminate the role of estrogen in colonic hyperalgesia and its underlying mechanisms. METHODS We established a CPS plus CAS rodent model in which the balloon was used to distend the colorectum. The single-fiber recording in vivo and patch clamp experiments in vitro were used to monitor the colonic neuron’s activity. The reverse transcription-polymerase chain reaction, western blot, and immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity. We used ovariectomy and letrozole to reduce estrogen levels of female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization. RESULTS Spontaneous activity and single fiber activity were significantly greater in females than in males. The enhanced sensitization in female rats mainly came from low-threshold neurons. CPS significantly increased single-unit afferent fiber activity in L6-S2 dorsal roots in response. Activity was further enhanced by CAS. In addition, the excitability of colon-projecting dorsal root ganglion (DRG) neurons increased in CPS + CAS rats and was associated with a decrease in transient A-type K+ currents. Compared with ovariectomy, treatment with the aromatase inhibitor letrozole significantly reduced estrogen levels in female rats, confirming the gender difference. Moreover, mice treated with letrozole had decreased colonic DRG neuron excitability. The intrathecal infusion of estrogen increased brain-derived neurotrophic factor (BDNF) protein levels and contributed to the response to visceral pain. Western blotting showed that nerve growth factor protein was upregulated in CPS + CAS mice. CONCLUSION This study adds to the evidence that estrogen-dependent sensitization of primary afferent colon neurons is involved in the development of chronic stress-induced visceral hypersensitivity in female rats.

Aims. The prognostic value of plasma D-dimer in patients with coronary artery disease (CAD) remains controversial. The study is aimed at investigating the relationship between plasma D-dimer levels and in-hospital heart failure (HF) in ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI). Methods. STEMI patients who underwent pPCI were enrolled in this study. Venous blood samples were collected from patients on admission before pPCI procedure. The study endpoint was the occurrence of in-hospital HF. The participants were divided into two groups according to plasma D-dimer levels and further compared baseline D-dimer levels between male and female. Logistic regression and receiver operating characteristic (ROC) curves were performed to evaluate the relationship of D-dimer and in-hospital HF. Results. A total of 778 patients were recruited in the study, of which 539 (69.3%) patients had normal D-dimer levels (≤0.5 mg/L) while 239 (30.7%) had increased D-dimer levels (>0.5 mg/L). The female patients have higher D-dimer levels and higher incident rate of in-hospital HF than that in male patients ( p < 0.001 ). The multivariate logistic regression model revealed that D-dimer was an independent predictor for in-hospital HF in overall population (adjusted odds ratio [OR]: 1.197, 95% CI: 1.003-1.429, and p = 0.046 ) and female patients (adjusted OR: 1.429, 95% CI: 1.083-1.885, and p = 0.012 ). Conclusion. Increased plasma D-dimer levels were an independent risk factor for incidence of in-hospital HF in STEMI patients who underwent pPCI, especially in female patients, which provides guidance for clinicians in identifying patients at high risk of developing HF and lowering their risk.

What is known and objective Optimal airway management is crucial in strabismus surgery due to the inaccessibility of the airway throughout the procedure. Laryngeal mask airway offers advantages over tracheal intubation in ophthalmic surgery as it does not increase the intraocular pressure. The purpose of this study was to determine the median effective dose of propofol required, when combined with 0.2 µg/kg of sufentanil, for smooth insertion of Ambu AuraFlex in the first attempt in children undergoing strabismus surgery, and to compare it with that for Ambu AuraOnce. Methods Forty-three paediatric patients undergoing strabismus surgery under general anaesthesia were recruited. For induction, the initial dosage of propofol was 2 mg/kg in the AuraOnce group or 3 mg/kg in the AuraFlex group. In accordance with Dixon's up-and-down method, the dose of propofol for consecutive patients in each group was adjusted in increments or decrements of 0.25 mg/kg based on the previous patient's "three-point, six-category scale" response to the first attempt of insertion of the randomized device. Insertion of the device was attempted when the bispectral index was ≤60 for 5 s after propofol administration without the use of neuromuscular blocking agents. Results and discussion The median effective dose (95% confidence interval) of propofol was significantly lower in the Ambu AuraOnce group than in the Ambu AuraFlex group (1.92 [1.50-2.32] mg/kg vs. 2.98 [2.49-3.94] mg/kg; p = 0.002). The incidence of dislodgement of the device was significantly higher with the use of the Ambu AuraOnce than with the use of AuraFlex (p = 0.023), whereas insignificant differences were observed between the two groups in the incidence of other perioperative adverse events. What is new and conclusion Ambu AuraFlex requires a significantly higher dose of propofol for insertion and provides more effective and stable airway management in strabismus surgery than AuraOnce.

We present results from the first 6 years of this major U.K. government funded project to accelerate and enhance collaborative research and development in climate science, forge a strong strategic partnership between U.K. and Chinese climate scientists, and demonstrate new climate services developed in partnership. The development of novel climate services is described in the context of new modeling and prediction capability, enhanced understanding of climate variability and change, and improved observational datasets. Selected highlights are presented from over 300 peer reviewed studies generated jointly by U.K. and Chinese scientists within this project. We illustrate new observational datasets for Asia and enhanced capability through training workshops on the attribution of climate extremes to anthropogenic forcing. Joint studies on the dynamics and predictability of climate have identified new opportunities for skillful predictions of important aspects of Chinese climate such as East Asian summer monsoon rainfall. In addition, the development of improved modeling capability has led to profound changes in model computer codes and climate model configurations, with demonstrable increases in performance. We also describe the successes and difficulties in bridging the gap between fundamental climate research and the development of novel real-time climate services. Participation of dozens of institutes through subprojects in this program, which is governed by the Met Office Hadley Centre, the China Meteorological Administration, and the Institute of Atmospheric Physics, is creating an important legacy for future collaboration in climate science and services.

BACKGROUND The simultaneous occurrence of schwannoma and meningioma in the absence of neurofibromatosis (NF) or a previous history of irradiation is exceedingly rare, as only 10 intracranial cases have been reported to date. Herein, we report a case of a coexistent cavernous sinus meningioma and ipsilateral vestibular schwannoma (VS) in a female patient without NF or a history of exposure to irradiation. CASE SUMMARY A 63-year-old woman presented with progressive left-side hearing loss and tinnitus over the previous year. In the past 6 mo, she developed facial numbness and intermittent headaches. Magnetic resonance imaging showed two lesions that were located on the left side of the cerebellopontine angle and parasellar region. Both lesions were totally resected via the left retrosigmoid approach. Histopathological examination revealed a VS and a meningioma. The patient did not have a family history or clinical or radiological signs of NF. CONCLUSION The coincident occurrence of VS and meningioma within close vicinity is very rare, and the pathogenesis is unclear. A careful whole-body examination needs to be conducted to exclude NF. Surgical treatment with the goal of total tumor resection is the best therapy. Additional studies are needed for a better understanding of the mechanisms that lead to the development of tumor growth in multiple locations.

Background The optimal posttreatment surveillance strategy for nasopharyngeal carcinoma (NPC) remains unclear. Circulating cell-free Epstein-Barr virus (cfEBV) DNA has been recognized as a promising biomarker to facilitate early detection of NPC recurrence. Therefore, we aim to determine whether integrating circulating cfEBV DNA into NPC follow-up is cost-effective. Methods For each stage of asymptomatic nonmetastatic NPC patients after complete remission to primary NPC treatment, we developed a Markov model to compare the cost-effectiveness of the following surveillance strategies: routine follow-up strategy, i.e., (1) routine clinical physical examination; routine imaging strategies, including (2) routine magnetic resonance imaging plus computed tomography plus bone scintigraphy (MRI + CT + BS); and (3) routine 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT); cfEBV DNA-guided imaging strategies, including (4) cfEBV DNA-guided MRI + CT + BS and (5) cfEBV DNA-guided PET/CT. Clinical probabilities, utilities, and costs were derived from published studies or databases. Sensitivity analyses were performed. Results For all disease stages, cfEBV DNA-guided imaging strategies demonstrated similar survival benefits but were considerably more economical than routine imaging strategies. They only required approximately one quarter of the number of imaging studies compared with routine imaging strategies to detect one recurrence. Specifically, cfEBV DNA-guided MRI + CT + BS was most cost-effective for stage II (incremental cost-effectiveness ratio [ICER] $57,308/quality-adjusted life-year [QALY]) and stage III ($46,860/QALY) patients, while cfEBV DNA-guided PET/CT was most cost-effective for stage IV patients ($62,269/QALY). However, routine follow-up was adequate for stage I patients due to their low recurrence risk. Conclusions The cfEBV DNA-guided imaging strategies are effective and cost-effective follow-up methods in NPC. These liquid biopsy-based strategies offer evidence-based, stage-specific surveillance modalities for clinicians and reduce disease burden for patients.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that facilitates insulin secretion and preserves β cell function. hypertriglyceridemia plays an important role in the pathogenesis of insulin resistance and T2DM. The purpose of this study was to measure fasting active GLP-1 levels in hypertriglyceridemia subjects and analyse the relationship between GLP-1 and insulin resistance. We recruited 146 subjects including 38 diabetes patients with hypertriglyceridemia, 33 diabetes patients without hypertriglyceridemia, 35 hypertriglyceridemia subjects, and 40 healthy subjects as the normal control group. Serum fasting active GLP-1 was tested with ELISA in the four groups, and associations with insulin resistance were analysed. Serum fasting active GLP-1 levels were significantly increased in hypertriglyceridemia subjects with or without T2DM compared with healthy controls, particularly hypertriglyceridemia patients with T2DM (p

More frequent and severe shocks combined with more plentiful data and increasingly powerful predictive algorithms heighten the promise of data science in support of humanitarian and development programming. We advocate for embrace of, and investment in, machine learning methods for poverty and malnutrition targeting, mapping, monitoring, and early warning while also cautioning that distinct tasks require different data inputs and methods. In particular, we highlight the differences between poverty and malnutrition targeting and mapping, identification of those in a state of structural versus stochastic deprivation, and the modeling and data challenges of developing early warning systems. Overall, we urge careful consideration of the purpose and possible use cases of big data and machine learning informed models.

Since the first report of the coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, the outbreak of the disease is currently continuously evolving. Previous studies have shown varying degrees of liver damage in patients with COVID-19. However, the exact causes of liver injury and the relationship between COVID-19 and liver injury is unclear. This article describes liver injury induced by COVID-19, analyzes its causes, and discusses the treatment and prognosis of liver damage in patients with COVID-19.

Objective To investigate the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in assessing disease activity in Takayasu arteritis (TA). Methods Ninety-one patients with TA were recruited from a Chinese cohort. Clinical data, acute-phase reactants and 18F-FDG-PET/CT findings were simultaneously recorded. The value of using 18F-FDG-PET/CT to identify active disease was evaluated, using ESR as a reference. Disease activity assessment models were constructed and concordance index (C-index), net reclassification index (NRI), and integrated discrimination index (IDI) were evaluated to compare the benefits of the new modes with ESR and the Kerr score. Results In total, 64 (70.3%) cases showed active disease. Higher levels of ESR and CRP, and lower IL-2 receptor (IL-2R) levels were observed in active cases. 18F-FDG-PET/CT parameters measured by determining the standard uptake value (SUV), including SUVmean, SUVratio1, SUVratio2, sum of SUVmean and sum of SUVmax, were significantly higher in active disease groups. The C-index threshold of ESR to indicate active disease was 0.78 (95% CI: 0.69, 0.88). The new activity assessment model combining ESR, sum of SUVmean and IL-2R showed significant improvement in C-index over the ESR method (0.96 vs 0.78, P Conclusions A novel 18F-FDG-PET/CT-based method that involves combining the sum of SUVmean with ESR score and IL-2R levels demonstrated superiority in identifying active TA compared with conventional methods.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide health emergency. Patients infected with SARS-CoV-2 present with diverse symptoms related to the severity of the disease. Determining the proteomic changes associated with these diverse symptoms and in different stages of infection is beneficial for clinical diagnosis and management. Here, we performed a tandem mass tag-labeling proteomic study on the plasma of healthy controls and COVID-19 patients, including those with asymptomatic infection (NS), mild syndrome, and severe syndrome in the early phase and the later phase. Although the number of patients included in each group is low, our comparative proteomic analysis revealed that complement and coagulation cascades, cholesterol metabolism, and glycolysis-related proteins were affected after infection with SARS-CoV-2. Compared to healthy controls, ELISA analysis confirmed that SOD1, PRDX2, and LDHA levels were increased in the patients with severe symptoms. Both gene set enrichment analysis and receiver operator characteristic analysis indicated that SOD1 could be a pivotal indicator for the severity of COVID-19. Our results indicated that plasma proteome changes differed based on the symptoms and disease stages and SOD1 could be a predictor protein for indicating COVID-19 progression. These results may also provide a new understanding for COVID-19 diagnosis and treatment.

We aimed to construct and validate a risk assessment model to identify risk factors for heart failure (HF) in patients with Takayasu’s arteritis (TAK). Three hundred sixty-five patients with TAK were recruited in the East China Takayasu Arteritis Cohort from January 2012 to December 2019. Patients were assigned into training and validation sets following a 2:1 ratio according to the date of enrollment. Clinical characteristics were compared between heart failure (HF) and non-HF subgroups in the training set, and a risk assessment model for HF and its scoring algorithm was established based on logistic regression, which was tested in the validation set. Among total of 74 (20.27%) TAK patients exhibited HF, and 55 cases (74.32%) were in the training set. The risk factors for HF of TAK patients included onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension. We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients in the training set with the score ≥ 3 appeared to be associated with an increased risk of HF with an area under curve (AUC) of 0.88 and 0.90 in Model 1 and Model 2 respectively. The AUC reached to 0.88 and 0.89 in the validation set that proved the accuracy of the model. We presented a risk assessment model of HF in TAK, which may help clinicians alert the complication of HF in the patients with specifically cardiac impairments.

Estimated to comprise approximately 10% of lung cancer cases, multiple pulmonary lesions pose a diagnostic and therapeutic challenge in thoracic oncology. Distinction between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) directly affects tumor staging and clinical management. In equivocal cases in which the lesions are histopathologically indistinguishable, targeted sequencing can provide key additional evidence for differential diagnosis. Herein, we describe an unusual patient who presented with seven lung lesions that consisted of primary tumors and metastatic lesions, each showing distinct clonality status based on histomolecular findings. Specifically, the 45-year-old female never-smoker underwent a surgery that removed one invasive lepidic predominant adenocarcinoma and five microinvasive adenocarcinomas. Next-generation sequencing revealed three of the lesions to carry a clonal driver mutation EGFR p.L858R, supporting an IMP diagnosis. EGFR p.L858R was not detected in two other surgical specimens, which instead harbored respective oncogenic BRAF p.G469A and an uncommon EGFR p.G779F. These results led to diagnosis of the two lesions as primary tumors of lineages different from that of the metastases. The patient had achieved a recurrence-free survival of 21 months as of the latest follow-up. In this rare case that presented with evidence of both MPLC and IPM, targeted sequencing proved valuable in facilitating the diagnostic workup.

Wireless charging for electric vehicles has been investigated in recent years. One of the critical issues of the research is to improve the weak interoperability between two popular charging pads—rectangular pad (RCP) and double-D pad (DDP). This article intends to model the interoperability under pad misalignment and improve it by adjusting the pads’ relative position. First, the variation of interoperability with pad misalignment is analyzed by the flux model. Full output power and high transmission efficiency can be achieved when the two pads are misaligned to a certain distance. Second, the optimal misalignment is obtained by flux calculation and simulation. Third, an adaptive position adjustment method for the transmitting pad based on the variable-step perturbation and observation algorithm is proposed. By searching the maximum dc input current, the optimal position of the transmitting pad can be found. Finally, in the experiment, a 3.3 kW output with 95% coil-coil efficiency is realized when the RCP and DDP interoperate at the optimal position. Compared with the scenario without position adjustment, the improvement of output power and efficiency proves that the proposal can optimize the interoperability between the RCP and DDP.

BACKGROUND Laparoscopic living donor hepatectomy (LLDH) has been successfully carried out in several transplant centers. Biliary reconstruction is key in living donor liver transplantation (LDLT). Reliable biliary reconstruction can effectively prevent postoperative biliary stricture and leakage. Although preoperative magnetic resonance cholangiopancreatography and intraoperative indocyanine green cholangiography have been shown to be helpful in determining optimal division points, biliary variability and limitations associated with LLDH, multiple biliary tracts are often encountered during surgery, which inhibits biliary reconstruction. A reliable cholangiojejunostomy for multiple biliary ducts has been utilized in LDLT. This procedure provides a reference for multiple biliary reconstructions after LLDH. CASE SUMMARY A 2-year-old girl diagnosed with ornithine transcarbamylase deficiency required liver transplantation. Due to the scarcity of deceased donors, she was put on the waiting list for LDLT. Her father was a suitable donor; however, after a rigorous evaluation, preoperative magnetic resonance cholangiopancreatography examination of the donor indicated the possibility of multivessel variation in the biliary tract. Therefore, a laparoscopic left lateral section was performed on the donor, which met the estimated graft-to-recipient weight ratio. Under intraoperative indocyanine green cholangiography, 4 biliary tracts were confirmed in the graft. It was difficult to reform the intrahepatic bile ducts due to their openings of more than 5 mm. A reliable cholangiojejunostomy was, therefore, utilized: Suture of the jejunum to the adjacent liver was performed around the bile duct openings with 6/0 absorbable sutures. At the last follow-up (1 year after surgery), the patient was complication-free. CONCLUSION Intrahepatic cholangiojejunostomy is reliable for multiple biliary ducts after LLDH in LDLT.

e15110 Background: Immune checkpoint inhibitors (ICIs) yield remarkable clinical efficacy in the treatment of cancer. With the increasing use of ICI therapies, the dissemination of immune-related adverse events (irAEs) data is essential. This study aimed to investigate the pattern of onset and resolution of ICI-induced irAEs in cancer. Methods: Phase II–III clinical trials with single or multiple arms studying ICI-based treatments in cancer published between January 2007 and December 2019 were included. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were analyzed based on irAE categories and severity grades using the metamedian package of the R software. Subgroup analyses were performed based on different ICI drugs, ICI doses, and cancer types. Results: Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. On average, irAEs occurred at 6.1 weeks (95% confidence interval [95% CI], 5.7–7.4) after the initial ICI-based treatment. The first four irAEs with the shortest PMT-O were hypersensitivity/infusion reaction (3.1 weeks), neurological (4.0 weeks), skin (4.1 weeks), and gastrointestinal (6.1 weeks) events. IrAEs were resolved within 4.5 weeks (95% CI, 4.0–6.1), with the shortest and longest PMT-R for hypersensitivity/infusion reaction (0.1 weeks) and endocrine events (28.7 weeks), respectively. The application of immune-modulation drugs prolonged the general resolution time to 5.9 weeks, with the shortest and longest PMT-IMR for hypersensitivity/infusion reaction (0.2 weeks) and endocrine events (56.6 weeks), respectively. Grade ≥ 3 irAEs showed a significantly longer PMT-O (7.9 vs. 6.1 weeks; P < 0.01) compared with all grade irAEs. Nivolumab + ipilimumab had a significantly shorter PMT-O than nivolumab alone (6.0 vs. 8.2 weeks; P < 0.01). A significantly shorter PMT-O was observed for lung cancer compared with that for melanoma (4.7 vs. 6.1 weeks; P = 0.02). Conclusions: This study revealed the pattern and kinetics of the time to onset and resolution of irAEs in pan-cancers, which will promote the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

Non-suicidal self-harm (NSSH) and chronic insufficient sleep are both major health problems during the transition from childhood to adolescence. We examined to identify sleep duration trajectories from childhood to adolescence and their associations with subsequent risk of NSSH. A cohort of children around the period of pubertal onset (7–9 years old) were followed from 2013 over 6 years. Group-based trajectory modeling was recruited to identify sleep duration trajectories derived from 5 repeated measures. Association between sleep duration trajectories with the risk of NSSH was examined using multivariate logistic regression model. Nonlinear dose–response associations between sleep duration and NSSH risk were also assessed using restricted cubic spline models. Of the 1973 participants included in the study (mean ± SD, 8.1 ± 0.9 years age at baseline, 41.1% female). Three sleep duration trajectories were identified: persistent sleeping ≥ 8 h/day (27.7%), moderately decreasing (60.8%) and rapidly decreasing (11.5%) sleep duration groups. After multivariable adjustment for covariates, compared with the persistent sleeping ≥ 8 h/day group, the odds ratio of NSSH was 2.58 (95% CI 1.92, 3.45) for the moderately decreasing group, and 4.16 (2.86, 6.04) for rapidly decreasing group. In dose–response analysis, sleep duration was associated with NSSH risk in a non-linear fashion (χ2 = 25.16, Pnonlinearity

Objective This study aimed to describe the implementation of the surgical safety check policy and the surgical safety checklist for invasive procedures outside the operating room (OR) and evaluate its effectiveness. Methods In 2017, to improve the safety of patients who underwent invasive procedures outside of the OR, the hospital quality and safety committee established the surgery safety check committee responsible for developing a new working plan, revise the surgery safety check policy, surgery safety check form, and provide training to the related staff, evaluated their competency, and implemented the updated surgical safety check policy and checklist. The study compared the data of pre-implementation (Apr to Sep 2017) and two post-implementation phases (Apr to Sep 2018, Apr to Sep 2019). It also evaluated the number of completed surgery safety checklist, correct signature, and correct timing of signature. Results The results showed an increase in the completion rate of the safety checklist after the program implementation from 41.7% (521/1,249) to 90.4% (3,572/3,950), the correct rates of signature from 41.9% (218/521) to 99.0% (4,423/4,465), and the correct timing rates of signature from 34.4% (179/521) to 98.5% (4,401/4,465), with statistical significance (P Conclusion Implementing the updated surgery safety check significantly is a necessary and effective measure to ensure patient safety for those who underwent invasive procedures outside the OR. Implementing surgical safety checks roused up the clinical staff’s compliance in performing safety checks, and enhanced team collaboration and communication.

In this study, we developed a long noncoding RNA (lncRNA)‐based prognostic signature for stratification of patients with head a nd neck squamous cell carcinoma (HNSCC). In total, 493 HNSCC samples obtained from the Cancer Genome Atlas database were divided into training and testing cohorts (3:2 ratio). We identified 3913 immune‐related lncRNAs in the HNSCC training cohort by Pearson correlation analysis; only seven were independently associated with overall survival and were used to develop an immune‐related lncRNA prognostic signature (IRLPS) grouping of HNSCC patients into high‐ and low‐IRLPS subgroups. Univariate and multivariate Cox analyses revealed that low‐IRLPS patients had a better prognosis in all the cohorts, which was retained after stratification by sex, grade, and HPV status. Although the TNM stage was also an independent prognostic factor, the IRLPS had a better discriminability with higher AUC at the 3‐ and 5‐year follow‐ups in all cohorts. Low‐IRLPS samples had more immune cell infiltration and were enriched in immune‐related pathways, while high‐ IRLPS samples were enriched in metabolic pathways. A nomogram constructed including age, TNM stage, and IRLPS showed good calibration. Thus, IRLPS improves the prognostic prediction and also distinguishes different tumor microenvironment (TME) in HNSCC patients., We developed an immune‐related lncRNA signature for head and neck squamous cell carcinoma (HNSCC) patients, which could improve the prognostic prediction and distinguish different tumor microenvironments (TMEs) in HNSCC patients.

Background In lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP. Case presentation Case 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months. Conclusion Our cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions.

Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity. However, the inherent properties of these drugs, such as large molecular weight, poor stability, and conformational flexibility, make them difficult to be formulated and delivered. Injection is the primary route for clinical administration of protein and peptide drugs, which usually leads to poor patient's compliance. As a portable, minimally invasive device, microneedles (MNs) can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation. In this review, we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs. Emphasis was given to the latest development in representative MNs design and fabrication. We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery, especially in the field of infectious disease, diabetes, cancer, and other disease therapy. Finally, the current status of clinical translation and a perspective on future development are also provided., Graphical abstract Proteins and peptides have become a significant therapeutic modality for various diseases, and microneedles provide a great prospect for the transdermal delivery of proteins and peptides.Image 1

The value assessment of job skills is important for companies to select and retain the right talent. However, there are few quantitative ways available for this assessment. Therefore, we propose a data-driven solution to assess skill value from a market-oriented perspective. Specifically, we formulate the task of job skill value assessment as a Salary-Skill Value Composition Problem, where each job position is regarded as the composition of a set of required skills attached with the contextual information of jobs, and the job salary is assumed to be jointly influenced by the context-aware value of these skills. Then, we propose an enhanced neural network with cooperative structure, namely Salary-Skill Composition Network (SSCN), to separate the job skills and measure their value based on the massive job postings. Experiments show that SSCN can not only assign meaningful value to job skills, but also outperforms benchmark models for job salary prediction., The value assessment of job skills is critical for companies to select and retain the right talent and for individuals to develop them. Here the authors show that a data-driven method based on an enhanced neural network can assign meaningful value to job skills in a quantitative way and outperforms benchmark models for job salary prediction.

DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1/ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy.

This cross‐sectional and longitudinal descriptive analysis aimed to track the evolving landscape of global immuno‐oncology (IO) trials and provide insight into the resolution of IO‐related controversies. Clinical trials (n = 4510) registered on ClinicalTrials.gov in 2007 to 2019 studying immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), cancer vaccines and immune modulators were included. Most of IO trials are Phase 2 and focus on ICIs and multiple IO therapies. The United States leads global IO research, with stable growth and the best methodological quality. Mainland China ranks first in the number of ACT trials but has the lowest article publication rate (6.2%). A multiple‐arm comparative design is often adopted in multiple IO therapies trials (44.0%). Trials studying ICIs and multiple IO therapies are likely to use early registration (80.0% and 86.6%) and stringent corticosteroid‐/infection‐related criteria. Hospitals have provided the most extensive and strongest support for all IO categories. Big pharma prefers to fund Phase 3‐4 ICI trials (6.98%), while small pharma has a wider sponsorship favoring Phase 1‐2 trials. The “partial‐use‐of‐corticosteroids” strategy is generally well accepted in ICI trials with a definitive trend (32.5%; P, What's new? In recent decades, immunotherapy has emerged and advanced to become a key part of cancer‐fighting strategies. The rapid growth of immuno‐oncology, however, has been accompanied by controversy in suitable interventions and trial design. In this cross‐sectional and longitudinal analysis, disparities in design were found to be common in immuno‐oncology trials, with differences influenced by factors such as cancer type and trial sponsor. Trials with strict limitations on corticosteroid use had significantly higher publications rates than trials permitting partial corticosteroid administration. The data further suggest that timely publication of immuno‐oncology trials is the third year after trial completion.