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Abstract Extremely low‐frequency (ELF) electromagnetic (EM) waves adeptly propagate in harsh cross‐medium environments, overcoming rapid decay that hinders high‐frequency counterparts. Traditional antennas, however, encounter challenges concerning size, efficiency, and power. Here, drawing inspiration from nature, we present a groundbreaking piezo‐actuated, bionic flapping‐wing magnetic‐dipole resonator (BFW‐MDR), operating in the electro‐mechano‐magnetic coupling mechanism, designed for efficient ELF EM wave transmission. The unique rigid‐flexible hybrid flapping‐wing structure magnifies rotation angles of anti‐phase magnetic dipoles by tenfold, leading to constructive superposition of emitted magnetic fields. Consequently, the BFW‐MDR exhibits a remarkable quality factor of 288 and an enhanced magnetic field emission of 514 fT at 100 meters with only 6.9 mW power consumption, surpassing traditional coil antennas by three orders of magnitude. The communication rate is doubled by the ASK+PSK modulation method. Its robust performance in cross‐medium communication, even amidst various interferences, underscores its potential as a highly efficient antenna for underwater and underground applications.

Abstract The coupling capacitance between the line and the transducer cannot be ignored when making non‐contact voltage measurements on low‐voltage three‐phase power lines. This leads to an increase in the number of unknown capacitances, and the number of correlatable response voltage equations is less than the number of unknown coupling capacitances. In this paper, a simplified decoupling method is proposed based on the characteristics of triangular three‐phase lines erected in distribution areas. Firstly, the equivalent circuit measured by the voltage sensing mechanism during three‐phase operation is established, and the three‐phase line response voltage equation is derived. Secondly, this paper proposes a three‐phase line response voltage decoupling algorithm after designing the decoupling matrix. Then, this paper uses the least squares method to solve the coefficients in the equations. Finally, the three‐phase voltage fluctuations of the actual low‐voltage stations are simulated by simulation. The measured sensor voltage values are substituted into the algorithm to invert and calculate the three‐phase line voltage. The three‐phase phase error is less than 2°. The amplitude error is less than 1.77%. The experiment verifies the stability and accuracy of the proposed decoupling method.

Abstract Intestinal ischemia/reperfusion (I/R) injury is a life‐threatening condition with no effective treatment currently available. Curcumin (CCM), a polyphenol compound in Curcuma Longa, reportedly has positive effects against intestinal I/R injury. However, the mechanism underlying the protective effect of CCM against intestinal I/R injury has not been fully clarified. To determine whether the protective effect of CCM was mediated by epigenetic effects on Wnt/β‐catenin signaling, the effect of CCM was examined in vivo and in vitro. An intestinal I/R model was established in Sprague–Dawley (SD) rats with superior mesenteric artery occlusion, and Caco‐2 cells were subjected to hypoxia/reoxygenation (H/R) for in vivo simulation of I/R. The results showed that CCM significantly reduced inflammatory, cell apoptosis, and oxidative stress induced by I/R insult in vivo and in vitro. Western blot analysis showed that CCM preconditioning reduced the protein levels of β‐catenin, p‐GSK3β, and cyclin‐D1 and increased the protein level of GSK3β compared with the I/R group. Overexpressing β‐catenin aggravated H/R injury, and knocking down β‐catenin relieved H/R injury by improving intestinal permeability and reducing the cell apoptosis. Moreover, Naked cuticle homolog 2(NKD2) mRNA and protein levels were upregulated in the CCM‐pretreated group. 5‐aza‐2′‐deoxycytidine (5‐AZA) treatment improved intestinal epithelial barrier impairment induced by H/R. Besides, the protein levels of total β‐catenin, phosphor‐β‐catenin and cyclin‐D1 were reduced after overexpressing NKD2 in Caco‐2 cells following H/R insult. In conclusion, Our study suggests that CCM could attenuate intestinal I/R injury in vitro and in vivo by suppressing the Wnt/β‐catenin signaling pathway via inhibition of NKD2 methylation.

Abstract Introduction This study aimed to validate the effectiveness, safety and feasibility of water‐filtered infrared A radiation (WIRA) whole‐body hyperthermia combined with immune checkpoint inhibitor (ICI) therapy (HIT) and evaluate the real‐world clinical application prospects. Methods This open‐label single‐arm phase 2 clinical trial (NCT06022692) aimed to enrol advanced gastrointestinal tumour (GIT) patients with the MSS/pMMR phenotype. The patients were treated with whole‐body hyperthermia on Days 1 and 8 of each HIT cycle along with administration of tislelizumab on Day 2. Results Between 1 June 2020 and 31 May 2022, 18 patients were enrolled in the study, including those with gastric cancer (n = 6), colon cancer (n = 7), rectal cancer (n = 3) and appendiceal cancer (n = 2). As of 19 May 2023, 17 of the 18 patients had died, including 14 deaths caused by tumour progression and three deaths caused by diseases other than cancer, while one patient was still undergoing follow‐up. In terms of efficacy, the median DCR was 55.6%, while the median PFS and OS were 53.5 days and 134 days, respectively. Four patients (22.2%) experienced immune‐related adverse events, and none of the patients reported grade 3 or higher irAEs. Hyperthermia was followed by an increase in the number of tumour immune‐activated cells. Conclusions HIT can provide survival benefits in patients with GITs by activating antitumour immune function and shows good safety and feasibility.

Abstract Background Immune checkpoint inhibitor (ICI) combination therapies have shown promise in the first‐line treatment of advanced biliary tract cancer (BTC). However, the best partner remains to be validated. Moreover, progress on biomarkers predicting the efficacy of ICI in BTC is slow. This study aimed to assess the efficacy and investigate reliable predictive biomarkers of programmed cell death protein‐1 (PD‐1) antibody combination therapy in the first‐line treatment of advanced BTC. Methods Clinical data from patients with advanced BTC who received chemotherapy or anti‐PD‐1 combination therapy as first‐line were collected. The primary outcome was overall survival (OS). Biomarkers, including peripheral blood inflammation scores, genetic alterations, and tumor microenvironment were investigated. Findings Sixty‐four patients were recruited and divided into four treatment groups: chemotherapy, anti‐PD‐1 plus chemotherapy, anti‐PD‐1 plus targeted therapy, and triple group (anti‐PD‐1 plus chemotherapy and targeted therapy). The median OS was 7.9, 11.3, 12.8, and 28.7 months, respectively. Compared to chemotherapy, mOS significantly prolonged in the triple group (p = 0.031). It showed that patients with five different peripheral blood inflammation scores had significantly prolonged mOS (p 2) group showed significantly superior OS (p = 0.003). Interpretation First‐line anti‐PD‐1 combination therapy was superior to chemotherapy, and triple therapy significantly improved survival. Peripheral blood immune‐inflammation score, FOXP3/CD8 ratio, and PLUS have potential as biomarkers for predicting the efficacy of first‐line anti‐PD‐1 therapy in advanced BTC.

Abstract Introduction Dexmedetomidine (DEX) is primarily utilized for sedation in the context of general anesthesia or intensive care. However, the exact regulatory mechanism by which DEX affects cytokines remains unclear. This study aims to investigate the underlying mechanism by which DEX inhibits proinflammatory factors through activation of the β2 adrenergic receptor (β2 AR). Methods The inflammatory cell model of human mononuclear macrophage (THP‐1) cells induced by lipopolysaccharide (LPS) was established to study the effect of DEX on the expression of cell‐related inflammatory factors. ADRA2A gene knockout THP‐1 cells (THP‐1KO) were constructed by CRISPR technology, and the effect of DEX on the expression of inflammatory factors of THP‐1KO cells was detected. The target sites of DEX on β2 AR were screened by molecular docking. Reversion experiments were performed using ADRB2‐siRNA. Western blot was used to detect the activation of β2 AR/PKA/CREB pathway and NF‐κB, and ELISA was used to detect the release level of inflammatory factors. Results The results demonstrated a significant reduction in the expression levels of MCP‐1, interleukin‐06, and IL‐8 in both THP‐1 and THP‐1KO cells when induced by LPS following treatment with DEX. Additionally, DEX treatment led to an increase in IL‐10 expression. Immunofluorescence analysis revealed an upregulation of β2 AR expression after DEX treatment. Western blot results indicated that DEX notably enhanced the activation of the β2 AR and PKA/CREB pathways, while concurrently suppressing the activation of NF‐κB. Notably, the use of ADRB2 siRNA reversed the effects of DEX treatment and promoted the release of inflammatory cytokines. Conclusion DEX initiates the activation of the PKA/CREB pathway through the activation of β2 AR. Simultaneously, it exerts an inhibitory effect on the activation of NF‐κB, consequently reducing the transcription of proinflammatory factors while increasing the transcription of anti‐inflammatory factors.

Abstract Background We aimed to explore the associations of adherence to an overall healthy lifestyle with cardiometabolic diseases (CMDs) among schoolteachers in China. Methods We conducted a cross‐sectional analysis among 2983 teachers (aged 39.8 ± 9.3 years, 73.8% women) in Zhejiang Province, China. A healthy lifestyle score (0–7) was constructed based on seven low‐risk factors: healthy diet, noncurrent smoking, noncurrent drinking, regular exercise, normal body mass index (BMI), adequate sleep duration, and limited sedentary behavior. CMDs included self‐reported hyperlipidemia, hypertension, diabetes, coronary heart disease, and stroke. Multivariable‐adjusted logistic regression models were used to evaluate the associations between healthy lifestyle and CMD. Results A total of 493 (16.5%) participants had at least one CMD, with hyperlipidemia, hypertension, and diabetes being the three leading CMDs. Each point increment in a healthy lifestyle score was associated with 20% lower odds of having CMD (p‐trend

An implementable algorithm for solving nonsmooth nonconvex constrained optimization is proposed by combining bundle ideas, proximity control, and the exact penalty function. We construct two kinds of approximations to nonconvex objective function; these two approximations correspond to the convex and concave behaviors of the objective function at the current point, which captures precisely the characteristic of the objective function. The penalty coefficients are increased only a finite number of times under the conditions of Slater constraint qualification and the boundedness of the constrained set, which limit the unnecessary penalty growth. The given algorithm converges to an approximate stationary point of the exact penalty function for constrained nonconvex optimization with weakly semismooth objective function. We also provide the results of some preliminary numerical testing to show the validity and efficiency of the proposed method.

Abstract A simple and effective method was reported for the rapid synthesis of zeolite X from kaolin by adding a template agent. The results of X‐ray diffraction confirm the good crystallinity of the synthesized X‐zeolite with lamellar structure. Transmission electron microscopy images clearly demonstrate the lamellar structure of the synthesized X‐zeolite. The corresponding selective electron diffraction pattern suggests that the crystal structure of X‐type zeolite is octahedral. The co‐existence and uniform distribution of Si, Al, O, and Na in the layered structure of the synthesized X‐type zeolite are detected by element mapping. In addition, N2 adsorption–desorption measurement indicates that the specific surface area of the lamellar zeolite X is 153.4625 m2 g−1. The micropore surface area is 148.8374 m2 g−1, and the micropore volume is 0.073377 m2 g−1. After exploring the influence of different temperatures on the adsorption of carbon dioxide, the research shows that two‐dimensional zeolite X has the best adsorption capacity for carbon dioxide. The adsorption and separation performance of CO2/CH4 was investigated. The study showed that the adsorption and separation coefficient of two‐dimensional zeolite X was the highest.

Abstract Background To evaluate the diagnostic performance of radiologists on breast cancer with or without artificial intelligence (AI) support. Methods A retrospective study was performed. In total, 643 mammograms (average age: 54 years; female: 100%; cancer: 62.05%) were randomly allocated into two groups. Seventy‐five percent of mammograms in each group were randomly selected for assessment by two independent radiologists, and the rest were read once. Half of the 71 radiologists could read mammograms with AI support, and the other half could not. Sensitivity, specificity, Youden's index, agreement rate, Kappa value, the area under the receiver operating characteristic curve (AUC) and the reading time of radiologists in each group were analyzed. Results The average AUC was higher if the AI support system was used (unaided: 0.84; with AI support: 0.91; p

Abstract Background The lack of standardized delineation of lymph node station in lung cancer radiotherapy leads to nonstandard clinical target volume (CTV) contouring, especially in patients with bulky lump gross target volume lymph nodes (GTVnd). This study defines lymph node region boundaries in radiotherapy for lung cancer and automatically contours lymph node stations based on the International Association for the Study of Lung Cancer (IASLC) lymph node map. Methods Computed tomography (CT) scans of 200 patients with small cell lung cancer were collected. The lymph node zone boundaries were defined based on the IASLC lymph node map, with adjustments to meet radiotherapy requirements. Contours of lymph node stations were confirmed by two experienced oncologists. A model (DiUNet) was constructed by incorporating the contours of GTVnd to precisely contour the boundaries. Quantitative evaluation metrics and clinical evaluations were conducted. Results The mean 3D Dice similarity coefficient (Dice similarity coefficient) values of DiUNet in most lymph node stations was greater than 0.7, 98.87% of the lymph node station slices are accepted. The mean DiUNet score was not significantly different from that of the man contoured in the evaluation of lymph node stations and CTV. Conclusion This is the first study to propose a method that automatically contours lymph node regions station by station based on the IASLC lymph node map with bulky lump GTVnd. Delineation of lymph node stations based on the DiUNet model is a promising strategy to obtain accuracy and efficiency for CTV delineation in lung cancer patients, especially for bulky lump GTVnd.

Background and Purpose. Motor dysfunction of the lower limb is a common sequela in stroke patients. The aim was to evaluate the efficacy of cathodal transcranial direct current stimulation (ctDCS) combined with conventional gait rehabilitation (CGR) to compare and clarify the clinical rehabilitation efficacy of ctDCS on motor dysfunction of the lower limbs after stroke to improve the walking ability of stroke patients. Methods. A pilot double-blind and randomized clinical trial. Ninety-one subjects with subacute stroke were treated with cathodal/sham stimulation tDCS based on CGR (physiotherapy 40 min/d and occupational therapy 20 min/d) once daily for 20 consecutive working days. Computer-based stratified randomization (1 : 1) was employed by considering age and sex, with concealed assignments in opaque envelopes to ensure no allocation errors after disclosure at the study’s end. Patients were evaluated at T0 before treatment, T1 immediately after the posttreatment assessment, and T2 assessment one month after the end of the treatment. The primary outcome index was assessed: lower limb Fugl-Meyer motor score (FMA-LE); secondary endpoints were other gait assessment and relevant stroke scale assessment. Results. Patients in the trial group performed significantly better than the control group in all primary outcome indicators assessed posttreatment T1 and at follow-up T2: FMA-LE outcome indicators between the two groups in T1 (P=0.032; effect size 1.00, 95% CI: 0.00 to 2.00) and FMA-LE outcome indicators between the two groups in T2 (P=0.010; effect size 2.00, 95% CI: 1.00 to 3.00). Conclusion. In the current pilot study, ctDCS plus CGR was an effective treatment modality to improve lower limb motor function with subacute stroke. The effectiveness of cathodal tDCS in poststroke lower limb motor dysfunction is inconclusive. Therefore, a large randomized controlled trial is needed to verify its effectiveness.

Objective. Many stroke victims have severe swallowing problems. Previous neuroimaging studies have found that several brain regions scattered in the frontal, temporal, and parietal lobes, such as Brodmann’s areas (BA) 6, 21, and 40, are associated with swallowing function. This study sought to investigate changes in swallowing function and resting-state functional magnetic resonance imaging (rs-fMRI) in stroke patients with dysphagia following action observation treatment. It also sought to detect changes in brain regions associated with swallowing in stroke patients. Methods. In this study, 12 healthy controls (HCs) and 12 stroke patients were recruited. Stroke patients were given 4 weeks of action observation therapy. In order to assess the differences in mfALFF values between patients before treatment and HCs, the fractional amplitude of low-frequency fluctuations (fALFF) in three frequency bands (conventional frequency band, slow-4, and slow-5) were calculated for fMRI data. The significant brain regions were selected as regions of interest (ROIs) for subsequent analysis. The mfALFF values were extracted from ROIs of the three groups (patients before and after treatment and HCs) and compared to assess the therapeutic efficacy. Results. In the conventional band, stroke patients before treatment had higher mfALFF in the inferior temporal gyrus and lower mfALFF in the calcarine fissure and surrounding cortex and thalamus compared to HCs. In the slow-4 band, there was no significant difference in related brain regions between stroke patients before treatment and HCs. In the slow-5 band, stroke patients before treatment had higher mfALFF in inferior cerebellum, inferior temporal gyrus, middle frontal gyrus, and lower mfALFF in calcarine fissure and surrounding cortex compared to HCs. We also assessed changes in aberrant brain activity that occurred both before and after action observation therapy. The mfALFF between stroke patients after therapy was closed to HCs in comparison to the patients before treatment. Conclusion. Action observation therapy can affect the excitability of certain brain regions. The changes in brain function brought about by this treatment may help to further understand the potential mechanism of network remodeling of swallowing function.

Abstract Background Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community‐dwelling healthy menopausal women. Methods Estimated SMM was derived from whole‐body dual‐energy X‐ray absorptiometry. We performed integrated analyses on whole‐genome sequencing, shotgun metagenomic sequencing, and serum short‐chain fatty acids (SCFAs), as well as available host SMM measurements among community‐dwelling healthy menopausal women (N = 482). We combined the results with summary statistics from genome‐wide association analyses for human gut microbiome (N = 952) and SMM traits (N = 28 330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one‐sample and two‐sample Mendelian randomization (MR) analyses, respectively. Results In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels [Spearman correlation coefficient (SCC) = 0.13, P = 0.02] and skeletal muscle index (SCC = 0.084, P = 0.002). Of interest was the finding that two main butyrate‐producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate [Faecalibacterium prausnitzii (SCC = 0.25, P = 6.6 × 10−7) and Butyricimonas virosa (SCC = 0.15, P = 0.001)] and for skeletal muscle index [F. prausnitzii (SCC = 0.16, P = 6.2 × 10−4) and B. virosa (SCC = 0.17, P = 2.4 × 10−4)]. One‐sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.04, 95% confidence interval 0.029 to 0.051, P = 0.003). Two‐sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.06, 95% confidence interval 0 to 0.13, P = 0.06). Conclusions Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.

Abstract Aims The management of heart failure (HF) in young children is challenging. The present study aimed to clarify the effect of left univentricular epicardial pacing on dilated cardiomyopathy with left bundle branch block (LBBB) in children. Methods and results A total of five cases (30.86 ± 16.39 months, three female) of children weighing 5.8–15 kg with dilated cardiomyopathy and LBBB were included in this study. LBBB in one child occurred after device closure of peri‐membranous ventricular septal defects, and the remaining four were idiopathically discovered early after birth. Before implantation, all children suffered from refractory HF and cardiac dilatation; the left ventricular ejection fraction was 33.48 ± 5.84% with Ross Heart Failure Classification III–IV. Electrical and mechanical dyssynchrony were observed in all children with QRS duration >140 ms and prolonged septal‐to‐left posterior wall motion delay. Left univentricular epicardial pacing was successfully implanted via left axillary minithoracotomy in the five children. Sensed atrioventricular delays (83 ± 15 ms) were optimized by velocity time integral of aortic blood flow before discharge. During the follow‐up period (10.8 ± 2.68 months), the dilated failing heart was reversed significantly in terms of decreased left ventricular dimension (55.62 ± 3.46 vs. 38.94 ± 3.69 mm, P = 0.005), while the left ventricular ejection fraction improved to 60.18 ± 8.78% (P = 0.006). Conclusions In young children with low body weight, if HF is caused by or related to LBBB, left ventricular epicardial pacing still has an excellent effect.

Abstract Background Little is known about the prognostic advantage of sex for pulmonary adenocarcinoma among Chinese patients. In this study, we aimed to investigate the true sex differences in prognosis by adjusting for confounders and to explore whether the differences were time‐varying. Methods We identified 4438 lung adenocarcinoma patients who underwent surgery at a regional Cancer Center of China from 2008 to 2016, retrospectively. Sex, age group, smoking history, year of diagnosis and pathological stage were collected. Time‐dependent Cox regression models with inverse probability of treatment weighting (IPTW) based on propensity score were used to assess the effect of sex and account for confounders. Landmark analyses were conducted to assess survival before, and after, five years. Results Of these patients, 1761 (39.7%) were men and 2677 (60.3%) were women. Median follow‐up time was 52.6 months. After IPTW adjustment, women were found to have significantly better survival than men varying with time in both crude and IPTW models (hazard ratio [HR] [t] = 0.453*1.015t, where t is the length of time from treatment and its unit is month, p

Abstract Qingke Pingchuan granules (QKPCG), a patented traditional Chinese medicine, clinically, are recommended for acute tracheobronchitis, cough, community‐acquired pneumonia, and other respiratory diseases. However, its potential protective effect and mechanism of action in acute lung injury (ALI) have not been explored. We aimed to explore the mechanisms underlying the protective role of QKPCG in ALI. The therapeutic efficacy of QKPCG was investigated in a lipopolysaccharide (LPS)‐induced ALI mouse model. Mice were divided into three groups, namely, the Control, LPS, and LPS + QKPCG groups. Mice in the LPS + QKPCG group were administered QKPCG intragastrically as a treatment once a day for a total of three days. QKPCG effectively increased survival and reduced lung injury in treated mice. It significantly reduced the LPS‐induced expression of interleukin (IL)‐6, tumor necrosis factor‐α (TNF‐α), IL‐1α, and IL‐1β. RNA‐sequencing followed by real‐time quantitative polymerase chain reaction validation suggested a critical role of the secretoglobin family 1A member 1 (Scgb1a1) gene in mediating the protective effect of QKPCG. Further, QKPCG reversed the LPS‐induced downregulation of the Clara cell 10 kDa protein (CC10), a pulmonary surfactant protein encoded by Scgb1a1, which is mainly secreted by club cells in the lungs. Exogenous supplementation of CC10 alleviated LPS‐induced ALI. Hematoxylin and eosin staining and enzyme‐linked immunosorbent assay results further confirmed the anti‐inflammatory properties of CC10, which were suggested as mediated via the inhibition of NFκB phosphorylation. In summary, our study provides evidence of the beneficial role of QKPCG in alleviating lung injury, mediated via the decreased disruption of club cells and higher expression of CC10, which leads to NFκB pathway inhibition.

Abstract Background Relative telomere length (RTL) in leukocytes has been linked to risks of many cancers, although how leukocyte RTL contributes to adult glioma has rarely been studied Aim We performed a case‐control study to evaluate the association between RTL in leukocytes and glioma risk in 565 glioma patients and 1130 healthy controls Methods and results Overall, mean leukocyte RTL was significantly higher in cases than controls (P

Abstract Objectives To develop computerized adaptive testing (CAT) and short forms of self‐report oral health measures that are predictive of both the children's oral health status index (COHSI) and the children's oral health referral recommendation (COHRR) scales, for children and adolescents, ages 8–17. Material and methods Using final item calibration parameters (discrimination and difficulty parameters) from the item response theory analysis, we performed post hoc CAT simulation. Items most frequently administered in the simulation were incorporated for possible inclusion in final oral health assessment toolkits, to select the best performing eight items for COHSI and COHRR. Results Two previously identified unidimensional sets of self‐report items consisting of 19 items for the COHSI and 22 items for the COHRR were administered through CAT resulting in eight‐item short forms for both the COHSI and COHRR. Correlations between the simulated CAT scores and the full item bank representing the latent trait are r = .94 for COHSI and r = .96 for COHRR, respectively, which demonstrated high reliability of the CAT and short form. Conclusions Using established rigorous measurement development standards, the CAT and corresponding eight‐item short form items for COHSI and COHRR were developed to assess the oral health status of children and adolescents, ages 8–17. These measures demonstrated good psychometric properties and can have clinical utility in oral health screening and evaluation and clinical referral recommendations.

Adherence with antiretroviral therapy is important for preventing disease progression and HIV transmission. The co‐encapsulated pill sensor system sends a signal through a cutaneous patch and allows real‐time monitoring of pill ingestion. A 16‐week pilot study used a sensor system in 15 HIV‐infected individuals with real‐time monitoring of pill‐taking with a personalized short message system text. System acceptability was assessed by survey at weeks 4, 8, 12, and 16. Follow‐up occurred in 80% of subjects through 8 weeks. The system effectively collected measures of pill ingestion, which triggered text message reminders. Only 2 of 14 participants stated that co‐encapsulated pills were “unable to take” or “poorly tolerated.” At least 75% of respondents stated at each visit that the patch was very or somewhat comfortable. With regard to text message reminders, only 10–15% of the participants at any visit did not find the messages to be helpful. Larger studies will define the utility of this system to assess antiretroviral adherence relative to standard measures.

With the evolution of space exploration, large flexible appendages have been developed in space structures. External perturbation or attitude maneuvering stimulates the vibration (low frequencies) of the aforementioned structures. In this research, a novel joint mechanism was developed in conjunction with active control to inhibit the low-frequency vibration of a large flexible appendage. A compact active joint, based on the idea of electromagnetic direct drive, was designed. The dynamic equations for the large flexible appendage system and the active joint were derived using the Lagrange function with the assumed-modes approach. Single- and multi-frequency excitations were simulated by two noncontact strategies for periodic vibration stimulation along the direction of rotation. The research results revealed that the interference signal had a primary frequency bandwidth of 0.07–0.63 Hz, and the vibration attenuation was prominent between 5.95 and 32.41 dB within the valid bandwidth. Effective inhibition of both the larger and the smaller amplitude vibrations at frequencies lower than 1 Hz could be realized using the proposed active joint without attachment of intelligent materials onto the flexible appendage surface.

The aim of the study is to further understand the rule of conversion of bottom hole pressure of a vertical well in a dual-permeability reservoir, which is about the dual permeability under different outer boundary (infinite, close, and constant value) conditions. However, there are few articles dealing with the model of a vertical well in a dual permeability reservoir under these three different outer boundary conditions. Hence, the paper proposes a model of a vertical well in a dual permeability reservoir under three outer boundary conditions. The model is solved with a Laplace space equation. We find the solution to the model that has a similar structure under three different outer boundary conditions by combining it with the similar structure theory. Therefore, we put forward a similar constructing method (SCM) that solves our model. The concrete steps of the SCM are given in this paper. At the same time, we draw the curves of the bottom hole pressure and pressure derivative using the modified Stehfest inversion formula and MATLAB software. In addition, we investigate the evolution of the pressure by changing the parameters (mobility ratio K, storability ratioω, and crossflow coefficientλ). The solution to such a reservoir model obtained in this paper could be used as a basis for analyzing other typical reservoirs with vertical wells.

Abstract Engineered cartilage derived from mesenchymal stromal cells (MSCs) always fails to maintain the cartilaginous phenotype in the subcutaneous environment due to the ossification tendency. Vascular invasion is a prerequisite for endochondral ossification during the development of long bone. As an oral antitumor medicine, Inlyta (axitinib) possesses pronounced antiangiogenic activity, owing to the inactivation of the vascular endothelial growth factor (VEGF) signaling pathway. In this study, axitinib‐loaded poly(ε‐caprolactone) (PCL)/collagen nanofibrous membranes are fabricated by electrospinning for the first time. Rabbit‐derived MSCs‐engineered cartilage is encapsulated in the axitinib‐loaded nanofibrous membrane and subcutaneously implanted into nude mice. The sustained and localized release of axitinib successfully inhibits vascular invasion, stabilizes cartilaginous phenotype, and helps cartilage maturation. RNA sequence further reveals that axitinib creates an avascular, hypoxic, and low immune response niche. Timp1 is remarkably upregulated in this niche, which probably plays a functional role in inhibiting the activity of matrix metalloproteinases and stabilizing the engineered cartilage. This study provides a novel strategy for stable subcutaneous chondrogenesis of mesenchymal stromal cells, which is also suitable for other medical applications, such as arthritis treatment, local treatment of tumors, and regeneration of other avascular tissues (cornea and tendon).

Abstract Methicillin‐resistant Staphylococcus aureus (MRSA) biofilm infections after orthopedic implant increase the risk of failure and potentially cause amputation of limbs or life‐threatening sepsis in severe cases. Additionally, satisfactory bone‐implant integration is another important indicator of an ideal implant. Here, an antibiotic‐free antibacterial nanofilm based on oxide perovskite‐type calcium titanate (CTO)/fibrous red phosphorus (RP) on titanium implant surface (Ti‐CTO/RP) in which the P–N heterojunction and internal electric field are established at the heterointerface, is designed. Near‐infrared light‐excited electron–hole pairs are effectively separated and transferred through the synergism of the internal electric field and band offset, which strongly boosts the photocatalytic eradication of MRSA biofilms by reactive oxygen species with an efficacy of 99.42% ± 0.22% in vivo. Additionally, the charge transfer endows the heterostructure with hyperthermia to assist biofilm eradication. Furthermore, CTO/RP nanofilm provides a superior biocompatible and osteoconductive platform that enables the proliferation and osteogenic differentiation of mesenchymal stem cells, thus contributing to the subsequent implant‐to‐bone osseointegration after eradicating MRSA biofilms.

Abstract Background The correct classification of an adverse drug reaction (ADR) as allergy (immunological) or intolerance (non-immunological) has important clinical implications. The aim of this study was to examine the ability of health professionals to discriminate between allergy and intolerance, classify the severity of the ADR and degree of contraindication. Methods Health professionals were presented ten ‘real-life’ ADR scenarios using an online questionnaire and asked to: categorise the reaction as allergy or intolerance, rate the severity of the reaction and judge the level of contraindication of the causative drug. The number and proportion of responses were calculated for each of the cases presented and associations between classification of reaction type, severity and level of contraindication were examined. Results A total of 394 responses were received. Overall 59.0% (SD 28.9) correctly categorised the cases, 60.8% (SD 16.8) classified the severity correct, and less than half (44.7%, SD 28.6) correctly identified the level of contraindication. The proportion of health professionals correctly answering the type, severity and level of contraindication for the allergy case was significantly higher (p

A milestone step in translational science to transform basic scientific discoveries into therapeutic applications is the advancement of a drug candidate from preclinical studies to initial human testing. First‐in‐human (FIH) trials serve as the link to advance new promising drug candidates and are conducted primarily to determine the safe dose range for further clinical development. Cross‐functional collaboration is essential to ensure efficient and successful FIH trials. The aim of this publication is to serve as a tutorial for conducting FIH trials for both small molecule and biological drug candidates with topics covering regulatory requirements, preclinical safety testing, study design considerations, safety monitoring, biomarker assessment, and global considerations. An emphasis is placed on FIH trial design considerations, including starting dose selection, study size and population, dose escalation scheme, and implementation of adaptive designs. In light of the recent revision of the European Medicines Agency (EMA) guideline on FIH trials to promote safety and mitigate risk, we also discuss new measures introduced in the guideline that impact FIH trial design.

Underwater object detection plays an important role in research and practice, as it provides condensed and informative content that represents underwater objects. However, detecting objects from underwater images is challenging because underwater environments significantly degenerate image quality and distort the contrast between the object and background. To address this problem, this paper proposes an optical prior-based underwater object detection approach that takes advantage of optical principles to identify optical collimation over underwater images, providing valuable guidance for extracting object features. Unlike data-driven knowledge, the prior in our method is independent of training samples. The fundamental novelty of our approach lies in the integration of an image prior and the object detection task. This novelty is fundamental to the satisfying performance of our approach in underwater environments, which is demonstrated through comparisons with state-of-the-art object detection methods.

For CVaR (conditional value-at-risk) portfolio nonsmooth optimization problem, we propose an infeasible incremental bundle method on the basis of the improvement function and the main idea of incremental method for solving convex finite min-max problems. The presented algorithm only employs the information of the objective function and one component function of constraint functions to form the approximate model for improvement function. By introducing the aggregate technique, we keep the information of previous iterate points that may be deleted from bundle to overcome the difficulty of numerical computation and storage. Our algorithm does not enforce the feasibility of iterate points and the monotonicity of objective function, and the global convergence of the algorithm is established under mild conditions. Compared with the available results, our method loosens the requirements of computing the whole constraint function, which makes the algorithm easier to implement.

Abstract Objectives Epstein–Barr virus (EBV) infection is associated with a better response to anti‐PD1 immunotherapy. We hypothesised that genetic alterations induced by EBV infection are responsible for the activation of key immune responses and hence are predictive of anti‐PD1 efficacy. Methods With transcriptome data of gastric cancer (GC), we explored differentially expressed genes (DEGs) specific for EBV infection and performed coexpression network analysis using the DEGs to identify the consistent coexpression genes (CCGs) between EBV‐positive and EBV‐negative GC tissues. We selected the tag genes of the CCGs and validated them using RNA sequencing and immunohistochemistry. We established murine models and collected tissues from clinical patients to test the value of SLAMF8 in predicting anti‐PD1 treatment. The location and expression of SLAMF8 were characterised by multiplex immunofluorescence and quantitative PCR. Moreover, exogenous overexpression and RNA‐sequencing analysis were used to test the potential function of SLAMF8. Results We identified 290 CCGs and validated the tag gene SLAMF8 in transcriptome data of gastrointestinal cancer (GI). We observed that the T‐cell activation pathway was significantly enriched in high‐expression SLAMF8 GI cancers. Higher SLAMF8 expression was positively associated with CD8 expression and a better response to anti‐PD1 treatment. We further observed dynamically increased expression of SLAMF8 in murine models relatively sensitive to anti‐PD1 treatment. SLAMF8 was mainly expressed on the surface of macrophages. Exogenous overexpression of SLAMF8 in macrophages resulted in enrichment of positive regulation of multiple immune‐related pathways. Conclusion Higher SLAMF8 expression may predict better anti‐PD1 immunotherapy efficacy in GI cancer.

Abstract Background Brain metastases explain the majority of mortality associated with lung cancer, which is the leading cause of cancer death. Cytology analysis of the cerebrospinal fluid (CSF) remains the diagnostic gold standard, however, the circulating tumor cells (CTCs) in CSF (CSF‐CTCs) are not well defined at the molecular and transcriptome levels. Methods We established an effective CSF‐CTCs collection procedure and isolated individual CSF cells from five lung adenocarcinoma leptomeningeal metastases (LUAD‐LM) patients and three controls. Three thousand seven hundred ninety‐two single‐cell transcriptomes were sequenced, and single‐cell RNA sequencing (scRNA‐seq) gene expression analysis was used to perform a comprehensive characterization of CSF cells. Results Through clustering and expression analysis, we defined CSF‐CTCs at the transcriptome level based on epithelial markers, proliferation markers, and genes with lung origin. The metastatic‐CTC signature genes are enriched for metabolic pathway and cell adhesion molecule categories, which are crucial for the survival and metastases of tumor cells. We discovered substantial heterogeneity in patient CSF‐CTCs. We quantified the degree of heterogeneity and found significantly greater among‐patient heterogeneity compared to among‐cell heterogeneity within a patient. This observation could be explained by spatial heterogeneity of metastatic sites, cell‐cycle gene, and cancer‐testis antigen (CTA) expression profiles as well as the proportion of CTCs displaying mesenchymal and cancer stem cell properties. In addition, our CSF‐CTCs transcriptome profiling allowed us to determine the biomarkers during the progression of an LM patient with cancer of unknown primary site (CUP). Conclusions Our results will provide candidate genes for an RNA‐based digital detection of CSF‐CTCs from LUAD‐LM and CUP‐LM cases, and shed light on the therapy and mechanism of LUAD‐LM.

Cardiovascular disease, which can lead to angina and shortness of breath, remains one of the most serious threats to human health. Owing to its imperceptible symptoms, it is difficult to determine the pathogenesis and treatment methods for cardiovascular disease. Nuclear factor erythropoietin-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) is a protein found in all cells of the human body. It is activated, transferred to the nucleus, and bound to DNA by antioxidant response elements (AREs). As a regulator of the antioxidant system, it upregulates the expression of HO-1 to reduce oxidative stress. Nrf2/HO-1 also has the ability to modulate calcium levels to prevent ferroptosis, pyroptosis, autophagy, programmed cell necrosis, alkaliptosis, and clockophagy. In view of the importance of Nrf2/HO-1 in the regulation of homeostasis, this review summarizes current research on the relationship between cardiovascular disease and Nrf2/HO-1. Normal cardiovascular diseases, such as viral myocarditis and myocardial ischemia-reperfusion injury, have been treated with Nrf2/HO-1. Rheumatic heart disease, cardiac tumors, arteriosclerosis, arrhythmia, hypertensive heart disease, and myocardial infarction have also been treated during experiments. Research has demonstrated the clinical application of Nrf2/HO-1 in pediatric cardiovascular disease; further clinical trials will help elucidate the potential of the Nrf2/HO-1 signaling axis.

Objective. Type 2 diabetes mellitus (T2DM) is featured by insulin resistance and lipid metabolism dysregulation. A large number of miRNAs were identified in exosomes derived from adipose tissue macrophages associated with T2DM pathogenesis, but its pathogenic roles remain unknown. This study is aimed at investigating the function of miR-210 in diabetic obesity. Methods. Exosomes from mouse macrophage RAW264.7 cells were characterized by electron microscopy, combined with biomarker expression by western blot. Expression of miR-210 was determined by quantitative RT-PCR. Glucose uptake was measured by a fluorometric method, and the mitochondrial respiratory chain activity was evaluated by ELISA. The target gene of miR-210 was validated by dual-luciferase reporter and pull-down assays. A mouse obese diabetic model was established by a high-fat diet and streptozocin treatment. Results. miR-210 was highly expressed in exosomes derived from high glucose-induced macrophage RAW264.7 cells. Macrophage-derived exosomes impaired glucose uptake and mitochondrial CIV complex activity and suppressed NADH dehydrogenase ubiquinone 1 alpha subcomplex 4 (NDUFA4) expression in 3T3-L1 adipocytes. miR-210 directly bind with mRNA sequences of NDUFA4 gene. Inhibition of miR-210 mitigated the effects of macrophage-derived exosomes on the glucose uptake and complex IV (CIV) activity in 3T3-L1 adipocytes, and NDUFA4 overexpression offset the inhibition of glucose uptake and CIV activity by macrophage-derived exosomes. Furthermore, mice with miR-210 knockout showed greatly repressed diabetic obesity development. Conclusion. miR-210 derived from adipose tissue macrophages promotes mouse obese diabetes pathogenesis by regulating glucose uptake and mitochondrial CIV activity through targeting NDUFA4 gene expression.

Cardiovascular diseases are an important group of diseases that seriously affect quality of life. Thus, their treatment warrants further study. Heparin-binding protein (HBP) is a granulocyte protein derived from neutrophils. When an infection occurs, neutrophils release HBP, which can lead to elevated HBP levels in the blood. Therefore, HBP family members are said to be important indicators of infection. However, basic evidence is still lacking to confirm the possible relationship between HBP and cardiovascular diseases. Using bioinformatics methods, we investigated the role of the HBP network in normal hearts and hearts from patients with cardiovascular disease. First, we used the Open Targets database to obtain a list of HBP-encoding mRNAs related to atherosclerosis, myocarditis, myocardial infarction, and myocardial ischemia. Then, we constructed an HBP gene interaction network map using STRING. Clustering coefficients were calculated using Cytoscape, and MCODE was used for subnet analysis. Finally, the proposed interstitial network of HBPs was established and analyzed by Metascape enrichment analysis of the relevant signaling pathways. The aggregation coefficient of the HBP interaction network was higher among hearts with the four cardiovascular diseases, atherosclerosis (0.496), myocarditis (0.631), myocardial infarction (0.532), and myocardial ischemia (0.551), than in normal hearts. Metascape analysis showed that “NABA_MATRISOME_ASSOCIATED” was a typical pathway with the highest p value associated with epithelialization in all four diseases. Moreover, a large number of important HBPs were identified that may be significant for the treatment of these diseases. Therefore, HBPs do have a highly atopic connectivity network in cardiovascular diseases, and specific HBPs or signaling pathways may be used as targets for the development of new treatments for cardiovascular diseases.

As the major cause of female anovulatory infertility, polycystic ovary syndrome (PCOS) affects a great proportion of women at childbearing age. Although glucagon-like peptide 1 receptor agonists (GLP-IRAs) show therapeutic effects for PCOS, its target and underlying mechanism remains elusive. In the present study, we identified that, both in vivo and in vitro, GLP-1 functioned as the regulator of proliferation and antiapoptosis of MGCs of follicle in PCOS mouse ovary. Furthermore, forkhead box protein O1 (FoxO1) plays an important role in the courses. Regarding the importance of granulosa cells (GCs) in oocyte development and function, the results from the current study could provide a more detailed illustration on the already known beneficial effects of GLP-1RAs on PCOS and support the future efforts to develop more efficient GLP-1RAs for PCOS treatment.

Chondrogenesis and subsequent osteogenesis of mesenchymal stem cells (MSCs) and angiogenesis at injured sites are crucial for bone fracture healing. Amygdalin, a cyanogenic glycoside compound derived from bitter apricot kernel, has been reported to inhibit IL-1β-induced chondrocyte degeneration and to stimulate blood circulation, suggesting a promising role of amygdalin in fracture healing. In this study, tibial fractures in C57BL/6 mice were treated with amygdalin. Fracture calluses were then harvested and subjected to radiographic, histological, and biomechanical testing, as well as angiography and gene expression analyses to evaluate fracture healing. The results showed that amygdalin treatment promoted bone fracture healing. Further experiments using MSC-specific transforming growth factor- (TGF-) β receptor 2 conditional knockout (KO) mice (Tgfbr2Gli1-Cre) and C3H10 T1/2 murine mesenchymal progenitor cells showed that this effect was mediated through TGF-β/Smad signaling. We conclude that amygdalin could be used as an alternative treatment for bone fractures.

Abstract Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive and memory loss. The vicious circle between dysfunctional microglia and amyloid‐β (Aβ) is a crucial pathological event and accelerates the progression of AD. Herein, a zwitterionic poly(carboxybetaine) (PCB)‐based nanoparticle (MCPZFS NP) with normalizing the dysfunctional microglia and Aβ recruitment is established for the treatment of AD. Compared with the neural polyethylene glycol (PEG)‐based nanoparticles (MEPZFS NPs), the MCPZFS NPs significantly alleviate the priming of microglia by decreasing the level of proinflammatory mediators and promoting the secretion of BDNF. Most importantly, quite different from PEG, the PCB‐based NPs exhibit the behavior to recruit Aβ into microglia, which significantly enhances the Aβ phagocytosis. Moreover, the Aβ degradation is changed from the conventional lysosomal/autophagy to the proteasomal pathway in the presence of MCPZFS NPs. After the treatment with MCPZFS NPs, the Aβ burden, neuron damages, memory deficits, and neuroinflammation of APPswe/PS1dE9 mice are significantly attenuated in the brain. Therefore, the PCB‐based MCPZFS NPs have great potential to serve as an “Aβ cleaner” and provide a new insight into the therapeutic strategy for AD therapy.

This study aimed to investigate the expression of miRNA-21 during intestinal barrier dysfunction induced by intestinal ischemia reperfusion. Forty SPF SD rats were divided into 5 groups randomly. Intestinal ischemia-reperfusion injury (IRI) was induced by mesenteric artery occlusion for 1 h and reperfusion for 1 h, and the rats were sacrificed at 1, 3, 6 and 12 h after reperfusion. Fresh intestine tissues were immediately isolated for the measurement of transepithelial electrical resistance (TER). The levels of cytokines, ICAM-1, DAO, iFABP and MPO in serum were determined by ELISA. Intestinal tight junction proteins occludin and claudin-1 were detected by immunofluorescence analysis and Western blot analysis. miR-21 expression in intestinal tissues was measured by RT-PCR. Compared with sham group, the levels of pro-inflammatory cytokines TNF-α and IL-6 and ICAM-1, DAO, iFABP and MPO increased while IL-10 level decreased in intestinal ischemia-reperfusion group. In addition, the levels of intestinal tight junction proteins occludin and claudin-1 decreased while miR-21 level increased in intestinal ischemia-reperfusion group, compared with sham group. In conclusion, miR-21 expression is upregulated during intestinal barrier dysfunction induced by IRI. miR-21 may play an important role in the regulation of intestinal barrier function. Keywords: Intestinal epithelial barrier, MicroRNA-21, Ischemia-reperfusion injury, Tight junction

Sepsis is a systemic inflammatory response syndrome caused by infection. With high morbidity and mortality of this disease, there is a need to find early effective diagnosis and assessment methods to improve the prognosis of patients. Heparin-binding protein (HBP) is a granular protein derived from polynuclear neutrophils. The biosynthetic HBP in neutrophils is rapidly released under the stimulation of bacteria, resulting in increased vascular permeability and edema. It is reasonable to speculate that the HBP in plasma may serve as a novel diagnostic marker for sepsis, bacterial skin infection, acute bacterial meningitis, leptospirosis, protozoan parasites, and even some noncommunicable diseases. It implies that in the detection and diagnosis of sepsis, it will be possible to make relevant diagnosis through this new indicator in the future. In this review, we summarize the typical biological function of HBP and its latest research progress to provide theoretical basis for clinical prediction and diagnosis of sepsis.

BackgroundBreastfeeding confers substantial benefits to child health and has also been associated with lower risk of maternal cardiovascular diseases (CVDs) in later life. However, the evidence on the effects of CVD is still inconsistent, especially in East Asians, in whom the frequency and duration of breastfeeding significantly differ from those in the West. Methods and ResultsIn 2004–2008, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30 to 79 years from 10 diverse regions across China. During 8 years of follow‐up, 16 671 incident cases of coronary heart disease and 23 983 cases of stroke were recorded among 289 573 women without prior CVD at baseline. Cox regression yielded adjusted hazard ratios (HRs) and 95% CIs for incident CVD by breastfeeding. Overall, ≈99% of women had given birth, among whom 97% reported a history of breastfeeding, with a median duration of 12 months per child. Compared with parous women who had never breastfed, ever breastfeeding was associated with a significantly lower risk of CVD, with adjusted HRs of 0.91 (95% CI, 0.84–0.99) for coronary heart disease and 0.92 (95% CI, 0.85–0.99) for stroke. Women who had breastfed for ≥24 months had an 18% (HR, 0.82; 0.77–0.87) lower risk of coronary heart disease and a 17% (HR, 0.83; 0.79–0.87) lower risk of stroke compared with women who had never breastfed. Among women who ever breastfed, each additional 6 months of breastfeeding per child was associated with an adjusted HR of 0.96 (95% CI, 0.94–0.98) for coronary heart disease and 0.97 (95% CI, 0.96–0.98) for stroke. ConclusionsAmong Chinese women, a history of breastfeeding was associated with an ≈10% lower risk of CVD in later life and the magnitude of the inverse association was stronger among those with a longer duration of breastfeeding.

To identify a new regimen to optimize treatment for patients with newly diagnosed type 2 diabetes (T2DM) by short-term continuous subcutaneous insulin infusion (CSII) alone. Methods. 60 patients with newly diagnosed T2DM were randomized into two groups (n=30 each) and treated for 2 weeks with CSII alone (CSII group) or with CSII plus sitagliptin (CSII + Sig group). The glycemic variability of the patients was measured using a continuous glucose monitoring system (CGMS) for the last 72 hours. A standard meal test was performed before and after the interventions, and the levels of glycated albumin, fasting glucose, fasting C-peptide, postprandial 2 h blood glucose, and postprandial 2 h C-peptide were examined. Results. Compared with the CSII group, the indicators of glycemic variability, such as the mean amplitude of glycemic excursion (MAGE) and the standard deviation of blood glucose (SDBG), were decreased significantly in the CSII + Sig group. The changes before and after treatment in the C-peptide reactivity index (ΔCPI) and the secretory unit of islet in transplantation index (ΔSUIT) indicated a significant improvement in the CSII + Sig group. Conclusions. Add-on therapy with sitagliptin may be an optimized treatment for patients with newly diagnosed T2DM compared with short-term CSII alone.

Barrier coverage is a fundamental problem for lots of applications in wireless sensor networks. In reality, sensor nodes' true locations may not be known to us considering that not every sensor node is equipped with a GPS. The measured locations of sensor nodes obtained by applying node localization algorithm often have errors, which makes it difficult to form a line-based barrier with mobile sensor nodes. In this paper, we study how to efficiently schedule mobile sensor nodes to form a barrier when sensor nodes suffer from location errors. We explore the relationship between the existence of uncovered hole and location errors and find that the lengths of uncovered holes are decided by the cumulative location errors. We also propose a method in frequency domain to efficiently calculate the distributions of the cumulative location errors. The possibility of the existence of uncovered holes can be derived by analyzing the step responses of the cumulative location errors. Extensive experimental results demonstrate the effectiveness of the proposed algorithm.

The incidence of sensorineural hearing loss (SNHL) increased gradually in the past decades. High-resolution computed tomography (HRCT) and magnetic resonance (MR) imaging, as an important part of preimplantation evaluation for children with SNHL, could provide the detailed information about the inner ear, the vestibulocochlear nerve, and the brain, so as to select suitable candidate for cochlear implantation (CI). Brain abnormalities were not rare in the brain MR imaging of SNHL children; however, its influence on the effect of CI has not been clarified. After retrospectively analyzing the CT and MR imaging of 157 children with SNHL that accepted preoperative evaluation from June 2011 to February 2013 in our hospital and following them during a period of 14.09±5.08 months, we found that the white matter change, which might be associated with the history of medical condition, was the most common brain abnormality. Usually CI was still beneficial to the children with brain abnormalities, and the short-term hearing improvement could be achieved. Further study with more patients and longer follow-up time was needed to confirm our results.

Under the condition that the values of the objective function and its subgradient are computed approximately, we introduce a cutting plane and level bundle method for minimizing nonsmooth nonconvex functions by combining cutting plane method with the ideas of proximity control and level constraint. The proposed algorithm is based on the construction of both a lower and an upper polyhedral approximation model to the objective function and calculates new iteration points by solving a subproblem in which the model is employed not only in the objective function but also in the constraints. Compared with other proximal bundle methods, the new variant updates the lower bound of the optimal value, providing an additional useful stopping test based on the optimality gap. Another merit is that our algorithm makes a distinction between affine pieces that exhibit a convex or a concave behavior relative to the current iterate. Convergence to some kind of stationarity point is proved under some looser conditions.

An implementable algorithm for solving a nonsmooth convex optimization problem is proposed by combining Moreau-Yosida regularization and bundle and quasi-Newton ideas. In contrast with quasi-Newton bundle methods of Mifflin et al. (1998), we only assume that the values of the objective function and its subgradients are evaluated approximately, which makes the method easier to implement. Under some reasonable assumptions, the proposed method is shown to have a Q-superlinear rate of convergence.