Robust voltage-controlled transcutaneous energy transfer system for artificial anal sphincter.

BACKGROUND: The artificial anal sphincter (AAS) system has gained significant attention as a solution for treating fecal incontinence (FI). It relies on transcutaneous energy transfer (TET) as its primary energy source. However, changes in posture or biological tissue can cause misalignment of the coil, resulting in unstable power reception. Inadequate power affects charging efficiency, while excessive power leads to excessive heating at the receiver side. Consequently, achieving safe and constant voltage charging for the AAS becomes a complex challenge. METHODS: To maintain a consistent charging voltage and overcome the issue of variations in load and coil coupling strength, this article proposes a wireless charging control system that utilizes an LCC-S-type resonant network and phase shift to adjust the transmitting voltage based on feedback charging voltage in real time. In particular, the PI controller and neural network are introduced to change the phase-shift angle swiftly. The dynamic performance is then evaluated under different misalignments and presented with comparative results. RESULTS: The results indicate that the multilayer perceptron control system outperforms the PI. Under the complex misalignment disturbance, the average error of receiver side load voltage is only 0.007 V, with an average settling time of 960 ms. Additionally, the average temperature at the receiver side is 40.4°C. CONCLUSION: The experiments demonstrate that the proposed system effectively addresses the misalignment issue in TET during the charging, ensuring constant voltage charging at the receiver side and thermal safety.

Simulation of artificial anal sphincter motion and interaction with intestinal environment using SOFA.

BACKGROUND: Artificial anal sphincter is an implantable medical device for treating fecal incontinence. Reasonable simulation facilitates the advancement of research and reduces experiments on biological tissue. However, the device's clamping motion and sensor interaction with the intestine in the simulation still require further exploration. This article presents a simulation of the artificial anal sphincter's clamping and sensing and its interaction with the intestinal environment using the Simulation Open Framework Architecture (SOFA). METHODS: Firstly, the proposed simulation algorithm and its principles in SOFA are analyzed. Secondly, the clamping motion and sensor system of the artificial anal sphincter are simulated. Thirdly, a finite element model of intestine is established based on the properties of intestinal soft tissue. Finally, the in vitro experiments are performed. RESULTS: The simulation results indicate that the sensor system of the artificial anal sphincter has good sensing performance during the clamping motion and fecal accumulation process. Experiments have shown that optimal sensory capabilities can be achieved as the posture of the artificial anal sphincter with a roll angle between 20° and 40°. The comparison demonstrates a mean absolute error of 10%-20% between simulation and in vitro experimental results for sensor forces, which verifies the effectiveness of the simulation. CONCLUSION: The proposed novel simulation achieves a more comprehensive interaction between the artificial anal sphincter motion and intestinal environment. This study may provide more effective simulation data for guidance in improving the performance of sensor perception of artificial anal sphincter for further research.

Correction: Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma.

[This corrects the article DOI: 10.1371/journal.pgen.1007888.].

On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial.

BACKGROUND: Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown. METHODS: Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values. RESULTS: Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy. CONCLUSION: On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03668496.

Design and evaluation of perception reconstruction with sensor system for artificial anal sphincter based on vector similarity.

BACKGROUND: Artificial organs are playing an increasingly important role in medical field. Artificial anal sphincter, as an example, is a widely used medical device for fecal incontinence. Though it could help patients maintain continence, the issue of perception reconstruction is still unsolved, which means that patients cannot control defecation as desired. METHODS: In this paper, a novel sensor system based on vector similarity has been analyzed and evaluated. The sensor system is a self-packaged strain gauge sensor with a small size 14.5 mm × 6 mm, especially for medical device implanted in body to reconstruct perception function. In order to overcome the disadvantages of single threshold judgment, a more accurate and reliable judgment standard for content pressure detection in rectum is developed by using vector similarity method. Therefore, in the novel sensor system, standard multi-parameters are comprehensive considered. Furthermore, weight-optimization of sensors are investigated since each sensor has played a different role in detection. Finally, sensor calibration, in vitro and in vivo experiments are established. RESULTS: In sensor calibration, the result R2 > 0.99 presents the strain gauge pressure sensor has a good linearity. After that, a series of in vitro experiments have been conducted. The optimized sensor system shows a high accuracy rate in perception reconstruction, which is 87.5% on early warning and 95% on the alarm. In the following in vivo experiments. The results indicate that the average accuracy of the proposed perception reconstruction module has increased by 17.7%, compared with that without optimized sensor system. CONCLUSIONS: All of these have proven that the novel perception reconstruction module with sensor system based on vector similarity is more acceptable and reliable.

Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma.

Brain metastasis (BM) is a major complication of lung adenocarcinoma (LAD). An investigation of the pathogenic mechanisms of BM, as well as the identification of appropriate molecular markers, is necessary. The aim of this study was to determine the expression patterns of microRNAs (miRNAs) in LAD with BM, and to investigate the biological role of these miRNAs during tumorigenesis. miRNA array profiles were used to identify BM-associated miRNAs. These miRNAs were independently validated in 155 LAD patients. Several in vivo and in vitro assays were performed to verify the effects of miRNAs on BM. We identified six miRNAs differentially expressed in patients with BM as compared to patients with BM. Of these, miR-4270 and miR-423-3p were further investigated. miR-4270 and miR-423-3p directly targeted MMP19 and P21, respectively, to influence cell viability, migration, and colony formation in vitro. miR-4270 downregulation and miR-423-3p upregulation was associated with an increased risk of BM in LAD patients. Thus, our results suggested that miR-4270 and miR-423-3p might play an important role in BM pathogenesis in LAD patients, and that these miRNAs might be useful prognostic and clinical treatment targets.

An artificial anal sphincter based on a novel clamping mechanism: Design, analysis, and testing.

An artificial anal sphincter is a device to help patients with fecal incontinence rebuild the ability to control the excrement through the anus. In this article, an artificial anal sphincter based on a novel clamping mechanism (AASNCM) is proposed to improve the safety and reliability. The AASNCM, which is powered by a transcutaneous energy transfer system, consists of a novel clamping mechanism, a receiving coil and a control unit. According to design requirements, the novel clamping mechanism model was established. After that, its kinematics and dynamics were analyzed. The results of force tests on the prototype AASNCM show that the maximum values of clamping force and expanding force are 15.859 and 31.029 N, respectively. Comparing the experimental results with theoretical analysis, a good match can be concluded. Finally, in vitro experiments were conducted, and have verified the safety and reliability of the proposed AASNCM.

The evaluation of GI-pill gastrointestinal electronic capsule for colonic transit test in patients with slow transit constipation.

OBJECTIVE: The evaluation of GI-pill gastrointestinal electronic capsule for colonic transit test in patients with slow transit constipation (STC) was studied. MATERIALS AND METHODS: STC patients (n = 162) were randomly divided into experimental group (n = 84, orally taken GI-pill gastrointestinal electronic capsule and X-ray granule capsule) and control group (n = 78, orally taken X-ray granule capsule). Comparison of the time in colonic transit test between the two groups was conducted. The data of GI-pill gastrointestinal electronic capsule in vivo time, time of capsule passing through the colon, the number of high amplitude propagating contractions (HAPCs), and physiological response ratio were analyzed. RESULTS: There were no significant differences in the whole colonic transit test time, right colonic transit time, left colonic transit time, and rectosigmoid colonic transit time between experimental group and control group (p > 0.05). All patients had no abdominal pain, nausea, vomiting, black stool, difficulty in electronic capsule excretion, or any other discomfort during the test. CONCLUSION: GI-pill gastrointestinal electronic capsule can continuously evaluate the dynamic characteristics of digestive tract in STC patients and is consistent with X-ray granule capsule, which is meaningful to clinical application.

Design and evaluation of puborectalis-like artificial anal sphincter that replicates rectal perception.

While fecal incontinence (FI) is not fatal, it can dramatically decrease the patient's quality of life. An artificial anal sphincter (AAS) is an implantable device that treats FI by replacing a diseased or damaged anal sphincter, thus allowing the patient's continence to be maintained. Here, we report a novel implantable puborectalis-like artificial anal sphincter (PAAS) that replicates rectal perception and has a low risk of ischemia necrosis. Using the pressure sensors embedded in the PAAS, the relationship between the mass of feces and the pressure was determined, and a feces mass estimation model was developed based on in vitro studies. Rectal perception is provided through the real-time monitoring of rectal feces, and the feeling of defecation is quantified based on a comparison between the feces mass and a preset threshold mass. In vivo studies were performed for validation, and the accuracy of the model was determined to be as high as 90%. The performance of the PAAS in the real-time monitoring of rectal feces and its in vivo biocompatibility were also evaluated. The device should further the functionality of existing AAS systems while improving their biosafety and thus expand the applicability of implantable AAS systems in the treatment of FI.

[Design of Wearable Wireless Health Monitoring System and Status Recognition Algorithm].

A wearable wireless health monitoring system for drug addicts in compulsory rehabilitation centers was proposed. The system can continuously monitor multiple physiological parameters of drug addicts in real time, and issue early warning information when abnormal physiological parameters occur, so as to play the role of timely medical practice. In addition, this study proposes a convolutional neural network (CNN)model, which can evaluate the health status of drug addicts based on multiple physiological parameters. Experiments show that the model can be applied to the task of body state recognition in the open physiological parameter data set, and the recognition accuracy can reach up to 100% in a single physiological parameter data set; when the whole physiological data set is used, the recognition accuracy can reach 99.1%. The recognition accuracy exceeds the performance of the traditional pattern recognition method on this task, which verifies the superiority of the model.

A novel power supply system for puborectalis-like artificial anal sphincter.

Puborectalis-like artificial anal sphincter (PAAS) is an innovative new type of artificial anal sphincter (AAS). It overcomes many drawbacks and inadequacies of various previous AASs, and it has successfully been implanted in vivo for almost 3 weeks. During in vivo testing, PAAS shows its ability to retain continence with low risk of ischemia necrosis, and somehow truly helps to remodel rectal perception. However, there are still many defects that influence the long-term implantation of PAAS, especially in the power supply system (PSS). This article presents a new designed PSS which includes a new transcutaneous energy transfer (TET) system, a heat reduction system, and a safety usage system. The new PSS reduces the total size of PAAS by at least 30%. Newly designed TET system can satisfy the Qi standard, and render a power of 3W to fulfill the requirement of fast charging and normal use of PAAS at the distance of 15.5 mm when frequency of TET system is 110 kHz, which previous TET systems can hardly achieve. Heat reduction system helps to reduce the heat generated during TET charging. It can reduce heat by 40% during the same period of time of TET charging. Safety usage system helps the user control PAAS more properly which can reduce the rate of failure of PAAS system.

Smart Scanning Ion-Conductance Microscopy Imaging Technique Using Horizontal Fast Scanning Method.

To solve extended acquisition time issues inherent in the conventional hopping-scanning mode of scanning ion-conductance microscopy (SICM), a new transverse-fast scanning mode (TFSM) is proposed. Because the transverse motion in SICM is not the detection direction and therefore presents no collision problem, it has the ability to move at high speed. In TSFM, the SICM probe gradually descends in the vertical/detection direction and rapidly scans in the transverse/nondetection direction. Further, the highest point that decides the hopping height of each scanning line can be quickly obtained. In conventional hopping mode, however, the hopping height is artificially set without a priori knowledge and is typically very large. Consequently, TFSM greatly improves the scanning speed of the SICM imaging system by effectively reducing the hopping height of each pixel. This study verifies the feasibility of this novel scanning method via theoretical analysis and experimental study, and compares the speed and quality of the scanning images obtained in the TFSM with that of the conventional hopping mode. The experimental results indicate that the TFSM method has a faster scanning speed than other SICM scanning methods while maintaining the quality of the images. Therefore, TFSM provides the possibility to quickly obtain high-resolution three-dimensional topographical images of extremely complex samples.

Optimal Design of Litz Wire Coils With Sandwich Structure Wirelessly Powering an Artificial Anal Sphincter System.

Transcutaneous energy transfer system (TETS) is widely used to energize implantable biomedical devices. As a key part of the TETS, a pair of applicable coils with low losses, high unloaded Q factor, and strong coupling is required to realize an efficient TETS. This article presents an optimal design methodology of planar litz wire coils sandwiched between two ferrite substrates wirelessly powering a novel mechanical artificial anal sphincter system for treating severe fecal incontinence, with focus on the main parameters of the coils such as the wire diameter, number of turns, geometry, and the properties of the ferrite substrate. The theoretical basis of optimal power transfer efficiency in an inductive link was analyzed. A set of analytical expressions are outlined to calculate the winding resistance of a litz wire coil on ferrite substrate, taking into account eddy-current losses, including conduction losses and induction losses. Expressions that describe the geometrical dimension dependence of self- and mutual inductance are derived. The influence of ferrite substrate relative permeability and dimensions is also considered. We have used this foundation to devise an applicable coil design method that starts with a set of realistic constraints and ends with the optimal coil pair geometries. All theoretical predictions are verified with measurements using different types of fabricated coils. The results indicate that the analysis is useful for optimizing the geometry design of windings and the ferrite substrate in a sandwich structure as part of which, in addition to providing design insight, allows speeding up the system efficiency-optimizing design process.

Determination of the cellulase activity distribution in Clostridium thermocellum and Caldicellulosiruptor obsidiansis cultures using a fluorescent substrate.

This study took advantage of resorufin cellobioside as a fluorescent substrate to determine the distribution of cellulase activity in cellulosic biomass fermentation systems. Cellulolytic biofilms were found to express nearly four orders greater cellulase activity compared to planktonic cultures of Clostridium thermocellum and Caldicellulosiruptor obsidiansis, which can be primarily attributed to the high cell concentration and surface attachment. The formation of biofilms results in cellulases being secreted close to their substrates, which appears to be an energetically favorable stategy for insoluble substrate utilization. For the same reason, cellulases should be closely associated with the surfaces of suspended cell in soluble substrate-fed culture, which has been verified with cellobiose-fed cultures of C. thermocellum and C. obsidiansis. This study addressed the importance of cellulase activity distribution in cellulosic biomass fermentation, and provided theoretical foundation for the leading role of biofilm in cellulose degradation. System optimization and reactor designs that promote biofilm formation in cellulosic biomass hydrolysis may promise an improved cellulosic biofuel process.

[A method for bleeding detection in endoscopy images using SVM].

Because the huge number of images of the digestive tract by Wireless Capsule Endoscopy (WCE) are left to the medical personnels detected by their eyes, huge burden leaves to doctors. This article provides a classification of method based on SVM (Support Vector Machine) for the capsule endoscopy bleeding intelligent recognition. We created a new kind of feature parameter, and the experiment result can reach 83% specificity and 94% sensitivity.

The expression of miR-21 and miR-375 predict prognosis of esophageal cancer.

BACKGROUND: MicroRNA is a class of small, well-conserved, non-coding RNAs, and could play a potential role as diagnostic and prognostic biomarkers of esophageal cancers. We aimed to review comprehensively the evidence of microRNA as prognostic biomarkers in esophageal cancers. METHODS: Studies were identified by searching PubMed, Embase and Web of Science until November 2013. Descriptive characteristics of studies were described and an additional meta-analysis for specific microRNAs which were studied most frequently was performed. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. Fixed model or random model method was chosen depending on the heterogeneity among the studies. RESULTS: Twenty-two studies including a total of 1946 participants were enrolled after a strict filtering and qualifying process. Among 33 prognostic microRNAs identified for esophageal cancer, miR-21 and miR-375 appeared more frequently. The median study size was 70.5 patients (29-249 patients) and the median HR was 3.305 (IQR=1.615-7.31). For the studies evaluating miR-21's association with overall survival (OS), the pooled HR suggested that high level of miR-21 has a negative impact on OS (HR=1.52[1.17-1.98], P=0.001). As for miR-375, the pooled HR for OS (high/low) was 0.53 (95% CI: 0.39-0.73, P<0.001), indicated that low level of miR-375 has a negative impact on OS. These results indicated that microRNAs show promising associations with prognosis in esophageal cancer. Up-regulation of miR-21 and down-regulation of miR-375 can predict unfavourable prognosis in esophageal cancer.

In-depth characterization of secondary effluent from a municipal wastewater treatment plant located in northern China for advanced treatment.

This study provided insight into the characterization of secondary effluent from a wastewater treatment plant located in northeastern China. The secondary effluent was separated into three fractions, the dissolved, the near-colloidal and the suspended, to study their individual characteristics. It revealed that most of the organics in the secondary effluent existed in the dissolved form, accounting for 78.1-86.5% of the total chemical oxygen demand and 82.6-86.6% of the total organic carbon. Results from the molecular weight distribution study further indicated that organics with MW < 1k Da constituted 56.3-62.7% of total organics. Moreover, the particle size distribution study suggested that particles between 2.0 and 6.8 µm in diameter made up 80.0% of the total suspended solids. Both biological oxygen demand/chemical oxygen demand and biological dissolved organic carbon/dissolved organic carbon were measured ranging from 0.2 to 0.3, suggesting the most secondary effluent organics were biologically refractory. This conclusion was further strengthened by the functional groups information obtained from the GC/MS (gas chromatography/mass spectrometry) analysis. The characteristics information revealed from this study will help the design and selection of water quality-specific tertiary treatment technologies for secondary effluent water purification and reuse.

Anhydrous volatile fatty acid extraction through omniphobic membranes by hydrophobic deep eutectic solvents: Mechanistic understanding and future perspective.

Volatile fatty acids (VFAs) derived from arrested anaerobic digestion (AD) can be recovered as a valuable commodity for value-added synthesis. However, separating VFAs from digestate with complex constituents and a high-water content is an energy-prohibitive process. This study developed an innovative technology to overcome this barrier by integrating deep eutectic solvents (DESs) with an omniphobic membrane into a membrane contactor for efficient extraction of anhydrous VFAs with low energy consumption. A kinetic model was developed to elucidate the mechanistic differences between this novel omniphobic membrane-enabled DES extraction and the previous hydrophobic membrane-enabled NaOH extraction. Experimental results and mechanistic modeling suggested that VFA extraction by the DES is a reversible adsorption process facilitating subsequent VFA separation via anhydrous distillation. High vapor pressure of shorter-chain VFAs and low Nernst distribution coefficients of longer-chain VFAs contributed to DES-driven extraction, which could enable continuous and in-situ recovery and conversion of VFAs from AD streams.

Effects of Hydrothermal Pretreatment and Anaerobic Digestion of Pig Manure on the Antibiotic Removal and Methane Production.

Whether advanced biological waste treatment technologies, such as hydrothermal pretreatment (HTP) integrated anaerobic digestion (AD), could enhance the removal of different antibiotics remains unclear. This study investigated the outcome of antibiotics and methane productivity during pig manure treatment via HTP, AD, and HTP + AD. Results showed improved removal efficiency of sulfadiazine (SDZ), oxytetracycline (OTC), and enrofloxacin (ENR) with increased HTP temperatures (70, 90, 120, 150, and 170 °C). OTC achieved the highest removal efficiency of 86.8% at 170 °C because of its high sensitivity to heat treatment. For AD, SDZ exhibited resistance with a removal efficiency of 52.8%. However, OTC and ENR could be removed completely within 30 days. When HTP was used prior to AD, OTC and ENR could achieve complete removal. However, residual SDZ levels reduced to 20% and 16% at 150 and 170 °C, respectively. The methanogenic potential showed an overall upward trend as the HTP temperature increased. Microbial analysis revealed the antibiotics-induced enrichment of specific microorganisms during AD. Firmicutes were the dominant bacterial phylum, with their abundance positively correlated with the addition of antibiotics. Methanobacterium and Methanosarcina emerged as the dominant archaea that drove methane production during AD. Thus, HTP can be a potential pretreatment before AD to reduce antibiotic-related risks in manure waste handling.

Regulatory feedback loop between circ-EIF4A3 and EIF4A3 Enhances autophagy and growth in colorectal cancer cells.

Recent studies indicate that circular RNAs (circRNAs) are crucial in the progression of colorectal cancer (CRC). Eukaryotic translation initiation factor 4A3 (EIF4A3) has been identified as a promoter of circRNA production. The biological roles and mechanisms of EIF4A3-derived circRNA (circEIF4A3) in CRC cell autophagy remain poorly understood. This study explores the effects of circEIF4A3 on CRC cell growth and autophagy, aiming to elucidate the underlying molecular mechanisms. We discovered that EIF4A3 and circEIF4A3 synergistically enhance CRC cell growth. CircEIF4A3 sequesters miR-3126-5p, consequently upregulating EIF4A3. Further, circEIF4A3 increases EIF4A3 expression, which promotes autophagy by stabilizing ATG5 mRNA and enhances ATG7 protein stability through the stabilization of USP14 mRNA, a deubiquitinating enzyme. Upregulation of ATG5 and ATG7 counteracts the growth-inhibitory effects of EIF4A3 knockdown on CRC cells. Moreover, our findings demonstrate that EIF4A3 induces the formation of circEIF4A3 in CRC cells. In conclusion, a positive feedback loop between circEIF4A3 and EIF4A3 supports CRC cell growth by facilitating autophagy.