Olaparib and niraparib as maintenance therapy in patients with newly diagnosed and platinum-sensitive recurrent ovarian cancer: A single-center study in China.

BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes (BRCA) mutations (BRCAm) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs. 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs. 91.4% (32/35), P <0.001]. The 24-month PFS rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCAm, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS: Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCAm, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.

A Sensitivity-Enhanced Vertical-Resonant MEMS Electric Field Sensor Based on TGV Technology.

In order to enhance the sensitivity of wafer-level vacuum-packaged electric field sensors, this paper proposed a vertical-resonant MEMS electric field sensor based on TGV (Through Glass Via) technology. The microsensor is composed of the electric field sensing cover, the drive cover, and the SOI-based microstructures between them. TGV technology is innovatively used to fabricate the electric field sensing cover and the vertically-driven cover. The external electric field is concentrated and transmitted to the area below the silicon plate in the center of the electric field sensing cover through a metal plate and a metal pillar, reducing the coupling capacitance between the silicon plate and the packaging structure, thereby achieving the enhanced transmission of the electric field. The sensitivity-enhanced mechanism of the sensor is analyzed, and the key parameters of the sensor are optimized through finite element simulation. The fabrication process is designed and realized. A prototype is tested to characterize its performance. The experimental results indicate that the sensitivity of the sensor is 0.82 mV/(kV/m) within the electrostatic electric field ranging from 0-50 kV/m. The linearity of the sensor is 0.65%.

A Highly Sensitive and High-Resolution Resonant MEMS Electrostatic Field Microsensor Based on Electrostatic Stiffness Perturbation.

This paper proposes a highly sensitive and high-resolution resonant MEMS electrostatic field sensor based on electrostatic stiffness perturbation, which uses resonant frequency as an output signal to eliminate the feedthrough interference from the driving voltage. The sensor is composed of a resonator, driving electrode, detection electrode, transition electrode, and electrostatic field sensing plate. The working principle is that when there is an electrostatic field, an induction charge will appear at the surface of the electrostatic field sensing plate and induce electrostatic stiffness on the resonator, which will cause a resonant frequency shift. The resonant frequency is used as the output signal of the microsensor. The characteristics of the electrostatic field sensor are analyzed with a theoretical model and verified by finite element simulation. A device prototype is fabricated based on the Silicon on Insulator (SOI) process and tested under vacuum conditions. The results indicate that the sensitivity of the sensor is 0.1384Hz/(kV/m) and the resolution is better than 10 V/m.

A retrospective analysis for investigating the relationship between FIGO stage IVA/IVB and cytoreductive surgery with prognosis in epithelial ovarian cancer.

Objective: To investigate the effect of primary debulking surgery (PDS), NACT followed by interval debulking surgery (NACT-IDS), and chemotherapy alone on the prognosis of FIGO stage IV epithelial ovarian cancer (EOC) with different metastatic patterns. Methods: We retrospectively analyzed 133 cases of FIGO stage IV EOC with pleural effusion (stage IVA), parenchymal metastases (stage IVB), or extra-abdominal lymph node metastases (stage IVB) at our Hospital between January 2014 and July 2021. Results: Among 133 cases with stage IV disease, 16.5% (n=22) presented with pleural effusion, 46.6% (n=62) with parenchymal metastases, and 36.9% (n=49) with extra-abdominal lymph node metastases. Regardless of the metastatic patterns, the 90.2% (n=120) of cases who underwent PDS/NACT-IDS exhibited a significantly superior overall survival (OS) compared to the 9.8% cases (n=13) who received chemotherapy alone (32 vs 17 months, p=0.000). The cohort was further stratified into 58 cases (48.3%) with R0, 41 cases (34.2%) with R1, and 21 cases (17.5%) with R2. The median OS of cases with R0 was significantly better than that of cases with R1/R2 (74 vs 27 months, p=0.000). There was no significant difference in median OS between PDS and NACT-IDS (43 vs 31 months, p=0.676), as well as between FIGO IVA and IVB (35 vs 31 months, p=0.582). Additionally, the metastatic patterns and the number of neoadjuvant chemotherapy cycles (≤4 or >4) did not demonstrate any prognostic significance for median OS (p=0.820 and 33 vs 26 months, p=0.280, respectively). Conclusion: Regardless of FIGO IVA and IVB stages or metastatic patterns, patients diagnosed with stage IV EOC may benefit from cytoreductive surgery with abdominal R0, compared with chemotherapy alone.

Wafer-Level Vacuum-Packaged Electric Field Microsensor: Structure Design, Theoretical Model, Microfabrication, and Characterization.

This paper proposes a novel wafer-level vacuum packaged electric field microsensor (EFM) featuring a high quality factor, low driving voltage, low noise, and low power consumption. The silicon-on-insulator (SOI) conductive handle layer was innovatively used as the sensing channel to transmit the external electric field to the surface of the sensitive structure, and the vacuum packaging was realized through anodic bonding between the SOI and glass-on-silicon (GOS). The fabrication process was designed and successfully realized, featured with a simplified process and highly efficient batch manufacturing, and the final chip size was only 5 × 5 mm. A theoretical model for the packaged device was set up. The influence of key parameters in the packaging structure on the output characteristics of the microsensor was analyzed on the basis of the proposed model. Experiments were conducted on the wafer-level vacuum-packaged EFM to characterize its performance. Experimental results show that, under the condition of applying 5 V DC driving voltage, the required AC driving voltage of the sensor was only 0.05 VP, and the feedthrough was only 4.2 mV. The quality factor was higher than 5000 and was maintained with no drop in the 50-day test. The vacuum in the chamber of the sensor was about 10 Pa. A sensitivity of 0.16 mV/(kV/m) was achieved within the electrostatic field range of 0-50 kV/m. The linearity of the microsensor was 1.62%, and the uncertainty was 4.42%.

Design and Testing of a Non-Contact MEMS Voltage Sensor Based on Single-Crystal Silicon Piezoresistive Effect.

The paper presents a novel non-contact microelectromechanical systems (MEMS) voltage sensor based on the piezoresistive effect of single-crystal silicon. The novelty of the proposed sensor design lies in the implementation of unique single-crystal silicon piezoresistive beams for voltage measurement. The sensitive structure of the sensor produces electrostatic force deformation due to the measured voltage, resulting in the resistance change of single-crystal silicon piezoresistive beams which support a vibrating diaphragm. The voltage can be measured by sensing the resistance change. Moreover, the sensor does not need an additional driving signal and has lower power consumption. The prototype of the sensor was fabricated using an SOI micromachining process. The piezoresistive characteristics of the sensor and the corresponding output response relationship were analyzed through theoretical analysis and finite element simulation. The voltage response characteristics of the sensor were achieved at power frequencies from 50 Hz to 1000 Hz in the paper. The experimental results showed that they were in good agreement with simulations results with the theoretical model and obtained good response characteristics. The sensor has demonstrated that the minimum detectable voltages were 1 V for AC voltages at frequencies from 50 Hz to 300 Hz and 0.5 V for AC voltages at frequencies from 400 Hz to 1000 Hz, respectively. Moreover, the linearities of the sensor were 3.4% and 0.93% in the voltage measurement range of 900-1200 V at the power frequency of 50 Hz and in the voltage measurement range of 400-1200 V at the frequency of 200 Hz, respectively.

Resolution-Enhancing Structure for the Electric Field Microsensor Chip.

Electrostatic voltage is a vital parameter in industrial production lines, for reducing electrostatic discharge harms and improving yields. Due to such drawbacks as package shielding and low resolution, previously reported electric field microsensors are still not applicable for industrial static monitoring uses. In this paper, we introduce a newly designed microsensor package structure, which enhances the field strength inside the package cavity remarkably. This magnification effect was studied and optimized by both theoretical calculation and ANSYS simulation. By means of the digital synthesizer and digital coherent demodulation method, the compact signal processing circuit for the packaged microsensor was also developed. The meter prototype was calibrated above a charged metal plate, and the electric field resolution was 5 V/m, while the measuring error was less than 3 V, from -1 kV to 1 kV in a 2 cm distance. The meter was also installed into a production line and showed good consistency with, and better resolution than, a traditional vibratory capacitance sensor.

A non-intrusive voltage measurement scheme based on MEMS electric field sensors: Theoretical analysis and experimental verification of AC power lines.

A non-interference AC voltage measurement system based on a resonant electric field microsensor is proposed. The equivalent circuit of the proposed system is established, which shows that the frequency response function is only related to the capacitances of the system structure in the kHz low-frequency range. Furthermore, the sensitivity analysis and experiments demonstrate that the amplitude sensitivity is independent of the frequency of an unknown AC voltage. Therefore, this technique is very suitable for measuring arbitrary waveform voltage. A functional prototype was developed and tested to acquire AC power-line voltages. The prototype responded well to the transient waveform of the AC input signal, yet with a phase delay of 177.24°. The output of the system was linear in the range of 0-1000 Vrms at 50-Hz and the linearity was 0.54%, whereas the maximum relative deviation of the rms voltage measurements above 10 V was -0.83%. Finally, the shielding ability of the system against interference and noise was verified through the AC interference voltage measurement.

An Electric Field Microsensor with Mutual Shielding Electrodes.

This paper proposes an electric field microsensor (EFM) with mutual shielding electrodes. Based on the charge-induction principle, the EFM consists of fixed electrodes and piezoelectric-driving vertically-movable electrodes. All the fixed electrodes and movable electrodes work as both sensing electrodes and shielding electrodes. In other words, all the fixed and movable electrodes are sensing electrodes, and they are mutually shielding electrodes simultaneously. The movable electrodes are driven to periodically modulate the electric field distribution at themselves and the fixed electrodes, and the induced currents from both movable and fixed electrodes are generated simultaneously. The electrode structure adopts an interdigital structure, and the EFM has been simulated by finite element methods. Simulation results show that, since the sensing area of this EFM is doubled, the variation of induced charge is twice, and therefore the output signal of the sensor is increased. The piezoelectric material, lead zirconate titanate (PZT), is prepared by the sol-gel method, and the microsensor chip is fabricated.

Choosing the right timing for interval debulking surgery and perioperative chemotherapy may improve the prognosis of advanced epithelial ovarian cancer: a retrospective study.

BACKGROUND: Primary debulking surgery (PDS) is the main treatment for patients with advanced ovarian cancer, and neoadjuvant chemotherapy (NACT) is for bulky stage III-IV patients who are poor surgical candidates and/or for whom there is a low likelihood of optimal cytoreduction. NACT can increase the rate of complete cytoreduction, but this advantage has not translated to an improvement in survival. Therefore, we aimed to identify factors associated with the survival of patients who received NACT followed by interval debulking surgery (IDS). METHODS: A retrospective study was conducted in FIGO stage IIIC-IV epithelial ovarian cancer patients who underwent PDS or IDS in our center between January 1st, 2013, and December 31st, 2018. RESULTS: A total of 273 cases were included, of whom 20 were lost to follow-up. Progression-free survival (PFS) and overall survival (OS) of the IDS and PDS groups were found to be similar, although the proportion of patients in stage IV and serum carbohydrate antigen 125 (CA125) levels before treatment in the IDS group were significantly higher than that in the PDS group. Body mass index (BMI), CA125 level before IDS, residual disease after surgery, and the interval between preoperative and postoperative chemotherapy were all found to be independent prognostic factors for PFS; FIGO stage, residual disease after surgery, and CA125 level before IDS were independent prognostic factors for OS. We found that PFS and OS were both significantly longer in patients with normal CA125 levels before IDS and when the interval between preoperative and postoperative chemotherapy was < 35.5 days (IDS-3 group) than for patients in the PDS group. CONCLUSIONS: The results suggested the importance of timely IDS and postoperative chemotherapy and potentially allowed the identification of patients who would benefit the most from NACT. Normal CA125 levels before IDS and an interval between preoperative and postoperative chemotherapy no longer than 5 weeks were associated with improved prognosis in advanced ovarian cancer patients.

Blockchain for Vehicular Internet of Things: Recent Advances and Open Issues.

The vehicular Internet of Things (IoT) comprises enabling technologies for a large number of important applications including collaborative autonomous driving and advanced transportation systems. Due to the mobility of vehicles, strict application requirements, and limited communication resources, the conventional centralized control fails to provide sufficient quality of service for connected vehicles, so a decentralized approach is required in the vicinity to satisfy the requirements of delay-sensitive and mission-critical applications. A decentralized system is also more resistant to the single point of failure problem and malicious attacks. Blockchain technology has been attracting great interest due to its capability of achieving a decentralized, transparent, and tamper-resistant system. There are many studies focusing on the use of blockchain in managing data and transactions in vehicular environments. However, the application of blockchain in vehicular environments also faces some technical challenges. In this paper, we first explain the fundamentals of blockchain and vehicular IoT. Then, we conduct a literature review on the existing research efforts of the blockchain for vehicular IoT by discussing the research problems and technical issues. After that, we point out some future research issues considering the characteristics of both blockchain and vehicular IoT.

AC/DC Fields Demodulation Methods of Resonant Electric Field Microsensor.

Electric field microsensors have the advantages of a small size, a low power consumption, of avoiding wear, and of measuring both direct-current (DC) and alternating-current (AC) fields, which are especially suited to applications in power systems. However, previous reports were chiefly concerned with proposing new structures or improving the resolution, and there are no systematic studies on the signal characteristics of the microsensor output and the demodulation methods under different electric fields. In this paper, the use of an improved resonant microsensor with coplanar electrodes, and the signal characteristics under a DC field, power frequency field, and AC/DC hybrid fields were thoroughly analyzed respectively, and matching demodulation methods derived from synchronous detection were proposed. We theoretically obtained that the frequencies of the detectable electric fields should be less than half of the resonant frequency of the microsensor, and that the sensitivities of the microsensor were identical for AC/DC hybrid fields with different frequencies. Experiments were conducted to verify the proposed demodulation methods. Within electric field ranges of 0-667 kV/m, the uncertainties were 2.4% and 1.5% for the most common DC and 50 Hz power frequency fields, respectively. The frequency characteristic test results of the microsensor were in agreement with those of the theoretical analysis in the range of 0-1 kHz.

Design, Fabrication and Characterization of a MEMS-Based Three-Dimensional Electric Field Sensor with Low Cross-Axis Coupling Interference.

One of the major concerns in the development of three-dimensional (3D) electric field sensors (EFSs) is their susceptibility to cross-axis coupling interference. The output signal for each sensing axis of a 3D EFS is often coupled by electric field components from the two other orthogonal sensing axes. In this paper, a one-dimensional (1D) electric field sensor chip (EFSC) with low cross-axis coupling interference is presented. It is designed to be symmetrical, forming a pair of in-plane symmetrically-located sensing structures. Using a difference circuit, the 1D EFSC is capable of sensing parallel electric fields along symmetrical structures and eliminating cross-axis coupling interference, which is contrast to previously reported 1D EFSCs designed for perpendicular electric field component measurement. Thus, a 3D EFS with low cross-axis coupling interference can be realized using three proposed 1D EFSCs. This 3D EFS has the advantages of low cross-axis coupling interference, small size, and high integration. The testing and calibration systems of the proposed 3D EFS were developed. Experimental results show that in the range of 0-120 kV/m, cross-axis sensitivities are within 5.48%, and the total measurement errors of this 3D EFS are within 6.16%.

A High Sensitivity Electric Field Microsensor Based on Torsional Resonance.

This paper proposes a high sensitivity electric field microsensor (EFM) based on torsional resonance. The proposed microsensor adopts torsional shutter, which is composed of shielding electrodes and torsional beams. The movable shielding electrodes and the fixed sensing electrodes are fabricated on the same plane and interdigitally arranged. Push-pull electrostatic actuation method is employed to excite the torsional shutter. Simulation results proved that the torsional shutter has higher efficiency of charge induction. The optimization of structure parameters was conducted to improve its efficiency of charge induction further. A micromachining fabrication process was developed to fabricate the EFM. Experiments were conducted to characterize the EFM. A good linearity of 0.15% was achieved within an electrostatic field range of 0-50 kV/m, and the uncertainty was below 0.38% in the three roundtrip measurements. A high sensitivity of 4.82 mV/(kV/m) was achieved with the trans-resistance of 100 MΩ, which is improved by at least one order of magnitude compared with previously reported EFMs. The efficiency of charge induction for this microsensor reached 48.19 pA/(kV/m).

Nonalcoholic fatty liver disease as a predictor of atrial fibrillation: a systematic review and meta-analysis.

INTRODUCTION: Numerous epidemiologic studies have investigated the link between nonalcoholic fatty liver disease (NAFLD) and long-term atrial fibrillation (AF) risk, but the results are surprisingly conflicting. AIM: Therefore, we systematically reviewed all published studies assessing the risk of AF in patients with NAFLD and conducted a meta-analysis. MATERIAL AND METHODS: We performed a literature search using PubMed, EMBASE and Cochrane Library databases in February 2017 with no restrictions. Two cohort studies and two cross-sectional studies were identified, involving a total of 5150 subjects (NAFLD: 1655; controls: 3495) in this meta-analysis. Data from selected studies were extracted and a meta-analysis was performed using a random effects model. RESULTS: Nonalcoholic fatty liver disease patients had a significantly higher risk of AF compared to controls (relative risk (RR): 2.61; 95% confidence interval (CI): 1.34-5.06, p = 0.00; I2 = 52.5%, p = 0.097). In a further analysis stratified by presence of type 2 diabetes, the increased risk was present predominantly in patients with type 2 diabetes (RR = 5.10; 95% CI: 2.43-10.7, p < 0.001; I2 = 0, p = 0.958). However, subjects without type 2 diabetes were at slightly increased risk of AF but the relative risk did not reach statistical significance (RR = 1.68; 95% CI: 0.99-2.82, p = 0.05; I2 = 0, p = 0.461). CONCLUSIONS: Our meta-analysis suggested that ultrasound-diagnosed NAFLD patients have a significantly higher risk for AF after adjustment for numerous important clinical risk factors for AF. These results need to be confirmed in large prospective studies.

Association between polycystic ovary syndrome and the risk of stroke and all-cause mortality: insights from a meta-analysis.

Many epidemiologic literatures have investigated the link between PCOS and long-term stroke risk and all-cause mortality, but the results are surprisingly conflicting. A meta-analysis was performed to examine the link between polycystic ovary syndrome (PCOS) and the risk of stroke, death from any cause, and assessed whether BMI might explain a higher risk of stroke. We searched the PUBMED, EMBASE, and Cochrane Library databases with no restrictions. Nine Cohort studies were identified, involving a total of 237,647 subjects. Compared with those without PCOS, subjects with PCOS were significantly associated with a increased risk of developing stroke (OR = 1.36; 95% CI 1.09-1.70; p = .007). However, no significant association was observed between PCOS and all-cause death (OR = 1.21; 95% CI 0.88-1.66; p = .25). Moreover, after pooling the five studies with risk estimates adjusted for BMI, the association between PCOS and stroke was slightly attenuated, although the odds ratios did not reach statistical significance (OR = 1.24; 95% CI 0.98-1.59). In conclusion, PCOS is associated with significant increased risk for stroke, while there is no consistent evidence to indicate that PCOS influences all-cause death outcomes. Increased BMI is an important contributor to the relationship between PCOS and stroke risk. Further study is needed to clarify which subgroups of subjects with the PCOS are at higher risk for stroke and should focus on developing reliable device for risk stratification.

Prediction of protein-protein interactions based on feature selection and data balancing.

Computational approaches are able to analyze protein-protein interactions (PPIs) from a different angle of view by complementing the experimental ones. And they are very efficient in determining whether two proteins can interact with each other. In this paper, KNNs (K-nearest neighbors) is applied to predict the PPIs by coding each protein with the physical and chemical properties of its residues, predicted secondary structures and amino acid compositions. mRMR (minimum-redundancy maximum-relevance) feature selection is adopted to select a compact feature set, features of which are considered to be important for the determination of PPI-nesses. Because the size of the negative dataset (containing non-interactive protein pairs) is much larger than that of the positive dataset (containing interactive protein pairs), the negative dataset is divided into 5 portions and each portion is combined with the positive dataset for one prediction. Thus 5 predictions are performed and the final results are obtained through voting. As a result, the prediction achieves an overall accuracy of 0.8369 with sensitivity of 0.7356. The predictor, developed by this research for the prediction of the fruit fly PPI-nesses, is available for public use at http://chemdata.shu.edu.cn/ppip.

HIV-1 protease cleavage site prediction based on two-stage feature selection method.

Knowledge of the mechanism of HIV protease cleavage specificity is critical to the design of specific and effective HIV inhibitors. Searching for an accurate, robust, and rapid method to correctly predict the cleavage sites in proteins is crucial when searching for possible HIV inhibitors. In this article, HIV-1 protease specificity was studied using the correlation-based feature subset (CfsSubset) selection method combined with Genetic Algorithms method. Thirty important biochemical features were found based on a jackknife test from the original data set containing 4,248 features. By using the AdaBoost method with the thirty selected features the prediction model yields an accuracy of 96.7% for the jackknife test and 92.1% for an independent set test, with increased accuracy over the original dataset by 6.7% and 77.4%, respectively. Our feature selection scheme could be a useful technique for finding effective competitive inhibitors of HIV protease.

Humidity-induced charge leakage and field attenuation in electric field microsensors.

The steady-state zero output of static electric field measuring systems often fluctuates, which is caused mainly by the finite leakage resistance of the water film on the surface of the electric field microsensor package. The water adsorption has been calculated using the Boltzmann distribution equation at various relative humidities for borosilicate glass and polytetrafluoroethylene surfaces. At various humidities, water film thickness has been calculated, and the induced charge leakage and field attenuation have been theoretically investigated. Experiments have been performed with microsensors to verify the theoretical predictions and the results are in good agreement.

Predicting the metabolic pathways of small molecules based on their physicochemical properties.

How to correctly and efficiently map small molecule to its possible metabolic pathway is a meaningful topic to metabonomics research. In this work, a novel approach to address this problem was introduced to encode physicochemical properties of small molecules. Based on this encoding method, a two stage feature selection method called mRMR-FFSAdaBoost was adopted to map small molecules to their corresponding metabolic pathways possible. As a result, the accuracies of 10-folds cross-validation test and independent set test for predicting the metabolic pathways of small molecules reached 83.88% and 85.23%, respectively. An online server for predicting metabolic pathways of unknown small molecules as described in this paper is accessible at http://chemdata.shu.edu.cn:8080/PathwayPrediction/.