Design of CMOS Analog Front-End Local-Field Potential Chopper Amplifier With Stimulation Artifact Tolerance for Real-Time Closed-Loop Deep Brain Stimulation SoC Applications.

A CMOS analog front-end (AFE) local-field potential (LFP) chopper amplifier with stimulation artifact tolerance, improved right-leg driven (RLD) circuit, and improved auxiliary path is proposed. In the proposed CMOS AFE LFP chopper amplifier, common-mode artifact voltage (CMAV) and differential-mode artifact voltage (DMAV) removal using the analog template removal method are proposed to achieve good signal linearity during stimulation. An improved auxiliary path is employed to boost the input impedance and allow the negative stimulation artifact voltage passing through. The common-mode noise is suppressed by the improved RLD circuit. The chip is implemented in 0.18- µm CMOS technology and the total chip area is 5.46-mm2. With the improved auxiliary path, the measured input impedance is larger than 133 M[Formula: see text] in the signal bandwidth and reaches 8.2 G[Formula: see text] at DC. With the improved RLD circuit, the measured CMRR is 131 - 144 dB in the signal bandwidth. Under 60-µs pulse width and 130-Hz constant current stimulation (CCS) with ±1-V CMAV and ±50-mV DMAV, the measured THD at the SC Amp output of fabricated AFE LFP chopper amplifier is 1.28%. The measurement results of In vitro agar tests have shown that with ±1.6-mA CCS pulses injecting to agar, the measured THD is 1.69%. Experimental results of both electrical and agar tests have verified that the proposed AFE LFP chopper amplifier has good stimulation artifact tolerance. The proposed CMOS AFE LFP chopper amplifier with analog template removal method is suitable for real-time closed-loop deep drain stimulation (DBS) SoC applications.

Machine Learning Predictive Models for Evaluating Risk Factors Affecting Sperm Count: Predictions Based on Health Screening Indicators.

In many countries, especially developed nations, the fertility rate and birth rate have continually declined. Taiwan's fertility rate has paralleled this trend and reached its nadir in 2022. Therefore, the government uses many strategies to encourage more married couples to have children. However, couples marrying at an older age may have declining physical status, as well as hypertension and other metabolic syndrome symptoms, in addition to possibly being overweight, which have been the focus of the studies for their influences on male and female gamete quality. Many previous studies based on infertile people are not truly representative of the general population. This study proposed a framework using five machine learning (ML) predictive algorithms-random forest, stochastic gradient boosting, least absolute shrinkage and selection operator regression, ridge regression, and extreme gradient boosting-to identify the major risk factors affecting male sperm count based on a major health screening database in Taiwan. Unlike traditional multiple linear regression, ML algorithms do not need statistical assumptions and can capture non-linear relationships or complex interactions between dependent and independent variables to generate promising performance. We analyzed annual health screening data of 1375 males from 2010 to 2017, including data on health screening indicators, sourced from the MJ Group, a major health screening center in Taiwan. The symmetric mean absolute percentage error, relative absolute error, root relative squared error, and root mean squared error were used as performance evaluation metrics. Our results show that sleep time (ST), alpha-fetoprotein (AFP), body fat (BF), systolic blood pressure (SBP), and blood urea nitrogen (BUN) are the top five risk factors associated with sperm count. ST is a known risk factor influencing reproductive hormone balance, which can affect spermatogenesis and final sperm count. BF and SBP are risk factors associated with metabolic syndrome, another known risk factor of altered male reproductive hormone systems. However, AFP has not been the focus of previous studies on male fertility or semen quality. BUN, the index for kidney function, is also identified as a risk factor by our established ML model. Our results support previous findings that metabolic syndrome has negative impacts on sperm count and semen quality. Sleep duration also has an impact on sperm generation in the testes. AFP and BUN are two novel risk factors linked to sperm counts. These findings could help healthcare personnel and law makers create strategies for creating environments to increase the country's fertility rate. This study should also be of value to follow-up research.

The Health Check-Up Data-Analysis for Risk Assessment of Chronic Kidney Disease (CKD) in Taiwan.

Early detection of chronic kidney disease (CKD) for high-risk population adults is very important. It has a common risk factor and causal relationship with chronic diseases such as diabetes, hypertension and cardiovascular disease etc. The results of this study provide that for early high-risk factors detection in CKD healthy population can be used by home care to recommend adjuvant treatment.

A 0.3V 10b 3MS/s SAR ADC With Comparator Calibration and Kickback Noise Reduction for Biomedical Applications.

This paper presents a 10-bit successive approximation analog-to-digital converter (ADC) that operates at an ultralow voltage of 0.3 V and can be applied to biomedical implants. The study proposes several techniques to improve the ADC performance. A pipeline comparator was utilized to maintain the advantages of dynamic comparators and reduce the kickback noise. Weight biasing calibration was used to correct the offset voltage without degrading the operating speed of the comparator. The incorporation of a unity-gain buffer improved the bootstrap switch leakage problem during the hold period and reduced the effect of parasitic capacitances on the digital-to-analog converter. The chip was fabricated using 90-nm CMOS technology. The data measured at a supply voltage of 0.3 V and sampling rate of 3 MSps for differential nonlinearity and integral nonlinearity were +0.83/-0.54 and +0.84/-0.89, respectively, and the signal-to-noise plus distortion ratio and effective number of bits were 56.42 dB and 9.08 b, respectively. The measured total power consumption was 6.6 µW at a figure of merit of 4.065 fJ/conv.-step.

A 0.35-V 240-µW Fast-Lock and Low-Phase-Noise Frequency Synthesizer for Implantable Biomedical Applications.

For implantable frequency synthesizers, realizing ultra-low voltage (ULV) and low power in addition to meeting PLL targets, fast lock and low phase noise, poses a difficult challenge. This paper presents techniques to achieve PLL targets as well as ULV and low power in the same chip through the use of a regular CMOS technology node. A curvature-PFD technique achieves both faster locking and lower jitter compared with conventional techniques. A two-step switching technique substantially reduces the power consumption in current mirrors and reduce noise when switching from a charge pump. Leakage analysis and subthreshold-leakage-reduction technique reduce reference spur and jitter to the voltage-controlled oscillator (VCO). A dither technique randomizes and averages reference spurs. The proposed chip was implemented in 90-nm CMOS technology; the 0.35-V medical-band frequency synthesizer consumes 238-µW power while generating output clock of 401.8 to 431.31-MHz and exhibiting a phase noise of -105.7 dBc/Hz at 1-MHz frequency offset with 20 µs locking time.

Factors Influencing Technology Integration in the Curriculum for Taiwanese Health Profession Educators: A Mixed-Methods Study.

In this study, we explored the considerations and the influencing factors for the technological integration of educational curricula based on the technological pedagogical content knowledge (TPCK) framework for health profession educators (HPEs). A mixed methodology was used that included semi-structured interviews with 15 HPEs and an online TPCK survey with a randomly selected sample of 319 HPEs from 217 Taiwanese universities. Five themes emerged, namely, supplementing traditional teaching methods, improving immediate educator-student interactions, tracking the learning process and improving the record-keeping, keeping up with technological trends, and advancing professional learning objectives for different student needs. The presence of pre-existing platforms and inspiration from colleagues and students were facilitators, whereas the risk of technological problems and the need to invest extra time into the preparation process were impediments to technology integration in the curriculum. Of the online respondents (n = 210), 64.2% have integrated at least one technological method into their curriculum. The logistic regression model revealed that gender, prior knowledge regarding how to incorporate technology with teaching, high mean TPCK scores, and relevant school policies were significant predictors of technology integration in the curriculum. Based on these results, recommendations for development in the health profession included efforts to equip HPEs with TPCK, in order to integrate technology into the curriculum effectively.

Increase Trichomonas vaginalis detection based on urine routine analysis through a machine learning approach.

Trichomonas vaginalis (T. vaginalis) detection remains an unsolved problem in using of automated instruments for urinalysis. The study proposes a machine learning (ML)-based strategy to increase the detection rate of T. vaginalis in urine. On the basis of urinalysis data from a teaching hospital during 2009-2013, individuals underwent at least one urinalysis test were included. Logistic regression, support vector machine, and random forest, were used to select specimens with a high risk of T. vaginalis infection for confirmation through microscopic examinations. A total of 410,952 and 428,203 specimens from men and women were tested, of which 91 (0.02%) and 517 (0.12%) T. vaginalis-positive specimens were reported, respectively. The prediction models of T. vaginalis infection attained an area under the receiver operating characteristic curve of more than 0.87 for women and 0.83 for men. The Lift values of the top 5% risky specimens were above eight. While the most risky vigintile was picked out by the models and confirmed by microscopic examination, the incremental cost-effectiveness ratios for T. vaginalis detection in men and women were USD$170.1 and USD$29.7, respectively. On the basis of urinalysis, the proposed strategy can significantly increase the detection rate of T. vaginalis in a cost-effective manner.

Design and In Vivo Verification of a CMOS Bone-Guided Cochlear Implant Microsystem.

OBJECTIVE: To develop and verify a CMOS bone-guided cochlear implant (BGCI) microsystem with electrodes placed on the bone surface of the cochlea and the outside of round window for treating high-frequency hearing loss. METHODS: The BGCI microsystem consists of an external unit and an implanted unit. The external system-on-chip is designed to process acoustic signals through an acquisition circuit and an acoustic DSP processor to generate stimulation patterns and commands that are transmitted to the implanted unit through a 13.56 MHz wireless power and bidirectional data telemetry. In the wireless power telemetry, a voltage doubler/tripler (2X/3X) active rectifier is used to enhance the power conversion efficiency and generate 2 and 3 V output voltages. In the wireless data telemetry, phase-locked loop based binary phase-shift keying and load-shift keying modulators/demodulators are adopted for the downlink and uplink data through high-Q coils, respectively. The implanted chip with four-channel high-voltage-tolerant stimulator generates biphasic stimulation currents up to 800 µA. RESULTS: Electrical tests on the fabricated BGCI microsystem have been performed to verify the chip functions. The in vivo animal tests in guinea pigs have shown the evoked third wave of electrically evoked auditory brainstem response waveforms. It is verified that auditory nerves can be successfully stimulated and acoustic hearing can be partially preserved. CONCLUSION AND SIGNIFICANCE: Different from traditional cochlear implants, the proposed BGCI microsystem is less invasive, preserves partially acoustic hearing, and provides an effective alternative for treating high-frequency hearing loss.

Development of an ELISA for myeloperoxidase on microplate: normal reference values and effect of temperature on specimen preparation.

BACKGROUND: Myeloperoxidase (MPO), a leukocyte enzyme, is implicated in both the pathogenesis and the progression of atherosclerosis. METHODS: We developed a sandwich ELISA on microplate using commercial antibodies for the measurement of plasma MPO. RESULTS: The in-house ELISA has a sensitivity of 15 ng/ml. Both within-day and between-day imprecision were <10%. The in-house assay was well correlated with the commercial kit from Oxis (gamma=0.96). We have established normal reference range for MPO for apparently healthy Chinese. No statistical difference was found between males and females and the various age groups. Because the coating antibodies used by two different kits are different in their affinities for MPO, the analysis by the in-house ELISA that was approximately three times that of the Oxis kit when testing the same specimens. We found that it is necessary to keep the heparinized whole blood on ice before centrifugation in order to prevent further release of MPO from the leukocytes at room temperature. For the same reason, serum is not recommended for MPO measurement. We also found that either pooled human plasma or serum containing MPO can be used as calibrators. CONCLUSIONS: We believe that this ELISA for MPO is useful to assess risk for inflammation, oxidative stress, nitrosative stress, and for predicting cardiac events.