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Abstract Surface atmospheric electric field (AEF) measurements were conducted using a Kelvin water dropper equalizer by the Japan Meteorological Agency's geomagnetic observatory at Kakioka, Ibaraki Prefecture, Japan, from 1929 to February 28, 2021. To obtain AEF data successive to the water dropper measurement, we independently installed the field mills at Kakioka. In this present study, we estimated the calibration coefficients based on comparisons between the water dropper and the field mills through parallel observations over 3 days. The results revealed that the new observations could be regarded as continuous data. Our new data from the field mills in this study have begun the process of being distributed in GLObal Coordination of Atmospheric Electricity Measurements (GloCAEM) as both archived and real‐time data in 1 min and 1 s samplings.

Objective: Initial tension at graft fixation is one of key factors for good outcomes in anterior cruciate ligament (ACL) reconstruction. Identifying the pre-operative factors that influence postoperative knee laxity under the anterior tibial load is useful in determining the initial tension at graft fixation. Thus, the purpose of this study was to clarify the pre-operative factors affecting the side-to-side difference in anterior laxity immediately after the anatomic double-bundle ACL reconstruction with a constant initial tension. Methods: Fifty-five patients underwent the anatomic double-bundle ACL reconstruction with hamstring tendon grafts. Anterior tibial displacement (ATD) was measured on both knees using KT-2000 Knee Arthrometer under anterior drawer load of 67 N, 89 N, 134 N and manual maximum load at 30° of flexion before ACL reconstruction under anesthesia, and was also measured on the operated knees under 89 N immediately after ACL reconstruction under anesthesia. Then, side-to-side difference (SSD) before and immediately after ACL reconstruction was calculated. Correlative relation between the SSD immediately after ACL reconstruction and the ATD/the SSD in each condition was analyzed. Results: The side-to-side difference of ATD immediately after surgery was −3.8 ± 1.7 mm (0 to -8mm) in response of 89 N of anterior load. There was correlation between the SSD immediately after ACL reconstruction and all ATD on both knees except for the ATD under manual maximum load on the injured knee, while little correlation between the SSD immediately after ACL reconstruction and that before ACL reconstruction was found. Especially, ATD under 89 N on the opposite knees and ATD under 134 N on the injured knees showed selective correlation with the SSD immediately after surgery in the step-wise multiple regression analysis. Conclusion: As the anterior tibial displacements under 89 N on the contra-lateral knee and under 134 N on the injured knee had a significant correlation with the SSD immediately after ACL reconstruction, those values may be helpful in determining the increase or decrease in initial tension at graft fixation.

Objective This study aimed to evaluate whether the methane (CH4) to carbon dioxide (CO2) ratio (CH4/CO2) and methane-related traits obtained by the sniffer method can be used as indicators for genetic selection of Holstein cows with lower CH4 emissions. Methods The sniffer method was used to simultaneously measure the concentrations of CH4 and CO2 during milking in each milking box of the automatic milking system to obtain CH4/CO2. Methane-related traits, which included CH4 emissions, CH4 per energy-corrected milk, methane conversion factor (MCF), and residual CH4, were calculated. First, we investigated the impact of the model with and without body weight (BW) on the lactation stage and parity for predicting methane-related traits using a first on-farm dataset (Farm 1; 400 records for 74 Holstein cows). Second, we estimated the genetic parameters for CH4/CO2 and methane-related traits using a second on-farm dataset (Farm 2; 520 records for 182 Holstein cows). Third, we compared the repeatability and environmental effects on these traits in both farm datasets. Results The data from Farm 1 revealed that MCF can be reliably evaluated during the lactation stage and parity, even when BW is excluded from the model. Farm 2 data revealed low heritability and moderate repeatability for CH4/CO2 (0.12 and 0.46, respectively) and MCF (0.13 and 0.38, respectively). In addition, the estimated genetic correlation of milk yield with CH4/CO2 was low (0.07) and that with MCF was moderate (−0.53). The on-farm data indicated that CH4/CO2 and MCF could be evaluated consistently during the lactation stage and parity with moderate repeatability on both farms. Conclusion This study demonstrated the on-farm applicability of the sniffer method for selecting cows with low CH4 emissions.

Abstract Purpose This study aims to elucidate changes in the tibiofemoral relationship over time following anterior cruciate ligament (ACL) injury, and investigate the correlation between the tibiofemoral relationship and patient‐related outcome measures (PROMs). Methods Overall, 203 primary ACL reconstructions were performed using autologous hamstring grafts. Medial and lateral anterior tibial translation (ATT) in the sagittal plane and tibial tubercle‐trochlear groove (TT‐TG) distance in the axial plane were measured using pre‐operative magnetic resonance imaging and post‐operative computed tomography. The difference between pre‐operative and post‐operative values for each parameter was calculated: ΔMesdial ATT, ΔLateral ATT and ΔTT‐TG distance. The correlation between each calculated value and the time elapsed since ACL injury, and the correlation between each calculated value and PROMs—evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS)—were assessed. Results Sixty‐four patients were enroled. Medial ATT, lateral ATT and TT‐TG distance were significantly different pre‐operatively compared to post‐operative values, with the tibia translating anteriorly and rotating internally relative to the femur. ΔMedial ATT, ΔLateral ATT and ΔTT‐TG distance were 1.6, 8.8 and −4.8 mm, respectively. A negative correlation was observed between the ΔTT‐TG distance and the time elapsed since the injury (r = −0.44, p

In online video understanding, which has a wide range of real-world applications, inference speed is crucial. Many approaches involve frame-level visual feature extraction, which often represents the biggest bottleneck. We propose RetinaViT, an efficient method for extracting frame-level visual features in an online video stream, aiming to fundamentally enhance the efficiency of online video understanding tasks. RetinaViT is composed of efficiently approximated Transformer blocks that only take changed tokens (event tokens) as queries and reuse the already processed tokens from the previous timestep for the others. Furthermore, we restrict keys and values to the spatial neighborhoods of event tokens to further improve efficiency. RetinaViT involves tuning multiple parameters, which we determine through a multi-step process. During model training, we randomly vary these parameters and then perform black-box optimization to maximize accuracy and efficiency on the pre-trained model. We conducted extensive experiments on various online video recognition tasks, including action recognition, pose estimation, and object segmentation, validating the effectiveness of each component in RetinaViT and demonstrating improvements in the speed/accuracy trade-off compared to baselines. In particular, for action recognition, RetinaViT built on ViT-B16 reduces inference time by approximately 61.9% on the CPU and 50.8% on the GPU, while achieving slight accuracy improvements rather than degradation.

Bone tunnel creation in the anatomical location is essential in anterior cruciate ligament (ACL) reconstruction with an autogenous graft and is commonly performed with a drill bit matched to graft diameter. Anatomic rectangular tunnel ACL reconstruction with a bone–patellar tendon–bone autograft has been developed to anatomically create bone tunnels inside the ACL footprints and has been reported to achieve excellent outcomes. To make the rectangular tunnel, the surgeon needs to dilate 2 adjacent bone tunnels after creation of 2 round tunnels with a drill bit, while the tunnel wall occasionally cracks during dilating. An ultrasonic (US) device was developed with improvement of output power and has been implemented with a rectangular shape blade in the field of arthroscopic surgery. This US device can provide a precise and effective bone cut compared to drills. We introduced this device to clinically create a rectangular tunnel during ACL reconstruction. The US device can be useful for rectangular femoral tunnel creation and can create a precise rectangular femoral tunnel in the ACL footprint.

Abstract This study, which included serological and cellular immunity tests, evaluated whether coronavirus disease 2019 (COVID-19) vaccination adequately protected healthcare workers (HCWs) from COVID-19. Serological investigations were conducted among 1600 HCWs (mean ± standard deviation, 7.4 ± 1.4 months after the last COVID-19 vaccination). Anti-SARS-CoV-2 antibodies N-Ig, Spike-Ig (Roche), N-IgG, Spike-IgM, and -IgG (Abbott), were evaluated using a questionnaire of health condition. 161 HCWs were analyzed for cellular immunity using T-SPOT® SARS-CoV-2 kit before, and 52 HCWs were followed up until 138.3 ± 15.7 days after their third vaccination. Spike-IgG value was 954.4 ± 2282.6 AU/mL. Forty-nine of the 1600 HCWs (3.06%) had pre-existing SARS-CoV-2 infection. None of the infectious seropositive HCWs required hospitalization. T-SPOT value was 85.0 ± 84.2 SFU/106 cells before the third vaccination, which increased to 219.4 ± 230.4 SFU/106 cells immediately after, but attenuated later (to 111.1 ± 133.6 SFU/106 cells). Poor counts (

Abstract Background Aortopulmonary mediastinal paragangliomas are rare. Complete resection of the tumor is desirable regardless of tumor size in view of the risk of sudden death induced by adjacent organ compression and poor prognosis after partial resection or untreated observation. Due to the hypervascularity of the tumor, the risk of intraoperative bleeding is significant, and cardiopulmonary bypass is often required for complete resection. Case presentation The patient was diagnosed as having bilateral carotid body tumors and supposedly an aortic body tumor at the age of 43 and eventually underwent resections of bilateral carotid body tumors at the age of 52. The pathology of the carotid body tumors was compatible with paraganglioma on both sides. A familial succinate dehydrogenase subunit D mutation was subsequently identified. Five years later, a contrast-enhanced computed tomography scan showed an enlarged tumor of 45 mm in size in the aortopulmonary mediastinum. Based on the previously known genetic mutation, the tumor was thought to be a paraganglioma. After confirming with an endocrinologist that the aortic body tumor was non-functional, radiologists performed preoperative embolization of the feeding vessels. Subsequently, a surgical team consisting of thoracic and cardiovascular surgeons resected the aortic body tumor using a video-assisted small left thoracotomy approach combined with a median sternotomy approach. The procedure was completed without cardiopulmonary bypass or blood transfusion. The patient was discharged home on postoperative day 9 uneventfully. Conclusions After conduction of preceding interventional embolization of multiple feeding vessels, we employed a video-assisted thoracoscopic surgical approach to dissect the aspects of the tumor adjacent to the esophagus, descending thoracic aorta, and left pulmonary artery, followed by a median sternotomy approach to dissect the other aspects of the tumor adjacent to the ascending aorta, aortic arch, right pulmonary artery, and trachea. There have been no reports on scheduled preoperative embolization of feeding vessels to an aortopulmonary mediastinal paraganglioma. Multidisciplinary approach was effective for complete resection of this challenging rare mediastinal tumor.

We evaluated the detection efficiency and location accuracy of lightning discharges in Japan using Blitzortung.org, a volunteer-based network for locating lightning discharges from sferics measured by very low frequency (VLF) electromagnetic receivers that have been deployed worldwide in recent years. A comparison of the flash rate (the detected lightning rate per area and period) from Blitzortung.org with that from the satellite-based OTD/LIS and the ground-based World Wide Lightning Location Network (WWLLN) observations showed that Blitzortung.org clearly observed intense lightning activity in and around the Kanto area, including Tokyo, in summer, which is typical of Japanese lightning activity. However, it did not clearly observe lightning activity in and around the Nansei Islands, including Okinawa. Conversely, Blitzortung.org observed winter lightning activity in the Hokuriku area and off the Kanto. In addition, event studies have compared the detection efficiency and location accuracy of Blitzortung.org with those of the Japanese Lightning Location Network (JLDN) to infer their absolute values. The latest detection efficiency of Blitzortung.org in the Kanto area was estimated at roughly 90%. The mean location accuracy was estimated at up to 5.6 km.

We measured the greenhouse gas (GHG) emissions following beef cattle feeding and evaluated the manure management in northeast Thailand (Khon Kaen) to obtain the country-specific emission factor (EF) and replace the Intergovernmental Panel on Climate Change (IPCC) default value. We fed four Thai native cattle their typical diet of the region and then used the head-cage and dynamic chamber methods to measure the enteric methane (CH4) and GHG emissions during manure storage, respectively. The effect of amending the cattle manure with rice straw on the manure’s GHG emission was evaluated. The manure microbiome was monitored by 16S rRNA gene amplicon sequencing and qPCR assay of the functional genes that are required for the methanogenesis and nitrification/denitrification process. The estimated CH4 conversion factor (Ym: 6.87 ± 0.11% gloss energy intake (GEI)) was slightly higher than the IPCC default value. The CH4 emission from the manure accounted for 0.69 ± 0.26% GEI. The addition of rice straw slightly lowered the CH4 emission from the manure, but the manure microbiome analysis results showed that it significantly reduced the relative abundance of methanogens (Methanobacteriales), and the functional estimation of manure microbiome agreed with this inhibition effect. The addition of rice straw also showed potential mitigation of the N2O emission with lowered nitrification activity and lower nitrifier abundance, but the results were not consistent between runs. Together these findings will be useful for the higher-tier approach to GHG emissions from beef cattle production systems in tropical regions.

Abstract We report the first observations of periodic oscillations of an atmospheric electric field simultaneously derived by field mills at four observation sites at a distance of 50–65 km in metropolitan Tokyo. Oscillations were detected during a snowfall event on 23–24 November, 2016. The main period of the oscillations of the atmospheric electric field at CHB was 78 min, which was similar to those at other sites. The periods of 39.0, 54.6, and 78.0 min observed at Chiba (CHB) were similar to those observed by W-band cloud radar (FALCON-I) reflectivity below a height of 5 km. High coherence of the 78-min period between the atmospheric electric field at CHB and the X-band phased array weather radar reflectivity suggest that the periodic oscillations of the atmospheric electric field during snowfall were caused by vertically convective cells in snow clouds with a radius of 60 km centered on CHB.

Nowadays, the use of electric vehicles is increasing leading to a growing demand for more efficient use of lithium-ion batteries. The state-of-charge (SOC) has been estimated in previous studies to optimize energy management of batteries. For more efficient battery utilization, detecting degradation is important. However, it is difficult for conventional methods to distinguish the effect of the model parameters including different time constants. Identifying model parameters of multiple RC parallel branches, which represent the impedance of wider frequency ranges, is a necessary requirement to detect the degradation of parts. In this study, we present a method for estimating the model parameters of multiple RC parallel branches. We designed the Markov Chain Monte Carlo algorithm by setting a search range limit and moving window, which enable estimation of the model parameters of parallel branches of different time constants. Through validation of the algorithm based on simulation, the model parameters of a third-order circuit were estimated to be within the error range of 15.2 %. In addition, impedance was calculated from the estimated model parameters in the test using a real battery dataset. The error of impedance was less than 10 % from 0.01 to 100 Hz which was sufficiently low to monitor the change of the parameters owing to degradation. As the impedance in the high-frequency band above 0.1 Hz is more likely to change because of degradation, the proposed method can be used to monitor the model parameters that change as a result of degradation.

Summary The effects of cashew nut shell liquid (CNSL) feeding on the methane (CH4) emission and the ruminal microbiome of Lai Sind beef cattle were investigated. Changes in the methane production and rumen microbiome by CNSL feeding were monitored by a respiration chamber and 16S rRNA gene amplicon sequencing respectively. The results demonstrated that CNSL feeding mitigated 20.2%–23.4% of the CH4 emission in vivo without apparent adverse effects on feed intake and feed digestibility. The rumen fluid analysis revealed a significant increase in the proportion of propionate in the total short‐chain fatty acids. The relative abundance of methanogen (order Methanobacteriales) decreased significantly, indicating the direct inhibitory effect of CNSL on methanogens. The predicted function of the rumen microbiome indicated that carbohydrate and lipid metabolisms including propionate production were upregulated by CNSL feeding, whereas CH4 metabolism was downregulated. A network analysis revealed that methanogen changed its partner bacteria after CNSL feeding. The δ13C of CH4 ranged from −74.2‰ to −66.6‰ with significant fluctuation by CNSL feeding, in agreement with the shift of the rumen microbiome. Our findings demonstrate that CNSL feeding can mitigate the CH4 emission from local cattle production systems in South‐East Asia by modifying the rumen microbiome and its function.

Abstract A 37‐year‐old man was admitted to our hospital with chest pain and fever. Computed tomography showed pleural effusion and irregularly marginated, elevated lesions inside diffuse pleural thickening. Detailed medical examination showed swelling of the left testicle. 18F‐fluorodeoxyglucose positron emission tomography showed uptakes at the thickened pleura and left testis. Pelvic magnetic resonance imaging showed a mass in the left testis with a heterogeneous and partially calcified tumour present interiorly. Thoracoscopy was performed under local anaesthesia, enabling the observation of masses at the pleura and biopsy of the mass, which was diagnosed as malignant pleural mesothelioma. The affected testicle was resected and diagnosed as tunica vaginalis testis mesothelioma. Thus, simultaneous tunica vaginalis testis and pleural mesothelioma were diagnosed. It is necessary to closely examine parts of the body other than the chest.

Livestock manure and its management are significant sources of greenhouse gas (GHG). In most Southeast Asian countries, the current GHG emissions are estimated by the Intergovernmental Panel on Climate Change (IPCC) Tier 1 approach using default emission factors. Sun-drying is the dominant manure treatment in Vietnam, and in this study, we measured GHG emissions during manure drying using a chamber-based approach. Results show the emission factors for CH4 and N2O were 0.295 ± 0.078 g kg−1 volatile solids (VS) and 0.132 ± 0.136 g N2O-N kg−1 Ninitial, respectively. We monitored the total bacterial/archaeal community using 16S rRNA gene amplicon sequencing and measured the abundance of functional genes required for methanogenesis (mcrA), nitrification (amoA) and denitrification (nirK, nirS and nosZ) processes. Methane emission occurred only at the beginning of the drying process (days 1 to 3). The results of amplicon sequencing indicated that the relative abundance of methanogens also decreased during this period. Although some nitrification activity was detected, there was no significant N2O emission. These findings well describe the manure management system in south Vietnam and the GHG emission from this manure category, paving the way for higher Tier estimations using country-specific values.

Healthcare workers (HCWs), especially frontline workers against coronavirus disease 2019 (COVID-19), are considered to be risky because of occupational exposure to infected patients. This study evaluated the correlation between seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies among HCWs and the implementation of personal protective equipment (PPE) & infection prevention and control (IPC). We recruited 1237 HCWs from nine public COVID-19-designated hospitals in Shiga Prefecture, central Japan, between 15-26 February 2021. All participants answered a self-administered questionnaire and provided blood samples to evaluate SARS-CoV-2 antibodies. A total of 22 cases (1·78%) were seropositive among the 1237 study participants. An unavoidable outbreak of SARS-CoV-2 had occurred at the terminal care unit of one hospital, before identifying and securely isolating this cluster of cases. Excluding with this cluster, 0·68% of HCWs were suspected to have had previous SARS-CoV-2 infections. Binomial logistic regression from individual questionnaires and seropositivity predicted a significant correlation with N95 mask implementation under aerosol conditions (p = 8.63e-06, aOR = 2.47) and work duration in a red zone (p = 2.61e-04, aOR = 1.99). The institutional questionnaire suggested that IPC education was correlated with reduced seropositivity at hospitals. Seroprevalence and questionnaire analyses among HCWs indicated that secure implementation of PPE and re-education of IPC are essential to prevent SARS-CoV-2 infection within healthcare facilities. Occupational infections from SARS-CoV-2 in healthcare settings could be prevented by adhering to adequate measures and appropriate use of PPE. With these measures securely implemented, HCWs should not be considered against as significantly risky or dirty by local communities.

Recently, Transformer-based video recognition models have achieved state-of-the-art results on major video recognition benchmarks. However, their high inference cost significantly limits research speed and practical use. In video compression, methods considering small motions and residuals that are less informative and assigning short code lengths to them (e.g., MPEG4) have successfully reduced the redundancy of videos. Inspired by this idea, we propose Informative Patch Selection (IPS), which efficiently reduces the inference cost by excluding redundant patches from the input of the Transformer-based video model. The redundancy of each patch is calculated from motions and residuals obtained while decoding a compressed video. The proposed method is simple and effective in that it can dynamically reduce the inference cost depending on the input without any policy model or additional loss term. Extensive experiments on action recognition demonstrated that our method could significantly improve the trade-off between the accuracy and inference cost of the Transformer-based video model. Although the method does not require any policy model or additional loss term, its performance approaches that of existing methods that do require them.

Abstract Introduction Bronchial thermoplasty (BT) is a bronchoscopic procedure that involves the delivery of thermal radiofrequency energy to the bronchial wall for treating severe asthma. It has been suggested that too many radiofrequency activations could induce serious adverse events (SAEs) at an early stage. We aimed to examine the number of radiofrequency activations at each session and early lung function changes from baseline to determine whether these are related to SAEs. Methods We retrospectively investigated 13 consecutive patients who underwent three sessions each of BT for severe asthma from February 2015 to January 2016. Lung function tests were performed on the day before and after each BT procedure. Since we compared the number of activations and lung function changes from baseline after each session, a total of 39 sessions were reviewed. The relationship between the number of radiofrequency activations and each lung function change from baseline was also examined by linear regression analysis. Results A total of 10 SAEs (4 of pneumonia, 3 of atelectasis, 2 of bronchial asthma exacerbation and 1 of hemoptysis) were observed following the 39 BT sessions. When we compared sessions with and without SAEs, there were no differences in the number of activations (mean ± SD, 71.5 ± 28.6 times in sessions with SAEs; 66.5 ± 25.1 times in sessions without SAEs; p = 0.772) and lung function changes (mean changes in FVC/%FVC/FEV1/%FEV1/%PEF from baseline; − 0.49 l/− 14.2%/− 0.36 l/− 11.7%/− 9.6% in sessions with SAEs; − 0.43 l/− 13.3%/− 0.34 l/− 12.1%/− 9.4% in sessions without SAEs; p > 0.05 for all the above). Increase in the number of activations correlated with decreased FEV1 (R 2 = 0.17, p = 0.0088) and %FEV1 (R 2 = 0.11, p = 0.0357). Conclusions Increase in the number of radiofrequency activations during BT is related to a decrease in FEV1 and %FEV1 from baseline. The number of radiofrequency activations, however, is not associated with SAEs after BT.

Abstract Background The baculovirus (BV) Autographa californica multiple nuclear polyhedrosis virus has been used in numerous protein expression systems because of its ability to infect insect cells and serves as a useful vaccination vector with several benefits, such as its low clinical risks and posttranslational modification ability. We recently reported that dendritic cells (DCs) infected with BV stimulated antitumor immunity. The recombinant BV (rBV) also strongly stimulated peptide-specific T-cells and antitumor immunity. In this study, the stimulation of an immune response against EG7-OVA tumors in mice by a recombinant baculovirus-based combination vaccine expressing fragment C-ovalbumin (FrC-OVA-BV; rBV) was evaluated. Results We constructed an rBV expressing fragment C (FrC) of tetanus toxin containing a promiscuous MHC II-binding sequence and a p30-ovalbumin (OVA) peptide that functions in the MHC I pathway. The results showed that rBV activated the CD8+ T-cell-mediated response much more efficiently than the wild-type BV (wtBV). Experiments with EG7-OVA tumor mouse models showed that rBV significantly decreased tumor volume and increased survival compared with those in the wild-type BV or FrC-OVA DNA vaccine groups. In addition, a significant antitumor effect of classic prophylactic or therapeutic vaccinations was observed for rBV against EG7-OVA-induced tumors compared with that in the controls. Conclusion Our findings showed that FrC-OVA-BV (rBV) induced antitumor immunity, paving the way for its use in BV immunotherapy against malignancies.

Abstract Background Ultrasonic (US) devices are used in laparoscopic, dental, and spinal surgeries, while it is difficult to use for the joint under irrigation and perfusion solutions due to lack of power. A new US device is developed with greater voltage improvement and has been implemented in the arthroscopic field. The aim is to compare the characteristics of the US devices with the conventional ones in water. Methods Twenty bone blocks from the porcine femur were settled in a holder in water. A 4.0 mm diameter abrader burr moved 15 mm along the long axis of the bone block in ten blocks for three times. A 4.3 mm wide curette blade powered by ultrasonic vibration was moved in the same manner in the other ten blocks. The gutter shape, including the gutter depth and the bottom angle of the gutter, and the curetted area ratio of the gutter were assessed. Forty bones blocks from the porcine femurs were clamped with a holder in water, while the cortical bone surface must be located on the side. A 5 mm diameter drill excavated the bone along the previously-inserted guide wire to the 15 mm depth for twenty blocks. Next, the US excavation probe of 5x4mm rectangular shape was moved to the same depth in the other twenty blocks. Each ten block was cut in half along the bone tunnel and was assessed the surface roughness at three area, while the cross-sectional area (CSA) of the tunnel were measured and the ratio of the measured CSA was calculated based on an expected CSA in the remaining ten blocks for each device. Results The depth of curettage and bottom angle were significantly smaller with the US device than with the abrader burr at all planes, while the curetted area ratio created by each device was mostly equal to the other. Surface roughness was similar in two evacuating devices except one area. CSA ratio with the US excavation device was significantly smaller than that with the drill. Conclusion US curettage has an advantage to flatly curette bone surfaces, while a bone tunnel can be accurately created with the US device.

Objective The main objective of this study was to evaluate the effect of different feeding levels of a total mixed ration silage-based diet on feed intake, total tract digestion, enteric methane emissions, and energy partitioning in two beef cattle genotypes. Methods Six mature bulls (three Thai natives, and three Thai natives - Charolais crossbreeds) were assigned in a replicated 3×3 Latin square design, with cattle breed genotype in separate squares, three periods of 21 days, and three energy feeding above maintenance levels (1.1, 1.5, and 2.0 MEm, where MEm is metabolizable energy requirement for maintenance). Bulls were placed in a metabolic cage equipped with a ventilated head box respiration system to evaluate digestibility, record respiration gases, and determine energy balance. Results Increasing the feeding level had no significant effect on digestibility but drastically reduced the enteric methane emission rate (p

Transient luminous events (TLEs) are electrical discharges in the upper atmosphere caused by vigorous thunderstorms. Six sprites, which are part of TLEs, were observed on 22 July 2013 from Mt. Fuji (3776 m above sea level), Japan. All the six sprites were associated with intense positive cloud-to-ground strikes (+CGs), whose causative positive charges can reside in the stratiform region. Consequently, we assumed that the main sprites causative charges could generate an in situ charging mechanism, accompanied by precipitation growth in the extensive stratiform region. Thus, we supposed that there can be a relationship between the time sequence of surface precipitation intensity and the sprite emissions. In this study, we conclude that time sequences and horizontal evolution of Mesoscale Convective Systems (MCSs) precipitation are associated with sprites. As the result, prior to sprites 1–5, the areal amount of strong precipitation (≥8 mm/h) increased considerably, and only a small increase occurred during sprite 6. Analyzing the time sequence of the percentage of strong and weak precipitation with respect to the total precipitation, it was found that sprites 1–6 occurred within 20 min after the local peaks with respect to strong precipitation compared to total precipitation. In particular, sprites 2–5 occurred very close to local peaks. The rise time to the first peak of the strong precipitation rate associated with the first sprite was 80 min, while the rise time to the last peak associated with sprite 6 was 30 min. The temporal differences until the peaks suggest that the charging speeds, or mechanisms, related to precipitation differ between sprites 1–5 and sprite 6 in parent MCSs.

Five sprites produced above the stratiform region and one sprite above the convective region in the mesoscale convective system (MCS) were observed on 22 July 2013 from the summit of Mt. Fuji. Four of the five sprites occurred in the stratiform region after the stratiform region was cut off from the convective region. The five sprite-producing +CGs (SP + CGs) occurred in and close to these cells with low lightning activity, although in-cloud lightning locations extensively spread out in the stratiform region. This suggests that positive charges were sufficient to produce the SP + CGs that accumulated extensively in the stratiform region due to a local (in situ) charge generation mechanism. One sprite occurred above the MCS convective region, and the SP + CG was also located at the MCS convective region. Video images indicated that the optical cloud flash associated with the SP + CG continued at least 150 ms until sprite emission. The optical cloud flash light occurred repeatedly at strong and weak intensities, and this characteristic indicated that the M components in the lightning occurred in the cloud. The SP + CG might have gathered sufficient positive charges to produce the sprite with a continuing current.

Preseismic VLF electromagnetic pulses occasionally increase a few days before large earthquakes, especially inland earthquakes. More than two decades ago, the Tokai University group developed a digital recording system for collecting the preseismic electromagnetic pulse data and showed remarkable results. However, due to the limitations of personal computers’ data storage and CPU power during that time, they discontinued the observation. We relaunched this research using current technology. This paper shows the development of the new observation system and presents preliminary results. In addition, we introduce an electromagnetic-wave arrival discrimination algorithm that combines the autoregressive model and the Akaike information criterion, which are commonly used for automatic waveform reading in seismology, to obtain accurate data on the time of arrival (TOA) of electromagnetic waves. Then, source positioning was performed using TOA of electromagnetic waves. Seven electromagnetic pulses near the epicenter were observed 2 days before the largest inland earthquake (M = 5.6) that occurred near the observation network during the observation period (2016–2020). These VLF pulses may be a seismic precursory phenomenon because they were not electromagnetic pulses originating from lightning. These results encourage future observations.

With improvement in arthroscopic techniques, partial meniscectomy with repair for symptomatic discoid lateral meniscus (DLM) has been the preferred treatment to restore meniscal function. It was reported that DLM exhibited deformation and extrusion shortly after saucerization with repair. Therefore it is desirable to minimize removal of the DLM. The anterior zone of the DLM is often tighter than that of the normal meniscus and anatomic variant. It is considered that the anterior and anterocentral dislocation types in the majority of symptomatic DLM can be related to both peripheral instability and anterior tightness. We present a technique that, first, the inside-out repair technique is applied from the posterior to middle segment of the DLM; next, the tension of the anterior zone during knee flexion–extension is confirmed to determine the released amount of that part; and, finally, all sutures are tied to reproduce the normal meniscus movement. Meniscus repair with anterior cord release without any meniscectomy could resolve peripheral instability of DLM and prevent degeneration of the articular cartilage.

Objective This study was conducted to assess the effects of replacing rice straw with different proportions of cassava pulp on growth performance, feed intake, digestibility, rumen microbial population, energy partitioning and efficiency of metabolizable energy utilization in beef cattle. Methods Eighteen yearling Thai native beef cattle (Bos indicus) with an average initial body weight (BW) of 98.3±12.8 kg were allocated to one of three dietary treatments and fed ad libitum for 149 days in a randomized complete block design. Three dietary treatments using different proportions of cassava pulp (100, 300, and 500 g/kg dry matter basis) instead of rice straw as a base in a fermented total mixed ration were applied. Animals were placed in a metabolic pen equipped with a ventilated head box respiration system to determine total digestibility and energy balance. Results The average daily weight gain, digestible intake and apparent digestibility of dry matter, organic matter and non-fiber carbohydrate, total protozoa, energy intake, energy retention and energy efficiency increased linearly (p

It has been reported that an accelerometer-based portable navigation device can achieve accurate bone cuts, but there have been few studies of clinical outcomes after total knee arthroplasty (TKA) using such a device. The aim of this study was to evaluate lower limb alignment and clinical outcomes after TKA using an accelerometer-based portable navigation device. Thirty-five patients (40 knees) underwent primary TKAs using an accelerometer-based portable navigation device. Postoperative radiographic assessments included the hip-knee-ankle angle, femoral component angle (FCA), and tibial component angle (TCA) in the coronal plane and the sagittal FCA and sagittal TCA in the sagittal plane. Clinical outcomes were evaluated by the Japanese Orthopedic Association score for osteoarthritic knees, Japanese Knee Osteoarthritis Measure, and the New Knee Society Score. The frequency of outliers (>3 degrees) was 10% for the hip-knee-ankle angle, 8% for FCA, 0% for TCA, 19% for sagittal FCA, and 9% for sagittal TCA. The Japanese Orthopedic Association score and Japanese Knee Osteoarthritis Measure were significantly improved postoperatively. The postoperative New Knee Society Score was 67.2% for symptoms, 50.3% for satisfaction, 58.6% for expectation, and 44.1% for function. TKA using an accelerometer-based portable navigation device achieved good results for both lower limb alignment and clinical outcomes. Keywords: Total knee arthroplasty, Accelerometer-based portable navigation device, Lower limb alignment, Self-reported clinical outcome

Abstract Background Yellow nail syndrome (YNS) is a rare disease characterized by the triad of thickened, slow-growing yellow nails, lymphedema, and chronic respiratory manifestations. The cause of YNS is not known; however, it is suggested to be due to a congenital lymph abnormality. Since YNS is accompanied by chronic bronchial infection in more than half of patients, we hypothesized that treatment with clarithromycin (CAM) could be effective. We therefore evaluated the effectiveness of CAM against nail discoloration and respiratory manifestation in patients with YNS. Methods We conducted an observational study involving 5 patients with YNS who were treated at our institution between January 2005 and January 2016. CAM was prescribed for every patient. Patient demographic information, comorbidities, medications, chest radiographs, and clinical data such as nail color were extracted to evaluate clinical outcome. Results Mean patient age was 71.6 years, and 2 patients (40%) were male. Four patients had sinusitis, and 2 had rheumatoid arthritis. Regarding respiratory manifestations, 4 patients had sinobronchial syndrome and 2 had pleural effusion. Nail discoloration improved in every patient after CAM treatment. Four patients also experienced improvement in their respiratory manifestations. Conclusions In patients with YNS, the anti-inflammatory activity of macrolides might improve their systemic inflammation. This improvement could help to reduce lymphedema and promote nail growth. Trial registration Ethical approval was provided by the institutional review board of the National Center of Global Health and Medicine (NCGM-G-002143-00), in January 2017. This study is retrospectively registered for UMIN Clinical Trial Registry (UMIN000028514) in August 4th, 2017.

There are various methods for reconstructing the anterior cruciate ligament (ACL) from other muscles or tendons. Initial tension of the reconstructed ACL is one of the key elements affecting postoperative outcomes. However, tension cannot be measured after graft fixation. The only intraoperative assessment is pull probing, which is performed by pulling joint soft tissues with the arthroscopic probe and can be measured quantitatively. Therefore, its value might be used as an alternative value for the mechanical property of the ACL. Using a probing device one author developed to measure the resistance force of soft tissues quantitatively while probing, we measured the resistance force of dissected ACLs and used tensile testing to investigate the correlation between the resistance force and the mechanical property of the ligaments. According to the results, when a certain amount of tension (strain; 16.6%) was applied, its mechanical properties were moderately correlated (r = 0.56 [p = 0.045]) with the probing force. Therefore, the tension of the reconstructed ACL after fixation under real ACL reconstruction surgery can be derived from the value of the probing device.

Andersen-Tawil syndrome (ATS) is a rare inherited channelopathy. The cardiac phenotype in ATS is typified by a prominent U wave and ventricular arrhythmia. An effective treatment for this disease remains to be established. We reprogrammed somatic cells from three ATS patients to generate induced pluripotent stem cells (iPSCs). Multi-electrode arrays (MEAs) were used to record extracellular electrograms of iPSC-derived cardiomyocytes, revealing strong arrhythmic events in the ATS-iPSC-derived cardiomyocytes. Ca2+ imaging of cells loaded with the Ca2+ indicator Fluo-4 enabled us to examine intracellular Ca2+ handling properties, and we found a significantly higher incidence of irregular Ca2+ release in the ATS-iPSC-derived cardiomyocytes than in control-iPSC-derived cardiomyocytes. Drug testing using ATS-iPSC-derived cardiomyocytes further revealed that antiarrhythmic agent, flecainide, but not the sodium channel blocker, pilsicainide, significantly suppressed these irregular Ca2+ release and arrhythmic events, suggesting that flecainide's effect in these cardiac cells was not via sodium channels blocking. A reverse-mode Na+/Ca2+exchanger (NCX) inhibitor, KB-R7943, was also found to suppress the irregular Ca2+ release, and whole-cell voltage clamping of isolated guinea-pig cardiac ventricular myocytes confirmed that flecainide could directly affect the NCX current (INCX). ATS-iPSC-derived cardiomyocytes recapitulate abnormal electrophysiological phenotypes and flecainide suppresses the arrhythmic events through the modulation of INCX.

Rheumatoid arthritis-related interstitial pneumonia with a usual interstitial pneumonia (RA-UIP) has a poor prognosis and a new treatment strategy is required. The antifibrotic agent nintedanib reduces the annual rate of decline in forced vital capacity (FVC) in idiopathic pulmonary fibrosis (IPF) patients. Recently, the potential efficacy of antifibrotic agents against chronic progressive fibrotic diseases including RA-UIP has been attracting attention.A 74-year-old man diagnosed with IPF on high-resolution computed tomography (HRCT). His FVC was decreasing over time, and his exertional dyspnea and cough had progressed with progression of reticulation on imaging. He was treated with nintedanib, which resulted in decreased coughing together with a reduction in FVC decline, from −11.6%/year to −5.2%/year. A swollen joint appeared eight months after this intervention, and he was diagnosed with rheumatoid arthritis.In this patient, nintedanib was effective against RA-UIP. This is the first case in which nintedanib was shown to be effective for RA-UIP.

Rheumatoid arthritis (RA) is an autoimmune disease caused by inflammation of the synovium and characterized by chronic polyarthritis that destroys bone and cartilage. Fibroblast-like synoviocytes (FLSs) in the synovium of patients with RA can promote cartilage and bone destruction by producing proteins such as matrix metalloproteinases and receptor activator of NF-κB ligand, thereby representing an important therapeutic target for RA. FLSs have several phenotypes depending on which cell surface proteins and adhesion factors are expressed. Identifying the cellular functions associated with different phenotypes and methods of controlling them are considered essential for developing therapeutic strategies for RA. In this study, synovial tissue was collected from patients with RA and control subjects who required surgery due to ligament injury or fracture. Immunohistological analysis was used to investigate the rates of positivity for phosphorylated platelet-derived growth factor receptor-αβ (pPDGFRαβ) and cadherin-11 (CDH11) expression, and apoptosis-related markers were assessed for each cell phenotype. Next, FLSs were isolated in vitro and stimulated with tumor necrosis factor-α (TNF-α) in addition to a combination of PDGF and transforming growth factor (2GF) to investigate pPDGFRαβ and CDH11 expression and the effects of the inhibition of TNF and cyclin-dependent kinase (CDK) 4/6 on FLSs. Immunohistological analysis showed a large percentage of pPDGFRαβ+CDH11– cells in the sub-lining layer (SL) of patients with RA. These cells exhibited increased B-cell lymphoma-2 expression, reduced TNF receptor-1 expression, resistance to cell death, and abnormal proliferation, suggesting a tendency to accumulate in the synovium. Further, in vitro 2GF stimulation of FLSs lowered, whereas 2GF + TNF stimulation increased the pPDGFRαβ/CDH11 ratio. Hypothesizing that FLSs stimulated with 2GF + TNF would accumulate in vivo in RA, we determined the therapeutic effects of TNF and CDK4/6 inhibitors. The TNF inhibitor lowered the pPDGFRαβ/CDH11 ratio, whereas the CDK4/6 inhibitor suppressed cell proliferation. However, a synergistic effect was not observed by combining both the drugs. We observed an increase in pPDGFRαβ+CDH11– cells in the SL of the RA synovium and accumulation of these cells in the synovium. We found that the TNF inhibitor suppressed FLS activity and the CDK4/6 inhibitor reduced cell proliferation.

The manipulation of micro/nanoparticles has become increasingly important in biological and industrial fields. As a non-contact method for particle manipulation, acoustic focusing has been applied in sorting, enrichment and analysis of particles with microfluidic devices. Although the frequency and amplitude of acoustic waves and the dimensions of microchannels have been recognized as important parameters for acoustic focusing, the thickness of microfluidic devices has not been considered so far. Here, we report that thin glass microfluidic devices enhance acoustic focusing of micro/nanoparticles. It was found that the thickness of a microfluidic device strongly influences its ability to focus particles via acoustic radiation, because the energy propagation of acoustic waves is affected by the total mass of the device. Acoustic focusing of submicrometre polystyrene beads and Escherichia coli as well as enrichment of polystyrene beads were achieved in glass microfluidic devices as thin as 0.4 mm. Modifying the thickness of a microfluidic device can thus serve as a critical parameter for acoustic focusing when conventional parameters to achieve this effect are kept unchanged. Thus, our findings enable new approaches to the design of novel microfluidic devices.

In a numerical study, we consider the Allen–Cahn equation with a double-obstacle constraint. The constraint is a multivalued function that is provided by the subdi erential of the indicator function on a closed interval. Therefore, performing a numerical simulation of our problem poses diffculties. We propose a new approximate method for the constraint and demonstrate its validity. Moreover, we present stability criteria for the standard forward Euler method guaranteeing stable numerical experiments when using the approximating equation.

Objectives Orthopaedic surgery of the knee joint results in functional deterioration of the quadriceps femoris muscle. However, little is known about quadriceps femoris muscle dysfunction in the early postsurgical period. Therefore, we examined the stiffness of the quadriceps femoris muscle in the early postsurgical period.Methods Seven patients and seven healthy controls performed quadriceps contraction exercises. In resting and contraction conditions, the shear modulus, muscle thickness and pennation angle were measured for the vastus medialis (VM), vastus lateralis (VL) and the rectus femoris (RF) using ultrasound elastography.Results The shear moduli of the VM, VL and RF in the control group did not significantly interact, while the shear moduli in the patient group did show a significant interaction. In the resting condition, there was no difference between the unaffected and affected sides in the patient group, but the shear moduli of the VM and VL in the contraction condition was significantly lower on the affected side than the unaffected side.The contraction ratios between muscles by limbs did not significantly interact. However, there were main effects due to muscle and limb factors. The VM and VL had a significantly higher contraction ratio than the RF, and the control and unaffected limbs had a higher contraction ratio than the affected limb.Conclusion The results demonstrated a decrease in muscle stiffness during contraction in patients with quadriceps femoris dysfunction. Measurement of the shear modulus has potential as a new evaluation index and with high sensitivity to decreases in muscle contraction.

Mitochondrial diseases are heterogeneous disorders, caused by mitochondrial dysfunction. Mitochondria are not regulated solely by nuclear genomic DNA but by mitochondrial DNA. It is difficult to develop effective therapies for mitochondrial disease because of the lack of mitochondrial disease models. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS) is one of the major mitochondrial diseases. The aim of this study was to generate MELAS‐specific induced pluripotent stem cells (iPSCs) and to demonstrate that MELAS‐iPSCs can be models for mitochondrial disease. We successfully established iPSCs from the primary MELAS‐fibroblasts carrying 77.7% of m.3243A>G heteroplasmy. MELAS‐iPSC lines ranged from 3.6% to 99.4% of m.3243A>G heteroplasmy levels. The enzymatic activities of mitochondrial respiratory complexes indicated that MELAS‐iPSC‐derived fibroblasts with high heteroplasmy levels showed a deficiency of complex I activity but MELAS‐iPSC‐derived fibroblasts with low heteroplasmy levels showed normal complex I activity. Our data indicate that MELAS‐iPSCs can be models for MELAS but we should carefully select MELAS‐iPSCs with appropriate heteroplasmy levels and respiratory functions for mitochondrial disease modeling.

We propose a method for inferring the condition of factors influencing the temperature of heat-generating components in electronic equipment. Here, “factor” includes cooling components (fans, heat sinks, etc.), intake temperature, and the caloric value of the heat-generating component. The performance of these cooling components is reduced by unusual use or deterioration due to aging such as clogging or evaporation of grease. Such factors raise the temperature of heat-generating components. High temperatures of heat-generating components lead to system failure or a shortened life of the electronic equipment. Detecting decreases in the performance of cooling components allows timely provision of the required maintenance, possibly leading to increased product reliability. However, monitoring temperature alone is insufficient. The temperature of heat-generating components is also affected by factors such as intake temperature, and caloric value. In this study, we develop a method for inferring the condition of each factor influencing temperatures by using sensors installed at multiple locations. In this method, the effect of each factor on temperature depends on location, and the condition of each factor is expressed as a multivariate function using temperatures at multiple locations. The condition of each factor can then be inferred by measuring only temperatures. Furthermore, we can develop the method simply by mounting several temperature sensors on the board, making the method easy to implement. System failures can thus be prevented by performing maintenance based on the monitored factors. We conducted verification experiments using a computer to confirm the benefits of this method. In the case of inferring the conditions of four factors using four temperature sensors, the mean accuracy exceeded 90%.

Mesenchymal stem cell- (MSC-) based therapy is a promising treatment for cartilage. However, repair tissue in general fails to regenerate an original hyaline-like tissue. In this study, we focused on increasing the expression levels for insulin-like growth factor-1 (IGF-1) to improve repair tissue quality. The IGF-1 gene was introduced into human synovial MSCs with a lentiviral vector and examined the levels of gene expression and morphological status of MSCs under chondrogenic differentiation condition using pellet cultures. The size of the pellets derived from IGF-1-MSCs were significantly larger than those of the control group. The abundance of glycosaminoglycan (GAG) was also significantly higher in the IGF-1-MSC group. The histology of the IGF-1-induced pellets demonstrated similarities to hyaline cartilage without exhibiting features of a hypertrophic chondrocyte phenotype. Expression levels for the Col2A1 gene and protein were significantly higher in the IGF-1 pellets than in the control pellets, but expression levels for Col10, MMP-13, ALP, and Osterix were not higher. Thus, IGF-1 gene transfer to human synovial MSCs led to an improved chondrogenic differentiation capacity without the detectable induction of a hypertrophic or osteogenic phenotype.

We tested a hypothesis that an enhancement of IKs may play a pivotal role in ventricular proarrhythmia under high sympathetic activity. A 2-dimensional ventricular muscle layer was prepared in rabbit hearts, and action potential signals were analyzed by optical mapping. During constant stimulation, isoproterenol (ISP, 0.1 μM) significantly shortened action potential duration (APD); chromanol 293B (30 μM), a selective IKs-blocker, reversed the APD shortening. VTs induced in the presence of ISP lasted longer than in the control, and this was reversed by 293B. E-4031 (0.1 μM), a selective IKr-blocker, did not cause such reversal. Spiral-wave (SW) reentry with ISP was characterized by more stable rotation around a shorter functional block line (FBL) than in the control. After application of 293B, SW reentry was destabilized, and rotation around a longer FBL with prominent drift reappeared. The APD abbreviation by ISP close to the rotation center was more pronounced than in the periphery, leading to an opposite APD gradient (center < periphery) compared with controls. This effect was also reversed by 293B. In conclusion, β-adrenergic stimulation stabilizes SW reentry most likely though an enhancement of IKs. Blockade of IKs may be a promising therapeutic modality in prevention of ventricular tachyarrhythmias under high sympathetic activity.[Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.12008FP] Keywords:: β-adrenergic stimulation, IKs, spiral-wave reentry, optical mapping, ventricular tachycardia

Bepridil is effective for conversion of atrial fibrillation to sinus rhythm and in the treatment of drug-refractory ventricular tachyarrhythmias. We investigated the effects of bepridil on electrophysiological properties and spiral-wave (SW) reentry in a 2-dimensional ventricular muscle layer of isolated rabbit hearts by optical mapping. Ventricular tachycardia (VT) induced in the presence of bepridil (1 μM) terminated earlier than in the control. Bepridil increased action potential duration (APD) by 5% – 8% under constant pacing and significantly increased the space constant. There was a linear relationship between the wavefront curvature (κ) and local conduction velocity: LCV = LCV0 − D·κ (D, diffusion coefficient; LCV0, LCV at κ = 0). Bepridil significantly increased D and LCV0. The regression lines with and without bepridil crossed at κ = 20 – 40 cm−1, resulting in a paradoxical decrease of LCV at κ > 40 cm−1. Dye transfer assay in cultured rat cardiomyocytes confirmed that bepridil increased intercellular coupling. SW reentry in the presence of bepridil was characterized by decremental conduction near the rotation center, prominent drift, and self-termination by collision with boundaries. These results indicate that bepridil causes an increase of intercellular coupling and a moderate APD prolongation, and this combination compromises wavefront propagation near the rotation center of SW reentry, leading to its drift and early termination.[Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.10233FP] Keywords:: bepridil, spiral-wave reentry, intercellular coupling, optical mapping, ventricular tachycardia

Induced pluripotent stem cells (iPSCs) have been proposed as novel cell sources for genetic disease models and revolutionary clinical therapies. Accordingly, human iPSC-derived cardiomyocytes are potential cell sources for cardiomyocyte transplantation therapy. We previously developed a novel generation method for human peripheral T cell-derived iPSCs (TiPSCs) that uses a minimally invasive approach to obtain patient cells. However, it remained unknown whether TiPSCs with genomic rearrangements in the T cell receptor (TCR) gene could differentiate into functional cardiomyocyte in vitro. To address this issue, we investigated the morphology, gene expression pattern, and electrophysiological properties of TiPSC-derived cardiomyocytes differentiated by floating culture. RT-PCR analysis and immunohistochemistry showed that the TiPSC-derived cardiomyocytes properly express cardiomyocyte markers and ion channels, and show the typical cardiomyocyte morphology. Multiple electrode arrays with application of ion channel inhibitors also revealed normal electrophysiological responses in the TiPSC-derived cardiomyocytes in terms of beating rate and the field potential waveform. In this report, we showed that TiPSCs successfully differentiated into cardiomyocytes with morphology, gene expression patterns, and electrophysiological features typical of native cardiomyocytes. TiPSCs-derived cardiomyocytes obtained from patients by a minimally invasive technique could therefore become disease models for understanding the mechanisms of cardiac disease and cell sources for revolutionary cardiomyocyte therapies.