Deep learning-based model detects atrial septal defects from electrocardiography: a cross-sectional multicenter hospital-based study.

Background: Atrial septal defect (ASD) increases the risk of adverse cardiovascular outcomes. Despite the potential for risk mitigation through minimally invasive percutaneous closure, ASD remains underdiagnosed due to subtle symptoms and examination findings. To bridge this diagnostic gap, we propose a novel screening strategy aimed at early detection and enhanced diagnosis through the implementation of a convolutional neural network (CNN) to identify ASD from 12-lead electrocardiography (ECG). Methods: ECGs were collected from patients with at least one recorded echocardiogram at 3 hospitals from 2 continents (Keio University Hospital from July 2011 to December 2020, Brigham and Women's Hospital from January 2015 to December 2020, and Dokkyo Medical University Saitama Medical Center from January 2010 and December 2021). ECGs from patients with a diagnosis of ASD were labeled as positive cases while the remainder were labeled as negative. ECGs after the closure of ASD were excluded. After randomly splitting the ECGs into 3 datasets (50% derivation, 20% validation, and 30% test) with no patient overlap, a CNN-based model was trained using the derivation datasets from 2 hospitals and was tested on held-out datasets along with an external validation on the 3rd hospital. All eligible ECGs were used for derivation and validation whereas the earliest ECG for each patient was used for the test and external validation. The discrimination of ASD was assessed by the area under the receiver operating characteristic curve (AUROC). Multiple subgroups were examined to identify any heterogeneity. Findings: A total of 671,201 ECGs from 80,947 patients were collected from the 3 institutions. The AUROC for detecting ASD was 0.85-0.90 across the 3 hospitals. The subgroup analysis showed excellent performance across various characteristics Screening simulation using the model greatly increased sensitivity from 80.6% to 93.7% at specificity 33.6% when compared to using overt ECG abnormalities. Interpretation: A CNN-based model using 12-lead ECG successfully identified the presence of ASD with excellent generalizability across institutions from 2 separate continents. Funding: This work was supported by research grants from JST (JPMJPF2101), JSR corporation, Taiju Life Social Welfare Foundation, Kondou Kinen Medical Foundation, Research fund of Mitsukoshi health and welfare foundation, Tokai University School of Medicine Project Research and Internal Medicine Project Research, Secom Science and Technology Foundation, and Grants from AMED (JP23hma922012 and JP23ym0126813). This work was partially supported by One Brave Idea, co-funded by the American Heart Association and Verily with significant support from AstraZeneca and pillar support from Quest Diagnostics.

Integrated genome-wide differentiation and association analyses identify causal genes underlying breeding-selected grain quality traits in japonica rice.

Improving grain quality is a primary objective in contemporary rice breeding. Japanese modern rice breeding has developed two different types of rice, eating and sake-brewing rice, with different grain characteristics, indicating the selection of variant gene alleles during the breeding process. Given the critical importance of promptly and efficiently identifying genes selected in past breeding for future molecular breeding, we conducted genome scans for divergence, genome-wide association studies, and map-based cloning. Consequently, we successfully identified two genes, OsMnS and OsWOX9D, both contributing to rice grain traits. OsMnS encodes a mannan synthase that increases the white core frequency in the endosperm, a desirable trait for sake brewing but decreases the grain appearance quality. OsWOX9D encodes a grass-specific homeobox-containing transcription factor, which enhances grain width for better sake brewing. Furthermore, haplotype analysis revealed that their defective alleles were selected in East Asia, but not Europe, during modern improvement. In addition, our analyses indicate that a reduction in grain mannan content during African rice domestication may also be caused a defective OsMnS allele due to breeding selection. This study not only reveals the delicate balance between grain appearance quality and nutrition in rice but also provides a new strategy for isolating causal genes underlying complex traits, based on the concept of "breeding-assisted genomics" in plants.

Real-Time Estimation of Anaerobic Threshold during Exercise Using Electrocardiogram in Heart Failure Patients.

Exercise therapy at the aerobic level is highly recommended to improve clinical outcomes in patients with heart failure, in which cardiopulmonary exercise testing (CPX) is required to determine anaerobic thresholds (ATs) but is not available everywhere. This study aimed to validate a method to estimate the AT using heart rate variability (HRV) analysis from electrocardiography data in patients with heart failure. Between 2014 and 2019, 67 patients with symptomatic heart failure underwent CPXs in a single university hospital. During the CPX, RR intervals was measured continuously and the HRV threshold (HRVT), defined as the inflection point of <5 ms2 of a high-frequency component (HFC) using the power spectrum analysis, was determined. Patients were divided into two groups according to the mean HFC at rest (high-HFC group, n = 34 and low-HFC group, n = 33). The high-HFC group showed good correlation between the VO2 at AT and HRVT (r = 0.63, p < 0.001) and strong agreement (mean difference, -0.38 mL/kg, p = 0.571). The low-HFC group also showed modest correlation (r = 0.41, p = 0.017) but poor agreement (mean differences, 3.75 mL/kg, p < 0.001). In conclusion, the HRVT obtained from electrocardiography may be a useful indicator for estimating AT in patients with heart failure.

An analysis of sugary endosperm in sorghum: Characterization of mutant phenotypes depending on alleles of the corresponding starch debranching enzyme.

Sorghum is the fifth most important cereal crop. Here we performed molecular genetic analyses of the 'SUGARY FETERITA' (SUF) variety, which shows typical sugary endosperm traits (e.g., wrinkled seeds, accumulation of soluble sugars, and distorted starch). Positional mapping indicated that the corresponding gene was located on the long arm of chromosome 7. Within the candidate region of 3.4 Mb, a sorghum ortholog for maize Su1 (SbSu) encoding a starch debranching enzyme ISA1 was found. Sequencing analysis of SbSu in SUF uncovered nonsynonymous single nucleotide polymorphisms (SNPs) in the coding region, containing substitutions of highly conserved amino acids. Complementation of the rice sugary-1 (osisa1) mutant line with the SbSu gene recovered the sugary endosperm phenotype. Additionally, analyzing mutants obtained from an EMS-induced mutant panel revealed novel alleles with phenotypes showing less severe wrinkles and higher Brix scores. These results suggested that SbSu was the corresponding gene for the sugary endosperm. Expression profiles of starch synthesis genes during the grain-filling stage demonstrated that a loss-of-function of SbSu affects the expression of most starch synthesis genes and revealed the fine-tuned gene regulation in the starch synthetic pathway in sorghum. Haplotype analysis using 187 diverse accessions from a sorghum panel revealed the haplotype of SUF showing severe phenotype had not been used among the landraces and modern varieties. Thus, weak alleles (showing sweet and less severe wrinkles), such as in the abovementioned EMS-induced mutants, are more valuable for grain sorghum breeding. Our study suggests that more moderate alleles (e.g. produced by genome editing) should be beneficial for improving grain sorghum.

Effective use of legacy data in a genome-wide association studies improves the credibility of quantitative trait loci detection in rice.

Genome-wide association studies (GWASs) are used to detect quantitative trait loci (QTL) using genomic and phenotypic data as inputs. While genomic data are obtained with high throughput and low cost, obtaining phenotypic data requires a large amount of effort and time. In past breeding programs, researchers and breeders have conducted a large number of phenotypic surveys and accumulated results as legacy data. In this study, we conducted a GWAS using phenotypic data of temperate japonica rice (Oryza sativa) varieties from a public database. The GWAS using the legacy data detected several known agriculturally important genes, indicating reliability of the legacy data for GWAS. By comparing the GWAS using legacy data (L-GWAS) and a GWAS using phenotypic data that we measured (M-GWAS), we detected reliable QTL for agronomically important traits. These results suggest that an L-GWAS is a strong alternative to replicate tests to confirm the reproducibility of QTL detected by an M-GWAS. In addition, because legacy data have often been accumulated for many traits, it is possible to evaluate the pleiotropic effect of the QTL identified for the specific trait that we focused on with respect to various other traits. This study demonstrates the effectiveness of using legacy data for GWASs and proposes the use of legacy data to accelerate genomic breeding.

Regulator of Awn Elongation 3, an E3 ubiquitin ligase, is responsible for loss of awns during African rice domestication.

Two species of rice have been independently domesticated from different ancestral wild species in Asia and Africa. Comparison of mutations that underlie phenotypic and physiological alterations associated with domestication traits in these species gives insights into the domestication history of rice in both regions. Asian cultivated rice, Oryza sativa, and African cultivated rice, Oryza glaberrima, have been modified and improved for common traits beneficial for humans, including erect plant architecture, nonshattering seeds, nonpigmented pericarp, and lack of awns. Independent mutations in orthologous genes associated with these traits have been documented in the two cultivated species. Contrary to this prevailing model, selection for awnlessness targeted different genes in O. sativa and O. glaberrima. We identify Regulator of Awn Elongation 3 (RAE3) a gene that encodes an E3 ubiquitin ligase and is responsible for the awnless phenotype only in O. glaberrima. A 48-bp deletion may disrupt the substrate recognition domain in RAE3 and diminish awn elongation. Sequencing analysis demonstrated low nucleotide diversity in a ~600-kb region around the derived rae3 allele on chromosome 6 in O. glaberrima compared with its wild progenitor. Identification of RAE3 sheds light on the molecular mechanism underlying awn development and provides an example of how selection on different genes can confer the same domestication phenotype in Asian and African rice.

Predictors of Improvement in Exercise Tolerance After Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension.

Background Balloon pulmonary angioplasty (BPA) improves exercise tolerance and hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension. However, it is still unclear which patient characteristics contribute to the improvement in exercise tolerance after BPA in chronic thromboembolic pulmonary hypertension. Methods and Results We retrospectively analyzed 126 patients with chronic thromboembolic pulmonary hypertension (aged 63±14 years; female, 65%) who underwent BPA without concomitant programmed exercise rehabilitation at Keio University between November 2012 and April 2018. Hemodynamic data and 6-minute walk distance (6MWD), as a measure of exercise tolerance, were evaluated before and 1 year after BPA. The clinical characteristics that contributed to improvement in exercise tolerance were elucidated. The 6MWD significantly increased from 372.0 m (256.5-431.3) to 462.0 m (378.8-537.0) 1 year after BPA (P<0.001). The improvement rate in the 6MWD after BPA exhibited a good correlation with age, height, mean pulmonary artery pressure, and 6MWD at baseline (Spearman rank correlation coefficients=-0.28, 0.24, -0.40, and 0.44, respectively). Additional multivariable linear regression analysis revealed that young age, tall height, high mean pulmonary artery pressure, short 6MWD at baseline, and high lung capacity at baseline were significant predictors of the improvement in 6MWD by BPA (standardized partial regression coefficient -0.39, 0.22, 0.19, -0.62, and 0.25, P<0.001, 0.007, 0.011, <0.001, and <0.001, respectively). Conclusions BPA without concomitant programmed exercise rehabilitation significantly improves exercise tolerance. This was particularly true in young patients with high stature, high mean pulmonary artery pressure, short 6MWD, and lung capacity at the time of diagnosis.

Real-time analysis of heart rate variability during aerobic exercise in patients with cardiovascular disease.

Background: Exercise therapy for cardiovascular disease (CVD) is mainly evaluated based on the heart rate (HR) or Borg scale. However, these indices can be unreliable depending on the patient's medication or their subjective decisions; thus, alternative methods are required for easier and safer implementation of aerobic exercise. Here, we examined whether real-time analysis of HR variability (HRV) can help maintain exercise intensity at the ventilatory threshold (VT) during exercise. Methods: Twenty-eight patients with CVD treated at Keio University Hospital between August 2018 and March 2020 were enrolled. Initially, oxygen uptake (VO2) and HR at the VT were determined using the cardiopulmonary exercise test. Patients then performed aerobic exercise on a stationary bicycle for 30 min while a parameter of HRV, the high-frequency (HF) component, was monitored in real time using an electrocardiograph. The work rate during exercise was adjusted every 2 min to maintain the HF range between 5 and 10. The VO2 and HR values, recorded every 2 min during exercise, were compared with those at VT. The Bland-Altman method was used to confirm similarity. Results: VO2 and HR during exercise were closely correlated with those at VT (e.g., 19 min after exercise initiation; VO2: r = 0.647, HR: r = 0.534). The Bland-Altman plot revealed no bias between the mean values (e.g., 19 min; VO2: -0.22 mL/kg/min; HR: -0.07/min). Conclusion: Real-time HRV analysis with electrocardiograph alone during exercise can provide continuous and non-invasive exercise intensity measurements at VT, promoting safer and effective exercise strategies.

Impaired Left Atrial Function in Patients with Atrial Septal Defect and History of Atrial Fibrillation.

In patients with atrial septal defect (ASD), atrial left-to-right shunting causes left atrial (LA) remodeling and dysfunction, leading to atrial fibrillation (AF). In adults with ASD and concomitant AF, LA function should be evaluated after ASD closure plus AF radiofrequency catheter ablation (RFCA).This multicenter retrospective cohort study included patients who underwent transcatheter ASD closure at one of the four leading hospitals. Patients with a history of AF also underwent preceding RFCA. The association between AF history and LA ejection fraction (EF) (indicating LA global function) at 6-12 months following ASD closure was evaluated. To account for differences in baseline characteristics between patients with and without a history of AF, we conducted the following statistical methods: (1) multivariate regression analysis in the prepropensity score (PS)-matched cohort and (2) univariate comparisons in the PS-matched cohort.Overall, this study included 231 patients (30 with AF history, 201 without). Multiple regression analysis showed that AF history was independently associated with impaired LAEF (ß = -10.425, P < 0.001, model created prior to propensity matching). A one-to-one PS matching (25 pairs) showed that the LAEF at 6-12 months following ASD closure was significantly impaired in patients with ASD and AF history compared to that in patients without history of AF (median LAEF, 37.5% (interquartile range [IQR] 29.4%-48.5%) versus 52.3 [IQR 50.0%-56.6%]; P < 0.001).LA function was impaired in patients with ASD and a history of AF at 6-12 months after successful transcatheter ASD closure and on maintenance of sinus rhythm by RFCA.

OsGGC2, Gγ Subunit of Heterotrimeric G Protein, Regulates Plant Height by Functionally Overlapping with DEP1 in Rice.

Plant heterotrimeric G proteins have been shown to regulate the size of various organs. There are three types of Gγ subunits in plants: type A, consisting of a canonical Gγ domain; type B, possessing a plant-specific domain at the N-terminus of the Gγ domain; and type C, possessing a plant-specific domain at the C-terminal of the Gγ domain. There is one type A, one type B, and three type C of the five γ-subunits in the rice genome. In type C Gγ subunits, GS3, which controls grain size; DEP1, which controls plant height and panicle branching; and their homolog OsGGC2, which affects grain size, have been reported; however, the function of each gene, their interactions, and molecular mechanisms for the control of plant height have not yet been clarified. In this study, we generated loss-of-function mutants of DEP1 and OsGGC2, which have high homology and similar expression, and investigated their phenotypes. Since both dep1 and osggc2 mutants were dwarfed and the double mutants showed a synergistic phenotype, we concluded that both DEP1 and OsGGC2 are positive regulators of plant height and that their functions are redundant.

Reduction of Atrial Septal Defect Size After Catheter Ablation for Atrial Tachyarrhythmia and Its Predictive Factors.

The prevalence of atrial tachyarrhythmia is high in patients with atrial septal defect (ASD), and catheter ablation (CA) is often performed before percutaneous ASD closure. We aimed to clarify the effect of CA on the ASD size. We analysed 16 patients with secundum ASD who had a history of CA for atrial tachyarrhythmia and underwent ASD size evaluation before and after CA. The size of ASD significantly decreased after CA. Younger age and lower tricuspid regurgitation pressure gradients and pulmonary arterial systolic pressures were associated with size reduction. These factors are crucial for making strategies of percutaneous ASD closure.

La prévalence de la tachyarythmie auriculaire est élevée chez les patients qui présentent une communication interauriculaire (CIA), et l'on pratique souvent une ablation par cathéter avant la fermeture percutanée de la CIA. Notre objectif consistait à éclaircir l'effet de l'ablation par cathéter sur la taille de la CIA. Pour ce faire, nous avons analysé 16 patients présentant une CIA de type ostium secundum, ayant déjà subi une ablation par cathéter et chez qui la taille de la CIA a été évaluée avant et après l'intervention. La taille de la CIA a diminué de manière significative après l'ablation par cathéter. Les facteurs associés à la réduction de la taille de la communication comprennent un âge plus jeune, des gradients de pression plus faibles pour l'insuffisance tricuspidienne et une pression artérielle systolique moins élevée. Il est crucial de tenir compte de ces facteurs lors de l'établissement d'une stratégie pour la fermeture percutanée d'une CIA.

Exercise tolerance and quality of life in hemodynamically partially improved patients with chronic thromboembolic pulmonary hypertension treated with balloon pulmonary angioplasty.

The efficacy of extensive balloon pulmonary angioplasty (BPA) beyond hemodynamic improvement in chronic thromboembolic pulmonary hypertension (CTEPH) patients has been verified. However, the relationship between extensive BPA in CTEPH patients after partial hemodynamic improvement and exercise tolerance or quality of life (QOL) remains unclear. We prospectively enrolled 22 CTEPH patients (66±10 years, females: 59%) when their mean pulmonary artery pressure initially decreased to <30 mmHg during BPA sessions. Hemodynamic and echocardiographic data, cardiopulmonary exercise testing, and QOL scores using the 36-item short form questionnaire (SF-36) were evaluated at enrollment (entry), just after the final BPA session (finish), and at the 6-month follow-up (follow-up). We analyzed whether extensive BPA improves exercise capacity and QOL scores over time. Moreover, the clinical characteristics leading to improvement were elucidated. The peak oxygen uptake (VO2) showed significant improvement at entry, finish, and follow-up (17.3±5.5, 18.4±5.9, and 18.9±5.3 mL/kg/min, respectively; P<0.001). Regarding the QOL, the physical component summary (PCS) scores significantly improved (32±11, 38±13, and 43±13, respectively; P<0.001), but the mental component summary scores remained unchanged. Linear regression analysis revealed that age and a low peak VO2 at entry were predictors of improvement in peak VO2, while low PCS scores and low TAPSE at entry were predictors of improvement in PCS scores. In conclusion, extensive BPA led to improved exercise tolerance and physical QOL scores, even in CTEPH patients with partially improved hemodynamics.

Interstitial lung disease associated with adjuvant and neoadjuvant chemotherapy in early breast cancer.

BACKGROUND: Interstitial lung disease (ILD) is a rare adverse event in patients receiving adjuvant or neoadjuvant chemotherapy (NAC) for breast cancer. Few studies have reported the frequency of ILD in detail, and only small numbers of cases have been described in the literature. Given these previous findings concerning ILD, we retrospectively examined the clinicopathological characteristics of five cases of ILD who had received epirubicin and cyclophosphamide (EC) and compared their findings with non-ILD cases. METHODS: The present single-center retrospective study included breast cancer patients who underwent adjuvant chemotherapy or NAC at our hospital between January 2014 and January 2021. RESULTS: Thirty-nine patients who had received EC for operable breast cancer were enrolled in this study. ILD developed 5 out of 39 patients (12.8%). The incidence of ILD in patients with non-dose-dense (dd) or dd chemotherapy was statistically significantly different (p = 0.0149). ILD occurred in three patients during dd EC treatment and two during weekly paclitaxel (wPTX) after dd EC. ILD was detected in one patient with high Krebs von den Lungen-6 (KL-6) levels, in two patients with continuous pyrexia, and in two patients from computed tomography imaging, which was taken to estimate the efficacy of chemotherapy, in two patients. Three of the 5 ILD patients underwent bronchoalveolar lavage, and 2 of these patients were diagnosed with Pneumocystis jirovecii pneumonia (PCP). There were no cases of serious ILD that required steroid pulse therapy. CONCLUSIONS: Dd chemotherapy may be associated with an increased ILD frequency, which may reflect developing PCP. Careful monitoring and a timely diagnosis are useful for detecting early-stage ILD.

Predictors of New-Onset Atrial Tachyarrhythmias After Transcatheter Atrial Septal Defect Closure in Adults.

BACKGROUND: New-onset atrial tachyarrhythmia (ATA) often develops after atrial septal defect (ASD) closure. Its development raises some potential concerns such as stroke and bleeding complications caused by anticoagulant therapy and limited access to the left atrium for catheter ablation. Although it is essential to identify the risk factors of new-onset ATA, few studies have examined these factors. This study investigated unknown risk factors for the development of new-onset ATA after transcatheter ASD closure in patients without a history of ATA. METHODS: A total of 238 patients without a history of ATA, aged ≥18 years and who underwent transcatheter ASD closure at the current hospital were reviewed. Patient characteristics were compared between the groups with and without new-onset ATA. The factors associated with new-onset ATA were examined using univariate and multivariable analyses. RESULTS: Thirteen (13) (5.5%) patients experienced ATA during follow-up (mean, 21±14 months). Compared with patients without new-onset ATA, patients with new-onset ATA were older (48±18 vs 66±11 years; p<0.001) and had high brain natriuretic peptide (BNP) levels (36±36 vs 177±306 pg/mL; p<0.001). On multivariable analysis, BNP ≥40 pg/mL before ASD closure was associated with new-onset ATA after adjusting for age (OR, 4.91; 95% CI, 1.22-19.8; p=0.025). CONCLUSION: Patients with BNP levels >40 pg/mL before transcatheter ASD closure may have a higher risk of developing new-onset ATA.

A novel device for detecting anaerobic threshold using sweat lactate during exercise.

The lactate threshold (LT1), which is defined as the first rise in lactate concentration during incremental exercise, has not been non-invasively and conveniently determined in a clinical setting. We aimed to visualize changes in lactate concentration in sweat during exercise using our wearable lactate sensor and investigate the relationship between the lactate threshold (LT1) and ventilatory threshold (VT1). Twenty-three healthy subjects and 42 patients with cardiovascular diseases (CVDs) were enrolled. During exercise, the dynamic changes in lactate values in sweat were visualized in real-time with a sharp continuous increase up to volitional exhaustion and a gradual decrease during the recovery period. The LT1 in sweat was well correlated with the LT1 in blood and the VT1 (r = 0.92 and 0.71, respectively). In addition, the Bland-Altman plot described no bias between the mean values (mean differences: - 4.5 and 2.5 W, respectively). Continuous monitoring of lactate concentrations during exercise can provide additional information for detecting the VT1.

The dominance model for heterosis explains culm length genetics in a hybrid sorghum variety.

Heterosis helps increase the biomass of many crops; however, while models for its mechanisms have been proposed, it is not yet fully understood. Here, we use a QTL analysis of the progeny of a high-biomass sorghum F1 hybrid to examine heterosis. Five QTLs were identified for culm length and were explained using the dominance model. Five resultant homozygous dominant alleles were used to develop pyramided lines, which produced biomasses like the original F1 line. Cloning of one of the uncharacterised genes (Dw7a) revealed that it encoded a MYB transcription factor, that was not yet proactively used in modern breeding, suggesting that combining classic dw1or dw3, and new (dw7a) genes is an important breeding strategy. In conclusion, heterosis is explained in this situation by the dominance model and a combination of genes that balance the shortness and early flowering of the parents, to produce F1 seed yields.

Appropriate device selection for transcatheter atrial septal defect closure using three-dimensional transesophageal echocardiography.

Detail morphological evaluation for ASD is essential to achieve successful transcatheter closure. Three-dimensional transesophageal echocardiography (3D-TEE) is emerging, but few studies have comprehensively verified the usefulness of 3D-TEE. We divided 329 patients who underwent transcatheter ASD closure at our university hospital into 157 in the Conventional group evaluated with 2-dimensional transesophageal echocardiography and balloon sizing (BS), and 172 in the 3D-TEE group evaluated with 3D-TEE additionally. We assessed usefulness of 3D-TEE and consider appropriate device selection procedure. Overall, the percentage with re-sizing of device tended to be lower in the 3D-TEE group than in the Conventional group (10.1% vs 6.0%, p = 0.187). Among preprocedural modalities, the device size was mainly decided based on the BS diameter. A logistic regression analysis demonstrated that large atrial septum aneurysms (ASA) were associated with a ≥ 2 mm discrepancy of the BS diameter from the preprocedural 3D-TEE diameter (p < 0.05). Compared to the Amplatzer Septal Occluder, the differences in device size and the preprocedural ASD measurement were greater when using the Occlutech Figulla Flex II Occluder (FFII). Particularly, among the patients implanted with FFIIs, the discrepancies of the device size from the 3D-TEE measurement were greater in patients with large ASA than those with small ASA. Preprocedural 3D-TEE is useful to select the appropriate device size. Particularly, it is necessary to select a much larger device than that derived from the preprocedural 3D-TEE measurement when using FFII in patients with a septal aneurysm.

Feasibility of the deep learning method for estimating the ventilatory threshold with electrocardiography data.

Regular aerobic physical activity is of utmost importance in maintaining a good health status and preventing cardiovascular diseases (CVDs). Although cardiopulmonary exercise testing (CPX) is an essential examination for noninvasive estimation of ventilatory threshold (VT), defined as the clinically equivalent to aerobic exercise, its evaluation requires an expensive respiratory gas analyzer and expertize. To address these inconveniences, this study investigated the feasibility of a deep learning (DL) algorithm with single-lead electrocardiography (ECG) for estimating the aerobic exercise threshold. Two hundred sixty consecutive patients with CVDs who underwent CPX were analyzed. Single-lead ECG data were stored as time-series voltage data with a sampling rate of 1000 Hz. The data of preprocessed ECG and time point at VT calculated by respiratory gas analyzer were used to train a neural network. The trained model was applied on an independent test cohort, and the DL threshold (DLT; a time of VT estimated through the DL algorithm) was calculated. We compared the correlation between oxygen uptake of the VT (VT-VO2) and the DLT (DLT-VO2). Our DL model showed that the DLT-VO2 was confirmed to be significantly correlated with the VT-VO2 (r = 0.875; P < 0.001), and the mean difference was nonsignificant (-0.05 ml/kg/min, P > 0.05), which displayed strong agreements between the VT and the DLT. The DL algorithm using single-lead ECG data enabled accurate estimation of VT in patients with CVDs. The DL algorithm may be a novel way for estimating aerobic exercise threshold.

gw2 mutation increases grain width and culm thickness in rice (Oryza sativa L.).

Grain size is one of the most important agricultural traits in rice. To increase grain yield, we screened a large grain mutant from mutants with the 'Koshihikari' background. As a result, we obtained a mutant, KEMS39, that has a large grain size and increased yield. Cultivation tests revealed that this mutant had improved lodging resistance with thicker internodes. Next-generation sequencing analysis revealed the presence of a 67 bp deletion in the GW2 mRNA, owing to a mutation in the 3' splice site of the sixth intron of the GW2 gene. To determine whether this mutation was responsible for the larger grain and thicker internodes, we performed gene editing and obtained a mutant with a 7 bp deletion, including this 3' splice site. As this gw2 mutant had large grains and thicker internodes, the causal gene of KEMS39 was determined as GW2. Thicker internodes are attributed to the pleiotropic effect of gw2 mutation. On the basis of these results, we conclude that gw2 mutation has the potential to be an important genetic resource with the ability to achieve a well-balanced and high-yielding effect that simultaneously improves grain productivity and lodging resistance.

Proteomics Analysis of Plasma Membrane Fractions of the Root, Leaf, and Flower of Rice.

The plasma membrane regulates biological processes such as ion transport, signal transduction, endocytosis, and cell differentiation/proliferation. To understand the functional characteristics and organ specificity of plasma membranes, plasma membrane protein fractions from rice root, etiolated leaf, green leaf, developing leaf sheath, and flower were analyzed by proteomics. Among the proteins identified, 511 were commonly accumulated in the five organs, whereas 270, 132, 359, 146, and 149 proteins were specifically accumulated in the root, etiolated leaf, green leaf, developing leaf sheath, and developing flower, respectively. The principle component analysis revealed that the functions of the plasma membrane in the root was different from those of green and etiolated leaves and that the plasma membrane protein composition of the leaf sheath was similar to that of the flower, but not that of the green leaf. Functional classification revealed that the root plasma membrane has more transport-related proteins than the leaf plasma membrane. Furthermore, the leaf sheath and flower plasma membranes were found to be richer in proteins involved in signaling and cell function than the green leaf plasma membrane. To validate the proteomics data, immunoblot analysis was carried out, focusing on four heterotrimeric G protein subunits, Gα, Gß, Gγ1, and Gγ2. All subunits could be detected by both methods and, in particular, Gγ1 and Gγ2 required concentration by immunoprecipitation for mass spectrometry detection.