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In our department, total neoadjuvant therapy(TNT), which is a combination of preoperative chemotherapy and preoperative chemoradiotherapy(nCRT), has been introduced for the purpose of local and systemic disease control for lower rectal cancer. For patients in whom a clinical complete response(cCR)was obtained by TNT, we avoid the surgery and preserve organs, and follow-up strictly under the informed consent(watch and wait). In addition, for patients with remarkably reduced primary lesions(near cCR)without lymphadenopathy after TNT, the option of omitting total mesorectal excision (TME)and performing organ preservation by local excision can be introduced. Here, we report a case in which near cCR was obtained by TNT and organ preservation was performed by local excision. A 67-year-old man with lower rectal cancer(AV 5 cm, 15 mm, type 2, cT2N0M0, cStage Ⅰ)was referred to our department with a desire to preserve the anus. TNT with nCRT→CAPOX was performed, and near cCR was obtained. After that, full thickness local excision of the residual disease was performed by transanal minimally invasive surgery(TAMIS). The final pathological diagnosis was Rb, 0.7 mm, por2, ypT1a, ypPM0, ypDM0, ypRM0. No recurrence is recognized for 3 years and 10 months after the operation.

A 54-year-old man was diagnosed with descending colon cancer with metastases in the liver, para-aortic lymph nodes, and penis, and chemotherapy was introduced after construction of a colostomy. The patient reported only mild penile pain at the time of diagnosis; however, the pain gradually worsened and interfered with his daily life. Opioids did not provide sufficient analgesia, and the patient developed dysuria and priapism. Through construction of a cystostomy, palliative radiotherapy with QUAD Shot regimen (14 Gy in 4 fractions twice-daily on 2 days repeated every 4 weeks) to the penile metastasis was started for pain relief and tumor shrinkage. The radiation rapidly improved the penile symptoms, enabling opioid reduction and cystostomy removal. The patient remained pain-free and able to urinate on his own until his death. Metastatic penile tumors are rare, especially those derived from colon cancer. Penile metastases occur mainly in the late stages of cancer and may impair the patient's quality of life. In such cases, palliative radiotherapy, especially with QUAD Shot regimen, is useful with short treatment time, durable symptom control, and little adverse effect, maintaining quality of life., Competing Interests: Conflict of interestAll authors declare that they have no conflict of financial interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9,826 cases among 150,272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of >1 million individuals, including 77,690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis identified IL6R as a putative causal gene, suggesting the involvement of immune responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their potential for clinical applications., (© 2023. The Author(s).)

Background: In recent years, there has been considerable research on the use of artificial intelligence to estimate age and disease status from medical images. However, age estimation from chest X-ray (CXR) images has not been well studied and the clinical significance of estimated age has not been fully determined., Methods: To address this, we trained a deep neural network (DNN) model using more than 100,000 CXRs to estimate the patients' age solely from CXRs. We applied our DNN to CXRs of 1562 consecutive hospitalized heart failure patients, and 3586 patients admitted to the intensive care unit with cardiovascular disease., Results: The DNN's estimated age (X-ray age) showed a strong significant correlation with chronological age on the hold-out test data and independent test data. Elevated X-ray age is associated with worse clinical outcomes (heart failure readmission and all-cause death) for heart failure. Additionally, elevated X-ray age was associated with a worse prognosis in 3586 patients admitted to the intensive care unit with cardiovascular disease., Conclusions: Our results suggest that X-ray age can serve as a useful indicator of cardiovascular abnormalities, which will help clinicians to predict, prevent and manage cardiovascular diseases., (© 2022. The Author(s).)

Background: Because the early diagnosis of subclinical cardiac sarcoidosis (CS) remains difficult, we developed a deep learning algorithm to distinguish CS patients from healthy subjects using echocardiographic movies., Methods and results: Among the patients who underwent echocardiography from January 2015 to December 2019, we chose 151 echocardiographic movies from 50 CS patients and 151 from 149 healthy subjects. We trained two 3D convolutional neural networks (3D-CNN) to identify CS patients using a dataset of 212 echocardiographic movies with and without a transfer learning method (Pretrained algorithm and Non-pretrained algorithm). On an independent set of 41 echocardiographic movies, the area under the receiver-operating characteristic curve (AUC) of the Pretrained algorithm was greater than that of Non-pretrained algorithm (0.842, 95% confidence interval (CI): 0.722-0.962 vs. 0.724, 95% CI: 0.566-0.882, P=0.253). The AUC from the interpretation of the same set of 41 echocardiographic movies by 5 cardiologists was not significantly different from that of the Pretrained algorithm (0.855, 95% CI: 0.735-0.975 vs. 0.842, 95% CI: 0.722-0.962, P=0.885). A sensitivity map demonstrated that the Pretrained algorithm focused on the area of the mitral valve., Conclusions: A 3D-CNN with a transfer learning method may be a promising tool for detecting CS using an echocardiographic movie.

Deep learning models can be applied to electrocardiograms (ECGs) to detect left ventricular (LV) dysfunction. We hypothesized that applying a deep learning model may improve the diagnostic accuracy of cardiologists in predicting LV dysfunction from ECGs. We acquired 37,103 paired ECG and echocardiography data records of patients who underwent echocardiography between January 2015 and December 2019. We trained a convolutional neural network to identify the data records of patients with LV dysfunction (ejection fraction < 40%) using a dataset of 23,801 ECGs. When tested on an independent set of 7,196 ECGs, we found the area under the receiver operating characteristic curve was 0.945 (95% confidence interval: 0.936-0.954). When 7 cardiologists interpreted 50 randomly selected ECGs from the test dataset of 7,196 ECGs, their accuracy for predicting LV dysfunction was 78.0% ± 6.0%. By referring to the model's output, the cardiologist accuracy improved to 88.0% ± 3.7%, which indicates that model support significantly improved the cardiologist diagnostic accuracy (P = 0.02). A sensitivity map demonstrated that the model focused on the QRS complex when detecting LV dysfunction on ECGs. We developed a deep learning model that can detect LV dysfunction on ECGs with high accuracy. Furthermore, we demonstrated that support from a deep learning model can help cardiologists to identify LV dysfunction on ECGs.

To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. We detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improve the clinical characterization of CAD genetics and suggest the utility of trans-ancestry meta-analysis for PRS derivation in non-European populations.

The development of deep learning technology has enabled machines to achieve high-level accuracy in interpreting medical images. While many previous studies have examined the detection of pulmonary nodules in chest X-rays using deep learning, the application of this technology to heart failure remains rare. In this paper, we investigated the performance of a deep learning algorithm in terms of diagnosing heart failure using images obtained from chest X-rays. We used 952 chest X-ray images from a labeled database published by the National Institutes of Health. Two cardiologists verified and relabeled a total of 260 "normal" and 378 "heart failure" images, with the remainder being discarded because they had been incorrectly labeled. Data augmentation and transfer learning were used to obtain an accuracy of 82% in diagnosing heart failure using the chest X-ray images. Furthermore, heatmap imaging allowed us to visualize decisions made by the machine. Deep learning can thus help support the diagnosis of heart failure using chest X-ray images.

Background: Genome-wide association studies provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. Genome-wide association studies in diverse populations have the potential to advance our understanding of CAD., Methods: We conducted 2 genome-wide association studies for CAD in the Japanese population, which included 12 494 cases and 28 879 controls and 2808 cases and 7261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the coronary artery disease genome-wide replication and meta-analysis plus the coronary artery disease 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans., Results: We identified 3 new loci on chromosome 1q21 ( CTSS ), 10q26 ( WDR11-FGFR2 ), and 11q22 ( RDX - FDX1 ). Quantitative trait locus analyses suggested the association of CTSS and RDX - FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands, and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans., Conclusions: We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.

An error appeared in the article entitled "Diagnosing Heart Failure from Chest X-Ray Images Using Deep Learning" by Takuya Matsumoto, Satoshi Kodera, Hiroki Shinohara, Hirotaka Ieki, Toshihiro Yamaguchi, Yasutomi Higashikuni, Arihiro Kiyosue, Kaoru Ito, Jiro Ando, Eiki Takimoto, Hiroshi Akazawa, Hiroyuki Morita, Issei Komuro (Vol. 61, No. 4, 781-786, 2020). The Figure 5on page 784 should be replaced by the following figure.

Objective: The purpose of this study was to determine the effects of the lower-body positive pressure on surface blood flow during standing still and treadmill walking to explore cardiovascular safety for application to rehabilitation treatment. Thirteen healthy volunteers participated in the experiment and surface blood flows were measured in the forehead, thigh, calf, and the top of the foot during standing still and walking under various pressure conditions (0 kPa, 5 kPa, and 6.7 kPa)., Results: Lower-body positive pressure decreased the blood flow in the forehead and the thigh during walking (p < .05 for each), whereas an increasing trend in blood flow was observed during standing still (p < .05). Furthermore, in the forehead and thigh, the extent of blood flow increase at the onset of walking was found to decrease in accordance with the applied pressure (p < .01 for each). These findings suggest that during walking, lower-body positive pressure modulates the blood flow, which implies safeness of this novel apparatus for use during orthopedic rehabilitation treatment.

Introduction: Previous studies have indicated that the ratio of pulmonary artery (PA) to ascending aorta (Ao) diameter as measured by computed tomography (PA/Ao) is strongly associated with pulmonary artery pressure. However, the clinical significance of PA/Ao in heart failure (HF) has not been fully characterized. We sought to investigate the prognostic impact of PA/Ao in HF., Methods: Based on the prospective registry of patients admitted to our institution due to acute decompensated HF (ADHF), the records of the consecutive 761 patients admitted between 2011 and 2016 were reviewed. Thoracic computed tomography data during the hospital stays were obtained from 447 patients (median 78 (70-84) years of age; male, 62.2%). The diameters of PA and Ao were measured at the level of PA bifurcation. The subjects were divided into the H group (PA/Ao ≥ 1.0) and the L group (PA/Ao < 1.0) according to the PA/Ao values. The cutoff value was derived from receiver operating curve analysis., Results: There were no significant differences in age, sex or body mass index between the H and L groups. The H group was associated with significantly larger left atrial dimension (LAD), higher tricuspid regurgitation peak gradient (TRPG) and E/e' (LAD, H, 48 (42-55) mm vs L, 45 (39-50) mm, P < 0.001; TRPG, H, 34 (26-48) mm Hg vs L, 28 (22-38) mm Hg, P < 0.001; E/e', H, 23.3 (42-55) vs L, 18.4 (13.9-25), P < 0.001). Length of hospital stay was significantly longer in the H group than in the L group (H, 19 (14-32) days vs L, 16 (12-23) days, P < 0.001). In-hospital mortality was significantly higher in the H group compared with the L group (H, 5.4% vs L, 1.2%, P = 0.02). Age, sex, LAD and TRPG were independently associated with PA/Ao. The primary endpoint, defined as the composite of all-cause death and ADHF rehospitalization during a median of 479 days after discharge, was significantly more common in the H group (P < 0.001, log-rank test). PA/Ao was independently associated with the primary endpoint, even after adjusting for the other confounding factors (P = 0.002)., Conclusions: PA/Ao is a reliable marker for the prediction of the outcome of patients with ADHF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Three types of bamboo pellets as a ruminant feed: P1 (ground bamboo (GB) cultured with the fungus Ceriporiopsis subvermispora (CGB) : soybean curd residue (T) : soy sauce cake (S) in a 5:4:1 ratio on a dry matter (DM) basis); P2 (GB : T : S = 5:4:1 on a DM basis); and P3 (CGB : T : S = 5.5:0.8:3.7 on a DM basis) were prepared. Four wethers were assigned in a 4 × 4 Latin square design experiment to evaluate the applicability of the bamboo pellets. The experimental treatments were C (control): fed alfalfa hay cubes (AC) only, and T1, T2 and T3: fed P1, P2, and P3 with AC by 1:1 on a DM basis, respectively. The digestibility of the DM, organic matter and acid detergent fiber of P1 were significantly higher than those of P2 and P3 (P < 0.05). The total digestible nutrient (TDN) contents of AC, P1, P2 and P3 were 56.5%, 60.2%, 53.2% and 47.0%, respectively. No significant differences in nitrogen retention or ruminal pH and NH₃ were observed among the treatment groups. The results indicate that bamboo pellets cultured with C. subvermispora and mainly mixed with soybean curd residue improved nutritional quality of ground bamboo because of its high digestibility and TDN content., (© 2013 Japanese Society of Animal Science.)

We developed a multiplex reverse transcription polymerase chain reaction (RT-PCR) to detect six citrus viroids: Citrus exocortis viroid (CEVd), Citrus bent leaf viroid (CBLVd), Hop stunt viroid (HSVd), Citrus viroid III (CVd-III), Citrus viroid IV (CVd-IV) and Citrus viroid OS (CVd-OS) and Apple stem grooving virus (ASGV, synonym: Citrus tatter leaf virus (CTLV)) from citrus plants. The multiplex RT-PCR was also designed to distinguish CVd-I-LSS (a distinct variant of CBLVd) from CBLVd. By the multiplex RT-PCR, one to eight fragments specific to the pathogens were simultaneously amplified from one sample and identified by their specific molecular sizes in 6% polyacrylamide gel electrophoresis. The results of the multiplex RT-PCR were consistent with those of other diagnoses, such as uniplex RT-PCR, to detect each of the pathogens. The multiplex RT-PCR provides a simple and rapid method for detecting various viroids and ASGV in citrus plants, which will help diagnose many citrus plants at a time., (Copyright 2002 Elsevier Science B.V.)

ABSTRACT Sequential polyacrylamide gel electrophoresis analyses showed many viroid-like RNAs in samples collected from citrus trees in Japan. Reverse transcription polymerase chain reaction and sequencing analyses of the amplified fragments verified that they were derived from variants of six citrus viroids, Citrus exocortis viroid (CEVd), Citrus bent leaf viroid (CBLVd) including CVd-I-LSS (a distinct variant of CBLVd), Hop stunt viroid, Citrus viroid III, Citrus viroid IV, and Citrus viroid OS. The samples induced symptoms with variable severity in Arizona 861-S1 'Etrog' citrons (Citrus medica L.) likely due to the varying accumulation patterns produced by the different viroids. Some of the symptoms caused by the samples harboring the citrus viroids other than CEVd were as severe as those caused by CEVd. Some source citrus trees showing the severe bark scaling characteristic of exocortis disease in trifoliate orange (Poncirus trifoliata (L.) Raf.) rootstocks contained only citrus viroids other than CEVd in complex. This indicates that certain exocortis-like diseases in Japan were caused by some combination of citrus viroids not including CEVd.

A new viroid was obtained from a viroid sample, named 'OS', collected from a citrus plant. The viroid consists of 330-331 nucleotides, contains the central conserved region (CCR) characteristic of the genus Apscaviroid, and has the highest sequence similarity (only 68%) with Citrus III viroid (CVd-III) among known viroids. This viroid, by itself, caused only mild petiole necrosis and characteristically very mild leaf bending in Arizona 861-S1 Etrog citrons (Citrus medica L.), the degree of which differed from that induced by other citrus viroids. This viroid could be a new citrus viroid species belonging to the genus Apscaviroid; for convenience, it was tentatively named Citrus viroid OS (CVd-OS) after the original sample. CVd-OS has chimeric features related to other viroids. In particular, CVd-OS has high sequence similarity with CVd-III and Apple dimple fruit viroid in the putative central and terminal left domains, including a duplicative sequence from the lower CCR of the genus Pospiviroid in the left terminus. Further, CVd-OS shares high sequence similarity with Citrus exocortis viroid (CEVd) in the lower strand of the putative variable and terminal right domains, including the sequence identical to that of the right termini of CEVd and of Citrus IV viroid.

Polymerase chain reaction was used to amplify and sequence the 16S ribosomal RNA gene (rDNA) and 16S/23S intergenic region of several isolates of citrus greening organism (GO) from Japan, the Philippines, Indonesia, and Thailand. The sequences of 16S rDNA were identical among all the isolates studied, very similar to the published sequences of Thai (99.4 to 100% identity), Nepalese (100% identity), and Indian (98.8% identity) strains, and less similar to an African strain (97.5% identity). The sequences of the intergenic region between 16S and 23S rDNA were also identical among the isolates examined as well as the reported Nepalese and Thai isolates. They were close to the sequences of reported strains of India and China (99.2%) and apart from those of the African strain (85.5%). These results suggested that some isolates of GO from Japan, the Philippines, Indonesia, Thailand, and Nepal constitute one strain, which is similar to Indian and Chinese strains and distinct from the African strain.

Sequencing analyses showed a population of variants consisting of 325-330 nucleotides (nt) of a viroid closely related to citrus viroid (CVd)-I in citrus plants. These variants, for which we propose the tentative acronym CVd-I-LSS (low sequence similarity), have only 82-85% sequence similarities to CVd-I variants. A phylogenetic tree showed that the CVd-I-LSS variants formed an individual cluster that was distinct from that of the CVd-I variants, but no intermediate variants were found which could continuously connect the population of CVd-I-LSS variants with that of CVd-I variants. Citrons (Citrus medica L.) inoculated with the CVd-I-LSS seemed to show not only moderate leaf bending like citrons infected with CVd-I but also slightly more severe epinasty than citrons with CVd-I. Other biological properties of CVd-I-LSS, such as the host range, will need to be determined in order to clarify whether CVd-I-LSS is a new viroid species or a distinct strain of CVd-I. Most of the nucleotide changes between the CVd-I-LSS and CVd-I variants were found at complementary positions of the upper and lower strands within the putative pathogenic, variable, and right terminal domains, as well as in the region surrounding the central conserved region of the predicted secondary structure of CVd-I-LSS.