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Plants use nitrate, ammonium, and organic nitrogen in the soil as nitrogen sources. Since the elevated CO 2 environment predicted for the near future will reduce nitrate utilization by C 3 species, ammonium is attracting great interest. However, abundant ammonium nutrition impairs growth, i.e., ammonium toxicity, the primary cause of which remains to be determined. Here, we show that ammonium assimilation by GLUTAMINE SYNTHETASE 2 (GLN2) localized in the plastid rather than ammonium accumulation is a primary cause for toxicity, which challenges the textbook knowledge. With exposure to toxic levels of ammonium, the shoot GLN2 reaction produced an abundance of protons within cells, thereby elevating shoot acidity and stimulating expression of acidic stress-responsive genes. Application of an alkaline ammonia solution to the ammonium medium efficiently alleviated the ammonium toxicity with a concomitant reduction in shoot acidity. Consequently, we conclude that a primary cause of ammonium toxicity is acidic stress.

PurposeTo generate and evaluate fat-saturated T1-weighted (FST1W) image synthesis of breast magnetic resonance imaging (MRI) using pix2pix.Materials and methodsWe collected pairs of noncontrast-enhanced T1-weighted an FST1W images of breast MRI for training data (2112 pairs from 15 patients), validation data (428 pairs from three patients), and test data (90 pairs from 30 patients). From the original images, 90 synthetic images were generated with 50, 100, and 200 epochs using pix2pix. Two breast radiologists evaluated the synthetic images (from 1 = excellent to 5 = very poor) for quality of fat suppression, anatomic structures, artifacts, etc. The average score was analyzed for each epoch and breast density.ResultsThe synthetic images were scored from 2.95 to 3.60; the best was reduction in artifacts when using 100 epochs. The average overall quality scores for fat suppression were 3.63 at 50 epochs, 3.24 at 100 epochs, and 3.12 at 200 epochs. In the analysis for breast density, each score was significantly better for nondense breasts than for dense breasts; the average score was 2.88–3.18 for nondense breasts and 3.03–3.42 for dense breasts (P = 0.000–0.042).ConclusionPix2pix had the potential to generate FST1W synthesis for breast MRI.

BackgroundThe clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population.MethodsIn this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360.ResultsOf the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010).ConclusionsThe results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

Background and Objectives: Surgical smoke generated by energy devices during surgery contains hazardous substances and poses health risks to staff in the operating room. Exposure to surgical smoke must be reduced to minimize the risk of health hazards. Many studies have evaluated surgical smoke qualitatively, but few have performed quantitative assessment. The aim of this study was to quantify the number of particles generated during various breast surgery procedures. Materials and Methods: In this prospective, randomized study, breast surgeries performed at Tokyo Medical and Dental University Hospital (the present Institute of Science Tokyo Hospital) between December 2022 and August 2023 were randomly assigned to two groups: the electrosurgical device group and the electrosurgical device with smoke evacuator group. The number of particles generated by energy devices during surgery was measured using a particle counter. Results: Surgical smoke was generated in all procedures. The number of measured particles was significantly less in the electrosurgical device with smoke evacuator group than in the electrosurgical device group during all procedures (all p < 0.001). Conclusions: All breast surgery procedures produced a significant amount of surgical smoke, which was effectively reduced by using an electrosurgical device with a smoke evacuator. These findings support the routine use of smoke evacuators in breast surgery to reduce occupational exposure to hazardous particles. Implementation of such devices could improve operating room safety and may inform future guidelines and institutional policies regarding surgical smoke management.

PurposeImmediate breast reconstruction (IBR) is a standard option for breast cancer patients, although its utility in patients with advanced breast cancer requiring neoadjuvant chemotherapy (NAC) is debatable. We assessed the short-term complications and long-term prognosis of IBR after NAC.MethodsWe retrospectively analyzed 1135 patients with IBR and/or NAC between 2010 and 2018, 43 of whom underwent IBR after NAC.ResultsTwenty-five patients underwent reconstruction with a tissue expander (TE) followed by silicon breast implantation, 5 with a latissimus dorsi muscle transfer flap, and 13 with a deep inferior epigastric perforator flap. Complete surgical resection with a free margin confirmed by a pathological assessment was achieved in all patients. The evaluation of the short-term complications indicated no cases of total flap necrosis, two cases of partial flap necrosis, and one case of wound infection. Only one case required postponement of subsequent therapy due to partial flap necrosis. A long-term evaluation indicated no local recurrence, although distant metastasis was observed in 4 cases, 3 patients died, and TE removal after post-mastectomy radiotherapy (PMRT) was performed in 2 of 11 TE cases.ConclusionIBR may be a viable option in patients with advanced breast cancer who achieve complete surgical resection after NAC.

PurposeWe aimed to use deep learning with convolutional neural network (CNN) to discriminate between benign and malignant breast mass images from ultrasound.Materials and MethodsWe retrospectively gathered 480 images of 96 benign masses and 467 images of 144 malignant masses for training data. Deep learning model was constructed using CNN architecture GoogLeNet and analyzed test data: 48 benign masses, 72 malignant masses. Three radiologists interpreted these test data. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were calculated.ResultsThe CNN model and radiologists had a sensitivity of 0.958 and 0.583–0.917, specificity of 0.925 and 0.604–0.771, and accuracy of 0.925 and 0.658–0.792, respectively. The CNN model had equal or better diagnostic performance compared to radiologists (AUC = 0.913 and 0.728–0.845, p = 0.01–0.14).ConclusionDeep learning with CNN shows high diagnostic performance to discriminate between benign and malignant breast masses on ultrasound.

Two of the Arabidopsis thaliana SEC23 homologs, AtSEC23A and AtSEC23D, are expressed in the tapetum and play essential roles in pollen wall formation, exine patterning, and tapetum development. Abstract The specialized multilayered pollen wall plays multiple roles to ensure normal microspore development. The major components of the pollen wall (e.g. sporopollenin and lipidic precursors) are provided from the tapetum. Material export from the endoplasmic reticulum (ER) is mediated by coat protein complex II (COPII) vesicles. The Arabidopsis thaliana genome encodes seven homologs of SEC23, a COPII component. However, the functional importance of this diversity remains elusive. Here, we analyzed knockout and knockdown lines for AtSEC23A and AtSEC23D, two of the A. thaliana SEC23 homologs, respectively. Single atsec23a and atsec23d mutant plants, despite normal fertility, showed an impaired exine pattern. Double atsec23ad mutant plants were semi-sterile and exhibited developmental defects in pollen and tapetal cells. Pollen grains of atsec23ad had defective exine and intine, and showed signs of cell degeneration. Moreover, the development of tapetal cells was altered, with structural abnormalities in organelles. AtSEC23A and AtSEC23D exhibited the characteristic localization pattern of COPII proteins and were highly expressed in the tapetum. Our work suggests that AtSEC23A and AtSEC23D may organize pollen wall development and exine patterning by regulating ER export of lipids and proteins necessary for pollen wall formation. Also, our results shed light on the functional heterogeneity of SEC23 homologs.

   Summary We investigated the incidence/trend of osteonecrosis of the jaw by antiresorptive agent dose over a 5-year period in Kure city, Japan. The incidence was 24 times higher among osteoporosis patients with low-dose agents and 421 times higher among cancer patients with high-dose agents than in the population without agents. Purpose We launched the registry system of osteonecrosis of the jaw (ONJ) cases in 2015 to investigate the trend in ONJ incidence. The purpose of our study was to estimate the ONJ incidence among patients with antiresorptive agent use by dosage and people without antiresorptive agent use in Kure and its trend from 2016 to 2020. Methods From 2016 to 2021, 98 eligible ONJ patients were enrolled. Medication-related ONJ (MRONJ) was diagnosed based on the American Association of Oral and Maxillofacial Surgeons criteria. The annual number of those with and without antiresorptive agents was obtained from the claims database. Antiresorptive agents used for cancer and osteoporosis patients were defined as high- and low-dose medications, respectively. Results The annual incidence of high-dose MRONJ was 2305.8 per 100,000 and that of low-dose MRONJ was 132.5 per 100,000, while the ONJ incidence among people without antiresorptive agents was 5.1 per 100,000. The incidence ratio was 23.6 ( p  < 0.001, 95% confidence interval (CI) 13.3–41.8) among osteoporosis patients who used low-dose antiresorptive agents and 420.6 ( p  < 0.001, 95% CI 220.8–801.4) among cancer patients who used high-dose agents compared with people who did not use these agents. MRONJ incidence increased from 2016 to 2020, but the incidence of high-dose MRONJ decreased, although this was nonsignificant. Conclusion We demonstrated the incidence and trend of ONJ by antiresorptive agent dose over a 5-year period in Kure after launching the multiprofession study. This collaborative study for the early detection and prevention of ONJ will continue.