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Recent reports have described the practicality of laparoscopic intragastric surgery (l-IGS) as an alternative for resecting submucosal tumors (SMTs) near the esophagogastric junction (EGJ), where excision using an exogastric approach would be difficult. However, even using IGS to perform a full-thickness resection of SMTs that are in or extremely close to the EGJ is very difficult to do safely and avoid disrupting or causing stenosis of the EGJ, without advanced experience. This study retrospectively examined the usefulness of l-IGS for gastric SMTs located in or extremely close to the EGJ. Fourteen patients with gastric SMTs < 2 cm of the EGJ and underwent l-IGS were eligible for this study. We examined the tumor location, operative time, intraoperative hemorrhage, degree of deformation, gastroesophageal reflux disease, perioperative complications, and recurrence. Furthermore, we compared patients with tumors in the EGJ with those with tumors near the EGJ and patients in whom three-port l-IGS was performed with those who underwent single-incision laparoscopic surgery. The average tumor size, operative time, intraoperative hemorrhage, and postoperative hospitalization of the 14 patients were 30.9 ± 21.3 mm, 125.2 ± 31.1 min, 30.7 ± 103.3 mL, and 9.2 ± 3.1 d, respectively. No differences in these parameters according to the type of l-IGS or tumor location were observed. All patients underwent l-IGS without complications and were free from EGJ deformation or esophagitis. We believe that l-IGS is useful for gastric SMTs located < 2 cm of the EGJ as it can be safely performed for difficult tumor locations and does not cause deformation of the EGJ., (© 2024. Italian Society of Surgery (SIC).)

Background: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC., Methods: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival., Results: The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors., Conclusions: Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery., (© 2024. Society of Surgical Oncology.)

Plants recognize a variety of external signals and induce appropriate mechanisms to increase their tolerance to biotic and abiotic stresses. Precise recognition of attacking pathogens and induction of effective resistance mechanisms are critical functions for plant survival. Some molecular patterns unique to a certain group of microbes, microbe-associated molecular patterns (MAMPs), are sensed by plant cells as nonself molecules via pattern recognition receptors. While MAMPs of bacterial and fungal origin have been identified, reports on oomycete MAMPs are relatively limited. This study aimed to identify MAMPs from an oomycete pathogen Phytophthora infestans, the causal agent of potato late blight. Using reactive oxygen species (ROS) production and phytoalexin production in potato (Solanum tuberosum) as markers, two structurally different groups of elicitors, namely ceramides and diacylglycerols, were identified. P. infestans ceramides (Pi-Cer A, B, and D) induced ROS production, while diacylglycerol (Pi-DAG A and B), containing eicosapentaenoic acid (EPA) as a substructure, induced phytoalexins production in potato. The molecular patterns in Pi-Cers and Pi-DAGs essential for defense induction were identified as 9-methyl-4,8-sphingadienine (9Me-Spd) and 5,8,11,14-tetraene-type fatty acid (5,8,11,14-TEFA), respectively. These structures are not found in plants, but in oomycetes and fungi, indicating that they are microbe molecular patterns recognized by plants. When Arabidopsis (Arabidopsis thaliana) was treated with Pi-Cer D and EPA, partially overlapping but different sets of genes were induced. Furthermore, expression of some genes is upregulated only after the simultaneous treatment with Pi-Cer D and EPA, indicating that plants combine the signals from simultaneously recognized MAMPs to adapt their defense response to pathogens., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

We aimed to determine the frequency and prognosis of supraclavicular (#104) lymph node (LN) metastasis compared with other LN stations in patients with advanced thoracic esophageal cancer and to identify risk factors for metastasis to delineate the indications for three-field lymphadenectomy (3FL). The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography-positive LNs. The efficacy index (EI), calculated from the frequency of LN metastases and survival rates, was used as prognostic value of each LN station dissection for patient survival. Risk factors for #104 LN metastasis were determined by multivariable logistic regression. The frequency of #104 LN metastasis was 11.6% overall, 31.7% in upper and 8.3% in middle/lower third lesion. Neoadjuvant chemotherapy was administered to 71% of patients and chemo-radiation to 11%. The 5-year overall survival was 45.8%. The EI for #104 LNs (5.3) was similar to that for #101 LNs. Risk factors were age < 65 years, upper third lesion, clinical N2-3, #101/106rec LN metastasis and poorly differentiated carcinoma. The 5-year overall survival of patients with middle/lower lesions was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs. The prognosis of patients with #104 LN metastases is similar to that of patients with metastases in other regional LN stations. Therefore, we recommend 3FL exclusively for patients at a high risk of #104 LN metastasis due to the overall metastatic rate not being high., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The budding yeast Saccharomyces cerevisiae is an excellent model organism for studying chromatin regulation with high-resolution genome-wide analyses. Since newly generated genome-wide data are often compared with publicly available datasets, expanding our dataset repertoire will be beneficial for the field. Information on transcription start sites (TSSs) determined at base pair resolution is essential for elucidating mechanisms of transcription and related chromatin regulation, yet no datasets that cover two different cell types are available. Here, we present a CAGE (cap analysis of gene expression) dataset for a-cells and α-cells grown in defined and rich media. Cell type-specific genes were differentially expressed as expected, ensuring the reliability of the data. Some of the differentially expressed TSSs were medium-specific or detected due to unrecognized chromosome rearrangement. By comparing the CAGE data with a high-resolution nucleosome map, major TSSs were primarily found in +1 nucleosomes, with a peak approximately 30 bp from the promoter-proximal end of the nucleosome. The dataset is available at DDBJ/GEA.

A 66-year-old man presented with hemolytic anemia, which required frequent blood transfusion, 6 months after surgical repair of an ascending aortic pseudoaneurysm. Hemolysis was attributed to luminal stenosis caused by graft kinking by laboratory test, CT and four-dimensional magnetic resonance imaging. First, an Excluder cuff was placed at the stenotic site under rapid pacing, but it migrated distally. Thereafter a Palmaz XL stent was placed at the stenotic site, which led to resolution of anemia. In this case, a Palmaz XL stent was successfully used to treat hemolytic anemia caused by graft kinking following ascending aortic surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Meibomitis-related keratoconjunctivitis (MRKC) is characterized by meibomitis with corneal epithelial abnormalities, and can be divided into two types: MRKC accompanied with phlyctenular keratitis, and MRKC accompanied with keratoepitheliopathy that is similar to superficial punctate keratopathy (SPK). The purpose of this retrospective study was to investigate the characteristic features of keratoepitheliopathy and treatment outcomes for MRKC. This study involved 27 eyes of 18 MRKC patients (3 males and 15 females). National Eye Institute (NEI) scores and visual acuity were compared at pre and post treatment. All subjects were treated with a small-dose administration of clarithromycin. Keratoepitheliopathy characteristic to MRKC, yet different in appearance from SPK, was noted in 24 of the 27 eyes. Fluorescein staining revealed granular epithelial lesions generally larger than SPK that coexisted with small dark spots. In 17 eyes, keratoepitheliopathy was located within the pupillary zone, and the visual acuity in 12 eyes was less than 1.0. Our findings showed significant improvement in the NEI score in MRKC ( p < 0.0001) and in visual acuity ( p = 0.0157) post treatment, and the characteristic features of keratoepitheliopathy in MRKC that are often associated with decreased visual acuity were elucidated. The treatment of clarithromycin was found to be effective for MRKC with keratoepitheliopathy.

Most of esophageal squamous cell carcinoma (ESCC) develop in smoking males in Japan, but the genomic etiology and immunological characteristics of rare non-smoking female ECSS remain unclear. To elucidate the genomic and immunological features of ESCC in non-smoking females, we analyzed whole-genome or transcriptome sequencing data from 94 ESCCs, including 20 rare non-smoking female cases. In addition, 31,611 immune cells were extracted from four ESCC tissues and subject to single-cell RNA-seq. We compared their immuno-genomic and microbiome profiles between non-smoking female and smoking ESCCs. Non-smoking females showed much better prognosis. Whole-genome sequencing analysis showed no significant differences in driver genes or copy number alterations depending on smoking status. The mutational signatures specifically observed in non-smoking females ESCC could be attributed to aging. Immune profiling from RNA-seq revealed that ESCC in non-smoking females had high tumor microenvironment signatures and a high abundance of eosinophils with a favorable prognosis. Single-cell RNA-sequencing of intratumor immune cells revealed gender differences of eosinophils and their activation in female cases. ESCCs in non-smoking females have age-related mutational signatures and gender-specific tumor immune environment with eosinophils, which is likely to contribute to their favorable prognosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Understanding the transport and inhibition mechanisms of substrates by P-glycoprotein (P-gp) is one of the important approaches in addressing multidrug resistance (MDR). In this study, we evaluated a variety of rhodamine derivatives as potential P-gp inhibitors targeting CmABCB1, a P-gp homologue, with a focus on their ATPase activity. Notably, a Q-rhodamine derivative with an o , o '-dimethoxybenzyl ester moiety (Rh Q -DMB) demonstrated superior affinity and inhibitory activity, which was further confirmed by a drug susceptibility assay in yeast strains expressing CmABCB1. Results from a tryptophan fluorescence quenching experiment using a CmABCB1 mutant suggested that Rh Q -DMB effectively enters and binds to the inner chamber of CmABCB1. These findings underscore the promising potential of Rh Q -DMB as a tool for future studies aimed at elucidating the substrate-bound state of CmABCB1., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Dissolved radiocesium (mainly 134 Cs and 137 Cs) is thought to be leached mainly from suspended sediment in downstream rivers, while organic matter, such as leaf litter, contributes to catchments in forested headwater streams. It is also known that dissolved 137 Cs in headwater streams exhibit seasonal variation with water temperature. Some mechanisms have been proposed as the causes: ionic competition of potassium ion (K + ) and ammonium ion (NH 4 + ), leaching associated with the decomposition of organic matter, and thermodynamic adsorption-desorption processes. We investigated the relationship between K + and the dissolved organic carbon (DOC) concentrations and seasonal changes in dissolved 137 Cs concentration using a large number of samples from a headwater's small catchments. We examined temporal trends in 137 Cs concentrations in coarse organic matter, suspended sediments, and dissolved forms at four sites (one decontaminated site and three undecontaminated sites) in the Yamakiya area since 2011. The distribution coefficients (Kdcss and Kdorg) of dissolved 137 Cs concentrations relative to suspended sediment and coarse organic matter 137 Cs concentrations were calculated, and differences in temporal changes due to decontamination were investigated. In addition, we examined the relationship between water temperature and DOC, K + , NH 4 + and 137 Cs concentrations in the headwater catchments. The suspended sediment 137 Cs concentrations at the decontaminated headwater site (IBO) decreased significantly after decontamination and remained low thereafter. In contrast, dissolved 137 Cs concentrations decreased temporarily during the decontamination period, but returned to pre-decontamination levels. Almost no NH 4 + has been detected in headwater streams in our catchments. In the SET and ISH watersheds, where the distance from the groundwater spring is short, a correlation was found between DOC concentration and dissolved 137 Cs concentration. In contrast, in the IBO watershed, where the distance from the groundwater spring is long, temperature dependence and a good correlation between K + and 137 Cs were observed. Therefore, microbial decomposition of organic matter may have a significant effect on the seasonal variation of dissolved 137 Cs in forested headwater streams at short distances from the spring, but the influence of competing ions is expected to increase gradually as the water flows downstream., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuichi Onda reports financial support and travel were provided by University of Tsukuba. Yuichi Onda reports a relationship with University of Tsukuba that includes: employment., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We previously reported on 'Tear Film Oriented Diagnosis' (TFOD), a method for the dry eye (DE) subtype classification using fluorescein staining and an examination of fluorescein breakup patterns via slit-lamp biomicroscopy. Here, we report 'AI-supported TFOD', a novel non-invasive method for DE subtype classification using videokeratography (VK) and "Blur Value" (BV), a new VK indicator of the extent of blur in Meyer-ring images and deep learning (DL). This study involved 243 eyes of 243 DE cases (23 males and 220 females; mean age: 64.4 ± 13.9 (SD) years)-i.e., 31 severe aqueous-deficient DE (sADDE) cases, 73 mild-to-moderate ADDE (m/mADDE) cases, 84 decreased wettability DE (DWDE) cases, and 55 increased evaporation DE (IEDE) cases diagnosed via the fluorescein-supported TFOD pathway. For DL, a 3D convolutional neural network classification model was used (i.e., the original image and BV data of eyes kept open for 7 s were randomly divided into training data (146 cases) and the test data (97 cases), with the training data increased via data augmentation and corresponding to 2628 cases). Overall, the DE classification accuracy was 78.40%, and the accuracies for the subtypes sADDE, m/mADDE, DWDE, and IEDE were 92.3%, 79.3%, 75.8%, and 72.7%, respectively. 'AI-supported TFOD' may become a useful tool for DE subtype classification.

In this study, the severity of eye pain (EP) and associated objective findings were evaluated in aqueous-deficient dry eye (ADDE) patients using PainVision ® , a quantitative pain-measuring device. This study involved 53 eyes of 53 ADDE patients (6 males and 47 females; mean age: 64.4 ± 13.4 [mean ± SD] years). Of those, 18 eyes of 18 patients underwent punctal occlusion, and EP and objective findings in those patients were evaluated before and after treatment. In all patients, the severity of EP as measured by PainVision ® was assessed using the Pain Degree (PD). The median PD for the 53 patients was 30.6 µA/µA (interquartile range, 16.9-93.2), and the nasal and central corneal staining score and the upper lid-wiper epitheliopathy score were significantly correlated with PD (R = 0.33, 0.33, and 0.28, respectively) (all: p < 0.05). Using the least squares method, the central corneal staining score most significantly affected PD. In the 18 cases that underwent punctal occlusion, PD was significantly reduced (median PD: 24.8 to 7.1 µA/µA; p < 0.0001). Using the least squares method, the central corneal staining score and tear meniscus radius were significantly more influential as factors contributing to PD before and after treatment, and central corneal epithelial damage was the factor most associated with ADDE-related EP.

Punctal occlusion (PO) is considered to improve both tear-film instability and increased friction during blinking and may consequently affect blinks. The purpose of this study was to investigate the effect of PO on blinks. This study involved 16 eyes of 16 severe aqueous deficient dry eye (ADDE) patients (mean age: 65.7 years). In all eyes, tear meniscus radius (TMR), spread grade (SG) of the tear-film lipid layer (i.e., SG 1-5: 1 being the best), fluorescein break-up time (FBUT), corneal epithelial damage score (CED), conjunctival epithelial damage score, corneal filament (CF) grade, lid-wiper epitheliopathy (LWE) grade, and superior limbic keratoconjunctivitis (SLK) grade were evaluated at before and at more than 1-month after PO. Moreover, using a custom-made high-speed blink analyzer, palpebral aperture height, blink rate, upper-eyelid closing-phase amplitude/duration/maximum velocity, and upper-eyelid opening-phase amplitude/duration/maximum velocity were measured at the same time point. After PO, TMR, SG, FBUT, CED, and the CF, LWE, and SLK grades were significantly improved, and upper-eyelid opening/closing-phase amplitude and maximum velocity significantly increased (all p < 0.04). The findings of this study suggest that PO improves ocular surface lubrication and that blink-related parameters can reflect the friction that occurs during blinking in eyes with severe ADDE.

The pre-lens tear film (PLTF) over (i) delefilcon A silicone hydrogel water gradient (WG; 33-80% from core to surface) contact lenses (CLs) (SHWG-CLs) and (ii) subjects' own non-WG soft CLs (SCLs) (SO-SCLs) was studied in 30 eyes of 30 subjects to assess the hypothesized PLTF stabilization over SHWG-CLs. In both eyes, delefilcon A SHWG-CLs (DAILIES TOTAL1 ® ; Alcon, Fort Worth, TX, USA) or SO-SCLs were worn. After 15 min of wearing each lens, the tear meniscus radius (TMR, mm), lipid-layer interference grade (IG) and spread grade (SG), and non-invasive breakup time (NIBUT, seconds) were evaluated and compared between the SHWG-CLs and the SO-SCLs. The comparison between the SHWG-CL and SO-SCL groups (SHWG-CL and SO-SCL, mean ± SD) revealed that TMRs temporarily decreased and reached a plateau value after 15 min (0.21 ± 0.06; 0.21 ± 0.06) compared to the value prior to CL insertion (0.24 ± 0.08; 0.25 ± 0.08), with no significant difference between the two groups. The NIBUT, IG, and SG values after 15 min of wearing the CLs were (9.7 ± 3.7; 4.7 ± 4.2), (1.0 ± 0.2; 1.8 ± 1.0), and (1.1 ± 0.4; 1.9 ± 1.5), respectively, and all values were significantly better in the SHWG-CL group ( p < 0.0001, p = 0.0039, and p < 0.0001, respectively). We found that compared to the SO-SCLs, the maintenance of the PLTF on the SHWG-CLs was supported by the thicker and more stable PLTF.

Radionuclides released and deposited because of the 2011 Fukushima Dai-ichi Nuclear Power Plant accident caused an increase in air dose rates in Fukushima Prefecture forests. Although an increase in air dose rates during rainfall was previously reported, the air dose rates in the Fukushima forests decreased during rainfall. This study aimed to develop a method to estimate rainfall-related changes in air dose rates, even in the absence of soil moisture data, in Namie-Town and Kawauchi-Village, Futaba-gun, Fukushima Prefecture. Moreover, we examined the relationship between preceding rainfall (Rw) and soil moisture content. The air dose rate was estimated by calculating the Rw in Namie-Town from May to July 2020. We found that the air dose rates decreased with increasing soil moisture content. The soil moisture content was estimated from Rw by combining short-term and long-term effective rainfall using half-live values of 2 h and 7 d and considering the hysteresis of water absorption and drainage processes. Furthermore, the soil moisture content and air dose rate estimations showed a good agreement with coefficient of determination (R 2 ) scores >0.70 and >0.65, respectively. The same method was tested to estimate the air dose rates in Kawauchi-Village from May to July 2019. At the Kawauchi site, variation in estimated value is relatively large due to the presence of water repellency in dry conditions, and the amount of 137 Cs inventory was low, so estimating air dose from rainfall remained a challenge. In conclusion, rainfall data were successfully used to estimate soil moisture and air dose rates in areas with high 137 Cs inventories. This leads to the possibility of removing the influence of rainfall on measured air dose rate data and could contribute to the improvement of methods currently used to estimate the external air dose rates for humans, animals, and terrestrial forest plants., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuichi Onda reports financial support was provided by University of Tsukuba., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To explore the processes of soil erosion at the plot scale, Digital surface model of Differences (DoD) maps (Unmanned Aerial Vehicle - Structure from Motion (UAV-SfM) method) and data from Radio Frequency Identification (RFID) tags were analysed. The comparison of differences in accuracy of UAV-SfM and 3D terrestrial laser scanner (TLS) measurements, and the integration of the UAV-SfM method and soil particle tracing with RFID tag locations were conducted to assess sediment transport in a plot in Fukushima prefecture, Japan. The Universal Soil Loss Equation (USLE) plot was installed and kept with no vegetation and no cultivation. Water and sediment discharges were measured at the outlet of the plot, and the topographic index of runoff and sediment connectivity (IC) -focused on surface roughness- was also estimated. Based on field surveys, four periods were defined. Locations of RFID tags were firstly determined by using orthoimages derived from the UAV-SfM method and then compared with those locations measured with a laser total station. The mean and standard deviation of difference amounts of UAV-SfM were of 1 and 3.3 mm, respectively. On average, the RFID tags were located with an accuracy of 3.1 cm (RMSE). Although data of tags tracing showed short transport distances with rill erosion, the results of the UAV-SfM surveys showed an increase of sediment connectivity (SC) over the study period that may explain the largest sediment discharge, especially of fine soil particles. The concurrence of higher values of SC as well as the development of new and longer rills demonstrated the important activity of net soil loss in our study site. The combination of distinct methods and techniques, all providing accurate measurements, shed light on the sediment transport process at short distances, which affects the net water and sediment discharge at larger scales., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Basal plant immune responses are activated by the recognition of conserved microbe-associated molecular patterns (MAMPs), or breakdown molecules released from the plants after damage by pathogen penetration, so-called damage-associated molecular patterns (DAMPs). While chitin-oligosaccharide (CHOS), a primary component of fungal cell walls, is most known as MAMP, plant cell wall-derived oligosaccharides, cello-oligosaccharides (COS) from cellulose, and xylo-oligosaccharide (XOS) from hemicellulose are representative DAMPs. In this study, elicitor activities of COS prepared from cotton linters, XOS prepared from corn cobs, and chitin-oligosaccharide (CHOS) from crustacean shells were comparatively investigated. In Arabidopsis, COS, XOS, or CHOS treatment triggered typical defense responses such as reactive oxygen species (ROS) production, phosphorylation of MAP kinases, callose deposition, and activation of the defense-related transcription factor WRKY33 promoter. When COS, XOS, and CHOS were used at concentrations with similar activity in inducing ROS production and callose depositions, CHOS was particularly potent in activating the MAPK kinases and WRKY33 promoters. Among the COS and XOS with different degrees of polymerization, cellotriose and xylotetraose showed the highest activity for the activation of WRKY33 promoter. Gene ontology enrichment analysis of RNAseq data revealed that simultaneous treatment of COS, XOS, and CHOS (oligo-mix) effectively activates plant disease resistance. In practice, treatment with the oligo-mix enhanced the resistance of tomato to powdery mildew, but plant growth was not inhibited but rather tended to be promoted, providing evidence that treatment with the oligo-mix has beneficial effects on improving disease resistance in plants, making them a promising class of compounds for practical application., (© 2023 Scandinavian Plant Physiology Society.)

Purpose: To analyze the effectiveness of a newly developed indicator that quantitatively assesses disturbance in Meyer-ring (MR) images obtained via videokeratographer and assess its usefulness for the clinical evaluation of dry eye (DE)., Design: Cross-sectional study., Methods: This study involved 79 eyes of 79 DE patients (10 males and 69 females; mean age: 62.7 years). After MR images were obtained via videokeratographer, the degree of blur was quantified at multiple points on the ring, with the total value across the cornea being defined as the disturbance value (DV). Correlations between total DV (TDV; the sum of DV for 5 seconds after eye opening) and 12 DE symptoms, Dry Eye-Related Quality of Life Score (DEQS), tear meniscus radius (mm), tear film (TF) lipid-layer spread grade (SG; grades 1-5, 1 = best), TF noninvasive breakup time (NIBUT, seconds), fluorescein breakup time (FBUT, seconds), corneal epithelial damage score (CEDS; maximum: 15 points), conjunctival epithelial damage score (CjEDS; maximum: 6 points), and Schirmer 1 test value (mm) were analyzed via univariate and multivariate analyses., Results: No significant correlations were found between TDV and each DE symptom or DEQS, yet significant correlations were found between TDV and SG, NIBUT, FBUT, CEDS, and CjEDS (r = 0.56, -0.45, -0.45, 0.72, and 0.62, respectively, all P < .01). TDV was found to be described as 2334 + (412.1 × CEDS) - (302.0 × FBUT) (R 2  = 0.593, P < .0001)., Conclusions: Our newly developed indicator, DV, reflecting TF dynamics and stability and corneoconjunctival epithelial damage, may be useful for quantitatively assessing DE ocular-surface abnormalities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Gastric cancer patients with peritoneal metastasis (PM) are generally treated with systemic chemotherapy. When PM has disappeared because of chemotherapy, radical gastrectomy (so-called conversion surgery) is usually performed. We have previously reported the efficacy of conversion surgery, but there are no reports examining the efficacy of palliative gastrectomy for patients with residual PM after chemotherapy. The purpose of this study was to investigate the efficacy of palliative surgery for gastric cancer patients with PM who still have residual peritoneal dissemination after chemotherapy., Methods: Twenty-five gastric cancer patients with PM confirmed by laparoscopy and who had received chemotherapy but who still had residual PM were included in this study. Among the 25 patients, palliative surgery was performed in 20 patients (PS group) and chemotherapy was continued in 5 patients (CTx group), and their therapeutic outcomes were compared., Results: In the PS group, total and distal gastrectomies were performed. Clavien-Dindo grade I postoperative complications occurred in two patients (10%). There were no treatment-related deaths. Postoperative chemotherapy was performed all cases. In the PS group, the median survival time (MST) reached 22.5 months, with 1- and 2-year overall survival (OS) rates of 95% and 45%, respectively, whereas in the CTx group, the MST was 15.8 months, and the 1- and 2-year OS rates were 60% and 0%, respectively. The PS group had significantly longer OS than the CTx group (P=0.044)., Conclusions: Palliative surgery is safe and may prolong survival in gastric cancer patients with residual PM after chemotherapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The surgical strategy for thoracic esophageal cancer that invades the lungs is controversial. In particular, invasion of the pulmonary vein is often regarded unresectable. We successfully applied bilateral video-assisted thoracic surgery (VATS) in esophagectomy for esophageal cancer with left inferior pulmonary vein invasion following induction chemoradiotherapy (CRT), with a favorable response., Case Presentation: A 64-year-old woman was diagnosed with squamous cell carcinoma of the lower third of the esophagus. Computed tomography (CT) revealed that the tumor was suspected to be invading the main trunk of the left lower pulmonary vein and left lower lung. We initiated induction CRT comprising 5-fluorouracil, cisplatin, and concurrent radiotherapy at 50.4 Gy/28Fr. CT revealed shrinkage of the tumor, and the main trunk of the left inferior pulmonary vein was released from the tumor invasion. We considered the tumor to be completely resectable. VATS esophagectomy is usually performed using a right-sided approach. However, the right-sided approach is inappropriate for evaluating tumors around the left inferior pulmonary vein. We started with left-sided VATS to determine tumor resectability and dissected between the esophagus and the main trunk of the left inferior pulmonary vein. We only needed to perform partial resection of the left lower lobe. We then performed a right-sided VATS esophagectomy and lymphadenectomy with partial en bloc resection of the left lower lobe. Following this, we performed hand-assisted laparoscopic proximal gastrectomy and reconstruction using the gastric remnant. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Histopathological examination of the surgical specimen revealed a complete pathological response without any remnant tumor or lymph node metastasis. There were no signs of recurrence or metastasis at the 1-year follow-up., Conclusions: Curative resection for thoracic esophageal cancer that invades the pulmonary vein could be possible via the bilateral VATS approach following induction CRT with a favorable response., (© 2023. The Author(s).)

In Japan, the Ministry of Health, Labour and Welfare (MHLW) designates one specific virus strain for each component of the quadrivalent seasonal influenza vaccine, and four domestic manufacturers produce egg-based influenza vaccines with the same formulation (inactivated, split-virus) using uniform vaccine strains. Thus, discussions of the development of effective seasonal influenza vaccines so far has focused solely on the antigenic match between the vaccine strains and epidemic viruses. However, in 2017, the Japanese selection system of vaccine viruses demonstrated that even a candidate vaccine virus that is antigenically similar to the predicted circulating viruses is not necessarily suitable for vaccine production, given lower productivity of the vaccine. Taking this experience into account, the MHLW reformed the scheme of vaccine strain selection in 2018, and instructed the Vaccine Epidemiology Research Group created by the MHLW to probe how the virus strains for the seasonal influenza vaccine should be selected in Japan. In this context, a symposium, entitled "Issues of the Present Seasonal Influenza Vaccines and Future Prospects", was held as part of the 22nd Annual Meeting of the Japanese Society for Vaccinology in 2018, and subjects related to the influenza vaccine viruses were discussed among relevant administrators, manufacturers, and researchers. This report summarizes the presentations given at that symposium in order to convey the present scheme of vaccine virus selection, the evaluation of the resulting vaccines, and the efforts at new vaccine formulation in Japan. Notably, from March 2022, the MHLW has launched a discussion of the merits of the seasonal influenza vaccines produced by foreign manufacturers., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Takao Hozawa is an employee of Denka Co., Ltd. in Tokyo, Japan. All other authors declare that they are free of competing interests.’, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: This study retrospectively evaluated the 12-month outcomes of the Zenith Alpha Abdominal Endovascular graft (Zenith Alpha AAA, Cook, Inc, Bloomington, Indiana), which was launched partially in Japan in March 2019, starting with 9 selected sites., Methods: A retrospective analysis was performed of all endovascular aneurysm repairs (EVAR) for abdominal aortic aneurysms using the Zenith Alpha AAA. Late complications were defined as any aneurysm-related events occurring >30 days after EVAR, including an aneurysm sac enlargement of >5 mm and any reinterventions performed. Endoleaks without sac enlargement or reinterventions were excluded from late complications., Results: During the study period, 79 EVARs using the Zenith Alpha AAA were performed. The mean age was 76.6±6.9 years old, 91.1% of patients were male, and the mean aneurysm diameter was 51.1±7.5 mm. Instructions for use violation was observed in 27 patients (34.2%), most frequently being a severely angulated proximal neck (>60°). There were 4 intraoperative complications, including 2 unintentional partial renal artery coverages caused by the premature anchoring of the exposed suprarenal stent barb to the aortic wall, which was a result of the design change of the top cap deletion. Since it was a partial coverage without flow impairment and since renal stenting was unsuccessful, it was left untreated and had no subsequent renal function impairment. During the mean follow-up of 444±123 days, 74 patients completed 12 months of follow-up. Freedom from late complications at 12 months was 90.8%, which included 2 limb occlusions (2.5%). Of 71 patients with a 12-month computed tomography scan, there was only 1 type 1a endoleak (1.3%), 1 sac enlargement of >5 mm (1.3%), and an aneurysm sac shrinkage of >5 mm was observed in 42.2% of patients. There was no type 3 endoleak during the follow-up., Conclusions: This study demonstrated that the new generation of low-profile Zenith Alpha AAA has satisfactory early clinical outcomes, comparable to those obtained with the conventional Zenith endovascular graft. Long-term follow-up is needed to determine whether these favorable outcomes persist.

Olanzapine is an antipsychotic agent with species-dependent pharmacokinetic profiles in both humans and animals. In the present study, the metabolic profiles of olanzapine in vitro and in vivo were compared in non-transplanted immunodeficient NOG-TKm30 mice and chimeric mice with humanized livers (hereafter humanized-liver mice). Hepatic microsomal fractions prepared from humanized-liver mice and humans mediated olanzapine N10-glucuronidation, whereas fractions from cynomolgus monkeys, marmosets, minipigs, dogs, rabbits, guinea pigs, rats, CD1 mice, and NOG-TKm30 mice did not. The olanzapine N10-glucuronidation activity in liver microsomes from humanized-liver mice was inhibited by hecogenin, a human UDP-glucuronosyltransferase (UGT) 1A4 inhibitor. In addition, hepatocytes from humanized-liver mice suggest that olanzapine N10-glucuronidation was a major metabolic pathway in the livers of humanized-liver mice. After a single oral dose of olanzapine (10 mg/kg body weight) to humanized-liver mice and control NOG-TKm30 mice, olanzapine N10-glucuronide isomers and olanzapine N4'-glucuronide were detected only in the plasma of humanized-liver mice. In contrast, the area under the curve for N4'-demethylolanzapine, 2-hydroxymethylolanzapine, and 7-hydroxyolanzapine glucuronide was higher in NOG-TKm30 mice than that in humanized-liver mice. The cumulative excreted amounts of olanzapine N10-glucuronide isomers were high in the urine and feces from humanized-liver mice, whereas the cumulative excreted amounts of 2-hydroxymethylolanzapine were higher in NOG-TKm30 mice than in humanized-liver mice. Thus, production of human-specific olanzapine N10-glucuronide was observed in humanized-liver mice, which was consistent with the in vitro glucuronidation data. These results suggest that humanized-liver mice are useful for studying drug oxidation and conjugation of olanzapine in humans. SIGNIFICANCE STATEMENT: Human-specific olanzapine N10-glucuronide isomers were generated in chimeric NOG-TKm30 mice with humanized livers (humanized-liver mice), and high UGT1A4-dependent N10-glucuronidation was observed in the liver microsomes from humanized-liver mice. Hence, humanized-liver mice may be a suitable model for studying UGT1A4-dependent biotransformation of drugs in humans., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Introduction: The incidence of endometrial cancer (EC) has been increasing worldwide. However, because there are limited chemotherapeutic options for the treatment of EC, the prognosis of advanced-stage EC is poor., Methods: Gene expression profile datasets for EC cases registered in The Cancer Genome Atlas (TCGA) was reanalyzed. Highly expressed genes in advanced-stage EC (110 cases) compared with early-stage EC (255 cases) were extracted and Gene Ontology (GO) enrichment analysis was performed. Among the enriched genes, Kaplan-Meier (KM) plotter analysis was performed. Candidate genes expression was analyzed in HEC50B cells and Ishikawa cells by RT-qPCR. In HEC50B cells, LIM homeobox1 (LIM1) was knocked down (KD) and cell proliferation, migration, and invasion ability of the cells were evaluated. Xenografts were generated using LIM1-KD cells and tumor growth was evaluated. Ingenuity Pathway Analysis (IPA) of RNA-seq data using LIM-KD cells was performed. Expression of phospho-CREB and CREB-related proteins were evaluated in LIM1-KD cells by western blotting and in xenograft tissue by immunofluorescent staining. Two different CREB inhibitors were treated in HEC50B and cell proliferation was evaluated by MTT assay., Results: Reanalysis of TCGA followed by GO enrichment analysis revealed that homeobox genes were highly expressed in advanced-stage EC. Among the identified genes, KM plotter analysis showed that high LIM1 expression was associated with a significantly poorer prognosis in EC. Additionally, LIM1 expression was significantly higher in high-grade EC cell lines, HEC50B cells than Ishikawa cells. Knockdown of LIM1 showed reduced cell proliferation, migration and invasion in HEC50B cells. Xenograft experiments revealed that tumor growth was significantly suppressed in LIM1-KD cells. IPA of RNA-seq data using LIM-KD cells predicted that the mRNA expression of CREB signaling-related genes was suppressed. Indeed, phosphorylation of CREB was decreased in LIM1-KD cells and LIM1-KD cells derived tumors. HEC50B cells treated by CREB inhibitors showed suppression of cell proliferation., Conclusion and Discussion: Collectively, these results suggested that high LIM1 expression contributed to tumor growth via CREB signaling in EC. Inhibition of LIM1 or its downstream molecules would be new therapeutic strategies for EC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kato, Saeki, Imai, Onji, Yano, Yoshida, Sakaue, Fujioka, Sugiyama and Imai.)

Spot break (SB), a tear film breakup (TFBU) subtype seen in decreased wettability dry eye (DE), is characterized by a spot-like TFBU that appears immediately after eye opening. It is sometimes difficult to detect using currently available devices for evaluating non-invasive TFBU. The purpose of this study was to investigate the effectiveness of using a newly developed videokeratography indicator for detecting SB. The study involved 44 eyes of 44 DE patients (21 eyes with SB (SB group) and 23 eyes with random break in which fluorescein breakup time was ≤ 5 s (s) (RB group)). All eyes were examined using videokeratography, with digital Meyer-ring images being obtained. By calculation of the degree of luminance blur on the cornea in the Meyer-ring images, termed ‘disturbance value’ (DV), DVs at 0 s (DV(0)]), 2 s (DV(2)), and 5 s (DV(5)) after eye opening, and the changes of DV between each time, were compared between the SB and RB groups. Results: No significant differences in DV(2) and DV(5) and the rate of change between DV(2) and DV(5) were found between the two groups. However, DV(0) and rate of change between DV(0) and DV(2) in the SB group were significantly greater (p < 0.001) than those in the RB group. SB characteristics were successfully detected by videokeratography using a new videokeratography DV indicator.

To empower the next generation of students to become leaders that play active roles in various fields in society, research universities must offer attractive and meaningful doctor of philosophy (PhD) programs in their graduate schools. The Graduate School of Pharmaceutical Sciences, at Kyoto University has trained a large number of researchers who are leading drug discovery science and clinical pharmacy in academia as well as in the pharmaceutical industry, in medical organization and in government. However, due to changes in the trends of students and the evolving skill requirements of future PhD holders to handle the challenges of a changing society, it is necessary to revise the curriculum of our graduate school. Thus, we will reform the graduate and undergraduate school programs by implementing a so-called late specialization program and a double mentoring system and aim to nurture emergent researchers who will explore uncharted areas in pharmaceutical sciences. Toward this goal, we established the Division of Medical Frontier Sciences in April 2022 to replace the former Division of Bioinformatics and Chemical Genomics. This program is Japan's first five-year integrated doctoral course in the field of pharmaceutical sciences. In this review, I will introduce the background leading to its development construction and provide an overview of the characteristics of this five-year integrated doctoral program.

Introduction: This study aimed to clarify the impact of the average relative dose intensity (RDI) of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-NAC) for resectable locally advanced esophageal squamous cell carcinoma (ESCC)., Materials and Methods: To identify the optimal RDI, recurrence-free survival (RFS) and cumulative incidence function (CIF) for recurrence were calculated in low and high RDI groups with any cut-off points. The optimal RDI was defined as the highest RDI administered with a significant increase in either RFS or CIF. The clinicopathological characteristics of the two groups divided by optimal RDI were investigated. The preoperative prognostic factors associated with RFS were confirmed by multivariable Cox proportional hazards model., Results: Among the 150 eligible patients treated with DCF-NAC from 2010 to 2020, 3-year RFS and CIF were 56.3% and 37.8% in 90 patients in the less than 80% RDI group (<80% RDI) and 73.3% and 26.7% in 60 patients in the more than or equal to 80% RDI group (≥80% RDI), respectively. The optimal cut-off RDI was identified as 80%. The <80% RDI group included older individuals, a lower value of creatinine clearance, a higher Charlson Comorbidity Index, reduced RDI at first course, and grade 1-0 in the histopathological tumor response than the ≥80% RDI group. R0 resection and postoperative complication rates were equal in both groups. Cox proportional hazards model identified the response rate and RDI as predictors of RFS., Conclusion: An average RDI of more than or equal to 80% improved prognosis in patients receiving DCF-NAC for ESCC., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Despite the promising effectiveness of the coronavirus disease 2019 vaccination using an mRNA vaccine, the short efficacy duration and some poor responses to the vaccination remain major concerns. We aimed to clarify the monthly kinetics of the anti-SARS-CoV-2 spike receptor-binding domain antibody response after two doses of the BNT162b2 vaccine in a Japanese population. A chemiluminescent enzyme immunoassay (CLIA) and an enzyme-linked immunosorbent assay were used to measure the antibody levels in 81 Japanese adults (age, <65 years). The antibody levels increased 10-fold at 2−3 weeks following the second dose of BNT162b2 and declined thereafter to approximately 50%, 20%, and 10% of the peak levels at 2, 3, and 6 months, respectively. To compare the antibody titers among different groups, older adults (age, >65 years; n = 38) and patients with systemic lupus erythematosus (SLE, n = 14) were also investigated. A decline in the mean relative antibody titers was observed in older men compared with younger men and in patients with SLE compared with individuals aged <65 years. Although the antibody levels increased drastically following two BNT162b2 doses, they then declined rapidly. Furthermore, poor responders to the vaccination were observed. Repeated vaccinations are required to maintain high antibody levels.

Background: The global burden of influenza is substantial. It is a major disease that causes annual epidemics and occasionally, pandemics. Given that influenza primarily infects the upper respiratory system, it may be possible to diagnose influenza infection by applying deep learning to pharyngeal images., Objective: We aimed to develop a deep learning model to diagnose influenza infection using pharyngeal images and clinical information., Methods: We recruited patients who visited clinics and hospitals because of influenza-like symptoms. In the training stage, we developed a diagnostic prediction artificial intelligence (AI) model based on deep learning to predict polymerase chain reaction (PCR)-confirmed influenza from pharyngeal images and clinical information. In the validation stage, we assessed the diagnostic performance of the AI model. In additional analysis, we compared the diagnostic performance of the AI model with that of 3 physicians and interpreted the AI model using importance heat maps., Results: We enrolled a total of 7831 patients at 64 hospitals between November 1, 2019, and January 21, 2020, in the training stage and 659 patients (including 196 patients with PCR-confirmed influenza) at 11 hospitals between January 25, 2020, and March 13, 2020, in the validation stage. The area under the receiver operating characteristic curve for the AI model was 0.90 (95% CI 0.87-0.93), and its sensitivity and specificity were 76% (70%-82%) and 88% (85%-91%), respectively, outperforming 3 physicians. In the importance heat maps, the AI model often focused on follicles on the posterior pharyngeal wall., Conclusions: We developed the first AI model that can accurately diagnose influenza from pharyngeal images, which has the potential to help physicians to make a timely diagnosis., (©Sho Okiyama, Memori Fukuda, Masashi Sode, Wataru Takahashi, Masahiro Ikeda, Hiroaki Kato, Yusuke Tsugawa, Masao Iwagami. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.12.2022.)

Intraperitoneal chemotherapy, in which an anticancer drug is administered directly into the abdominal cavity through an intraperitoneal access port(IP port), is one of the treatment options for advanced gastric cancer with peritoneal metastasis. Herein, we report a case of sheath-like obstruction of the entire catheter of the IP port due to tissue reaction within a short period of time after IP port implantation. The case was a 35-year-old woman with advanced type 4 gastric cancer with peritoneal dissemination. The IP port was placed and intravenous and intraperitoneal chemotherapy using S-1 plus paclitaxel was started. However, in the middle of the second course, the entire catheter was covered with a fibrous capsule and a sheath-like obstruction occurred, so the IP port was removed and a new IP port was reinserted. One of the IP port troubles is obstruction, but such short-term and special obstruction is rare, and the cause is considered to be a foreign body reaction of the catheter.

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients' quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001-3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01)., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Induction or adjuvant therapies are not always beneficial for thoracic esophageal squamous cell carcinoma (ESCC) patients, and it is thus important to identify patients at high risk for postoperative ESCC recurrence. We investigated the usefulness of the total metabolic tumor volume (TMTV) for predicting the postoperative recurrence of thoracic ESCC., Methods: We retrospectively analyzed the cases of 163 thoracic ESCC patients (135 men, 28 women; median age of 66 [range 34-82] years) treated at our hospital in 2007-2012. The TMTV was calculated from the fluorine-18 fluorodeoxyglucose ( 18 F-FDG) uptake in the primary lesion and lymph node metastases. The optimal cut-off values for relapse and non-relapse were obtained by the time-dependent receiver operating curve analyses. Relapse-free survival (RFS) was evaluated by the Kaplan-Meier method, and between-subgroup differences in survival were analyzed by log-rank test. The prognostic significance of metabolic parameters and clinicopathological variables was assessed by a Cox proportional hazard regression analysis. The difference in the failure patterns after surgical resection was evaluated using the χ 2 -test., Results: The optimal cut-off value of TMTV for discriminating relapse from non-relapse was 3.82. The patients with a TMTV ≥3.82 showed significantly worse prognoses than those with low values (p < 0.001). The TMTV was significantly related to RFS (model 1 for preoperative risk factors: TMTV: hazard ratio [HR] =2.574, p = 0.004; model 2 for preoperative and postoperative risk factors: HR = 1.989, p = 0.044). The combination of the TMTV and cN0-1 or pN0-1 stage significantly stratified the patients into low-and high-risk recurrence groups (TMTV cN0-1, p < 0.001; TMTV pN0-1, p = 0.004). The rates of hematogenous and regional lymph node metastasis were significantly higher in the patients with TMTV ≥3.82 than those with low values (hematogenous metastasis, p < 0.001, regional lymph node metastasis, p = 0.011)., Conclusions: The TMTV was a more significantly independent prognostic factor for RFS than any other PET parameter in patients with resectable thoracic ESCC. The TMTV may be useful for the identifying thoracic ESCC patients at high risk for postoperative recurrence and for deciding the patient management., (© 2022. The Author(s).)

The March 2011 Fukushima Dai-ichi Nuclear Power Plant accident in Japan released 520 PBq of radionuclides compared to a total release of 5300 PBq from the Chornobyl Nuclear Power Plant accident. Both nuclear accidents resulted in deposition of radiocesium throughout the northern hemisphere, and a plethora of studies have been performed regarding radiocesium ( 137 Cs) behavior. However, few studies have assessed the impact of precipitation on 137 Cs deposition in forests. Wide-scale environmental measurements from 2011 and 2016 were used to determine the differences in 137 Cs deposition because of precipitation following the Fukushima accident. In areas where wet deposition processes were dominant, dense forests generally had lower ambient dose rates and levels of contamination on forest floors than other stands with fewer stems per hectare in 2011. Similar tendencies were not observed in areas that were primarily subject to dry deposition nor were any trends observed in 2016. 137 Cs was retained in dense forest canopies for an extended period regardless of the deposition mode. Additionally, it was found that the initial retention of radionuclides by forest canopies is in general higher for areas with predominantly dry deposition. Incorporation of radiocesium into wood tissues was the same for both wet and dry deposition.

The crystal structures and electron density distributions (EDDs) of Ca-deficient Sc-doped CaTiO 3 fast oxide-ion conductors, Ca 0.97 (Ti 0.97 Sc 0.03 )O 3-δ (CTS3) and Ca 0.96 (Ti 0.9 Sc 0.1 )O 3-δ (CTS10), were investigated in the temperature range of 298-1173 K in N 2 to analyze the effect of composition on the perovskite structure and oxide-ion transport mechanism. CTS3 and CTS10 exhibited orthorhombic Pnma symmetry in temperature ranges of 298-1173 K and 973-1173 K, respectively, with CTS10 exhibiting lower symmetry and reduction in oxide-ion conductivity below 973 K. The EDDs of CTS3 and CTS10 at 1173 K indicated unique chemical bonds and conduction paths. CTS3 and CTS10 showed covalent bonds between (Ti,Sc) and O1 (or O2) sites. CTS3, with a lower oxide-ion conductivity than that of CTS10, exhibited pseudo-one-dimensional (1D) zig-zag curved conduction paths for oxide-ions along the a -axis, unlike previously reported curved migration paths along the b -axis in CaTiO 3 , and chemical bonds between Ca and O1 sites, indicating oxide-ion conduction suppression. In CTS10, additional conduction paths were observed along the a -axis, forming three-dimensional (3D) zig-zag curved conduction paths in the ac -plane and along the b -axis, with the weakening of the chemical bonds between the Ca and O1 sites. The oxide-ion conductivity and mobile oxide-ion concentration of CTS10 were 3.6 and 2.0 times those of CTS3, respectively, at 1173 K; the higher oxide-ion conductivity of CTS10 could be attributed to an increase in the mobile oxide-ion concentration and mobility with a 1D to 3D change in the conduction paths and a weakening of chemical bonds between the Ca and O1 sites.

Background: The impact of psoas muscle area on overall survival is unknown for older patients undergoing elective thoracic endovascular aortic repair., Methods: We retrospectively reviewed 105 patients aged 75 years or more who underwent elective thoracic endovascular aortic repair for descending thoracic aortic aneurysm between January 2010 and December 2019. Psoas muscle area was measured at the L3 level with preoperative computed tomography and adjusted by height squared to derive psoas muscle mass index. The patients were stratified into two groups, sarcopenia and nonsarcopenia. sarcopenia was defined as a psoas muscle mass index less than 5.40 cm 2 /m 2 for men and less than 3.56 cm 2 /m 2 for women. The overall survival was compared with the age- and sex-matched general population using the one-sample log rank test. The propensity score adjusted Cox proportional hazards model was applied to determine the hazard ratio for all-cause mortality., Results: Twenty-three patients died during the follow-up period (median, 3 years). Thirty-eight patients (36%) were classified as sarcopenia. The 5-year overall survival rate was 46% (95% confidence interval, 29% to 73%) for sarcopenia and 84% (95% confidence interval, 74% to 94%) for nonsarcopenia. The overall survival was significantly lower in the sarcopenia group than in its matched general population (P = .004), whereas no statistically significant difference in overall survival was found between the nonsarcopenia group and its matched general population (P = .417). Sarcopenia was an independent risk factor for all-cause mortality (adjusted hazard ratio 2.64; 95% confidence interval, 1.02 to 6.82; P = .045)., Conclusions: Psoas muscle mass index may be a good predictor of mortality among older patients undergoing elective thoracic endovascular aortic repair for descending thoracic aortic aneurysm., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is primarily treated with platinum-based neoadjuvant chemotherapy (NAC). Some ESCCs respond well to NAC. However, biomarkers to predict NAC sensitivity and their response mechanism in ESCC remain unclear. We perform whole-genome sequencing and RNA sequencing analysis of 141 ESCC biopsy specimens before NAC treatment to generate a machine-learning-based diagnostic model to predict NAC reactivity in ESCC and analyzed the association between immunogenomic features and NAC response. Neutrophil infiltration may play an important role in ESCC response to NAC. We also demonstrate that specific copy-number alterations and copy-number signatures in the ESCC genome are significantly associated with NAC response. The interactions between the tumor genome and immune features of ESCC are likely to be a good indicator of therapeutic capability and a therapeutic target for ESCC, and machine learning prediction for NAC response is useful., Competing Interests: Declaration of interests All authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This study investigated the spatial distribution of radiocesium deposited by the Fukushima Daiichi Nuclear Power Plant accident in a densely planted Japanese cedar stand. Systematic grid sampling was conducted to determine 137 Cs inventories in the layers of deposited organic material and mineral soil at two different spatial scales (hillslope [60 m 2 ] and small [1 m 2 ]). The results showed that 137 Cs inventories along the hillslope were heterogeneously distributed, with coefficients of variation for the deposited organic material and mineral soil layers of 46.4% and 48.9%, respectively. The 137 Cs inventory in each layer tended to show a lognormal distribution. The correlation between the 137 Cs inventories in deposited organic material and mineral soil in the same sampling grid was weak. The controlling mechanisms of the 137 Cs inventories in the litter and mineral soil layers differed due to differences in the underlying key processes, such as canopy-forest floor transfer due to hydrological and biological processes. No significant correlation was found between the distance from the nearest tree trunk and the 137 Cs inventory in the deposited organic layer at each sampling point. In contrast, the 137 Cs inventory in the soil tended to increase as the distance from the nearest tree trunk increased at both the hillslope and small scales. It was found that the initial spatial patterns of 137 Cs in the soil layer due to atmospheric deposition were preserved in the cedar stand. Finally, we tested the effects of soil sampling density on the reliability of mean soil 137 Cs inventory estimations in the cedar stand. The results indicated that a soil sampling area greater than 0.06 m 2  at the hillslope scale and 0.008 m 2  at the small scale enabled the mean 137 Cs inventory to be estimated with an uncertainty of less than 20% in the cedar stand., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: In the selection of thoracic endovascular repair for aortic dissection (AD), it is important to distinguish between the subacute and chronic phases, but there is no reliable way to distinguish between them in patients with unknown onset of AD. The purpose of this study was to assess the diagnostic performance of 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG)-PET/computed tomography (PET/CT) for discriminating subacute AD from chronic AD., Methods: Thirteen patients with AD who were medically treated and followed up for 6 months were studied. 18F-FDG PET/CT images were obtained for each patient in the subacute phase (the first scan) and at 6 months (the second scan) after the onset. Target-to-background ratio (TBR) was measured as the maximum standardized uptake value (SUV) in the dissected aortic wall divided by blood pool SUV., Results: TBR was significantly higher in the first scan (mean ± SD, 1.97 ± 0.32) than in the second scan (1.69 ± 0.29, P = 0.007). The area under the receiver operating characteristic curve of TBR for discriminating subacute AD from chronic AD was 0.76. With a threshold of 1.74, the TBR showed the sensitivity, specificity, and positive and negative predictive value of 85%, 69%, 73%, and 82%, respectively, for the discrimination of subacute AD from chronic AD., Conclusion: Metabolic assessment of dissected aortic wall by 18F-FDG PET/CT is useful in differentiating between subacute and chronic AD and can provide important information in determining the appropriate indication for treatment for patients with AD of unknown onset., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Forest is an important part of the environmental system, which has a significant impact on soil hydrological characteristics and forest landscapes, because these processes are influenced by forest management and understory vegetation. Quantitative understory vegetation biomass (UVB) measurement and estimation are vital processes in forest ecology and environmental management. However, these estimations are difficult to make on a large scale especially dense planted forest. Here, we applied catchment-scale Structure from Motion and a manually operated ultralow-flying drone under the canopy of a dense planted (2000 stems/ha) Japanese cedar/cypress plantation forest to reconstruct the understory. An understory drone survey was performed over a 1.1-ha sub-catchment to generate a canopy height model based on dense point cloud data. A biomass survey of three 16-m 2 harvesting plots was conducted to compute understory vegetation volume data based on point clouds. Combined with harvested biomass data in the field, quantitative models were developed between the understory vegetation volume and biomass. Subsequently, the models were used to map spatial understory vegetation biomass distribution in the sub-catchments. Aerial photos taken by the ultralow-flying drones under the canopy yielded a high-resolution catchment-scale understory with point cloud density >10/cm 2 . Strong cubic model coefficients of determination (R 2  = 0.75) predicted the understory vegetation biomass based on the canopy height model. The mean understory vegetation biomass was 0.82 kg/m 2 and dominated by low ferns. In the present study, we successfully reconstructed the multilayered forest structure and generated understory vegetation biomass distribution models. This results also will be essential to evaluate the erosion and evapotranspiration in dense plantation forests and future environmental management., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

ABCB1, also known as P-glycoprotein, is an essential component of many physiological barriers and extrudes a variety of hydrophobic chemicals out of the cell. Structures of ABCB1 provided insights into the structural changes that occur upon ATP binding and the characteristic architecture of the substrate binding site. Yet, the structure-function relationship between substrate binding and transporting still remains largely obscured because there is no robust method for accurately measuring substrate binding constants. The methods currently used cannot identify whether the bound substrates are located in the inner chamber of the molecule in the transmembrane region or not because of the low spatial resolution. Here, we report a system for measuring the affinity of substrate binding to the Cyanidioschyzon merolae ABCB1 (CmABCB1) using site-specific tryptophan (Trp) fluorescence quenching. We designed a CmABCB1 mutant with an extrinsic Trp residue introduced into the inner chamber. Trp fluorescence was quenched by three substrates and one inhibitor, including rhodamine 6G, in a saturable fashion, allowing for accurate estimation of the dissociation constant (K D ) for each molecule. The K D for rhodamine 6G is similar to that determined using a reciprocal fluorescence quenching assay using rhodamine 6G fluorescence, suggesting that Trp fluorescence of the mutant was quenched by the interaction between the extrinsic Trp and substrates bound in the inner chamber. Structural comparison of the ABCB1 structures suggests that the system presented in this study could be ideal method of choice to determine the substrate binding affinities of compounds bound to the chamber of mammalian ABCB1., (© 2022 The Protein Society.)

Purpose: Lid wiper epitheliopathy (LWE) is an epitheliopathy of the marginal conjunctival portion of the eyelids that wipes the ocular surface during blinking. Although LWE is often observed in patients with dry eye, the factors determining LWE severity in dry eye remain unknown. Therefore, we investigated the relationship between LWE, tear abnormalities, and blinks in dry eye., Methods: This study involved 76 eyes of 76 female patients with dry eye (mean age: 57.2 yrs). In all eyes, tear meniscus radius, spread grade (SG) of the tear film lipid layer (ie, SG 1-5, with 1 being the best), fluorescein breakup time (FBUT), fluorescein breakup pattern, corneal and bulbar conjunctival epithelial damage (CED: 15 points maximum; CjED: 6 points maximum, respectively), upper eyelid LWE grade (3 points maximum), and Schirmer 1 test were evaluated. Blink rate, palpebral aperture height, upper eyelid opening/closing-phase amplitude, upper eyelid opening/closing-phase duration, and upper eyelid opening/closing-phase maximum velocity were measured by the use of a custom-made high-speed blink analyzer. Finally, the factors that determine the LWE grade were investigated by multiple regression analysis, in which the parameters were chosen using the stepwise procedure., Results: Significant correlations were found between LWE grade and tear meniscus radius, SG, FBUT, CED, CjED, and Schirmer 1 test (P < 0.002). LWE grade was found to be described as -0.001 + (0.283 × SG) - (0.253 × FBUT) + (0.003 × upper eyelid closing-phase maximum velocity) (R2 = 0.57, P < 0.0001). The prevalence and grade of LWE were significantly higher in aqueous deficient dry eye., Conclusions: Tear volume, tear film stability, and blink should be considered as factors for determining LWE severity., Competing Interests: N. Yokoi is a consultant for Rohto Co., Ltd.; S. Kinoshita is a consultant for Santen Pharmaceutical Co., Ltd. and Otsuka Pharmaceutical Co., Ltd. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The prognosis of gastric cancer patients with peritoneal metastasis (PM) remains dismal with standard systemic chemotherapy. Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has local effects on intra-abdominal cancer cells. According to this phenomenon, we have developed regimens combining single i.p. PTX administration with systemic chemotherapy. This treatment strategy is very promising; however, the effect of "conversion surgery" in patients responding to this chemotherapy is unclear. Therefore, we performed a retrospective study to evaluate the safety and efficacy of conversion surgery for gastric cancer patients with PM., Methods: We enrolled 52 gastric cancer patients with PM who were treated with single i.p. PTX plus systemic chemotherapy between 2005 and 2015. Conversion surgery was performed where PM was eliminated by combination chemotherapy., Results: Among 52 gastric cancer patients, the disappearance of PM was confirmed in 33 patients (63.5%). Gastrectomy with D2 lymph node dissection was performed in all these patients. Histological response of grade ≥ 1b was achieved in 13 patients (39%). Clavien-Dindo grade II postoperative complications occurred in three patients (9%). There were no treatment-related deaths. The median survival time and 1-, 3-, and 5-year overall survival rates of the 33 patients who underwent conversion surgery were 30.7 months and 78.8%, 36.3%, and 24.2%, respectively, and those of the 19 patients who did not undergo surgery were 12.5 months and 52.6%, 5.2%, and 0%, respectively., Conclusion: Conversion surgery is safe and may prolong survival for gastric cancer patients with PM who have responded to single i.p. PTX plus systemic chemotherapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aiming to fill a need for data regarding radiocesium transport via both branchflow and stemflow through forests impacted by radioactive fallout, this study examined the vertical variation of radiocesium flux from branchflow and stemflow through the canopies of young Japanese cedar (Cryptomeria japonica (L. f.) D. Don) and Japanese oak (Quercus serrata Murray) trees in the aftermath of the Fukushima Dai-ichi Nuclear Power Plant accident. In forested areas approximately 40 km northwest of the location of the Fukushima Dai-ichi accident, the 137 Cs concentration varied significantly among sampling periods and between the two forests, with the oak stand exhibiting higher 137 Cs concentrations and depositional fluxes than the cedar stand. Expressed per unit trunk basal area, the depositional flux of 137 Cs generated from the cedar and oak stands was 375 and 2810 Bq m -2  year -1 , respectively. Of this total, 71% and 48% originated from the cedar and oak canopy, respectively, while the remainder originated from the trunk. Accordingly, the origin of radiocesium was more balanced for the oak stand with almost half of the flux coming from the canopy (48%) and the other half from the trunk (52%). Only about a quarter (29%) of the radiocesium flux originated from the trunk in Japanese cedar. Results from this work provide needed data that can enable a more thorough conceptualization of radiocesium cycling in forests. Coupling these empirical results with a physically-based model would likely lead to better forest management and proactive strategies for rehabilitating radioactively-contaminated forests and reducing the exposure risk of radiation dose rate for those that utilize forest products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: This study was performed to verify the superiority of a new "non-tensioning method" for avoiding stricture of the cervical esophagogastric anastomosis by circular stapling compared with the conventional method., Methods: In total, 395 consecutive patients who underwent McKeown esophagectomy with gastric conduit (GC) reconstruction were reviewed. A 4 cm-wide GC was created and pulled up at the cervical site through the retrosternal route. The esophagogastrostomy site of the GC was planned as far caudally as possible on the greater curvature side. In the conventional technique, the stapler was fired while pulling the GC to avoid tissue slack. In the non-tensioning technique, the stapler was fired through the natural thickness of the stomach wall. The length of the blind end was changed from 4 to 2 cm in the non-tensioning technique. Anastomotic leakage and stricture formation were compared between the two techniques, and adjustment was performed using propensity score matching., Results: The conventional group comprised 315 patients, and the non-tensioning group comprised 80 patients. Anastomotic leakage occurred in 22 (7%) and 2 (2.5%) patients, respectively (P = 0.134) [and in 9 (2.9%) and 2 (2.5%) patients, respectively, if leakage at the blind end was excluded]. Anastomotic stricture occurred in 92 (29.2%) and 3 (3.8%) patients, respectively (P < 0.001). The propensity score-matching analysis including 79 pairs of patients confirmed a lower stricture rate in the non-tensioning than conventional group (2.5% vs. 29.1%, P < 0.001)., Conclusions: The non-tensioning technique significantly reduced the incidence of anastomotic stricture compared with the conventional technique., (© 2022. The Society for Surgery of the Alimentary Tract.)

A 67-year-old man had left upper lung cancer with invasion into the descending aorta. He underwent pre-emptive thoracic endovascular aortic repair using a Valiant Navion followed by left lung upper lobectomy with resection of the aortic wall. Because of continuous bleeding, he underwent re-thoracotomy. Since the surgically resected aortic wall was largely cleaved, bleeding around the stent-graft that herniated into the left pleural cavity was observed. Re-thoracic endovascular aortic repair using a GORE TAG was immediately performed to prevent further stent-graft herniation and impending lethal haemorrhage. It may be necessary to consider reinforcement of the resected aortic wall to prevent thoracic endovascular aortic repair-related complications., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objective: The purpose of the present study was to determine the most appropriate timing for thoracic endovascular aortic repair (TEVAR) of type B aortic dissection (TBAD) in terms of remodeling of the aorta., Methods: A total of 41 patients who had undergone TEVAR for the treatment of aortic dissection were included in the present study. The patients were divided into two groups: those who had undergone TEVAR in the acute or subacute phase (group A) and those who had undergone TEVAR in the chronic phase (group B). The indications for TEVAR as the treatment of TBAD were the presence of aortic rupture or malperfusion of the aortic branches, a maximum aortic diameter of ≥40 mm on the initial diagnostic computed tomography scan, and/or expansion of the aorta of ≥5 mm within 3 months for acute and subacute TBAD. The indication was a maximum aortic diameter of ≥50 mm or expansion of the aorta of ≥5 mm within 1 year for chronic TBAD. The diameters of the aorta, true lumen, and false lumen were measured at the level of the most dilated part of the descending aorta (level M) and at the diaphragm (level D) on the computed tomography scan obtained before TEVAR and at the 2-year follow-up examination., Results: The median interval between TEVAR and the onset of TBAD was 0.2 month (interquartile range, 0.03-0.7 month) in group A (n = 21) and 32 months (interquartile range, 4.7-35.2 months) in group B (n = 20). Except for the aortic diameter at level D in group B, favorable remodeling was obtained at both levels in both groups. The diameter change ratio of the aorta at level D was significantly greater in group A than in group B (P = .02). Receiver operating characteristic curve analysis of the interval for a significant decrease in the aortic diameter at level D yielded 4.2 months as the optimal threshold for performing TEVAR (area under the curve, 0.859; 95% confidence interval, 0.7-1.0)., Conclusions: TEVAR for TBAD will result in favorable outcomes, irrespective of the timing of the procedure. However, it might be more effective to perform TEVAR within 4.2 months of the onset of TBAD, provided that the TEVAR procedure can be performed safely., (Copyright © 2021. Published by Elsevier Inc.)

Background: To report our findings on quality of life (QoL) in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC)., Methods: Patients with HER2-negative MBC were randomly assigned to three different doses of q3w nab-PTX (SD 260 mg/m 2 vs. MD: 220 mg/m 2 vs. LD 180 mg/m 2 ). QoL was assessed at baseline and during the second, fourth and sixth courses of treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Cancer Fatigue Scale (CFS) and EuroQol 5-Dimension (EQ-5D). Comparisons were performed with mixed-model repeated measures (MMRM)., Results: A total of 141 patients were enrolled in the parent study, and 136 (96%) (44, 45 and 47 in the SD, MD, and LD groups) were included in the analysis. MMRM analysis showed that the difference from the baseline FACT-Taxane trial outcome index at MD and LD were significantly higher than that at SD (MD vs. SD P < 0.001, LD vs. SD P < 0.001). Differences from baseline for FACT-Taxane total, physical and emotional well-being, and taxane subscale scores at MD and LD were also higher than at SD. The difference from baseline for the CFS score at LD was lower than at SD (P = 0.013) and those for EQ-5D utility scores at MD and LD were higher than at SD (MD vs. SD P = 0.011, LD vs. SD P < 0.001)., Conclusion: QoL of patients treated with 220 or 180 mg/m 2 of q3w nab-PTX was significantly better than that of patients treated with 260 mg/m 2 ., Trial Registration: The protocol was registered at the website of the University Hospital Medical Information Network (UMIN), Japan (protocol ID: UMIN000015516), on 01/11/2014. Details are available at the following address: https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000017916., (© 2021. The Japanese Breast Cancer Society.)