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Abstract Xenon dual-phase time projections chambers (TPCs) have proven to be a successful technology in studying physical phenomena that require low-background conditions. With $$40\,\textrm{t}$$ 40 t of liquid xenon (LXe) in the TPC baseline design, DARWIN will have a high sensitivity for the detection of particle dark matter, neutrinoless double beta decay ( $$0\upnu \upbeta \upbeta $$ 0 ν β β ), and axion-like particles (ALPs). Although cosmic muons are a source of background that cannot be entirely eliminated, they may be greatly diminished by placing the detector deep underground. In this study, we used Monte Carlo simulations to model the cosmogenic background expected for the DARWIN observatory at four underground laboratories: Laboratori Nazionali del Gran Sasso (LNGS), Sanford Underground Research Facility (SURF), Laboratoire Souterrain de Modane (LSM) and SNOLAB. We present here the results of simulations performed to determine the production rate of $${}^{137}$$ 137 Xe, the most crucial isotope in the search for $$0\upnu \upbeta \upbeta $$ 0 ν β β of $${}^{136}$$ 136 Xe. Additionally, we explore the contribution that other muon-induced spallation products, such as other unstable xenon isotopes and tritium, may have on the cosmogenic background.

The plasma current start-up experiment is conducted through electron cyclotron (EC) heating in the QUEST spherical tokamak. During the EC heating, the application of a toroidal electric field in the opposite direction to the plasma current effectively inhibits the growth of energetic electrons. Observations show rapid increases in plasma current and hard x-ray count immediately following the cancellation of the retarding electric field. When a compact tokamak configuration maintains equilibrium on the high field side, along with the retarding field, it leads to effective bulk electron heating. This heating achieved an electron temperature of T _e ≈ 1 keV at electron density n _e > 1.0 × 10 ^18 m ^−3 . Ray tracing of the EC wave verifies that more power absorption into plasma through a single-pass occurs around the second resonance layer with higher values of electron density and temperature.

Background: Although pulmonary metastasectomy is a commonly-performed procedure, data are lacking on the feasibility and oncological efficacy of removal of pulmonary metastases from pancreatic cancer. In this study, we retrospectively compared features of pulmonary metastases from pancreatic cancer versus colorectal cancer (CRC, patients with CRC being common candidates for pulmonary metastasectomy) and outcomes of removing such metastases, with our aim being to identify specific features of the former., Methods: Data on removal of 182 pulmonary metastases (29 from pancreatic and 153 from CRC) performed from January 2013 to April 2024 were included in this analysis. Radio-pathological findings were compared between these groups. The study cohort comprised 139 pulmonary metastasectomies in 119 patients (24 with pancreatic cancer and 95 with CRC) in whom R0 resection was achieved and follow-up data were available., Results: Atypical radiological findings of pulmonary metastases, including polygonal-shape (P < 0.001), spiculae (P < 0.001), air bronchogram (P = 0.012), peripheral ground-glass opacities (P < 0.001), and pleural tags (P < 0.001) were present more frequently in metastases from pancreatic cancer than from CRC. Furthermore, pleural lavage cytology was more frequently positive in pulmonary metastases from pancreatic cancer than in those from CRC (P < 0.001). Disease-free survival was significantly shorter after the removal of metastases from pancreatic than from CRC (P < 0.001)., Conclusions: Some pulmonary metastases from pancreatic cancer have atypical radiological features. Surgical interventions for these may enable diagnosis. The prognosis is significantly poorer after removing metastases from pancreatic cancer than from CRC. The therapeutic significance of our findings requires further investigation., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Surrogate markers of minimal residual disease primarily include cell-free tumor DNA and circulating tumor cells. Cell-free tumor DNA might aid precise decision-making regarding who should receive adjuvant chemotherapy. However, there are no relevant reports on circulating tumor cells. Therefore, we aimed to verify whether perioperative clustered circulating tumour cells identification is a predictor of therapeutic efficacy in non-small cell lung cancer adjuvant chemotherapy., Methods: Circulating tumor cells were diagnosed under light microscopy using a size selection method in 128 patients with clinical stage I/II non-small cell lung cancer around surgery. The main endpoint was recurrence-free survival, and the effect of adjuvant chemotherapy was verified in both groups based on perioperative clustered circulating tumor cell identification., Results: In total, 49 and 79 patients were included in the clustered circulating tumor cell-positive and clustered circulating tumor cell-negative patient groups, respectively. In the clustered circulating tumor cell-positive patient group, adjuvant chemotherapy was performed in 18 patients (2-year recurrence-free survival rate, 71.8%). However, the 2-year recurrence-free survival rate was 36.3% in 31 patients who did not receive adjuvant chemotherapy (P < .01). In the clustered circulating tumor cell-negative patient group, adjuvant chemotherapy was provided in 11 patients (2-year recurrence-free survival rate, 90.9%). However, 68 patients did not receive adjuvant chemotherapy (2-year recurrence-free survival rate, 94.9%) (not significant)., Conclusions: In surgical cases of clinical stage I/II non-small cell lung cancer, patients with perioperative clustered circulating tumor cells had a poor prognosis, but adjuvant chemotherapy improved their prognosis., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Aims: To test the efficacy of artificial intelligence (AI)-assisted Ki-67 digital image analysis in invasive breast carcinoma (IBC) with quantitative assessment of AI model performance., Methods and Results: This study used 494 cases of Ki-67 slide images of IBC core needle biopsies. The methods were divided into two steps: (i) construction of a deep-learning model (DL); and (ii) DL implementation for Ki-67 analysis. First, a DL tissue classifier model (DL-TC) and a DL nuclear detection model (DL-ND) were constructed using HALO AI DenseNet V2 algorithm with 31,924 annotations in 300 Ki-67 digital slide images. Whether the class predicted by DL-TC in the test set was correct compared with the annotation of ground truth at the pixel level was evaluated. Second, DL-TC- and DL-ND-assisted digital image analysis (DL-DIA) was performed in the other 194 luminal-type cases and correlations with manual counting and clinical outcome were investigated to confirm the accuracy and prognostic potential of DL-DIA. The performance of DL-TC was excellent and invasive carcinoma nests were well segmented from other elements (average precision: 0.851; recall: 0.878; F1-score: 0.858). Ki-67 index data and the number of nuclei from DL-DIA were positively correlated with data from manual counting (ρ = 0.961, and 0.928, respectively). High Ki-67 index (cutoff 20%) cases showed significantly worse recurrence-free survival and breast cancer-specific survival (P = 0.024, and 0.032, respectively)., Conclusion: The performances of DL-TC and DL-ND were excellent. DL-DIA demonstrated a high degree of concordance with manual counting of Ki-67 and the results of this approach have prognostic potential., (© 2024 John Wiley & Sons Ltd.)

Dravet syndrome (DS) is characterized by recurrent convulsive seizures, including status epilepticus, and intellectual disability as a comorbidity. Seizures associated with DS are commonly resistant to antiseizure medications. Typical features of DS are recurrent episodes of status epilepticus, the presence of genetic mutations, and no abnormal magnetic resonance imaging (MRI) findings. Here, we report a rare case of DS in a 14-year-old girl who was negative for genetic mutations, had experienced status epilepticus only once, and had abnormal findings on brain MRI. Although our patient's case features are atypical of DS, they do not contradict the diagnostic criteria. Despite the difficulty in diagnosing DS because of the negative genetic testing results, we started our patient on fenfluramine (FFA). Long-term treatment with low-dose FFA effectively controlled our patient's seizures and resulted in cognitive and functional improvements., Competing Interests: 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., (© 2024 The Author(s).)

Background: The combination of laparoscopic and endoscopic approaches to neoplasia with a non-exposure technique (CLEAN-NET) is a laparoscopic and endoscopic cooperative surgery (LECS). It combines laparoscopic gastric resection and endoscopic techniques for local resection of gastric tumors, such as gastrointestinal stromal tumors (GIST), with minimal surgical margins. A conventional CLEAN-NET surgical procedure is complex, requiring careful techniques to preserve the cardia, particularly in case of nearby lesions. We describe the case of a patient who underwent a modified CLEAN-NET approach with a semi-circular seromuscular layer incision surrounding the base of the tumor, different from a circular shape seromuscular layer in the conventional CLEAN-NET: around the tumor to preserve mucosal continuity, which acts as a barrier to avoid intraoperative tumor dissemination., Case Presentation: A 43-year-old woman was referred to our hospital because of a gastric submucosal tumor near the cardia, detected on medical examination. The patient was diagnosed with gastric GIST based on the results of endoscopic ultrasound-guided fine-needle aspiration. Modified CLEAN-NET was performed with a semicircular incision of the seromuscular layer on the opposite side of the cardia, making the surgical procedure simple and minimizing partial resection of the gastric wall, including the tumor, while preserving the cardia. The operative time was 147 min, preoperative blood loss volume was 3 mL, and postoperative hospital stay was 9 days. The resected specimen revealed a minimal resection of the gastric wall, including the tumor. The cardia and gastric nerves were preserved, and the postoperative food intake was good., Conclusions: The modified CLEAN-NET with semicircular seromuscular layer dissection is a simple and reliable surgical procedure for GIST near the cardia., (© 2024. The Author(s).)

Background/aim: The prognostic impact of adjuvant cytotoxic chemotherapy for patients with resectable locally advanced non-small cell lung cancer (NSCLC) who underwent surgery after neoadjuvant chemotherapy remains unclear., Patients and Methods: A retrospective chart review was performed to identify patients who underwent surgery following neoadjuvant therapy for clinical T3N0 or N1-N2 resectable NSCLC between 2011 and 2016 at our hospital. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazard model., Results: Thirty-eight patients were identified. The median recurrence-free survival (RFS) was 50.6 months and overall survival (OS) was 75.2 months. Patients who had undergone adjuvant chemotherapy were not associated with a favorable RFS (hazard ratio=1.01, p=0.98) or OS (hazard ratio=0.72, p=0.55), as compared with those who had not. However, subgroup analysis revealed that hazard ratio based on RFS and OS varied greatly between subgroups, suggesting that selected patients might benefit from adjuvant therapy, while others might be harmed by it. For example, in surgical-pathological stage III disease, adjuvant therapy showed a favorable RFS (HR=0.22, 95%CI=0.02-2.57, p=0.23) and OS (HR=0.36, 95%CI=0.03-4.01, p=0.40). Conversely, in surgical-pathological stage 0-II disease, adjuvant therapy showed an unfavorable RFS (HR=1.40, 95%CI=0.49-3.96, p=0.53) and OS (HR=0.95, 95%CI=0.29-3.12, p=0.93)., Conclusion: Regardless of the negative findings in our overall patient cohort, our results may be beneficial in identifying patients who may likely benefit from adjuvant therapy. This contribution could assist the planning of large-scale prospective studies., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Rationale: Small bowel volvulus (SBV) is a rare cause of acute abdominal pain in adults, which requires surgical intervention to prevent small bowel necrosis. Primary SBV is rare, and its preoperative diagnosis is challenging. This report describes a case of primary SBV diagnosed preoperatively and treated laparoscopically., Patient Concerns: A 56-year-old man presented complaining of sudden-onset abdominal pain of 3-hour duration. Physical examination revealed tenderness in periumbilical and upper abdominal regions with no signs of peritonitis., Diagnosis: Contrast-enhanced computed tomography revealed a 360°-clockwise rotation of the small intestine when viewed caudally at the mesenteric base. At this region, the superior mesenteric vein was interrupted. Although no dilation of the small intestine was observed, increased density in the mesentery of the affected area was observed. Minimal ascites was observed in the pelvic cavity. No evidence of congenital or secondary SBV was observed, supporting the diagnosis of primary SBV., Interventions: Laparoscopic detorsion of the SBV was performed approximately 6 hours after the onset of symptoms. No signs of bowel necrosis were observed, and the procedure was concluded after releasing the torsion., Outcomes: Severe abdominal pain disappeared immediately after surgery. The postoperative course was uneventful, and the patient was discharged on the 8th postoperative day., Lessons: This case highlights the importance of preoperatively diagnosing SBV, which enables early laparoscopic devolvulation without bowel resection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

It is critical to understand molecular ordering processes in small-molecule organic semiconductor (OSC) films in optimizing electronic device applications, although it is difficult to observe and investigate the ordering characteristics at a mesoscopic or device scale. Here, we report that friction force microscopy (FFM) allows visualizing the ordering transformation process from a thermodynamically metastable phase to a stable phase at a mesoscopic scale. We utilized 2-octyl-benzothieno[3,2- b ]naphtho[2,3- b ]thiophene (2-C8-BTNT) as a typical highly layered-crystalline OSC. We found that the friction force between an AFM tip and spin-coated OSC films significantly depends on whether local film states are in metastable monolayer phase or stable bilayer-type herringbone (b-LHB) phase that exhibits high carrier mobility. The formation of the stable b-LHB phase leads to lower friction than the metastable monolayer phase, clearly visualizing the molecular order. Force map (Fmap) analysis indicates that the lower friction in the b-LHB phase should be associated with the reduction of interfacial adhesion force. Notably, the observed results demonstrate that the spin-coated thin film changes from continuous film with the monolayer phase to rugged microcrystal grains with the b-LHB phase when left at ambient conditions. By contrast, an appropriate post-thermal annealing process facilitates the phase transformation without inducing such morphological changes. The technique provides a unique and effective tool for revealing the relationship between processing conditions and device performance in polycrystalline OSC films.

Rationale: The mesodiverticular band (MDB) of a Meckel's diverticulum (MD) is a rare, yet notable etiology of small bowel obstruction (SBO) in adults. Due to the nonspecific symptoms and challenging diagnosis thereof, preoperative clinical suspicion and strategic management are crucial for achieving optimal outcomes. Therefore, we presented a case in which laparoscopic surgery was strategically performed to alleviate ileus, due to a preoperative diagnosis of SBO, suspected to be secondary to an MD with a concomitant MDB., Patient Concerns: A 32-year-old male patient presented with a half-day's duration of epigastric pain, abdominal distension, and tenderness, resulting in the working diagnosis of SBO., Diagnoses: Initial non-contrast computed tomography (CT) revealed SBO without signs of strangulation, postulated to be caused by an MD and concomitant MDB, resulting in conservative management. The symptoms persisted, necessitating contrast-enhanced CT. However, the dilated bowel loop suggestive of an MD that had been observed on non-contrast CT could not be confirmed on contrast-enhanced CT., Interventions: Decompression therapy using a long tube provided minimal relief, prompting laparoscopic surgery on the 5th day post-admission for diagnostic and therapeutic purposes., Outcomes: An MD resection effectively relieved the SBO. The histopathological analysis revealed a true diverticulum with ectopic pancreatic tissue, confirming the diagnosis of an MD. At the band site, vascular and neural structures were encased in a sheath, consistent with the remnants of the vitelline duct mesentery; and histopathologically diagnosed as an MDB. The postoperative course was uneventful, and the patient was discharged on the 9th day, postoperatively., Lessons: Decompression therapy and strategic laparoscopic surgery based on the preoperative working diagnosis of SBO yielded favorable outcomes, highlighting the importance of the early clinical suspicion of an MD and a concomitant MDB, as the etiology of SBO. The imaging variability and rarity of an MD in adults emphasizes the need for a heightened awareness and an accurate diagnosis for optimal management. Early intervention should be deliberated for patients with suspected intestinal ischemia. However, this case accentuates the clinical implications of strategic planning and employing minimally invasive techniques in the management of an MD-related SBO in adults., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

With increasing global life expectancy, the significance of geriatric assessment parameters has increased. Sarcopenia is a crucial assessment parameter and is defined as the age-related loss of muscle mass and strength. Sarcopenia is widely acknowledged as a risk factor for postoperative complications in diverse advanced malignancies and has a detrimental effect on the long-term prognosis. While most studies have primarily concentrated on the correlation between sarcopenia and advanced cancer, more recent investigations have focused on the relationship between sarcopenia and early-stage cancer. Endoscopic submucosal dissection (ESD), which is less invasive than surgical intervention, is extensively employed in the management of early-stage cancer, although it is associated with complications such as bleeding and perforation. In recent years, several reports have revealed the adverse consequences of sarcopenia in patients with early-stage cancer undergoing ESD. This literature review briefly summarizes the recent studies on the association between sarcopenia and ESD.

Bee pollen is an apicultural product collected by honeybees from flower stamens and used as a functional food worldwide. In the present study, we aim to elucidate the functions of Australian bee pollen. Australian bee pollen extracts and their main components were tested for catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAOB) inhibitory activities. These enzymes are key neurotransmitters involved in Parkinson's disease and depression. Myricetin (5), tricetin (6), and luteolin (7) exhibited high COMT inhibitory activities (half maximal inhibitory concentration [IC50] = 23.3, 13.8, and 47.4 µM, respectively). In contrast, 5, 7, and annulatin (8) exhibited MAOB inhibitory activities (IC50 = 89.7, 32.8, and 153 µM, respectively). Quantitative analysis via high-performance liquid chromatography revealed that 5 was abundant in Australian bee pollen extracts. Our findings suggest that 5 contributes to the COMT and MAOB inhibitory activities of Australian bee pollen., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Some rodlike organic molecules exhibit exceptionally high layered crystallinity when composed of a link between π-conjugated backbone (head) and alkyl chain (tail). These molecules are aligned side-by-side unidirectionally to form self-organized polar monomolecular layers, providing promising 2D materials and devices. However, their interlayer stacking arrangements have never been tunable, preventing the unidirectional arrangements of molecules in whole crystals. Here, it is demonstrated that polar/antipolar interlayer stacking can be systematically controlled by the alkyl carbon number n, when the molecules are designed to involve effectively weakened head-to-head affinity. They exhibit remarkable odd-even effect in the interlayer stacking: alternating head-to-head and tail-to-tail (antipolar) arrangement in odd-n crystals, and uniform head-to-tail (polar) arrangement in even-n crystals. The films show excellent field-effect transistor characteristics presenting unique polar/antipolar dependence and considerably improved subthreshold swing in the polar films. Additionally, the polar films present enhanced second-order nonlinear optical response along normal to the film plane. These findings are key for creating polarity-controlled optoelectronic materials and devices., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Gastritis cystica profunda (GCP), commonly observed in remnant gastric anastomosis, is associated with developing gastric cancer., Case: This case report describes a patient with GCP in a previously unoperated stomach that mimicked a pyloric submucosal tumor and caused anorexia, which is rare in clinical practice., Patient Concerns: A 72-year-old woman presented with loss of appetite and weight., Diagnoses: Gastroscopy detected a 20 mm diameter submucosal tumor near the pylorus. Computed tomography and magnetic resonance imaging identified a cystic lesion, unlike a usual submucosal tumor in the stomach. The diagnosis was difficult, even with endoscopic ultrasound-guided fine-needle aspiration., Interventions: Surgery was performed for diagnosis and treatment. The lesion was resected using a submucosal dissection technique after an incision of the gastric wall during open laparotomy. Histopathological examination confirmed the diagnosis of GCP and revealed no dysplasia or cancer., Outcomes: Anorexia resolved after the surgery. Residual or recurrent lesions were not detected during follow-up examinations performed 1 year after surgery., Lessons: GCP occurring in a previously unoperated stomach as a macroscopic lesion like a submucosal tumor causing some symptoms is rare. GCP is associated with a risk of developing cancer. Therefore, careful evaluation and management during treatment are required., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Xeroderma pigmentosum (XP) is an extremely rare and severe form of photosensitivity. It is classified into types A-G or V according to the gene responsible for the disease. The progression and severity of symptoms vary depending on the type. Although dysphagia caused by decreased swallowing function and dental malposition due to stenosis of the dentition in the facial and oral regions is common, it has not been reported in detail. We report three cases of type A XP, in which central and peripheral neurological symptoms appeared early on and progressed rapidly. We describe the oral function of these patients, focusing on the swallowing function and dentition malposition., Case Presentation: Two males (27 and 25 years old) and one female (28 years old) presented with diverse neurological symptoms. We focused on the relationship between the changes in swallowing and oral functions and conditions due to decline in physical function. Some effects were observed by addressing the decline in swallowing and oral functions. In particular, a dental approach to manage the narrowing of the dentition, which was observed in all three patients, improved the swallowing and oral functions and maintained the current status of these functions., Conclusions: In type A XP, early decline in oral and swallowing functions is caused by the early decline in physical function, and it is necessary to monitor the condition at an early stage., (© 2024. The Author(s).)

Purpose: Tegafur-uracil (UFT) is the standard postoperative adjuvant therapy for stage IB lung adenocarcinoma (LUAD) in Japan. This study aimed to determine whether UFT is effective in stage IB LUAD with and without epidermal growth factor receptor (EGFR) mutations., Methods: This retrospective study included 169 patients with stage IB LUAD who underwent complete resection at our department between 2010 and 2021. We investigated the clinicopathological and prognostic impact of EGFR mutations as well as the postoperative use of UFT., Results: EGFR mutation-positive cases tended to show a higher cumulative recurrence rate than EGFR mutation-negative cases (p = 0.081), while overall survival was comparable between the groups (p = 0.238). In the entire cohort, UFT administration was not an independent prognostic factor in the multivariate regression analysis (p = 0.112). According to a stratification analysis, UFT administration was independently associated with favorable overall survival (p = 0.031) in EGFR mutation-negative cases, while it was not associated with recurrence-free survival (p = 0.991) or overall survival (p = 0.398) in EGFR mutation-positive cases., Conclusion: UFT administration can improve the prognosis of EGFR mutation-negative LUAD but not EGFR mutation-positive LUAD. Thus, clinical trials of adjuvant-targeted therapy for EGFR mutation-positive stage IB LUAD should also be conducted in Japan.

Introduction: This case report describes a patient who underwent laparoscopic resection of the mucocele of the appendix secondary to endometriosis, a rarity in clinical practice., Patient Concerns: The patient was a 38-year-old woman with a history of endometriosis and an ovarian cyst who sought medical advice with a chief complaint of mild right lower abdominal pain., Diagnoses: Computed tomography and ultrasonography of the abdomen revealed a cystic lesion at the distal end of the appendix without definitive findings of malignancy. Colonoscopy revealed a submucosal tumor-like elevation at the appendiceal orifice. Appendiceal mucocele was suspected preoperatively., Interventions: The lesion was resected laparoscopically. Secondary ileocecal resection with lymphadenectomy was possible if the resected specimen was pathologically diagnosed as a malignant tumor with the risk of lymph node metastasis., Outcomes: The resected specimen was pathologically diagnosed as an appendiceal mucocele secondary to endometriosis; therefore, additional surgery was avoided., Conclusion: Although appendiceal mucoceles secondary to endometriosis are rare, laparoscopic surgery in which only the lesion was resected is a useful strategy for the treatment and pathological diagnosis of appendiceal mucoceles without findings of malignancy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Production of D-amino acids (D-AAs) on a large-scale enables to provide precursors of peptide therapeutics. In this study, we designed a novel L-amino acid oxidase, HTAncLAAO2, by ancestral sequence reconstruction, exhibiting high thermostability and long-term stability. The crystal structure of HTAncLAAO2 was determined at 2.2 Å by X-ray crystallography, revealing that the enzyme has an octameric form like a "ninja-star" feature. Enzymatic property analysis demonstrated that HTAncLAAO2 exhibits three-order larger k cat /K m values towards four L-AAs (L-Phe, L-Leu, L-Met, and L-Ile) than that of L-Trp. Through screening the variants, we obtained the HTAncLAAO2(W220A) variant, which shows a > 6-fold increase in k cat value toward L-Trp compared to the original enzyme. This variant applies to synthesizing enantio-pure D-Trp derivatives from L- or rac-forms at a preparative scale. Given its excellent properties, HTAncLAAO2 would be a starting point for designing novel oxidases with high activity toward various amines and AAs., (© 2023. Springer Nature Limited.)

Vasculitis is a systemic autoimmune disease characterized by leukocyte infiltration into blood vessels. Various microorganisms have been associated with the pathogenesis of vasculitis; however, the causal microbial agents and underlying mechanisms are not fully understood, possibly because of the technical limitations of pathogen detection. In the present study, we characterized the microbiome profile of patients with cutaneous vasculitis using comprehensive metagenome shotgun sequencing. We found that the abundance of the SEN virus was increased in the affected skin and serum of patients with vasculitis compared to healthy donors. In particular, the abundance of SEN virus reads was increased in the sera of patients with cutaneous arteritis. Among the bacteria identified, Corynebacteriales was the most differentially associated with vasculitis. Linear discriminant analysis effect size also indicated differences in the microbial taxa between patients with vasculitis and healthy donors. These findings demonstrate that vasculitis is associated with considerable alteration of the microbiome in the blood and skin and suggest a role for the infectious trigger in vasculitis., (© 2023. Springer Nature Limited.)

Resin components, such as methyl methacrylate (MMA) can cause allergic contact dermatitis (ACD). Allergic reactions to resin are usually delayed. Only a few studies have reported dental resin allergy with acute symptoms. Here, a case of ACD with acute facial swelling after dental treatment using resin material is reported. A 55-year-old woman with a history of periungual inflammation when using gel nail polish had repeated episodes of facial swelling after dental treatment with resin material. The resin temporary crown was removed, and symptoms were alleviated with antihistamines and corticosteroids. With the suspicion of resin allergy, skin tests were performed. Patch testing revealed positive reactions to self-adhesive resin cement (primer and polymerized), self-curing acrylic resin (liquid and polymerized), 2-hydroxyethyl methacrylate (2-HEMA), and ethylene glycol dimethacrylate (EGDMA), whereas the prick test was negative for all allergens. Complement C4 and C1 inhibitor activity were reference values in the tests for hereditary angioedema. Based on these findings, the patient was diagnosed with ACD to 2-HEMA and EGDMA. Since diagnosis, no similar symptoms have been observed in subsequent dental treatment with non-resin materials. The use of dental resin materials may cause ACD with an acute reaction. This report alerts dentists who routinely use resin materials.

We propose a framework to analyze the relationship between the movement features of a wheel gymnast around the mounting phase of Unit 2 of the vault event and execution (E-score) deductions from a machine-learning perspective. We first developed an automation system from a video of a wheel gymnast performing a tuck-front somersault to extract the four frames highlighting its Unit 2 performance of the vault event, such as take-off, pike-mount, the starting point of time on the wheel, and final position before the thrust. We implemented this automation using recurrent all-pairs field transforms (RAFT) and XMem, i.e., deep network architectures respectively for optical flow estimation and video object segmentation. We then used a markerless pose-estimation system called OpenPose to acquire the coordinates of the gymnast's body joints, such as shoulders, hips, and knees then calculate the joint angles at the extracted video frames. Finally, we constructed a regression model to estimate the E-score deductions during Unit 2 on the basis of the joint angles using an ensemble learning algorithm called Random Forests, with which we could automatically select a small number of features with the nonzero values of feature importances. By applying our framework of markerless motion analysis to videos of male wheel gymnasts performing the vault, we achieved precise estimation of the E-score deductions during Unit 2 with a determination coefficient of 0.79. We found the two movement features of particular importance for them to avoid significant deductions: time on the wheel and angles of knees at the pike-mount position. The selected features well reflected the maturity of the gymnast's skills related to the motions of riding the wheel, easily noticeable to the judges, and their branching conditions were almost consistent with the general vault regulations., Competing Interests: No: The authors have declared that no competing interests exist., (Copyright: © 2023 Kitajima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Calendula officinalis is a medicinal plant in the Asteraceae family, and it has a broad range of biological activities. In this study, we focused on the roots of C. officinalis, which have remarkable anti-inflammatory properties. By using a bioassay-guided fractionation approach, prenylated acetophenones 1 and 2-of which 1 was previously unknown-were isolated, and their structures were determined by spectroscopic analysis. Both compounds decreased lipopolysaccharide-stimulated NO production in J774.1 cells. This study could lead to the use of the Calendula roots as a natural source of inflammatory mediators., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: Lymphangioma is a relatively rare benign congenital malformation composed of dilated cystic lymphatic vessels; however, its occurrence in adults and manifestation as mediastinal lymphangioma are even rarer. In general, the incidence of mediastinal lymphangiomas has been reported to range from 0.01 to 4.5% of all mediastinal tumors. Mediastinal lymphangiomas tend to increase in size and can sometimes stretch the phrenic nerve that are present in the mediastinum, resulting in phrenic nerve palsy. Dynamic digital radiography (DDR) allows for quantitative evaluation over time and has recently been utilized in actual clinical practice. The distance between the apex of the lung and diaphragm can be measured, and the movement of the left and right lungs and diaphragm can be evaluated separately. In this report, we describe a case in which DDR demonstrated the improvement of phrenic nerve palsy., Case Presentation: A 32-year-old woman with no medical history and no smoking history reported dyspnea on exertion, and abnormalities were noted on chest X-ray. Close examinations revealed thymic, pericardial, bronchogenic, and teratoid cysts, and since they appeared to be growing in size, the patient was referred for surgery. Because the giant cyst prevented visualization of the thoracic cavity, puncture was performed for aspiration. The stretched phrenic nerve was identified in the giant cyst wall and was dissected to avoid damaging it. The cyst wall was detachable and excised without obvious mediastinal invasion. The patient had a good postoperative course and was discharged on postoperative day 5. Dynamic digital radiography on postoperative days 3 and 17 showed movement of the left diaphragm, with improvement over time., Conclusions: Mediastinal lymphangiomas tend to grow in size and can sometimes stretch the phrenic nerves that are present in the mediastinum, resulting in phrenic nerve palsy. Dynamic digital radiography (DDR) is a modality that can also be evaluated quantitatively and over time and can comprehensively determine improvement in transverse paralysis., (© 2023. The Author(s).)

The cartilage-conduction hearing aid (CC-HA) is a new hearing device that is suitable for use in patients with conductive hearing loss. It has been 5 years since the introduction of the CC-HA. Although the number of users has increased, the CC-HA is not yet widely known. This study examines the effects of CC-HA on patients with conductive hearing loss and investigates factors that affect the willingness to use the device by comparing purchasers and non-purchasers of CC-HA in patients with unilateral conductive hearing loss. Eight patients had bilateral conductive hearing loss, and 35 had unilateral conductive hearing loss. Each patient underwent sound field tests and speech audiometry, and the effects of the CC-HA were compared with those of conventional bone conduction hearing aids (BC-HA). In patients with bilateral conductive hearing loss, the CC-HA was non-inferior to BC-HA. The CC-HA improved the hearing thresholds and speech recognition in patients with unilateral conductive hearing loss. Moreover, in patients with unilateral conductive hearing loss, experiencing the effect of wearing the CC-HA under conditions such as putting noise in the better ear could affect patients' willingness to use the CC-HA.

Factors influencing oral problems, such as malocclusion and oral motor dysfunction, in patients with prolonged disorders of consciousness (DOC) remain unclear. This study aimed to clarify the relationship between oral problems and physical function, communication, respiration, and oral intake status, as well as related factors in patients with DOC receiving long-term care at home. A cross-sectional study was conducted in October 2018; 127 patients who developed DOC > 5 years ago were analyzed. The differences between patients with and without oral problems were examined, and a binomial logistic regression analysis was performed to examine factors associated with oral problems, with the presence of oral problems as the dependent variable, and age, the number of years since onset, drooling, oral intake status, and the presence of a family dentist as explanatory variables. A post hoc power analysis of the binomial logistic regression analysis for oral problems (odds ratio: 2.05, alpha value: 0.05, incidence of oral problems: 0.80, and total sample size: 127) demonstrated an observed power of 93.09%. Oral intake status ( p = 0.010) and the number of years since onset ( p = 0.046) were significantly related to oral problems. Preventive oral management and rehabilitation from the early stage after onset may be effective for oral problems in patients with DOC.

Mechanical properties of structural alloys, including Ni-based superalloy 718 (Alloy718), are degraded when hydrogen (H) is supplied: hydrogen embrittlement (HE). The presence of H notably deteriorates fatigue crack growth (FCG) property, which renders the growth rate much higher and shortens the lifetime of the components operating in the hydrogenating environment. Hence, the mechanisms behind such acceleration phenomenon in FCG should be understood comprehensively toward developing promising alloys resistant to hydrogen occlusion. In particular, Alloy718 has a meager resistance to HE, even regularly displaying superior mechanical and physical performances. Notwithstanding, the present study unveiled that the FCG acceleration by dissolved H in Alloy718 can be negligible. An abnormal deceleration of FCG can instead be pronounced by optimizing the metallurgical state, a hopeful prospect in Ni-based alloys applied to the hydrogenating environment., (© 2023. The Author(s).)

Pulmonary fibrosis is a process characterized by epithelial injury and fibroblast activation. It is also well recognized as a predisposition to lung cancer. Here, we present a protocol to establish an in vivo model to evaluate the dynamics of alveolar epithelial type 2 cells and lung cancer cells in the context of the lung fibrogenic microenvironment. Utilizing the cell transfer technique, we detail a basis for therapeutic approaches in pulmonary fibrosis and tools for precision medicine against lung cancer. For complete details on the use and execution of this protocol, please refer to Miyata et al. (2022). 1 ., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Calendula officinalis is commonly known as marigold and its flowers are used in herbal medicines, cosmetics, perfumes, dyes, pharmaceutical preparations, and food products. However, the utility of its leaves has not been studied in depth. The purpose of the present study was to identify the major compounds in C. officinalis leaves and to determine the inhibitory properties of the isolated compounds toward human catechol- O -methyltransferase (COMT), a key neurotransmitter involved in Parkinson's disease and depression. We isolated and identified ten compounds, including two phenylpropanoids and seven flavonoids, from C. officinalis leaf extracts, of which four flavonoids were identified from C. officinalis leaves for the first time. Eight compounds exhibited COMT inhibitory activities with IC 50 values of less than 100 μM. Our results indicate that compounds in C. officinalis leaves are potentially effective for preventing Parkinson's disease and depression. Thus, C. officinalis leaves may hold promise as dietary supplements.

Although immune checkpoint inhibitors (ICIs) are widely used to treat unresectable malignant tumors, they can cause undesirable side effects called immune-related adverse events, including neurological toxicities. Here, we describe a case of ICI-related peripheral neuropathy (irPN) with characteristic cerebrospinal fluid (CSF) findings. In addition to pleocytosis and increased protein levels, the present case showed increased levels of CSF soluble interleukin-2 receptor (sIL-2R), IL-6, and IL-10, suggesting activated T cell-related autoimmunity. We believe that CSF cytokines and sIL-2R could be novel biomarkers of irPN., Competing Interests: Declaration of Competing Interest The authors declare no financial or other conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting., Methods: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects., Results: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort., Conclusions: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objectives: Lung cancer with distant metastases is associated with a very poor prognosis, and epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Therefore, elucidation and inhibition of EMT signaling in lung cancer may be a new therapeutic strategy for improving the prognosis of patients. We constructed a high-throughput screening system for EMT inhibitors. Using this system, we aimed to identify compounds that indeed inhibit EMT., Materials and Methods: We generated a luciferase reporter cell line using A549 human lung cancer cells and E-cadherin or vimentin as EMT markers. EMT was induced by transforming growth factor β1 (TGF-β1), and candidate EMT inhibitors were screened from a library of 2,350 compounds. The selected compounds were further tested using secondary assays to verify the inhibition of EMT and invasive capacity of cells., Results: Values obtained by the assay were adjusted for the number of viable cells and scored by determining the difference between mean values of the positive and negative control groups. Four compounds were identified as novel candidate drugs. Among those, one (avagacestat) and two compounds (GDC-0879 and levothyroxine) improved the expression of E-cadherin and vimentin, respectively, in epithelial cells. GDC-0879 and levothyroxine also significantly inhibited the invasive capacity of cells., Conclusion: We systematically screened approved, investigational, and druggable compounds with inhibitory effects using a reporter assay, and identified candidate drugs for EMT inhibition., 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 © 2022 Elsevier B.V. All rights reserved.)

Pigmentary mosaicism of the Ito type, also known as hypomelanosis of Ito, is a neurocutaneous syndrome considered to be predominantly caused by somatic chromosomal mosaicism. However, a few monogenic causes of pigmentary mosaicism have been recently reported. Eleven unrelated individuals with pigmentary mosaicism (mostly hypopigmented skin) were recruited for this study. Skin punch biopsies of the probands and trio-based blood samples (from probands and both biological parents) were collected, and genomic DNA was extracted and analyzed by exome sequencing. In all patients, plausible monogenic causes were detected with somatic and germline variants identified in five and six patients, respectively. Among the somatic variants, four patients had MTOR variant (36%) and another had an RHOA variant. De novo germline variants in USP9X, TFE3, and KCNQ5 were detected in two, one, and one patients, respectively. A maternally inherited PHF6 variant was detected in one patient with hyperpigmented skin. Compound heterozygous GTF3C5 variants were highlighted as strong candidates in the remaining patient. Exome sequencing, using patients' blood and skin samples is highly recommended as the first choice for detecting causative genetic variants of pigmentary mosaicism., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The aim of this study was to analyse the long-term survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma., Methods: Using a multi-institutional database, we performed a retrospective chart review to identify all patients who had undergone complete resection of stage I-III EGFR-mutated lung adenocarcinoma at 11 acute care hospitals between 2009 and 2016 and had received first-line EGFR-TKI treatment for postoperative recurrence. Adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using Kaplan-Meier analysis. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS., Results: The study sample comprised 154 patients with a median age of 69. The total numbers of events were 101 for PFS and 60 for OS. The median PFS and OS were 26.1 and 55.4 months, respectively. In the multivariable analysis, EGFR ex 21 L858R mutation (HR: 1.71, 95% CI: 1.15-2.55) and shorter disease-free intervals (HR: 0.98, 95% CI: 0.96-0.99) were significantly associated with shorter PFS. Age (HR: 1.03, 95% CI: 1.00-1.07), smoking history (HR: 2.31, 95% CI: 1.35-3.94) and pathological N2 disease at the initial surgery (HR: 2.30, 95% CI: 1.32-4.00) were significantly associated with shorter OS., Conclusions: First-line EGFR-TKI treatment was generally associated with favourable survival outcomes in patients with postoperative recurrent EGFR-mutated lung adenocarcinoma. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter PFS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Adjuvant cisplatin‑vinorelbine is a standard therapy for stage II/III lung cancer. However, a poor survival rate of patients with lung cancer is attributed to vinorelbine resistance arising from ATP‑binding cassette (ABC) sub‑family B member 1 (ABCB1) and phosphorylated Fyn (p‑Fyn) overexpression. However, the underlying mechanisms remain unclear. NF‑E2‑related factor 2 (Nrf2) regulates the ABC family and activates the nuclear transport of Fyn. The present study evaluated the roles of the Nrf2/p‑Fyn/ABCB1 axis in vinorelbine‑resistant (VR) cells and clinical samples. To establish VR cells, H1299 cells were exposed to vinorelbine, and the intracellular reactive oxygen species (ROS) level in the H1299 cells was determined using a DCFH‑DA assay. The total and subcellular expression of Nrf2, ABCB1 and p‑Fyn in VR cells was evaluated. Immunofluorescence was used to detect the subcellular localization of p‑Fyn in VR cells. A cell viability assay was used to examine whether the sensitivity of VR cells to vinorelbine is dependent on Nrf2 activity. Immunohistochemistry was performed on 104 tissue samples from patients with lung cancer who underwent surgery followed by cisplatin‑vinorelbine treatment. The results revealed that persistent exposure to vinorelbine induced intracellular ROS formation in H1299 cells. p‑Fyn was localized in the nucleus, and ABCB1 and Nrf2 were overexpressed in VR cells. ABCB1 expression was dependent on Nrf2 downstream activation. The decreased expression of Nrf2 restored the sensitivity of VR cells to vinorelbine. In the surgical samples, Nrf2 and ABCB1 were associated with disease‑free survival, and p‑Fyn was associated with overall survival (P<0.05). On the whole, the present study demonstrates that Nrf2 upregulates ABCB1 and, accompanied by the nuclear accumulation of p‑Fyn, induces vinorelbine resistance. These findings may facilitate the development of drug resistance prevention strategies or new drug targets against non‑small cell lung cancer.

The patient was a 72-year-old man with a chief complaint of abdominal pain. We performed laparoscopic left hemicolectomy of the colon after descending colon cancer ileus stenting, and postoperative pathology was pT4aN0M0, pStage Ⅱb. In 1.5 years postoperatively, 2 liver metastases and 1 lymph node metastasis were found, and each was resected. Chemotherapy was initiated for multiple lung metastases. Genetic testing was positive for BRAF V600E mutation, and the patient received 8 mFOLFOXIRI plus bevacizumab therapy courses. After 15 5-FU plus LV plus bevacizumab courses, the patient had a brain infarction and lung metastasis reincreased. Chemotherapy was changed to encorafenib plus binimetinib plus cetuximab. On day 2, visual impairment was observed, and serous retinal detachment CTCAE Grade 2 was diagnosed. On day 7, the symptoms improved and one-step dose reduction was resumed. On day 2 of re-treatment, serous retinal detachment recurred and treatment was discontinued. On day 4 of re-treatment, the symptoms improved, another dose reduction was performed, and treatment was resumed. Since subjective MEK inhibitor-induced ocular symptoms are often minor, conducting an interview and early ophthalmologic diagnosis is recommended.

The solvothermal synthesis of SnO 2 porous spheres was optimized by varying the reactants, solvents, additives, reaction temperature and reaction time. The products of these trials were characterized by X-ray diffraction, electron microscopy and X-ray fluorescence spectroscopy. SnO 2 possessing a highly ordered spherical structure based on the aggregation of nanometer-sized primary particles was obtained using a simple one-pot solvothermal approach. These spheres were porous with a high specific surface area of more than 200 m 2 g -1 . The electrical conductivity of this material equaled or exceeded that of commercially available SnO 2 . SnO 2 -based spherical porous composites including various elements were easily synthesized by incorporating additional materials in the precursor solution., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A mesenchymal cell activation is a hallmark event of pulmonary fibrosis. Alveolar type 2 (AT2) cells are progenitor cells that maintain alveolar homeostasis, and their damage is assumed to be an initiating event for pulmonary fibrosis. However, the interaction between the lung fibrogenic microenvironment and AT2 cell dynamics remains to be elucidated. Here, we report a unique role of the lung fibrogenic microenvironment, where cell type-specific tissue reconstruction is achieved by exogenous cell transplantation. We found that in the lung fibrogenic microenvironment the AT2 cell pool was depleted, whereas mesenchymal cells could promote intact AT2 cell proliferation in vitro . Furthermore, exogenously transplanted AT2 cells formed alveolar colonies and ameliorated pulmonary fibrosis. Exogenous tumor cells formed tumor nests with relevant histological and transcriptional properties. Human primary cells were adaptable to this microenvironment, facilitating epithelial cell-targeted therapy in pulmonary fibrosis and the establishment of patient-derived xenografts for precision medicine in lung cancer., Competing Interests: The authors have no financial conflicts of interest., (© 2022 The Author(s).)

Purpose: After our group described the first remote-access thyroidectomy series in 2000, the procedure has been further developed. Although a thoracoscopic approach with a conventional open cervical incision for thyroid goiters with mediastinal extension has been performed at many institutions, remote-access thyroidectomy for cervicomediastinal goiters has not been established. We have performed combined thoracoscopic and axillary subcutaneous endoscopic thyroidectomies (axillo-thoracic endoscopic thyroidectomies). Here, we describe a novel technique for performing a remote-access thyroidectomy for a cervicomediastinal goiter (CMG)., Patients and Methods: The patients with CMGs who agreed to an axillo-thoracic endoscopic thyroidectomy at one of two hospitals in Japan underwent a remote-access thyroidectomy., Results: We performed the axillo-thoracic endoscopic right or left hemithyroidectomy successfully, but most of the patients did not require the thoracoscopic procedure. None of the patients had complications, and none was converted to an open thyroidectomy., Conclusions: Most thyroid goiters with substernal extension can be removed by the axillary approach, but some cases require a thoracoscopic approach. The novel approach described herein (axillo-thoracic endoscopic thyroidectomy) enables the safe excision of a CMG with high patient satisfaction for selected patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The thermostability of purple yam was investigated to be used as natural colorants. In addition, the inhibitory properties of purple yam and its isolated anthocyanins toward human catechol-O-methyltransferase (COMT), a key neurotransmitter involved in Parkinson's disease and depression, were also investigated. The thermostability of purple yam was higher than that of the reference samples (purple sweet potato and purple potato). Quantitative HPLC analysis revealed that alatanin A (2) contributed to the thermostability of purple yam. Methanol extracts of purple yam exhibited the highest COMT inhibitory activity of the tested samples. Alatanin D (1) showed the highest inhibitory activity of the anthocyanins in purple yam (IC50 19 µM). This study revealed the thermostability and COMT inhibitory activity of purple yam and may lead to its use not only as a thermostable natural source of colorants, but also for the prevention and treatment of Parkinson's disease and depression., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)