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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.

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.)

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.

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.)

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.

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.)

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.)

Background: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers., Methods: In the present study, to investigate the roles and regulation of p63 in salivary duct adenocarcinoma (SDC), human SDC cell line A253 was transfected with siRNA-p63 or treated with the HDAC inhibitors trichostatin A (TSA) and quisinostat (JNJ-26481585)., Results: In a DNA array, the knockdown of p63 markedly induced mRNAs of the tight junction (TJ) proteins cingulin (CGN) and zonula occuludin-3 (ZO-3). The knockdown of p63 resulted in the recruitment of the TJ proteins, the angulin-1/lipolysis-stimulated lipoprotein receptor (LSR), occludin (OCLN), CGN, and ZO-3 at the membranes, preventing cell proliferation, and leading to increased cell metabolism. Treatment with HDAC inhibitors downregulated the expression of p63, induced TJ structures, recruited the TJ proteins, increased the epithelial barrier function, and prevented cell proliferation and migration., Conclusions: p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways is, therefore, useful in therapy for p63-positive SDC cells.

Objectives: To clarify survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) as first-line treatment for postoperative recurrence., Methods: A retrospective chart review was performed to identify consecutive patients who received EGFR-TKIs as first-line treatment for postoperative recurrence of non-small-cell lung cancer (NSCLC) harbouring EGFR gene mutations at our institution between August 2002 and October 2020. Therapeutic response, adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using the Kaplan-Meier analysis. The Cox proportional hazards model was used for univariable and multivariable analyses., Results: Sixty-four patients were included in the study. The objective response and disease control rates were 53% and 92%, respectively. Grade 3 or greater adverse events were noted in 4 (6.3%) patients, including 1 patient (1.6%) of interstitial pneumonia. The median follow-up period was 28.5 months (range 3-202 months). The total number of events was 43 for PFS and 23 for OS, respectively. The median PFS was 18 months, and the median OS was 61 months after EGFR-TKI treatment. In multivariable analysis, osimertinib showed a tendency to prolong PFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.12-1.1; P = 0.071], whereas the micropapillary component was significantly associated with shorter OS (HR 2.1, 95% CI 1.02-6.9; P = 0.045)., Conclusions: EGFR-TKIs as first-line treatment appeared to be a reasonable treatment option in selected patients with postoperative recurrent EGFR-mutated NSCLC. Osimertinib and the micropapillary component may be prognostic factors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Abstract: No studies have evaluated the retinal sensitivity (RS) for diabetic macular edema (DME) patients with good vision. Therefore, this study aimed to determine the effectiveness of microperimetry in evaluating the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) treatment for DME patients with relatively good vision.Twenty-seven eyes of 27 patients (mean age, 61.3 ± 11.2 years) with DME and decimal best-corrected visual acuity (BCVA) ≥0.6 were studied. All patients received 3 consecutive monthly injections of intravitreal anti-VEGF agents. The BCVA, central subfield macular thickness (CMT), and RS were evaluated by microperimetry (MAIA) within the 10 degree of the foveal center. To determine significant differences between the values, we used paired t tests.Patients were evaluated at baseline and 4 weeks after the third injection. The BCVA improved significantly from 0.18 ± 0.06 logarithm of the minimum angle of resolution (logMAR) units to 0.13 ± 0.13 logMAR units (P = .002; paired t test). The CMT decreased significantly from 464.3 ± 91.8 μm to 393.4 ± 129.0 μm (P = .005), and the RS also improved significantly from 21.8 ± 3.1 dB to 24.1 ± 2.8 dB at 4 weeks after treatment (P = .006). Among the patients with a decimal BCVA of 0.7 or better at baseline, there was no significant improvement in the BCVA (P = .28). However, the CMT decreased significantly from 479.5 ± 79.1 μm to 394.0 ± 99.8 μm at 4 weeks after treatment (P = .007). The RS also improved significantly from 22.0 ± 2.4 dB to 24.0 ± 3.1 dB at 4 weeks after treatment (P = .004).Measuring RS by microperimetry is a good option for evaluating the effectiveness of anti-VEGF treatment for DME patients with a relatively good BCVA., Competing Interests: Conflicts of Interest and Funding: MS received financial support from Alcon Pharma and Bayer and lecture fees from Alcon Pharma, Kowa Pharma, Senjyu Pharma, Daiichi Yakuhin Sangyo, Bayer, and Wakamoto Pharma; HM and MK received financial support from Alcon Pharma and Bayer; RM, KK, and YW declare that they have no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Antifreeze proteins (AFPs) are proteins that protect cellular fluids and body fluids from freezing by inhibiting the nucleation and growth of ice crystals and preventing ice recrystallization, thereby contributing to the maintenance of life in living organisms. They exist in fish, insects, microorganisms, and fungi. However, the number of known AFPs is currently limited, and it is essential to construct a reliable dataset of AFPs and develop a bioinformatics tool to predict AFPs. In this work, we first collected AFPs sequences from UniProtKB considering the reliability of annotations and, based on these datasets, developed a prediction system using random forest. We achieved accuracies of 0.961 and 0.947 for non-redundant sequences with less than 90% and 30% identities and achieved the accuracy of 0.953 for representative sequences for each species. Using the ability of random forest, we identified the sequence features that contributed to the prediction. Some sequence features were common to AFPs from different species. These features include the Cys content, Ala-Ala content, Trp-Gly content, and the amino acids' distribution related to the disorder propensity. The computer program and the dataset developed in this work are available from the GitHub site: https://github.com/ryomiya/Prediction-and-analysis-of-antifreeze-proteins., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Published by Elsevier Ltd.)

Coronavirus disease 2019 (COVID-19) is raging worldwide. This potentially fatal infectious disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the complete mechanism of COVID-19 is not well understood. Therefore, we analyzed gene expression profiles of COVID-19 patients to identify disease-related genes through an innovative machine learning method that enables a data-driven strategy for gene selection from a data set with a small number of samples and many candidates. Principal-component-analysis-based unsupervised feature extraction (PCAUFE) was applied to the RNA expression profiles of 16 COVID-19 patients and 18 healthy control subjects. The results identified 123 genes as critical for COVID-19 progression from 60,683 candidate probes, including immune-related genes. The 123 genes were enriched in binding sites for transcription factors NFKB1 and RELA, which are involved in various biological phenomena such as immune response and cell survival: the primary mediator of canonical nuclear factor-kappa B (NF-κB) activity is the heterodimer RelA-p50. The genes were also enriched in histone modification H3K36me3, and they largely overlapped the target genes of NFKB1 and RELA. We found that the overlapping genes were downregulated in COVID-19 patients. These results suggest that canonical NF-κB activity was suppressed by H3K36me3 in COVID-19 patient blood., (© 2021. The Author(s).)

The airway epithelium of the human nasal mucosa acts as a physical barrier that protects against inhaled substances and pathogens via bicellular and tricellular tight junctions (bTJs and tTJs) including claudins, angulin-1/LSR and tricellulin. High mobility group box-1 (HMGB1) increased by TGF-β1 is involved in the induction of nasal inflammation and injury in patients with allergic rhinitis, chronic rhinosinusitis, and eosinophilic chronic rhinosinusitis. However, the detailed mechanisms by which this occurs remain unknown. In the present study, to investigate how HMGB1 affects the barrier of normal human nasal epithelial cells, 2D and 2.5D Matrigel culture of primary cultured human nasal epithelial cells were pretreated with TGF-β type I receptor kinase inhibitor EW-7197 before treatment with HMGB1. Knockdown of angulin-1/LSR downregulated the epithelial barrier. Treatment with EW-7197 decreased angulin-1/LSR and concentrated the expression at tTJs from bTJs and increased the epithelial barrier. Treatment with a binder to angulin-1/LSR angubindin-1 decreased angulin-1/LSR and the epithelial barrier. Treatment with HMGB1 decreased angulin-1/LSR and the epithelial barrier. In 2.5D Matrigel culture, treatment with HMGB1 induced permeability of FITC-dextran (FD-4) into the lumen. Pretreatment with EW-7197 prevented the effects of HMGB1. HMGB1 disrupted the angulin-1/LSR-dependent epithelial permeability barriers of HNECs via TGF-β signaling in HNECs.

Introduction and Importance: Immunocompromised patients are at high risk of unexpectedly serious infections caused by uncommon bacteria or fungi. We experienced a case of Cryptococcus neoformans-induced necrotizing fasciitis (NF) of the lower extremities. The progress so far has been reported by the urology department [1]. Moreover, after the NF had been treated, the patient developed immune reconstitution inflammatory syndrome (IRIS). We report from surgeon's view point., Case Presentation: A 51-year-old male renal transplant patient complained of pain in both lower extremities (LE). After the initial debridement, periodic acid-Schiff after diastase digestion (D-PAS) staining confirmed the diagnosis. No symptoms were seen in the lungs or cerebrospinal system. The patient was reluctant to undergo surgical treatment but several debridement improved patient's condition. After the LE wound healed, prednisolone was discontinued, then painful nodules appeared on both LE. Based on the negative culture results and the fact that the patient had been treated with flucytosine and fluconazole, we suspected that the nodules had been caused by IRIS., Clinical Discussion: It was difficult to diagnose Cryptococcus-induced NF and paradoxical IRIS. Cooperation from other specialists was essential., Conclusion: We think this patient needed earlier and more definitive debridement. Fortunately, we were able to save the patient's life and maintain his LE function. In immunocompromised patients, cryptococcus can be a pathogen. In addition, IRIS can occur during treatment. Management of IRIS is the capital point of sepsis management, careful anti-inflammatory drug control by specialists is required., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Although lymph node (LN) metastases are not uncommon in thymic carcinomas, preoperative LN evaluation, intraoperative lymph node dissection (LND) and postoperative outcomes remain unknown. The aim of this study was to elucidate the characteristics of and outcomes in patients with thymic carcinomas and thymic neuroendocrine carcinomas undergoing LND., Methods: A retrospective chart review was performed using our multi-institutional database to identify patients who underwent resection and LND for thymic carcinoma or thymic neuroendocrine carcinoma between 1991 and 2018. An enlarged mediastinal LN was defined as having a short-axis diameter >1 cm. We assessed survival outcomes using the Kaplan-Meier analysis., Results: N1-level LND was performed in 41 patients (54.6%), N2-level LND in 14 patients (18.7%) and both-level LND in 16 patients (21.3%). Pathological LN metastasis was detected in 20 patients (26.7%) among the 75 patients undergoing LND. There was a significant difference in the number of LN stations (P = 0.015) and metastasis factor (P = 0.0042) between pathologically LN-positive and pathologically LN-negative patients. The sensitivity of enlarged LNs on preoperative computed tomography was 18.2%. There was a tendency towards worse overall survival of pathologically N2-positive patients, although the difference was not statistically significant (P = 0.15)., Conclusions: Preoperative CT appears to play a limited role in detecting pathological LN metastases. Our findings suggest that the significance of N1- and N2-level LND should be evaluated in prospective studies to optimize the postoperative management of patients with thymic carcinomas and neuroendocrine carcinomas., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Pyrazines are typically formed from amino acids and sugars in chemical reactions such as the Maillard reaction. In this study, we demonstrate that 3-ethyl-2,5-dimethylpyrazine can be produced from L-Thr by a simple bacterial operon. We conclude that EDMP is synthesized chemoenzymatically from L-Thr via the condensation reaction of two molecules of aminoacetone and one molecule of acetaldehyde. Aminoacetone is supplied by L-threonine 3-dehydrogenase using L-Thr as a substrate via 2-amino-3-ketobutyrate. Acetaldehyde is supplied by 2-amino-3-ketobutyrate CoA ligase bearing threonine aldolase activity from L-Thr when CoA was at low concentrations. Considering the rate of EDMP production, the reaction intermediate is stable for a certain time, and moderate reaction temperature is important for the synthesis of EDMP. When the precursor was supplied from L-Thr by these enzymes, the yield of EDMP was increased up to 20.2%. Furthermore, we demonstrate that this reaction is useful for synthesizing various alkylpyrazines., (© 2021. The Author(s).)

Vasculitis is an autoimmune disease characterized by the infiltration of leukocytes in blood vessels. An increasing number of studies on human and animal models have implicated various microorganisms in the pathogenesis of vasculitis. Previous studies have shown the presence of infectious agents, including viruses, bacteria, and fungi, in diseased vessels. However, despite continued research, the link between infection and vasculitis is not fully understood, possibly owing to the lack of appropriate animal models that mirror human disease and the technical limitations of pathogen detection in blood vessels. Among the pathogen-induced animal models, Candida albicans water-soluble fraction (CAWS)-induced coronary arteritis is currently considered one of the representative models of Kawasaki (KD) disease. Advances in metagenomic next-generation sequencing have enabled the detection of all nucleic acids in tissue, which can help identify candidate pathogens, including previously unidentified viruses. In this review, we discuss the findings from reports on pathogen-associated vasculitis in animal models and humans, with a specific focus on the investigation of the pathogenesis of vasculitis. Further studies on animal models and microbes in diseased vessels may provide important insights into the pathogenesis of vasculitis, which is often considered an idiopathic disease., Competing Interests: None, (Copyright © Japan Medical Association.)