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The CALorimetric Electron Telescope, CALET, has been measuring high-energy cosmic rays on the International Space Station since October 13, 2015. The scientific objectives addressed by the mission are to search for possible nearby sources of high-energy electrons and potential signatures of dark matter, and to investigate the details of galactic cosmic-ray acceleration and propagation. The calorimetric instrument, which is 30 radiation lengths or 1.3 proton interaction lengths thick with fine imaging capability, is optimized to measure cosmic-ray electrons by achieving large proton rejection and excellent energy resolution well into the TeV region. In addition, very wide dynamic range of energy measurement and individual charge identification capability enable us to measure proton and nuclei spectra from a few tens GeV to a PeV scale. Nearly 20 million cosmic-ray shower events over 10 GeV per month are triggered and the continuous observation has been kept without any major interruption since the start of operation. Using the data obtained over 6.5 years of operation, we will present a brief summary of the CALET observation including electron spectrum, and proton and nuclei spectra as well as the performance study on orbit with MC simulations.

Objective Endometrial cytology has been widely used as a screening tool in Japan. Traditionally, a three-tier reporting system, consisting of 'negative', 'suspicious' and 'positive' categories, has been used. However, a more descriptive system, the New Terminology in Endometrial Cytology ( NTEMC), which is based on the Bethesda System for uterine cervical cytology, was introduced recently. The objective of this study was to validate the NTEMC criteria. Methods Endometrial cytology specimens that had been categorised as 'suspicious' were collected in our hospital between 2003 and 2013, and from these, 106 specimens with corresponding histological results, were re-evaluated according to the NTEMC criteria. Diagnostic categories were assigned based on that chosen by the majority of the examining members. Results Negative, atypical endometrial cells, of undetermined significance ( ATEC- US), atypical endometrial cells for which atypical endometrial hyperplasia or worse cannot be excluded ( ATEC-A), endometrial hyperplasia, atypical endometrial hyperplasia and malignancy were selected as the diagnostic categories for 9 (8.5%), 34 (32.1%), 17 (16%), 34 (32.1%), 5 (4.7%) and 7 (6.6%) specimens, respectively. Corresponding histological categories of benign, endometrial hyperplasia, atypical endometrial hyperplasia and malignancy were established in 28 (82.4%), 1 (2.9%), 2 (5.9%) and 3 (8.8%) ATEC- US specimens, respectively, and in 6 (35.3%), 3 (17.6%), 2 (11.8%) and 6 (35.3%) ATEC-A specimens, respectively. The histological category distribution differed significantly ( P = 0.001), and there was a significant correlation between corresponding cytological and histological categories ( P = 0.005). Conclusion The ATEC category of NTEMC system works well in a practical setting and resembles the Bethesda reporting system ASC (atypical squamous cells) category for cervical cytology. [ABSTRACT FROM AUTHOR]

Background: The rose ketone β-damascone (β-Dam) elicits positive results in the in vitro micronucleus (MN) assay using human lymphocytes, but shows negative outcomes in the Ames test and combined in vivo MN and comet assays. This has led to the interpretation that the in vitro MN result is a misleading positive result. Oxidative stress has been suggested as an indirect mode of action (MoA) for in vitro MN formation, with the α, β-unsaturated carbonyl moiety of the β-Dam chemical structure expected to cause misleading positive results through this MoA. In this study, we investigated the role of oxidative stress in β-Dam-induced in vitro MN formation by co-treatment with the antioxidant N-acetyl-L-cysteine (NAC), thereby highlighting a possible link between mitochondrial dysfunction and aneugenicity., Results: β-Dam induced MN formation in both CHL/IU and BEAS-2B cells, with the response completely inhibited by co-treatment with NAC. Moreover, β-Dam induced oxidative stress-related reporter activity in the ToxTracker assay and increased reactive oxygen species levels, while decreasing glutathione levels, in BEAS-2B cells in the high-content analysis. All of these effects were suppressed by NAC co-treatment. These findings indicate that β-Dam elicits oxidative stress, which causes DNA damage and ultimately leads to MN induction. However, no significant DNA damage-related reporter activities were observed in the ToxTracker assay, nor was there an increased number of γH2AX foci in the high-content analysis. These data suggest that MN formation is not a DNA-reactive MoA. Considering recent reports of aneuploidy resulting from chromosome segregation defects caused by mitochondrial dysfunction, we investigated if β-Dam could cause such dysfunction. We observed that the mitochondrial membrane potential was dose-dependently impaired in BEAS-2B cells exposed to β-Dam., Conclusions: These findings suggest that the oxidative stress induced by β-Dam exposure may be explained through an aneugenic MoA via mitochondrial dysfunction, thereby contributing to MN formation in mammalian cells., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

MicroRNAs, including the tumor-suppressor miR-126 and the oncogene miR-221, regulate tumor formation and growth in colitis-associated cancer (CAC) and colorectal cancer (CRC). This study explores the impact of the epithelial cytokine heparin-binding epidermal growth factor (HB-EGF) and its receptor epidermal growth factor receptor (EGFR) on the pathogenesis of CAC and CRC, particularly in the regulation of microRNA-driven tumor growth and protease expression. In murine models of CRC and CAC, lack of miR-126 and elevated miR-221 expression in colonic tissues enhanced tumor formation and growth. MiR-126 downregulation in colon cells established a pro-tumorigenic proteolytic niche by targeting HB-EGF-active metalloproteinase-7, -9 (MMP7/MMP9), disintegrin, and metalloproteinase domain-containing protein 9, and modulating chemokine-mediated recruitment of HB-EGF-loaded inflammatory cells. Mechanistically, downregulation of HB-EGF and EGFR in the colon suppressed miR-221 and enhanced miR-126 expression via activating enhancer-binding protein 2 alpha. Reintroducing miR-126 reduced tumor development and HB-EGF expression. Combining miR-126 reintroduction, which targets specific HB-EGF-active proteases but not ADAM17, with MMP inhibitors like Batimastat or Marimastat effectively suppressed tumor growth. This combination normalized protease expression and balanced miR-126 and miR-221 levels in developing and growing tumors. These findings demonstrate that suppressing HB-EGF and EGFR1 shifts the balance from oncogenic miR-221 to tumor-suppressive miR-126 action. Consequently, normalizing miR-126 expression could open new avenues for treating patients with CAC and CRC, and this normalization is intertwined with the anticancer efficacy of MMP inhibitors., (© 2024. The Author(s).)

Objectives: The aim of this study was to assess the efficacy of pelvic osteotomy and ventral fixation of the ischium using cortical screws and polymethylmethacrylate (PMMA) for feline pelvic canal stenosis (PCS) associated with malunion after conservative management of pelvic fractures., Methods: Surgical pelvic enlargement was performed for PCS in six cats. The medical records, including information on the patients, surgical procedures, defecation and complications, were reviewed. The sacral index (SI) and colonic:lumbar:vertebral ratio (CLVR) were evaluated based on pre- and postoperative radiographs., Results: This study included five castrated male cats and one spayed female cat. Postoperative improvements in constipation and defecatory difficulty were noted in all cases. The postoperative SI was significantly higher (mean 0.93, range 0.72-1.13) than the preoperative SI (mean 0.59, range 0.45-0.74) ( P <0.001). However, no statistically significant change was found in the CLVR preoperatively and up to 3 months postoperatively. A successful union of the ilium was observed, without implant failures. One case developed necrosis of the pubic surgical wound., Conclusions and Relevance: This study indicated the potential benefits of pelvic osteotomy and ventral fixation of the pelvic floor using screws and PMMA for achieving pelvic cavity enlargement in treating feline PCS associated with defecatory problems., Competing Interests: Conflict of interestHF is employed by Platon Japan, Tokyo, Japan, the manufacturer of crank plates and screws used in this study. The authors declared that there were no other conflicts of interest.

IL-7 and IL-2 are evolutionarily related cytokines that play critical roles in the development and expansion of immune cells. Although both IL-7R and IL-2R activate similar signaling molecules, whether their signals have specific or overlapping functions during lymphocyte differentiation remains unclear. To address this question, we generated IL-7R α-chain (IL-7Rα)/IL-2R β-chain (IL-24β) (72R) knock-in mice expressing a chimeric receptor consisting of the extracellular domain of IL-7Rα and the intracellular domain of IL-2Rβ under the control of the endogenous IL-7Rα promoter. Notably, this 72R receptor induced higher levels of STAT5 and Akt phosphorylation in T cells. In the periphery of 72R mice, the number of T cells, B cells, and type 2 innate lymphoid cells (ILC2s) was increased, whereas early T cell progenitors and double-negative 2 thymocytes were reduced in the thymus. In addition, cell proliferation and Notch signaling were impaired in the early thymocytes of 72R mice, leading to their differentiation into thymic B cells. Interestingly, ILC2s were increased in the thymus of 72R mice. Early T cell progenitors from 72R mice, but not from wild-type mice, differentiated into NK cells and ILC2-like cells when cocultured with a thymic stromal cell line. Thus, this study indicates that the chimeric 72R receptor transduces more robust signals than the authentic IL-7Rα, thereby inducing the alternative differentiation of T cell progenitors into other cell lineages. This suggests that cytokine receptors may provide instructive signals for cell fate decisions., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Purpose: A consensus has been reached regarding diverting stoma (DS) construction in rectal cancer surgery to avoid reoperation related to anastomotic leakage. However, the incidence of stoma-related complications (SRCs) remains high. In this study, we examined the perioperative outcomes of DS construction in patients who underwent sphincter-preserving surgery for rectal cancer., Methods: We included 400 participants who underwent radical sphincter-preserving surgery for rectal cancer between 2005 and 2017. These participants were divided into the DS (+) and DS (-) groups, and the outcomes, including postoperative complications, were compared., Results: The incidence of ileus was higher in the DS (+) group than in the DS (-) group (P<0.01); however, no patients in the DS (+) group showed grade 3 anastomotic leakage. Furthermore, early SRCs were observed in 33 patients (21.6%) and bowel obstruction-related stoma outlet syndrome occurred in 19 patients (12.4%). There was no significant intergroup difference in the incidence of grade 3b postoperative complications. However, the most common reason for reoperation was different in the 2 groups: anastomotic leakage in 91.7% of patients with grade 3b postoperative complications in the DS (-) group, and SRCs in 85.7% of patients with grade 3b postoperative complications in the DS (+) group., Conclusion: Patients with DS showed higher incidence rates of overall postoperative complications, severe postoperative complications (grade 3), and bowel obstruction, including stoma outlet syndrome, than patients without DS. Therefore, it is important to construct an appropriate DS to avoid SRCs and to be more selective in assigning patients for DS construction.

Background: Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is a rare disease characterized by a persistent increase in NK cells in peripheral blood and is generally asymptomatic. If present, symptoms may include fatigue, B symptoms (fever, night sweats, and unintentional weight loss), autoimmune-associated diseases, splenomegaly, and infection due to neutropenia. Peripheral neuropathy, however, is uncommon with an incidence of 3%. Neurolymphomatosis is a neurological manifestation of non-Hodgkin lymphoma and leukemia in which neurotropic neoplastic cells infiltrate the nerves. Moreover, neurolymphomatosis caused by CLPD-NK is extremely rare, with even fewer cases of autonomic dysfunction. We report a case of neurolymphomatosis associated with CLPD-NK and developed autonomic dysfunction, including orthostatic hypotension and gastrointestinal symptoms., Case Presentation: The patient was a 61-year-old male who was referred to our hospital for leukocytosis. He was diagnosed with CLPD-NK; however, was untreated since he had no hepatosplenomegaly, and other systemic symptoms. He later developed numbness in his lower extremities. Cerebral spinal fluid examination revealed a markedly elevated protein level of 140 mg/dL, and contrast-enhanced magnetic resonance imaging showed bilateral L4 and 5 nerve roots with enlargement and contrast effect. An immune-mediated polyradiculoneuropathy was suspected, and he was treated with intravenous methylprednisolone and immunoglobulin followed by oral prednisolone and cyclosporine. Although his symptoms were relieved by the immunotherapy, significant autonomic dysfunction, including intractable diarrhea, decreased sweating, and orthostatic hypotension, appeared. Additionally, tests for onconeuronal antibodies, ganglionic nicotinic acetylcholine receptor (gAChR) antibody, NF155, CNTN1, Caspr1 antibody, and anti-ganglioside antibodies were all negative. A sural nerve biopsy revealed lymphocytic infiltration, and immunohistochemical staining of lymphocytes confirmed the infiltration of NK and T cells. Therefore, a diagnosis of neurolymphomatosis caused by CLPD-NK was made, and chemotherapy led to partial symptom improvement., Conclusions: We experienced a case of pathologically diagnosed neurolymphomatosis with autonomic dysfunction associated with CLPD-NK. In cases of subacute to chronic autonomic dysfunction, paraneoplastic neuropathy, amyloidosis, and autoimmune autonomic ganglionopathy are considered; however neurolymphomatosis caused by CLPD-NK, an important cause of autonomic dysfunction, is not. In difficult to make diagnosis, aggressive nerve biopsy is required., (© 2024. The Author(s).)

Background: Some congenital diaphragmatic hernias are diagnosed beyond 1 month. A late-presenting congenital diaphragmatic hernia shows a variety of clinical manifestations, and the preoperative clinical course is variable. We herein report a pediatric case of late-presenting congenital diaphragmatic hernia diagnosed as acute abdomen., Case Presentation: A 5-year-old boy was brought to our hospital because of herniation of the intestine into the left thoracic cavity, which was observed on radiography performed for abdominal pain. Enhanced computed tomography showed herniation of the small intestine and colon into the left thoracic cavity. Emergency laparoscopic surgery was performed based on the diagnosis of left diaphragmatic hernia. The entire small intestine and part of the colon herniated from the posterolateral defect of the diaphragm. We were able to retract the herniated intestine back into the abdomen but confirmed that the diaphragmatic defect and closure of the defect seemed to be technically challenging via laparoscopy; therefore, we converted the procedure to open laparotomy. The diaphragmatic defect was directly closed with interrupted sutures, and the thoracic cavity was degassed. Postoperatively, the left lung was found to be poorly expanded, but pulmonary hypoplasia was not evident in this case., Conclusions: We herein report a pediatric case of late-presenting congenital diaphragmatic hernia diagnosed as abdominal pain. Late-presenting congenital diaphragmatic hernias present with a wide variety of symptoms; therefore, it is important to be reminded of these conditions and check chest radiographs in children presenting with acute or chronic respiratory or gastrointestinal symptoms of unknown etiology., (© 2024. The Author(s).)

Background: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups., Methods: We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s)., Results: The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about "diagnosis-probable" patient cohort (n = 402) and the "diagnosis-confirmed" patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food., Conclusions: In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Transparent and brown La 2 O 3 -MoO 3 binary glasses were prepared in bulk form using a levitation technique. The glass-forming range was limited, with the primary composition being approximately 25 mol % La 2 O 3 . The 25La 2 O 3 -75MoO 3 glass exhibited a clear crystallization at 546 °C, while determining its glass transition temperature was difficult. Notably, despite its amorphous nature, the glass possessed a density and packing density comparable to those of crystalline La 2 Mo 3 O 12 . X-ray absorption fine structure and Raman scattering analyses revealed that the glass structure closely resembles La 2 Mo 3 O 12 due to the presence of isolated MoO 4 2- units, whereas disordered atomic arrangement around La atoms was confirmed. The glass demonstrated transparency ranging from 378 to 5500 nm, and the refractive index at 1.0 μm was estimated to be 2.0. The optical bandgap energy was 3.46 eV, which was slightly smaller than that of La 2 Mo 3 O 12 . Additionally, the glass displayed a transparent region ranging from 6.5 to 8.0 μm. This occurrence results from the decreased diversity of MoO n units and connectivity of Mo-O-Mo, which resulted in the reduced overlap of multiphonon absorption. This glass formation, with its departure from conventional glass-forming rules, resulted in distinctive glasses with crystal-like atomic arrangements.

Background: To evaluate the feasibility of the use and continuation of sentinel lymph node navigation surgery (SNNS) as an alternative to pelvic lymph node dissection (PLND) for patients with preoperatively estimated stage IA endometrial cancer., Methods: This retrospective study selected the electronic medical records of all patients who had received CT scans and MRI imaging before surgery from April 1, 2009 to March 31, 2021. Sentinel lymph nodes (SLNs) were detected by administrating 99m Tc-phytate and/or indocyanine green into the cervix, and the clinical outcomes of the patients who underwent SNNS or PLND were evaluated. Furthermore, in case of nodal recurrence, a new procedure to determine whether the facility should continue with SNNS or not was developed that compares the maximum likelihood hypothesis and an alternative one based on recurrence rates., Results: Among 137 patients, SLN biopsies with ultrastaging were performed on 91 patients. The SLN detection rate was 95.6%. Over a 59-month median observation period, no statistically significant differences were shown in overall survival, disease-specific survival and disease-free survival between the SNNS and PLND groups when introducing the propensity score method (p-values: 0.06, 0.153, and 0.625, respectively). Our procedure demonstrated that, in our department without recurrence up to the 65th attempt, it was possible to continue SNNS if a recurrence occurs at the 66th attempt., Conclusion: This study suggests the validity of SNNS as an alternative to PLND. Even in the absence of evidence from randomized controlled trials, we can confirm the validity of continuing SNNS using our procedure., (© 2024. The Author(s).)

We developed a prototype VR platform, VECTORS L&M (VLM), aiming to enhance the understanding of digestive surgery for students, interns, and young surgeons by limiting costs. Its efficacy was assessed via questionnaires before implementation in surgical education. The VLM provides nine-minute VR views of surgeries, from both 180- and 360-degree angles. It was created with L.A.B. Co., Ltd. and incorporates surgery videos from biliary malignancy patients. Following VLM development, a survey was conducted among surgeons who had experienced it. Twenty-eight participants (32% of observers) responded to the survey. A majority (81%) reported positive experiences with the VR content and showed interest in VR video production, though some reported sickness. Most respondents were experienced surgeons, and nearly all believed VR was important for medical education with a mean score of 4.14 on a scale of up to 5. VR was preferred over 3D printed models due to its application versatility. Participants expressed the desire for future VR improvements, such as increased mobility, cloud connectivity, cost reduction, and better resolution. The VLM platform, coupled with this innovative teaching approach, offers experiential learning in intraabdominal surgery, effectively enriching the knowledge of students and surgeons ahead of surgical education and training., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2023, Turkish Surgical Society.)

Purpose: To report our initiatives and treatment results for patients with colorectal cancer with metal allergy., Methods: A total of 27 patients (2.6%) with a history of metal contact dermatitis were identified among 1027 patients who underwent curative resection of colorectal cancer from 2014 to 2020. The results of the patch test, perioperative results, and postoperative colonoscopy findings were also investigated., Results: The patch test for metal allergens and staples was performed in 21 patients (77.8%), and 13 of them (61.9%) tested positive for at least one metal allergen. Ni (38.1%), Co (28.6%), and Pd (19.0%) showed higher positive rates than other metals, and 1 patient (4.8%) tested positive for staples. Stapled anastomosis/suturing was performed as planned in 15 of 27 patients. In 10 patients, the anastomosis method was changed from stapled to hand-sewn according to the no-patch test results (60%), positivity for multiple metals (20%), positivity for staples (10%), and surgeon's judgment (10%). No complications and abnormal colonoscopy findings were found to be associated with stapled anastomosis/suturing., Conclusion: The patch test is useful for selecting an optimal anastomosis method for patients with suspected metal allergy., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Inspired by the molecular classification of endometrial carcinoma (EC) proposed by The Cancer Genome Atlas Research Network (TCGA), we investigated tumor-infiltrating CD8-positive T-cell as well as DNA mismatch repair (MMR) protein and p53 protein expression, and we developed a new classification system for ECs to predict patients' prognosis using immunohistochemical methods., Methods: The study included 128 patients with ECs who underwent surgery. Paraffin-embedded tissue sections of the tumor were stained using antibodies against MMR protein, p53, and CD8. Cases were stratified into four classes by a sequential algorithm. An immunohistochemical classification system for ECs (ICEC) was created, including HCD8, MMR-D, LCD8, and p53 LCD8., Results: In ICEC, 16 cases (12.5%), 27 cases (21.09%), 67 cases (52.34%), and 18 cases (14.06%) belonged to HCD8, MMR-D, LCD8, and p53 LCD8, respectively. ICEC did not show any correlation with clinical stage, lymphovascular space invasion, or lymph node metastasis. However, the p53 LCD8 class contained a significantly higher proportion of G3 ECs and serous carcinoma ( p < 0.0001). ICEC showed prognostic significance in overall survival (OS) ( p < 0.0001) and disease-free survival (DFS) ( p < 0.0001). The class of p53 LCD8 showed the worst prognosis among the classes., Conclusions: ICEC classification is useful in predicting the prognosis of ECs.

Background: The use of organotypic human tissue models in genotoxicity has increased as an alternative to animal testing. Genotoxicity is generally examined using a battery of in vitro assays such as Ames and micronucleus (MN) tests that cover gene mutations and structural and numerical chromosome aberrations. At the 7th International Workshop on Genotoxicity Testing, working group members agreed that the skin models have reached an advanced stage of maturity, while further efforts in liver and airway models are needed [Pfuhler et al., Mutat. Res. 850-851 (2020) 503135]. Organotypic human airway model is composed of fully differentiated and functional respiratory epithelium. However, because cell proliferation in organotypic airway models is thought to be less active, assessing their MN-inducing potential is an issue, even in the cytokinesis-blocking approach using cytochalasin B (CB) [Wang et al., Environ. Mol. Mutagen. 62 (2021) 306-318]. Here, we developed a MN test using EpiAirway™ in which epidermal growth factor (EGF) was included as a stimulant of cell division., Results: By incubating EpiAirway™ tissue with medium containing various concentrations of CB, we found that the percentage of binucleated cells (%BNCs) almost plateaued at 3 μg/mL CB for 72 h incubation. Additionally, we confirmed that EGF stimulation with CB incubation produced an additional increase in %BNCs with a peak at 5 ng/mL EGF. Transepithelial electrical resistance measurement and tissue histology revealed that CB incubation caused the reduced barrier integrity and cyst formation in EpiAirway™. Adenylate kinase assay confirmed that the cytotoxicity increased with each day of culture in the CB incubation period with EGF stimulation. These results indicated that chemical treatment should be conducted prior to CB incubation. Under these experimental conditions, it was confirmed that the frequency of micronucleated cells was dose-dependently increased by apical applications of two clastogens, mitomycin C and methyl methanesulfonate, and an aneugen, colchicine, at the subcytotoxic concentrations assessed in %BNCs., Conclusions: Well-studied genotoxicants demonstrated capability in an organotypic human airway model as a MN test system. For further utilization, investigations of aerosol exposure, repeating exposure protocol, and metabolic activation are required., (© 2023. The Author(s).)