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Good syndrome (GS) is a combined immunodeficiency that is associated with thymomas. The cause of the reduction in B-cells in patients with GS may be multifactorial and may include dysregulated T-cell responses. It has been proposed that tumorigenesis in a normal thymus alters thymic epithelial cell function, which leads to attenuated elimination of T-cells autoreactive to B-cells. Although the comprehensive genetic analysis of thymoma has been performed and reported in many articles, the comprehensive genetic analysis specified for GS-related thymoma has not been reported. Herein, we report comprehensive genetic analysis of a thymoma taken from a patient with GS. Oncogenesis-associated genes that may contribute to thymoma development were detected. Additionally, alteration of VCAM1, which is required in the interaction between T-cells and thymic epithelial cells, was observed. Aberrantly expressed VCAM1 in thymic epithelial cells may decrease the efficacy of negative of selection autoreactive T-cells and contribute to autoimmunity to B-cells.

Pullout repair of medial meniscal posterior root tears (MMPRTs) is generally recommended for patients with well-aligned knees, whereas open-wedge high tibial osteotomy (OWHTO) is often recommended for patients with MMPRTs and varus osteoarthritis. Although the management of MMPRTs with OWHTO has been controversial, retaining meniscal function can be expected through pullout repair. Conventionally, bone tunnels in pullout repair are created from the proximal anteromedial tibia. However, this technique could cause a killer angle of the repaired meniscus and could have a risk of turning the guidewire toward the neurovascular band. Therefore, we create a bone tunnel from the proximal anterolateral tibia combined with open-wedge distal tibial tubercle osteotomy, which can prevent an increase in postoperative patellofemoral contact stress; moreover, the bone tunnel can be created easily from the lateral tibia compared with OWHTO. This Technical Note describes the combined surgical procedure for patients with MMPRTs and varus osteoarthritis, which has advantages including physiological pullout direction of the repaired meniscus, lower risk of neurovascular damage, and placement of a longer plate screw that could interfere with the bone tunnel. We highlight the meticulous consideration given to the interference of the bone tunnel between the osteotomy line and plate screw.

Citrin deficiency is a congenital secondary urea cycle disorder lacking useful disease models for effective treatment development. In this study, human induced pluripotent stem cells (iPSCs) were generated from two patients with citrin deficiency and differentiated into hepatocyte-like cells (HLCs). Citrin-deficient HLCs produced albumin and liver-specific markers but completely lacked citrin protein and expressed argininosuccinate synthase only weakly. In addition, ammonia concentrations in a medium cultured with citrin-deficient HLCs were higher than with control HLCs. Sodium pyruvate administration significantly reduced ammonia concentrations in the medium of citrin-deficient HLCs and slightly reduced ammonia in HLCs differentiated from control iPSCs, though this change was not significant. Our results suggest that sodium pyruvate may be an efficient treatment for patients with citrin deficiency. Citrin-deficient iPSCs are a pathological liver model for congenital urea cycle disorders to clarify pathogenesis and develop novel therapies.

Background: Infants born with weights below the 10th percentile of the expected birth weight for gestational age, defined as small for gestational age (SGA), have an increased risk of neonatal mortality and prematurity-related complications. However, the relationship between SGA and postneonatal (28 days to

Lysosome-associated membrane protein-2 (LAMP2) deficiency causes the human Danon disease and represents a lysosomal dysfunction because of its pivotal role in regulating autophagy and lysosome biogenesis. LAMP2-deficient mice exhibit a spectrum of phenotypes, including cardioskeletal myopathy, mental retardation, and retinopathy, similar to those observed in patients with Danon disease. Its pathology is thought to involve altered energy metabolism and lipid dysregulation; however, the lipidomic profiles of LAMP2-deficient animals have not been investigated. In this study, we investigated lipid alterations in LAMP2 KO mice tissues, including those of the liver, plasma, and retina, using liquid chromatography-mass spectrometry. Our results revealed significantly increased free fatty acid (FFA) levels and decreased in triglyceride (TG) levels in LAMP2 KO liver tissues at three and six months. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species significantly decreased in LAMP2 KO mice livers at six months. Similarly, plasma TG and PC/PE levels decreased in LAMP2 KO mice. In contrast, plasma FFA levels were significantly lower in LAMP2 KO mice. Retina FFA levels were elevated in LAMP2 KO mice, accompanied by a partial decrease in PC/PE at six months. In summary, FFA levels increased in several tissues but not in the LAMP2 KO mice plasma, suggesting the potential consumption of FFA as an energy source in the peripheral tissues. The depletion of TG and PC/PE accelerated with age, suggesting an underlying age-dependent energy crisis condition. Our findings underscore the dysregulated distribution of fatty acids in LAMP2-deficient animals and provide new mechanistic insights into the pathology of Danon disease.

Purpose: To compare the usefulness of microperimetry and static automated perimetry in patients with retinitis pigmentosa (RP), using macular anatomical metrics as a reference. Design: Prospective observational study. Participants: Forty-eight eyes of 48 patients with RP in Kyushu University Hospital who underwent microperimetry-3 (MP-3) and Humphrey Field Analyzer (HFA) 10-2 testing ≥3 times during ≥2 years were included. Methods: Macular anatomy (ellipsoid zone [EZ] length) was assessed by OCT, and macular function was assessed by MP-3 (mean retinal sensitivity at radii 2°, 4°, and 8°) and HFA10-2 program (mean retinal sensitivity at radii 2°, 4°, and 8°). Correlations between functional and anatomical parameters were analyzed cross sectionally at baseline and longitudinally by comparing the rate of progression. Main Outcome Measures: Correlation coefficients between anatomical and functional metrics. Results: The mean age at baseline was 50.1 ± 12.3 years, and the mean follow-up period was 2.8 ± 0.7 years. At baseline, EZ length was significantly correlated with MP-3 mean retinal sensitivity at radii 2°, 4°, and 8° (Spearman’s ρ = 0.65, 0.84, 0.89; all P

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

The analysis method proposed by Ruland et al. is widely used to analyze the void lengths in carbon fibers, but it could not apply to mesophase pitch-based carbon fibers. We thought that the reason for the inability to analyze pitch-based carbon fibers was the length distribution of voids that Ruland neglected. We investigated an analytical method that considers the length distribution of voids in carbon fibers. The proposed new method could be applied to various carbon fibers from polyacrylonitrile and mesophase pitch. The analysis results revealed that the average length of voids in mesophase pitch-based carbon fibers is not only long but also widely distributed. On the other hand, the voids of carbon fibers tend to be longer as the crystallite length is longer in both polyacrylonitrile-based and mesophase-based carbon fibers. It suggests that the growth of void length is strongly influenced by the growth of crystallites in the plane direction.

Summary: During aging, skin homeostasis is essential for maintaining appearance, as well as biological defense of the human body. In this study, we identified thrombospondin-1 (THBS1) and fibromodulin (FMOD) as positive and negative regulators, respectively, of the TGF-β1-SMAD4 axis in human skin aging, based on in vitro and in vivo omics analyses and mathematical modeling. Using transcriptomic and epigenetic analyses of senescent dermal fibroblasts, TGF-β1 was identified as the key upstream regulator. Bifurcation analysis revealed a binary high-/low-TGF-β1 switch, with THBS1 as the main controller. Computational simulation of the TGF-β1 signaling pathway indicated that THBS1 expression was sensitively regulated, whereas FMOD was regulated robustly. Results of sensitivity analysis and validation showed that inhibition of SMAD4 complex formation was a promising method to control THBS1 production and senescence. Therefore, this study demonstrated the potential of combining data-driven target discovery with mathematical approaches to determine the mechanisms underlying skin aging.

Introduction: Fuchs endothelial corneal dystrophy (FECD) is the leading cause of corneal blindness in developed countries. Corneal endothelial cells in FECD are susceptive to oxidative stress, leading to mitochondrial dysfunction and cell death. Oxidative stress causes many forms of cell death including parthanatos, which is characterized by translocation of apoptosis-inducing factor (AIF) to the nucleus with upregulation of poly (ADP-ribose) polymerase 1 (PARP-1) and poly (ADP-ribose) (PAR). Although cell death is an important aspect of FECD, previous reports have often analyzed immortalized cell lines, making the evaluation of cell death difficult. Therefore, we established a new in vitro FECD model to evaluate the pathophysiology of FECD. Methods: Corneal endothelial cells were derived from disease-specific induced pluripotent stem cells (iPSCs). Hydrogen peroxide (H2O2) was used as a source for oxidative stress to mimic the pathophysiology of FECD. We investigated the responses to oxidative stress and the involvement of parthanatos in FECD-corneal endothelial cells. Results: Cell death ratio and oxidative stress level were upregulated in FECD with H2O2 treatment compared with non-FECD control, indicating the vulnerability of oxidative stress in FECD. We also found that intracellular PAR, as well as PARP-1 and AIF in the nucleus were upregulated in FECD. Furthermore, PARP inhibition, but not pan-caspase inhibition, rescued cell death, DNA double-strand breaks, mitochondrial membrane potential depolarization and energy depletion, suggesting that cell death was mainly due to parthanatos. Conclusions: We report that parthanatos may be involved in the pathophysiology of FECD and targeting this cell death pathway may be a potential therapeutic approach for FECD.

Background: One of the pain-related factors in rotator cuff tears (RCTs) is abnormal scapular motion, which is thought to be related to the levator scapulae muscle activation. Additionally, attention has recently focused on the peak systolic velocity (PSV) as one of the causes of pain, but blood flow outside of the vessels supplying the rotator cuff has not been clarified. This study aimed to determine the difference in PSV in the dorsal scapular artery (DSA), which is the vessel that supplies the levator scapulae muscles, and the association between PSV and pain and shoulder function in patients with RCTs between the tear and nontear sides. Methods: This study included 31 patients with RCTs with tear and nontear sides. Magnetic resonance imaging and radiographic examinations included Cofield classification, Goutallier classification, thickening of the coracohumeral ligament, and measurement of the acromiohumeral interval. Clinical evaluation included an automatic range of motion (ROM) for flexion, abduction, and external rotation (ER), a visual analog scale, and the Shoulder36. PSV was evaluated using ultrasound pulsed Doppler mode to assess PSV of DSA. The PSV of DSA on the first rib was drawn in the medial aspect of the suprascapular angle in the long axis, and the maximum PSV waveform was measured three times. The average value was used for further analysis. Results: The PSV in the DSA was significantly higher (P = .04, 95% confidence interval: 0.2-7.6) on the tear (22.6 ± 7.4 cm/s) than the nontear sides (18.9 ± 6.9 cm/s). In addition, a significant negative correlation (r = −0.46, P = .0087) was found between PSV in DSA and ER on the tear side. Conclusion: This study revealed a significantly increased PSV in the DSA on the tear side in RCTs and negatively correlated with ER ROM. The results suggest that increased PSV in the DSA may contribute to ER ROM limitation in the glenohumeral joint.

This retrospective study examined 12 patients with infectious abdominal aortic aneurysms who underwent endovascular aneurysm repair (EVAR). The majority were older males with saccular aneurysms. The 30-day and 1-year mortality rates were 33 % and 50 %, respectively. Two patients required reoperation for infection extension. Among the six patients with saccular aneurysms, complete aneurysm shrinkage was observed post-EVAR. The study suggests EVAR may effectively treat certain infectious abdominal aneurysms, particularly saccular types. However, more evidence is needed to determine its suitability. Careful patient selection, considering factors such as aneurysm morphology, is critical as infection control can be insufficient in some cases. Overall, this small case series indicates that EVAR may be a suitable option for select cases of saccular infectious abdominal aortic aneurysms.

This study performed a spray-painting simulation based on the Large Eddy Simulation (LES) and Reynolds-Averaged Navier-Stokes (RANS) for spray painting using a rotary atomizer. The LES better reproduced the flow field and spray dispersion between the bell and target than the RANS. Also, the region called “over-spray” in the radially outside of the bell, in which the droplets stay, was formed, and the residence time became longer for droplets with larger diameter regardless of numerical methods for turbulent flow. Further, the transfer efficiency (TE) in the RANS was almost constant, independent of droplet diameter because all the eddy was modeled in the RANS, and the turbulent fluctuation a droplet received near the target was isotropic. In contrast, the TE in the LES varied depending on droplet diameter and showed the maximum value because only small eddies are modeled in the LES, and the turbulent fluctuation was more realistic.

Objective: Retinal vein occlusion (RVO) can lead to visual impairment, but the development of collateral vessels can sometimes mitigate significant damage. This study aimed to investigate the relationship between collateral vessels and hypertension, the most common underlying condition associated with RVO, by comparing spontaneously hypertensive rats (SHRs) and wild-type Wister rats (WWRs). We also examined the differences between WWRs and SHRs in terms of sphingosine 1-phosphate receptor 1 (S1PR1) expression and its product nitric oxide synthase 3 (NOS3) expression, which are involved in the formation of collateral vessels after vascular occlusion. Methods: Laser photocoagulation (PC) was used to occlude one randomly selected retinal vein in WWRs and SHRs, and the area surrounding the occluded vessel was examined using optical coherence tomography angiography. If reperfusion of the occluded vessel occurred within 2 weeks, the vessel was re-occluded repeatedly by PC. The number of eyes with successfully occluded vessels accompanied by collateral vessels was recorded. Then, WWRs and SHRs were divided into the following four groups: 1) control (no treatment), 2) vehicle (20% DMSO), 3) S1PR1 agonist (2 mg/mL SEW2871), and 4) S1PR1 antagonist (0.25 mg/mL VPC 23019) groups. The drugs were administered intravitreally in all groups except the control. The number of laser shots required for successful RVO was recorded. Histological evaluation and quantitative real-time PCR of S1PR1 and NOS3 were performed to elucidate the mechanisms underlying collateral vessel formation. Results: The proportion of eyes achieving successful vein occlusion was lower in SHRs (4/12 eyes, 33.3%) than in WWRs (8/10 eyes, 80%, p = 0.043). NOS3 expression at 6 h after PC was significantly higher in WWRs than in SHRs (p = 0.021). In WWRs treated with SEW2871, vein occlusion failed in 7 of 10 eyes (70%). The expression of NOS3 was significantly higher in the SEW2871 treatment group than in the untreated group (p

Sesame is a frequent cause of adverse food reactions in allergic patients. We developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) using two monoclonal antibodies and a unique extraction buffer for the detection and quantification of sesame proteins in processed foods and in raw food ingredients to clarify the validity of sesame labeling and for precautionary allergen labeling. The developed sandwich ELISA method is highly specific for sesame proteins. The limit of detection (LOD) and limit of quantification (LOQ) are 0.013 µg/g and 0.025 µg/g, respectively. The recoveries for incurred food samples, such as dressing, breads, sauce and pudding, ranged from 67 % to 81 %, while the repeatability and reproducibility coefficients of variation were less than 4.7 % and 4.5 %, respectively. The developed method has applicability for food products and is a reliable tool for the detection of hidden sesame proteins in raw food ingredients and in processed foods.

Summary: The hypothalamic suprachiasmatic nucleus (SCN) is composed of heterogenous populations of neurons that express signaling peptides such as vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) and regulate circadian rhythms in behavior and physiology. SCN neurons acquire functional and morphological specializations from waves of transcription factors (TFs) that are expressed during neurogenesis. However, the in vitro generation of SCN neurons has never been achieved. Here we supplemented a highly efficient neuronal conversion protocol with TFs that are expressed during SCN neurogenesis, namely Six3, Six6, Dlx2, and Lhx1. Neurons induced from mouse and human fibroblasts predominantly exhibited neuronal properties such as bipolar or multipolar morphologies, GABAergic neurons with expression of VIP. Our study reveals a critical contribution of these TFs to the development of vasoactive intestinal peptide (Vip) expressing neurons in the SCN, suggesting the regenerative potential of neuronal subtypes contained in the SCN for future SCN regeneration and in vitro disease remodeling.

Purpose: Primary orbital liposarcomas are rare. To the best of our knowledge, only four cases of primary dedifferentiated liposarcomas of the orbit have been reported. Furthermore, there have been no reports of primary orbital liposarcomas transitioning from a highly differentiated to a dedifferentiated form. Here, we report a case of primary orbital liposarcoma that was well-differentiated at the time of initial resection at our hospital but had dedifferentiated on recurrence 10 years after the initial resection. Observations: The patient was diagnosed with an inflammatory mass after an initial tumor resection by a previous physician at age 52. Thereafter, there were four recurrences (first to fourth recurrences), and the patient underwent five surgeries and radiotherapy. For the fifth recurrence, he first visited our hospital at age 64 and was diagnosed with a well-differentiated liposarcoma after undergoing tumor resection. When the tumor recurred 9 years later (the sixth recurrence), it was well-differentiated. When the tumor recurred (the seventh recurrence) six months after surgery at the age of 73 years, the patient underwent orbital exenteration because of rapid tumor growth, and pathological examination showed that the tissue had changed to a dedifferentiated liposarcoma. Conclusions and Importance: Primary well-differentiated orbital liposarcoma may transform to a dedifferentiated form over time. The risk of dedifferentiation at recurrence should be considered in developing a treatment plan, even if the initial pathology is a well-differentiated liposarcoma.

Background & Aims: Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known. Methods: We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS. In a real-world cohort of 840 patients with HCC from 22 centres included between 2018 and 2023, we directly compared the efficacy and safety of atezolizumab + bevacizumab (A+B) between sexes. Radiological response was reported according to RECIST v1.1. Uni- and multivariable Cox regression analyses were performed for OS and progression-free survival (PFS). Results: In the meta-analysis, immunotherapy was associated with a significant OS benefit only in male (pooled HR 0.79; 95% CI 0.73–0.86) but not in female (pooled HR 0.85; 95% CI 0.70–1.03) patients with HCC. When directly comparing model estimates, no differences in the treatment effect between sexes were observed. Among 840 patients, 677 (81%) were male (mean age 66 ± 11 years), and 163 (19%) were female (mean age 67 ± 12 years). Type and severity of adverse events were similar between the two groups. OS and PFS were comparable between males and females upon uni- and multivariable analyses (aHR for OS and PFS: 0.79, 95% CI 0.59–1.04; 1.02, 95% CI 0.80–1.30, respectively). Objective response rates (24%/22%) and disease control rates (59%/59%) were also similar between sexes. Conclusion: Female phase III trial participants experienced smaller OS benefit following ICI therapy for advanced HCC, while outcomes following A+B treatment were comparable between sexes in a large real-world database. Based on the ambiguous sex-related differences in survival observed here, further investigation of sex-specific clinical and biologic determinants of responsiveness and survival following ICIs are warranted. Impact and implications: While immune checkpoint inhibitors have emerged as standard of care for the treatment of hepatocellular carcinoma, there are conflicting reports on whether the efficacy of cancer immunotherapy differs between females and males. Our study suggests ambiguous sex-related differences in outcomes from immunotherapy in hepatocellular carcinoma. Further investigation of sex-specific clustering in clinicopathologic and immunologic determinants of responsiveness to immune checkpoint inhibitor therapy should be prioritised. Systematic review registration: PROSPERO CRD42023429625.

Fukutin (FKTN) c.647+2084G>T creates a pseudo-exon with a premature stop codon, which causes Fukuyama congenital muscular dystrophy (FCMD). We aimed to ameliorate aberrant splicing of FKTN caused by this variant. We screened compounds focusing on splicing regulation using the c.647+2084G>T splicing reporter and discovered that the branchpoint, which is essential for splicing reactions, could be a potential therapeutic target. To confirm the effectiveness of branchpoints as targets for exon skipping, we designed branchpoint-targeted antisense oligonucleotides (BP-AONs). This restored normal FKTN mRNA and protein production in FCMD patient myotubes. We identified a functional BP by detecting splicing intermediates and creating BP mutations in the FKTN reporter gene; this BP was non-redundant and sufficiently blocked by BP-AONs. Next, a BP-AON was designed for a different FCMD-causing variant, which induces pathogenic exon trapping by a common SINE-VNTR-Alu-type retrotransposon. Notably, this BP-AON also restored normal FKTN mRNA and protein production in FCMD patient myotubes. Our findings suggest that BPs could be potential targets in exon-skipping therapeutic strategies for genetic disorders.

Background/Objectives: In our previous laboratory experiment (room temperature of 25 °C), CO2-rich cool-water immersion (CCWI) suppressed subjects' core body temperature even during repeated exercise. It is unclear whether the suppression of body temperature elevation would also continue after CCWI in a hot outdoor environment. Herein we investigated the thermal effects of CCWI after regular exercise training in heat on subjects' core temperature (Tcore), three skin temperatures (Tskin), heart rate (HR), and the rate of perceived ice (RPI). Methods: Thirty-six subjects (25 males, 11 females) were randomly allocated into three groups (CCWI, CWI, and control). After training at their competitive clubs, each subject was immersed up to the chest in CCWI or CWI at 20 °C for 20 min, followed by a 60-min recovery period. Tcore, Tskin, HR, and RPI were measured at the initial rest, the end of immersion, and every 10 min during the recovery period. Results: Compared to the control, the CCWI subjects' Tcore was significantly lower at 50–60 min after the end of immersion (p

Press-forming technology is excellent for mass production. However, for micrometer-order forming, manufacturing press tools is unprofitable. Because laser-induced shock waves cannot rapidly accelerate heavier workpieces into molds, the workpieces are limited to thin metal foils. In this study, an explosion-derived high-impulse shock wave was applied to dynamically compress a polymer stamper into a metal plate. The stamper was pressed for a few microseconds, resulting in a well-imprinted submicron structure on the aluminum plate surface. Numerical simulation clarified the imprinting mechanism, which involved local compression and restoration of the stamper profile that occurred when the reflected shock wave generated at the boundary between the stamper and the workpiece reached the free surface of the stamper. It was discovered that the shock wave must continue to act for a significantly longer time than that required for the reflected shock wave to reach the free surface of the stamper. Therefore, explosion-derived shock waves with a long pressure duration are effective for imprinting. This method has the potential to be developed into a practical technique for imparting functional microsurfaces to structural components.

Clostridium perfringens bacteremia is a rare but rapidly fatal condition, especially in patients exhibiting massive intravascular hemolysis (MIH), gas gangrene, and septic shock. Herein, we present an autopsy case of C. perfringens septicemia exhibiting MIH, gas gangrene, and cytokine storm. The patient was an 84-year-old female with a history of biliary reconstruction surgery for congenital biliary dilatation. She developed MIH, elevated inflammatory mediator levels, thrombocytopenia, and coagulopathy. She went into shock within 1 h of the presentation and died within a few hours. Rapid progression was associated with the transformation of liver abscesses into gas-filled abscesses on computed tomography scan, suggesting the rapid outgrowth of gas-producing bacteria. The patient was finally diagnosed with MIH and gas gangrene due to C. perfringens infection based on the presence of this bacterium in the blood and bile. On autopsy, gas gangrene was observed in almost all organs, originating from the bile duct. Polymerase chain reactions targeting C. perfringens toxins identified the isolated bacterium as C. perfringens type A expressing α-toxin (CPA), perfringolysin O (PFO), and collagenase (ColA). Elevated interleukin 6 and tumor necrosis factor-α expression levels were observed in the serum, and such proinflammatory responses were partially mediated by Toll-like receptor 2. This study elucidated the association between the toxin profiles of clinically isolated C. perfringens and the host cytokine responses in the patient.

Background: NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs). Methods: This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW). Results: NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39–0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32–0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13–0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098–0.75, p = 0.012) than the Ab-negatives (n = 11). Conclusion: Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC.

Introduction: We aimed to assess the safety, pharmacokinetic profile, and antitumor activity of adavosertib monotherapy in Japanese patients with advanced solid tumors. Materials and methods: This was a single-center, open-label, phase I study with two consecutive cohorts (250 mg and 200 mg cohorts). Patients received adavosertib at 250 mg or 200 mg, orally once daily for 5 days on and 2 days off for Weeks 1 and 2 of a 21-day cycle. Results: Dose-limiting toxicities (Grade 3 febrile neutropenia) occurred in 2/6 patients in the 250 mg cohort. None of the three patients in the 200 mg cohort developed dose-limiting toxicities. The most frequent treatment-emergent adverse event was nausea (250 mg: 83.3 %; 200 mg: 100.0 %). Median time to peak drug concentration was 4.03 and 2.08 h after the first dose and 2.82 and 1.90 h after multiple dosing in the 250 and 200 mg cohorts, respectively; respective mean terminal elimination half-lives were 7.36 and 7.30 h (first dose) and 10.55 and 8.88 h (multiple dosing). Systemic exposure increased in a slightly more than dose-proportional manner. No RECIST v1.1 response was observed. Disease control rate was 0 % and 33.3 % in the 250 and 200 mg cohorts, respectively. One patient (33.3 %) in the 200 mg cohort showed a best overall response of stable disease at ≥ 8 weeks; the rest showed progressive disease. Conclusions: Adavosertib 200 mg once daily was well tolerated in this patient population and no safety concerns were raised. Exposure increased in a slightly more than dose-proportional manner and limited antitumor activity was shown. Trial registration: ClinicalTrials.gov, NCT04462952

Background: Neuromuscular blocking agents are used to control shivering in cardiac arrest patients treated with target temperature management. However, their effect on outcomes in patients treated with extracorporeal cardiopulmonary resuscitation is unclear. Methods: This study was a secondary analysis of the SAVE-J II study, a retrospective multicenter study of 2175 out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation in Japan. We classified patients into those who received neuromuscular blocking agents and those who did not and compared in-hospital mortality and incidence rates of favorable neurological outcome and in-hospital pneumonia between the groups using multivariable regression models and stabilized inverse probability weighting with propensity scores. Results: Six hundred sixty patients from the SAVE-J II registry were analyzed. Neuromuscular blocking agents were used in 451 patients (68.3%). After adjusting for potential confounders, neuromuscular blocking agents use was not significantly associated with in-hospital mortality (aHR 0.88; 95% CI, 0.67–1.14), favorable neurological outcome (aOR 0.85; 95% CI, 0.60–1.11), or pneumonia (aOR 1.52; 95% CI, 0.85–2.71). The results for in-hospital mortality (aHR 0.89; 95% CI, 0.64–1.25), favorable neurological outcome (aOR 0.94; 95% CI, 0.59–1.48) and pneumonia (aOR 1.59; 95% CI, 0.74–3.41) were similar after weighting was performed. Conclusions: Although data on the rationale for using neuromuscular blocking agents were unavailable, their use was not significantly associated with outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation and targeted temperature management. Neuromuscular blocking agents should be used based on individual clinical indications.

Summary: Interaction between the gut microbiome and host plays a key role in human health. Here, we perform a metagenome shotgun-sequencing-based analysis of Japanese participants to reveal associations between the gut microbiome, host genetics, and plasma metabolome. A genome-wide association study (GWAS) for microbial species (n = 524) identifies associations between the PDE1C gene locus and Bacteroides intestinalis and between TGIF2 and TGIF2-RAB5IF gene loci and Bacteroides acidifiaciens. In a microbial gene ortholog GWAS, agaE and agaS, which are related to the metabolism of carbohydrates forming the blood group A antigen, are associated with blood group A in a manner depending on the secretor status determined by the East Asian-specific FUT2 variant. A microbiome-metabolome association analysis (n = 261) identifies associations between bile acids and microbial features such as bile acid metabolism gene orthologs including bai and 7β-hydroxysteroid dehydrogenase. Our publicly available data will be a useful resource for understanding gut microbiome-host interactions in an underrepresented population.

Various diseases (e.g., hypertension and diabetes) are risk factors for the exacerbation of coronavirus 2019 (COVID-19). Patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) tend to develop severe COVID-19. Patients with severe COVID-19 present with acute respiratory distress syndrome (ARDS), and many COVID-19-related ARDS survivors eventually develop fibrosis. However, the appropriate management of patients with COVID-19 and ILD and post-COVID-19 ILD remains unclear. Thus, a better understanding of the pathology that exacerbates COVID-19 in patients with ILD is needed. We report the autopsy results of a patient with COVID-19 and combined pulmonary fibrosis and emphysema, whose lung organization and fibrosis progressed after the acute phase of infection. Histopathological findings suggest that fatal pulmonary fibrosis persists after the negative conversion of SARS-CoV-2. Elucidating the cause of death by autopsy may help determine therapeutic strategies in patients with COVID-19 and ILD. Vaccination and early administration of anti-inflammatory drugs or antifibrotic agents may be crucial for preventing disease progression and fatal lung fibrosis. This report aims to clarify the histopathological features of COVID-19 in patients with ILD via autopsy and discuss treatment strategies.

Purpose:: Although several factors related to the concomitant meniscal injury at anterior cruciate ligament reconstruction (ACL-R) have been investigated in a general population, few studies have identified the risk factors of meniscal tear severity in young patients in which the majority of ACL tears occur. The purpose of this study was to analyze the associated factors with meniscal injury and irreparable meniscal tear and the timeline for medial meniscal injury at ACL-R in young patients. Methods:: A retrospective analysis of young patients (13 to 29 years of age) who underwent ACL-R by a single surgeon from 2005 to 2017 was conducted. Predictor variables (age, sex,body mass index [BMI], time from injury to surgery [TS], and pre-injury Tegner activity level) for meniscal injury and irreparable meniscal tear were analyzed with multivariate logistic Results:: Four hundred and seventy-three consecutive patients with an average of 31.2 months post-operative follow-up were enrolled in this study. The risk factors for medial meniscus injury were TS (

In this study, we develop a system to provide information on the sterilization of baggage carts and arriving passenger baggage to airport (Hereafter referred as arrival baggage) by using ultraviolet (UV) sterilization and information communication technology as border quarantine measures at airports. This system sterilizes arrival baggage and baggage carts by UV irradiation, and allows passengers to easily view the sterilization information recognized by radio frequency indentation technology. This is to provide safety and security not only to passengers, but also to staff, who may come into direct contact with the arrival baggage, of airport, airline, customs, and so on. In addition, the passengers can be provided with baggage tracking information, such as the current location and estimated delivering time of the baggage. This makes it possible to keep social distancing at baggage claims as an infection prevention. Furthermore, we verify the feasibility of the developed system and identify the issues to be addressed for its practical application through a demonstration of proof of concept at Central Japan International Airport.

Objectives: To assess long-term survival and reoperation-free survival after the arterial switch operation (ASO) and analyze the outcomes of reoperations after hospital discharge. Methods: This was a single-institution retrospective study of 476 hospital survivors of ASO since August 1982. Preoperative diagnoses included 286 transpositions of the great arteries with intact septum, 143 transpositions with ventricular septal defect, and 47 double outlet right ventricles. There were 236 neonatal ASOs, 30 aortic arch repairs, 22 concomitant left ventricular outflow tract obstruction reliefs, 16 preoperative mild pulmonary regurgitations, and 13 intramural coronary arteries. Results: During a median follow-up of 21.1 years (range, 0.1-39.2 years), 25 late deaths (5.3%) and 91 reoperations in 69 patients (14.5%) were noted. The reoperations included 44 left-sided reoperations in 34 patients (7.1%), 35 right-sided reoperations in 30 patients (6.3%), and 12 other reoperations in 12 patients (2.5%). Among the 69 patients who underwent reoperation, those with left-sided reoperations had lower survival at 15 years after reoperation compared to those with non–left-sided reoperations (91.2% vs 100%; P = .015; log-rank, 5.9). Multivariable analysis identified non-neonatal ASO, preoperative pulmonary regurgitation, intramural coronary artery, aortic arch repair, and concomitant left ventricular outflow tract obstruction relief as risk factors for left-sided reoperations. Reoperation-free survival was significantly higher in neonatal ASO compared with non-neonatal ASO (89.2% vs 75.2% at 20 years; P

summary: Purpose: This study aimed to investigate the relationship between the expectations of unit-level nurses from nursing assistants (NAs), frequency of individual NAs' information-sharing behaviors with nurses, and the effect of NAs’ self-perceived roles on this relationship. NAs provide patient care along with nurses, and their information-sharing behaviors with nurses may be influenced by the expectations of the nurses. Methods: Nurses and NAs from 104 integrated community care (sub- and postacute) units were included in this Japanese cross-sectional study conducted from July to September 2018. Nurses' expectations from NAs and the NAs' self-perceived roles and information-sharing frequency were measured. Multilevel mediation analysis was performed for NAs’ information-sharing behaviors, such as expressing, asking, providing linguistic responses, and providing feedback. Results: Unit-level nurses' expectations from NAs were associated with the frequency of NAs' asking and responding behaviors with nurses (p

Background: Cardiomyopathy is a leading cause of sudden out-of-hospital death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. Such unexpected COVID-19-related cardiomyopathies are challenging to diagnose as specific pathological findings are not always identified. Case summary: We reported the autopsy findings of two cases of sudden death due to COVID-19-related cardiomyopathies. In one case, death occurred after SARS-CoV-2 infection, while in the other, after COVID-19 vaccination. We found common pathological findings in both hearts: decreased staining intensity with special stains, loss of rhabdomeres, and multivacuolation in cardiomyocytes without inflammatory cell infiltration. The remaining organs showed no findings that could have contributed to the deaths. Conclusion: In cases of sudden death after SARS-CoV-2 infection or COVID-19 vaccination, the decreased staining intensity with special stains may aid the diagnosis of sudden death due to COVID-19-related cardiomyopathy, even when H&E staining shows few findings.

Muscle echo intensity, as measured by ultrasonography, could be used as a new marker of functional performance in older populations. This scoping review aimed to present evidence on the utility of muscle echo intensity as determined by ultrasonography for assessing functional performance in older adults. The eligibility criterion included observational studies that investigated the associations between muscle echo intensity and functional performance in older adults. Terms, such as “echo intensity” and “older adults”, were searched for in databases, such as PubMed, Web of Science, the Cochrane database of systematic reviews, and the Cumulative Index of Nursing and Allied Health Literature, in April 2021. Two independent reviewers screened and extracted the data; 46 papers, of which almost one-third were Japanese, were subsequently identified for inclusion. The representative functional performances included in this review were muscle strength, gait speed, sit-to-stand test results, and timed up-and-go test results. Poor to moderate associations were found between muscle echo intensity and functional performance; however, heterogeneities were observed in the characteristics of study participants. Moreover, the accurate effect size and causal inferences between muscle echo intensity and functional performance remained unclear. Further longitudinal studies are needed to determine these causal inferences.

Background: The findings of previous studies support the efficacy of cold water immersion (CWI) with carbon dioxide (CO2) in enhancing muscle blood flow and maintaining aerobic performance efficiency. We hypothesize that the addition of hydrogen gas (H2), known for its antioxidant properties and role in inflammation regulation, to C-CWI can enhance recovery after eccentric exercise. Subjects: and Methods: Thirty-four healthy subjects performed a knee-extensor eccentric exercise. They were randomly allocated into four groups: control, CWI, CO2-rich CWI (C-CWI), and CO2 + H2 gas mixture CWI (CH-CWI). In the three CWI groups, all subjects were immersed in the appropriate bath at 20 °C for 20 min immediately after 60 repetitions of eccentric exercise. Before exercise and after 48 h of recovery, the subjects' maximal voluntary isometric contraction torque (MVC-ISO), maximal voluntary concentric (MVC-CON) contraction torque, countermovement jump (CMJ) height, knee flexion range of motion (ROM), muscle soreness, and muscle thickness were measured. Results: In the CH-CWI group only, the MVC-ISO, CMJ height, and ROM did not decrease significantly post-exercise, whereas all of these decreased in the other three groups. Muscle soreness at palpation, contraction, and stretching significantly increased post-exercise in all groups. Echo intensity and tissue hardness did not increase significantly in the CH-CWI group. Conclusions: CH-CWI stimulated recovery from impairments in MVC-ISO torque, CMJ height, knee-flexion ROM, tissue hardness, and echo intensity. These findings indicate that CH-CWI can promote recovery after eccentric exercise.

Summary: Interstitial lung disease (ILD) represents a large group of diseases characterized by chronic inflammation and fibrosis of the lungs, for which therapeutic options are limited. Among several causative genes of familial ILD with autosomal dominant inheritance, the mutations in the BRICHOS domain of SFTPC cause protein accumulation and endoplasmic reticulum stress by misfolding its proprotein. Through a screening system using these two phenotypes in HEK293 cells and evaluation using alveolar epithelial type 2 (AT2) cells differentiated from patient-derived induced pluripotent stem cells (iPSCs), we identified Cryptotanshinone (CPT) as a potential therapeutic agent for ILD. CPT decreased cell death induced by mutant SFTPC overexpression in A549 and HEK293 cells and ameliorated the bleomycin-induced contraction of the matrix in fibroblast-dependent alveolar organoids derived from iPSCs with SFTPC mutation. CPT and this screening strategy can apply to abnormal protein-folding-associated ILD and other protein-misfolding diseases.

The correlation between sensory light flash and proton beam delivery was evaluated by measuring the timing of pulse beam delivery and light flash sensing using an event recorder in an 83-year-old patient receiving proton beam therapy (PBT) for nasopharyngeal adenoid cystic carcinoma. The treatment dose was 65 Gy (RBE) in 26 fractions with 2 ports, and both beams included the visual pathway (retina, optic nerve, chiasma). Measurements were obtained in 13 of the 26 fractions. The patient sensed a light flash in all 13 fractions and pressed the recorder button for 426 of the 430 pulsed beam deliveries, giving a sensing rate of 99.1%. The median duration of button-pressing of 0.3 s was almost the same as that of the beam pulse of 0.2 s, with a reaction time lag of 0.35 s. These results suggest a consistency between light flash during PBT and the timing of irradiation.

In-situ cement-mixing lattice-shaped ground improvement (lattice wall) is one of the effective countermeasures for liquefiable grounds. However, its high cost hinders its wide applicability. This is mainly due to the conventional concept of seismic designs which do not allow any liquefaction of the ground against earthquakes.The recent seismic design code was revised to comply with the concept of performance-based design, which allows some displacement or slight damage to structures, such as pile foundations, during major earthquakes. In order to apply lattice walls to meet the concept of the recent design standard, especially against major earthquakes, it is necessary to establish a rational design method that considers the quantitative effect of lattice walls.In this study, therefore, a series of 1-g field shaking table tests was performed with a lattice wall, and the effect of the wall was carefully evaluated through the quantitative measurement of the stress–strain relationship of the liquefiable ground inside the lattice wall and in the free ground (without a lattice wall). It became possible to quantitatively examine the effect of the wall by installing small accelerometers into the ground with precision.Two major positive effects of the lattice wall were observed through the series of shaking table tests. One was the delay in the onset of liquefaction by the restriction of shear strain, and the other was the recovery of the shear stiffness of the ground even after the onset of liquefaction. These experimental results indicate that lattice walls can be applied as an effective liquefaction countermeasure method, especially when the performance-based design is applied to address large earthquakes.

Background: Parent-child saliva contact during infancy might stimulate the child’s immune system for effective allergy prevention. However, few studies have investigated its relation to allergy development in school-age children. Objective: We sought to investigate the relationship between parent-child saliva contact during infancy and allergy development at school age. Methods: We performed a large multicenter cross-sectional study involving Japanese school children and their parents. The self-administered questionnaires including questions from the International Study of Asthma and Allergies in Childhood were distributed to 3570 elementary and junior high school children in 2 local cities. Data were analyzed for the relationship between saliva contact during infancy (age

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by the infiltration of IgG4-positive plasma cells and fibrosis in organs throughout the body. IgG4-RD involvement in the gastrointestinal (GI) tract (IgG4-related GI disease; IgG4-GID) is rare, and the disease concept remains unclear. Generally, IgG4-GID has been reported with morphological changes, including ulcers, strictures, and submucosal tumors. Here, we report a case of IgG4-GID with persistent diarrhea and abdominal pain in which typical endoscopic findings were absent. This case suggests the unidentified clinical features of IgG4-GID.

Objective: There are many models to predict extracapsular extension (ECE) in patients with prostate cancer. We aimed to externally validate several models in a Japanese cohort. Methods: We included patients treated with robotic-assisted radical prostatectomy for prostate cancer. The risk of ECE was calculated for each patient in several models (prostate side-specific and non-side-specific). Model performance was assessed by calculating the receiver operating curve and the area under the curve (AUC), calibration plots, and decision curve analyses. Results: We identified ECE in 117 (32.9%) of the 356 prostate lobes included. Patients with ECE had a statistically significant higher prostate-specific antigen level, percentage of positive digital rectal examination, percentage of hypoechoic nodes, percentage of magnetic resonance imaging nodes or ECE suggestion, percentage of biopsy positive cores, International Society of Urological Pathology grade group, and percentage of core involvement. Among the side-specific models, the Soeterik, Patel, Sayyid, Martini, and Steuber models presented AUC of 0.81, 0.78, 0.77, 0.75, and 0.73, respectively. Among the non-side-specific models, the memorial Sloan Kettering Cancer Center web calculator, the Roach formula, the Partin tables of 2016, 2013, and 2007 presented AUC of 0.74, 0.72, 0.64, 0.61, and 0.60, respectively. However, the 95% confidence interval for most of these models overlapped. The side-specific models presented adequate calibration. In the decision curve analyses, most models showed net benefit, but it overlapped among them. Conclusion: Models predicting ECE were externally validated in Japanese men. The side-specific models predicted better than the non-side-specific models. The Soeterik and Patel models were the most accurate performing models.

We evaluated the usefulness of an oncolytic virus (Suratadenoturev; OBP-301) against radioresistant oral squamous cell carcinoma. We confirmed the expression of human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor in cell lines. Also, we examined the potential presence in a patient who has received existing therapy that is amenable to treatment with OBP-301. We evaluated: (1) the antitumor effects of OBP-301 alone and in combination with radiotherapy on radioresistant cell lines, (2) the molecular mechanism underlying the radiosensitizing effect and cell death increased by the combination therapy, and (3) the antitumor effect of the combination therapy in vivo using xenograft models (a radioresistant cell line-derived xenograft in mouse and a patient-derived xenograft). Human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor were expressed in all cell lines. OBP-301 decreased the proliferative activity of these cell lines in a concentration-dependent manner, and significantly enhanced the antitumor effect of irradiation. Phosphorylated STAT3 and its downstream molecules, which correlated with apoptosis and autophagy, showed significant changes in expression after treatment with OBP-301. The combination therapy exerted a significant antitumor effect versus radiotherapy alone in both xenograft models. Combination of OBP-301 with radiotherapy exerts a synergistic effect and may represent a promising treatment for radioresistant oral squamous cell carcinoma.

The installation of telescopes with larger primary mirrors in outer space is required for the study of the early universe. However, the shipping, assembling and maintenance of the primary mirror are technical challenges. The primary mirror made of low-melting-point metal (LMPM) enables to simplify these procedures. The rotating liquid metal surface is shaped into a parabola and solidified on the site. The technological feasibility depends on the dynamic transformation of the parabolic LMPM mirror and its optical reflectance. The dynamic transformation of LMPM mirror was clarified by means of experiments with liquid gallium (Ga) which has a melting point of 302.91 K. The parabolic shape of solid Ga mirror was produced by the axial rotation and the solidification. The parabolic shape agreed with the theoretical curve obtained by a physical model. The reflectance spectra on the surface of various LMPMs solidified (i.e., Ga, lead (Pb), tin (Sn), bismuth (Bi), lead-bismuth eutectic (Pb-Bi) and Wood’s metal (Bi-Pb-Sn-Cd)) were measured. The reflectance of Ga solidified was approximately 70 % and was not degraded in the near-infrared wavelength due to the favorable optical characteristics. The reflectance both for p-polarized and s-polarized light of Ga solidified was measured by the spectrophotometer with the polarizer at the angle of incidence of 30°, 45°, 60° and 75°. The trend of measured reflectance agreed with theoretical prediction.

Background: The efficacy of fish oil-based lipid emulsion (FOLE) in treating intestinal failure-associated liver disease and other cholestasis in children has been established. However, it has been found to be ineffective in some patients. This study aimed to identify factors negatively influencing FOLE administration. Methods: This study included 21 patients treated with FOLE, who were less than 100 days old, and had direct bilirubin (D. Bil) levels ≥1.0 mg/dL. Differences in patient backgrounds between patients who eventually had a reduction in jaundice and those who did not, as well as factors affecting treatment duration in the reduction group, were investigated. Results: All four patients of the non-reduction group died of cholestasis and severe comorbidities. The D. Bil level at treatment initiation was significantly higher in the no-reduction group than in the reduction group (p = 0.006). The duration of FOLE administration in the reduction group was negatively correlated with gestational age (ρ = −0.603, p = 0.01). In contrast, a positive correlation was observed between age (ρ = 0.708, p = 0.002) and the D. Bil level at treatment initiation (ρ = 0.490, p = 0.046). Conclusions: FOLE treatment may be ineffective in patients with severe comorbidities. Preterm birth, high D. Bil levels, and older age at treatment initiation may be factors that result in prolonged treatment duration. Level of evidence: III

Mesenchymal stromal cells in the muscle layer of the large intestine are essential for the regulation of intestinal motility. They form electrogenic syncytia with the smooth muscle and interstitial cells of Cajal (ICCs) to regulate smooth muscle contraction. Mesenchymal stromal cells are present in the muscle layer throughout the gastrointestinal tract. However, their area-specific characteristics remain ambiguous.In this study, we compared mesenchymal stromal cells from the large and small intestinal muscle layers. Histological analysis using immunostaining showed that the cells in the large and small intestines were morphologically distinct. We established a method to isolate mesenchymal stromal cells from wild-type mice with platelet-derived growth factor receptor-alpha (PDGFRα) as a marker on the cell surface and performed RNAseq. Transcriptome analysis revealed that PDGFRα+ cells in the large intestine exhibited increased expression levels of collagen-related genes, whereas PDGFRα+ cells in the small intestine exhibited increased expression levels of channel/transporter genes, including Kcn genes. These results suggest that mesenchymal stromal cells differ morphologically and functionally depending on gastrointestinal tract. Further investigations of the cellular properties of mesenchymal stromal cells in the gastrointestinal tract will aid in optimizing methods for the prevention and treatment of gastrointestinal diseases.

Summary: Some Wolbachia endosymbionts induce male killing, whereby male offspring of infected females are killed during development; however, the origin and diversity of the underlying mechanisms remain unclear. In this study, we identified a 76 kbp prophage region specific to male-killing Wolbachia hosted by the moth Homona magnanima. The prophage encoded a homolog of the male-killing gene oscar in Ostrinia moths and the wmk gene that induces various toxicities in Drosophila melanogaster. Upon overexpressing these genes in D. melanogaster, wmk-1 and wmk-3 killed all males and most females, whereas Hm-oscar, wmk-2, and wmk-4 had no impact on insect survival. Strikingly, co-expression of tandemly arrayed wmk-3 and wmk-4 killed 90% of males and restored 70% of females, suggesting their conjugated functions for male-specific lethality. While the male-killing gene in the native host remains unknown, our findings highlight the role of bacteriophages in male-killing evolution and differences in male-killing mechanisms among insects.

In late years, combination of Cisplatin and Docetaxel, S-1 (as follows: a TPS therapy) show a high effect in induction chemotherapy in the oral carcinoma, we are said to be it, and it is used. We receive TPS therapy for carcinoma in the oral floor (T2N2bM0) this time and report our experience with the case that had a complete response. 61-years-old men, with squamous cell carcinoma in the Left oral floor (T2N2bM0) was diagnosed than a clinical examination and image findings, an examination of histopathology. Because it was local progressive carcinoma, perform induction chemotherapy in a TPS therapy preoperative tumor reduction. The primary tumor, the cervical metastasis lymph nodes reduced after 1 course end remarkably. We performed floor of mouth part tumor resection and all left neck dissection. The histologic effect of treatment judgment were Grade3 for histopathology. Resist evaluation was CR. We follow it up, but it is primary and the cervical lymph nodes recurrence does not show it now either.

Introduction: Sleeve gastrectomy is the most common surgical procedure to reduce weight and treat metabolic complications in patients with moderate-to-severe obesity; however, it affects the musculoskeletal system. Dual-energy X-ray absorptiometry (DXA), which is commonly used to measure bone mineral density (BMD), may be affected by excess fat tissue around the bones, interrupting BMD measurement. Due to the strong correlation between DXA and the Hounsfield units (HU) obtained from computed tomography (CT) scans, BMD assessment using clinical abdominal CT scans has been useful. To date, there has been no report of detailed CT evaluation in patients with severe obesity after sleeve gastrectomy. Objective: This study investigated the effect of sleeve gastrectomy in severely obese patients on bone and psoas muscle density, and cross-sectional area using retrospective clinical CT scans. Methods: This was a retrospective observational study that included 86 patients (35 males and 51 females) who underwent sleeve gastrectomy between March 2012 and May 2019. Patients' clinical data (age at the time of surgery, sex, body weight, body mass index (BMI), comorbidities, and preoperative and postoperative blood test results, HU of the lumbar spine and psoas muscle and psoas muscle mass index (PMI)) were evaluated. Results: The mean age at the time of surgery was 43 years, and the body weight and BMI significantly reduced (p