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Abstract Evaluating complicated stress across the elbow under joint motion remains difficult. Here, we aimed to evaluate the distribution of the subchondral bone density in the normal elbow bones and further characterize their spatial relationships during elbow motion to estimate the loading stress across the articular surface using three-dimensional computed tomography bone models. The normal elbow joint exhibited a consistent distribution pattern of subchondral bone density. High-density regions were distributed in the capitellum and posterior humeral trochlea, sagittal ridge of the ulnar trochlear notch and ulnar-volar side of the radial head. Motion analyses revealed that the high-density regions proximate with elbow flexion with forearm pronation in the radiocapitellar joint and in the fully extended position in the ulnohumeral joint. This reasonably reflects the stress acting on the joint surface under actual loading conditions. These findings suggest that daily activities involving lifting or carrying objects in these positions are stress-prone activities.

Aim: To investigate the characteristics and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atz/Bev) who achieved a complete response (CR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Methods: A total of 120 patients with Eastern Cooperative Oncology Group performance status (PS) 0 or 1 and Child–Pugh A at the start of Atz/Bev treatment were included. Barcelona Clinic Liver Cancer stage C was recorded in 59 patients. Results: The CR rate with Atz/Bev alone was 15.0%. The median time to CR was 3.4 months, and the median duration of CR was 15.6 months. A significant factor associated with achieving CR with Atz/Bev alone was an AFP ratio of 0.34 or less at 3 weeks. Adding transarterial chemoembolization (TACE) in the six patients who achieved a partial response increased the overall CR rate to 20%. Among the 24 patients who achieved CR, the median progression-free survival was 19.3 months, the median overall survival was not reached, and 14 patients (58.3%) were able to discontinue Atz/Bev and achieve a drug-free status. Twelve of these patients developed progressive disease (PD), but eleven successfully received post-PD treatments and responded well. Conclusions: Achieving CR by mRECIST using Atz/Bev alone or with additional TACE can be expected to offer an extremely favorable prognosis.

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Forty patients were enrolled in this retrospective evaluation of treatment outcomes. According to the Response Evaluation Criteria for Solid Tumors version 1.1 at 8 weeks, the objective response (OR) rate was 25% and the disease control (DC) rate was 57.5%. The median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.39 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.08 in the non-8W-OR group (p = 0.0068); however, it was 1.22 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.53 in the 8W-DC group (p = 0.0006). Similarly, the median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.15 in the 8W-OR group, significantly lower than the 1.46 in the non-8W-OR group (p < 0.0001); however, it was 1.23 in the non-8W-DC group, significantly higher than the 0.49 in the 8W-DC group (p = 0.0215). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre.

Abstract Background Inherited glycosylphosphatidylinositol (GPI) deficiency is an autosomal recessive disease and a set of syndromes caused by different genes involved in the biosynthesis of phosphatidylinositol characterized by severe cognitive disability, elevated serum alkaline phosphatase (ALP) levels, and distinct facial features. This report presents a patient with inherited GPI deficiency caused by a homozygous frameshift variant of PGAP3 due to uniparental isodisomy (UPiD) on chromosome 17. Method Clinical characteristics of the patient were collected. Microarray analysis followed by adaptive sampling sequencing targeting chromosome 17 was used for the identification of variants. Sanger sequencing was used to confirm the variant in the target region. Results The patient was born at 38 weeks of gestation with a birthweight of 3893 g. He had a distinctive facial appearance with hypertelorism, wide nasal bridge, and cleft soft palate. Postnatal head magnetic resonance imaging revealed a Blake's pouch cyst. The serum ALP level was 940 IU/L at birth and increased to 1781 IU/L at 28 days of age. Microarray analysis revealed region of homozygosity in nearly the entire region of chromosome 17, leading to the diagnosis of UPiD. Adaptive sampling sequencing targeting chromosome 17 confirmed the homozygous variant NM_033419:c.778dupG (p.Val260Glyfs*14) in the PGAP3 gene, resulting in a diagnosis of inherited GPI deficiency. Conclusion This is the first report of inherited GPI deficiency caused by UPiD. Inherited GPI deficiency must be considered in patients with unexplained hyperphosphatasemia.

Abstract Osteogenesis imperfecta is characterized by frequent fractures, bone deformities, and other systemic symptoms. Severe osteogenesis imperfecta may progress to hydrocephalus; however, treatment strategies for this complication remain unclear. Here, we describe severe osteogenesis imperfecta in an infant with symptomatic hydrocephalus treated with ventriculosubgaleal shunt placement. Targeted next-generation sequencing revealed novel compound heterozygous CRTAP variants, i.e., NM_006371.5, c.241 G > T, p.(Glu81*) and NM_006371.5, c.923-2_932del. We suggest that ventriculosubgaleal shunt placement is an effective and safe treatment for hydrocephalus in patients with severe osteogenesis imperfecta.

Abstract Background Right atrial myxoma is a rare cardiac tumor, with few reports on its growth rate. Case presentation We found a right atrial myxoma in a male patient in his 80s with chronic kidney disease on the second echocardiogram that was performed for the creation of an arteriovenous fistula at 9 months after the initial echocardiogram, which showed no evidence of myxoma. Echocardiography revealed a mass measuring 37 mm × 28 mm in the right atrium. The patient was asymptomatic, and the tumor was surgically removed. Conclusions To the best of our knowledge, our patient is the oldest compared with all the patients in previously reported cases of rapidly growing right atrial tumors.

Abstract This study aimed to reproduce and analyse the in vivo dynamic rotational motion of the forearm and to clarify forearm motion involvement and the anatomical function of the interosseous membrane (IOM). The dynamic forearm rotational motion of the radius and ulna was analysed in vivo using a novel image-matching method based on fluoroscopic and computed tomography images for intensity-based biplane two-dimensional–three-dimensional registration. Twenty upper limbs from 10 healthy volunteers were included in this study. The mean range of forearm rotation was 150 ± 26° for dominant hands and 151 ± 18° for non-dominant hands, with no significant difference observed between the two. The radius was most proximal to the maximum pronation relative to the ulna, moved distally toward 60% of the rotation range from maximum pronation, and again proximally toward supination. The mean axial translation of the radius relative to the ulna during forearm rotation was 1.8 ± 0.8 and 1.8 ± 0.9 mm for dominant and non-dominant hands, respectively. The lengths of the IOM components, excluding the central band (CB), changed rotation. The transverse CB length was maximal at approximately 50% of the rotation range from maximum pronation. Summarily, this study describes a detailed method for evaluating in vivo dynamic forearm motion and provides valuable insights into forearm kinematics and IOM function.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Summary: Evidence of hot and cold igneous processes has been reported in small satellites and dwarf planets of the Solar System. Olivine and pyroxenes were detected in the spectral bands of both small satellites and dwarf planets. The aqueously altered form of olivine and serpentine has been detected in the spectrums of Ceres and Miranda hinting at possible hydrothermal processes in their interiors. Once more, the ubiquitous distribution of 26Al in the planetary nebula, then evolving in the protoplanetary disk, contributed to the primordial widespread heating. Volcanism, or cryovolcanism, then developed only in those bodies where long-lived radiogenic elements, and/or tidal processes, were available.

Background: Acute generalized eruptive pustulosis (AGEP) is a rare, but serious, drug-related adverse event. This study aimed to determine the relationships between AGEP and age, sex, primary disease, and prescription medications using a database of adverse drug events, namely, the Japanese Adverse Drug Event Report (JADER) database. Methods: In this retrospective observational study, we analyzed AGEP reports extracted from the JADER database based on the preferred term for AGEP (code 10048799). We evaluated the effects of causative drugs, underlying diseases, age, and sex. The association between AGEP and prescription drugs was analyzed using the reporting odds ratio and adjusted for covariates using multiple logistic regression. Association rule mining was performed to evaluate the correlation between each combination of factors and AGEP. Results: Between April 2004 and March 2023, 823,662 reports, including 869 reports on AGEP, were entered in the JADER database. The highest percentage of reports in each age group was in males aged

Background and Objectives: The predicted serum concentrations of vancomycin are determined using population pharmacokinetic parameters. However, the accuracy of predicting vancomycin serum concentrations in the older population remains unclear. Therefore, this study aimed to investigate the accuracy of predicting vancomycin serum concentrations and identifying elements that diminish the prediction accuracy in older people. Materials and Methods: A total of 144 patients aged 75 years or older were included. The serum vancomycin concentrations in the patients were predicted based on population pharmacokinetic parameters common in Japan. We examined the accuracy of serum vancomycin concentration prediction in elderly individuals by comparing the predicted and measured serum vancomycin concentrations in each patient. The prediction accuracy was evaluated using the mean prediction error (ME) and mean absolute error of prediction (MAE) calculated from the measured and predicted serum vancomycin concentrations in each patient. Results: The ME for all patients was 0.27, and the 95% CI included 0, indicating that the predicted values were not significantly biased compared to the measured values. However, the predicted serum concentrations in the Conclusions: Our prediction accuracy was satisfactory but tended to be lower in underweight patients, those with low creatinine levels, and patients admitted to the ICU. Patients with multiple of these factors may experience a greater degree of decreased predictive accuracy.

Monoclonal antibodies (Mabs) are widely used in a variety of fields, including protein identification, life sciences, medicine, and natural product chemistry. This review focuses on Mabs against naturally occurring active compounds. The preparation of Mabs against various active compounds began in the 1980s, and now there are fewer than 50 types. Eastern blotting, which was developed as an antibody staining method for low-molecular-weight compounds, is useful for its ability to visually represent specific components. In this method, a mixture of lower-molecular-weight compounds, particularly glycosides, are separated by thin-layer chromatography (TLC). The compounds are then transferred to a membrane by heating, followed by treatment with potassium periodate (KIO4) to open the sugar moiety of the glycoside on the membrane to form an aldehyde group. Proteins are then added to form Schiff base bonds to enable adsorption on the membrane. A Mab is bound to the glycoside moiety on the membrane and reacts with a secondary antibody to produce color. Double Eastern blotting, which enables the simultaneous coloration of two glycosides, can be used to evaluate quality and estimate pharmacological effects. An example of staining by Eastern blotting and a component search based on the results will also be presented. A Mab-associated affinity column is a method for isolating antigen molecules in a single step. However, the usefulness of the wash fractions that are not bound to the affinity column is unknown. Therefore, we designated the wash fraction the “knockout extract”. Comparing the nitric oxide (NO) production of a glycyrrhizin (GL)-knockout extract of licorice with a licorice extract revealed that the licorice extract is stronger. Therefore, the addition of GL to the GL-knockout extract of licorice increased NO production. This indicates that GL has synergic activity with the knockout extract. The GL-knockout extract of licorice inhibited high-glucose-induced epithelial–mesenchymal transition in NRK-52E cells, primarily by suppressing the Notch2 pathway. The real active constituent in licorice may be constituents other than GL, which is the causative agent of pseudohyperaldosteronism. This suggests that a GL-knockout extract of licorice may be useful for the treatment of diabetic nephritis.

Abstract Globally, bread wheat (Triticum aestivum) is one of the most important staple foods; when exposed to drought, wheat yields decline. Although much research has been performed to generate higher yield wheat cultivars, there have been few studies on improving end-product quality under drought stress, even though wheat is processed into flour to produce so many foods, such as bread, noodles, pancakes, cakes, and cookies. Recently, wheat cultivation has been affected by severe drought caused by global climate change. In previous studies, seed shrinkage was observed in wheat exposed to continuous drought stress during seed development. In this study, we investigated how progressive drought stress affected seed development by metabolomic and transcriptomic analyses. Metabolite profiling revealed the drought-sensitive line reduced accumulation of proline and sugar compared with the water-saving, drought-tolerant transgenic line overexpressing the abscisic acid receptor TaPYL4 under drought conditions in spikelets with developing seeds. Meanwhile, the expressions of genes involved in translation, starch biosynthesis, and proline and arginine biosynthesis was downregulated in the drought-sensitive line. These findings suggest that seed shrinkage, exemplifying a deficiency in endosperm, arose from the hindered biosynthesis of crucial components including seed storage proteins, starch, amino acids, and sugars, ultimately leading to their inadequate accumulation within spikelets. Water-saving drought tolerant traits of wheat would aid in supporting seed formation under drought conditions.

Abstract In Japan, wasabi (Eutrema japonicum) is an important traditional condiment, and is recognized as an endemic species. In the present study, we generated a chromosome-level and haplotype-resolved reference genome for E. japonicum using PacBio CLR (continuous long reads), Illumina, and Hi-C sequencing data. The genome consists of 28 chromosomes that contain 1,512.1 Mb of sequence data, with a scaffold N50 length of 55.67 Mb. We also reported the subgenome and haplotype assignment of the 28 chromosomes by read-mapping and phylogenic analysis. Three validation methods (Benchmarking Universal Single-Copy Orthologs, Merqury, and Inspector) indicated that our obtained genome sequences were a high-quality and high-completeness genome assembly. Comparison of genome assemblies from previously published genomes showed that our obtained genome was of higher quality. Therefore, our genome will serve as a valuable genetic resource for both chemical ecology and evolution research of the genera Eutrema and Brassicaceae, as well as for wasabi breeding.

We conducted a preliminary survey of the wild common palm civet Paradoxurus hermaphroditus in a secondary forest in Pangandaran Nature Reserve, West Java, Indonesia. We collected 125 fresh fecal samples between October 2018 and August 2019. We conducted faecal analyses after species confirmation by camera trapping and faecal DNA analysis. Almost all faeces contained fruits and seeds (frequency of occurrence: 97.6%), while the percentage of animal matter (including mammals, birds, insects, non-insect arthropods, and molluscs) was much lower (22.4%). We observed no seasonal differences in major faecal contents. Higher dependence on fruits by the common palm civets was similar to those in other study sites. Seeds of at least eight different plant species were found in the faeces of the common palm civets, which implied that the common palm civets would play roles as seed dispersal agents.

Abstract Vibration acceleration (VA) using a whole‐body vibration device is beneficial for skeletal muscles. However, its effect at the cellular level remains unclear. We aimed to investigate the effects of VA on muscles in vitro and in vivo using the C2C12 mouse myoblast cell line and cardiotoxin‐induced injury in male rat soleus muscles. Cell proliferation was evaluated using the WST/CCK‐8 assay and proportion of Ki‐67 positive cells. Cell migration was assessed using wound‐healing assay. Cell differentiation was examined by the maturation index in immunostained cultured myotubes and real‐time polymerase chain reaction. Regeneration of soleus muscle in rats was assessed by recruitment of satellite cells, cross‐sectional area of regenerated muscle fibers, number of centrally nucleated fibers, and conversion of regenerated muscle from fast‐ to slow‐twitch. VA at 30 Hz with low amplitude for 10 min promoted C2C12 cell proliferation, migration, and myotube maturation, without promoting expression of genes related to differentiation. VA significantly increased Pax7‐stained satellite cells and centrally nucleated fibers in injured soleus muscles on Day 7 and promoted conversion of fast‐ to slow‐twitch muscle fibers with an increase in the mean cross‐sectional area of regenerated muscle fibers on Day 14. VA enhanced the proliferation, migration, and maturation of C2C12 myoblasts and regeneration of injured rat muscles.

Abstract A 60‐year‐old man who had been keeping seven budgerigars and four cockatiels in his house for 2 years developed dyspnea and was admitted to our hospital the day after receiving the second dose of the messenger RNA coronavirus disease 2019 vaccination. Chest high resolution computed tomography (HRCT) showed bilateral ground glass opacities without nodules or mosaic attenuation. IgG specific for budgerigars was positive. Although his respiratory symptoms were resolved without corticosteroid therapy, he developed severe dyspnea soon after the discharge to his home. The results of bronchial alveolar lavage fluid obtained at the initial admission and after the provocation challenge showed elevation of lymphocytes (34%) and eosinophils (37%). We finally diagnosed him with non‐fibrotic bird‐related hypersensitivity pneumonitis. His condition and HRCT findings were improved by corticosteroid treatment. All his birds were given away. He has not experienced any recurrence or deterioration of respiratory function even after withdrawal of corticosteroid.

Food allergies (FAs) are caused by a failure of the immune system to regulate oral tolerance (OT). The use of soap containing hydrolyzed wheat overrides acquired OT to wheat through skin exposure. However, in mouse models, the experimental OT is robust, suggesting that acquired OT to allergens prevents the development of FAs. We aimed to analyze the mechanisms and developed a mouse model of FA that overrides acquired OT via skin exposure. Three murine FA models (intraperitoneal [IP], epicutaneous [EC], and intradermal [ID]) were compared to evaluate if allergies to ovalbumin (OVA) that had been previously tolerated orally could be induced. In the ID model, OT was overridden, and allergic reactions of severe anaphylaxis were developed. To analyze this effect in the ID model, we measured the migration of dendritic cells (DCs) into lymph nodes. The induction of OT promoted the migration of CD103+ dermal DCs; moreover, repeated percutaneous doses of OVA for sensitization gradually increased the migration of CD11b+ dermal DCs. The difference in the proportion of regulatory T cells between ID-sensitized groups at the first ID injection disappeared at the tenth injection. Although OT was robust in the IP model, ID sensitization was found to override OT.

Oral mucositis (OM) is one of the most common adverse events associated with antineoplastic drug treatment. Studies on the risk of antineoplastic drug-induced OM and its prevention are limited. We, therefore, conducted a disproportionality analysis of antineoplastic drug-induced OM and explored candidate preventive drugs for OM using the Japanese Adverse Drug Event Report (JADER) database. The JADER database showed that between April 2004 and March 2022, antineoplastic drug-related adverse events were reported in 210,822 cases, of which 2922 were OM. Forty-two drugs appeared to be associated with OM. The weibull distribution showed different patterns of time-to-onset depending on the type of antineoplastic drug administered. Cluster analyses classified antineoplastic drugs according to the typical symptoms of OM. These findings suggest that antineoplastic drug-induced OM should be monitored based on expression patterns of symptoms. Upon analyzing the inverse association, several concomitant drugs, including lenalidomide hydrate and febuxostat, were expected to be candidate preventive drugs for antineoplastic drug-induced OM. Concomitant drugs that showed an inverse association with antineoplastic drug-induced OM differed within the Anatomical Therapeutic Chemical classification. These findings could serve as a reference when considering drugs that should be prioritized to validate their prophylactic effect against antineoplastic-induced OM in the future.

Abstract Aim This study aimed to examine the effects of real‐time online clinical practice using real‐time virtual reality (VR) compared with 2D PC screening on reducing stigma toward dementia, and to investigate the feasibility of online clinical practice using VR. Methods A single‐center, open‐label, randomized controlled trial was conducted. Occupational therapy students were randomized to view occupational therapy evaluation screens for dementia patients using a VR headset or 2D monitor. The Attitudes Toward Dementia Scale (ADS), the Dementia Knowledge Scale (DKS), and Images of the Elderly with Dementia (IED) were assessed before and after the intervention. The level of clinical practice satisfaction and the System Usability Scale (SUS) were also assessed. Results The number of subjects in the intervention and control groups was 10 and 9, respectively. In ADS scores and IED, the main effect was shown in both groups and did not show interactions. In DKS scores, the main effect and interaction were not shown. The VR headset tended to be more usable than the 2D monitor in terms of usability. Satisfaction ratings indicated the characteristics of a realistic clinical experience through real‐time VR viewing. Conclusion Real‐time VR and 2D online clinical practice could reduce the stigma toward dementia, but there were no significant differences between the types. The real‐time VR experience was more similar to actual clinical practice than a 2D PC screening due to the sense of immersion, but issues in blinding and lack of audio and video quality were found.

Background: Pelvic lymphocele (lymphocyst) infection after lymphadenectomy is a rare complication that can cause the spread of inflammation to neighboring organs whose microbiology is not well known. Cutibacterium avidum causes various infections. However, no case reports of C. avidum pelvic lymphocele infection are available; therefore, its clinical characteristics in pelvic lymphocele infections remain unknown. Case presentation: A 38-year-old woman with obesity (body mass index: 38.1 kg/m2) and a history of pelvic lymphadenectomy and chemotherapy for endometrial cancer presented with worsening left lower quadrant (LLQ) pain with fever. Physical examination revealed decreased abdominal bowel sounds and tenderness on LLQ palpation with no signs of peritonitis. Computed tomography (CT) revealed an infected left pelvic lymphocele with inflammation spreading to the adjacent sigmoid colon. Following blood culture, ampicillin/sulbactam (2 g/1 g every 6 h) was administered intravenously. Anaerobic culture bottles revealed gram-positive rods on day 4 of incubation at 37 °C. No other disseminated foci were observed in enhanced whole-body CT and upon transthoracic echocardiography. The isolates grew aerobically and anaerobically on blood agar plates with strong hemolysis. The bacterium was identified as C. avidum using a combination of characteristic peak analysis with matrix-assisted laser desorption ionization (MALDI) and 16S rRNA gene sequencing. The patient was diagnosed with C. avidum pelvic lymphocele infection. Based on penicillin susceptibility, the patient was successfully treated with intravenous ampicillin/sulbactam and de-escalated with intravenous ampicillin (2 g every 6 h) for 10 days, followed by oral amoxicillin (2000 mg/day) for an additional 11 days without drainage. Conclusions: C. avidum should be considered a causative microorganism of pelvic lymphocele infection. Peak analysis using MALDI and distinctive growth on blood agar plates are suitable for identifying C. avidum. Mild pelvic lymphocele caused by C. avidum can be treated with a short course of appropriate antimicrobial treatment without surgical intervention.

Roads on peat grounds are subject to stringent requirements in terms of controlling the residual settlement during their service period in order to minimize the post-construction maintenance work. This paper addresses the applicability of the Finite Element Method (FEM) by incorporating a time-dependent model for peats to an evaluation of the residual settlement. The applicability of isotach viscoplasticity, used to describe the peats’ behavior under variable-rate compression, was confirmed in laboratory tests. Long-term consolidation test results and a model simulation revealed the particular importance of two mechanisms in the residual settlement in peat grounds, namely, the stress-dependency of the coefficient of consolidation, cv, and the viscosity-induced secondary consolidation. A model peat ground, capturing these mechanisms, was implemented for the FEM and applied to a case history of a high-standard road construction in Hokkaido, Japan. The viscoplastic parameters determined from standard oedometer tests successfully reproduced the observed long-term settlement in a peat-dominated section of the expressway. The analysis was extended to address the settlement in the peat ground with the installation of prefabricated vertical drains (PVDs). The results indicate that the delayed primary consolidation due to the stress-induced cv reduction can be significantly alleviated, while the settlement arising from the secondary consolidation over a longer term is little affected by the PVDs. These insights point to the importance of untangling the two mechanisms of long-term settlement for the sake of making accurate predictions of the residual settlement in different time scales.

A soil investigation was conducted in peatlands in Japan, using two types of tube sampling methods, and the quality of the samples was evaluated. Unlike clays, peats easily lose water by compressive actions involved in sampler intrusion and core extrusion, leading to a significant loss of pore water. It was shown that this effect could be minimized by careful thin-wall sampling with a stationary piston, whereas open-drive sampling without a piston led to the significant compression of the sample core. The consequence of this disturbance on the in-situ behavior was interpreted through an examination of the mechanical properties of peat samples subjected to the “strain paths” expected during sampling in laboratory tests. By observing the deformation characteristics through a series of constant-rate-of-strain consolidation, unconfined compression, triaxial compression, and bender element tests, it was demonstrated that, contrary to soft clays, fibrous peats with high initial permeability potentially lead to the underestimation of the settlement during construction and the overestimation of strength due to inappropriate sampling. These results can be explained by the dominance of densification by disturbance over soil structure degradation. It was also noted that the sample quality varied considerably within the sampling tube.

Abstract Background Hyalinizing trabecular tumor is a rare follicular cell-derived thyroid neoplasm that is considered to be a borderline tumor with malignant potential rather than a benign tumor. The detection of RET/PTC rearrangements and nuclear cytologic features suggests a relationship between hyalinizing trabecular tumor and papillary thyroid carcinoma. Some recent observations of pathogenic genetic alterations in hyalinizing trabecular tumor have indicated that hyalinizing trabecular tumor is not related to papillary thyroid carcinoma, and should be considered an independent entity. Here we present a case of papillary thyroid carcinoma with hyalinizing trabecular tumor-like features and discuss its interesting aspects and diagnostic issues from a histopathological perspective. Case presentation A 19-year-old Japanese woman with an enlarged thyroid gland was admitted to our hospital. Based on fine-needle aspiration cytology, the enlarged nodule was suspected to be a follicular lesion or follicular tumor. A nodular lesion approximately 3 cm in diameter was detected in the left lobe of the thyroid gland. Histological analysis revealed that the tumor cells were mainly arranged in follicles. Solid nests with occasional trabecular arrangements and papillary structures were intermingled, and the tumor cells showed ground-glass nuclei and occasional nuclear grooving. Petaloid and block-like periodic-acid-Schiff and periodic-acid-methenamine-positive basement membrane components were observed in the interstitium of the solid portions of the tumor. Incomplete membranous immunoreactivity of MIB-1 (Ki-67 (cell prolferation marker)) was also observed in the cells within the solid areas. Moreover, this tumor displayed extracapsular invasion and metastasis to the perithyroidal lymph nodes, suggesting that it may be a malignant tumor. However, BRAF V600E mutation, RET/PTC rearrangements, and PAX8/GLIS 1 and PAX8/GLIS 3 rearrangements were not detected. Conclusion We diagnosed the tumor as a papillary thyroid carcinoma with characteristic features of hyalinizing trabecular tumor. Importantly, this case may indicate a possible relationship between papillary thyroid carcinoma and hyalinizing trabecular tumor, although specific genetic alterations could not be detected. We also discuss the preoperative diagnostic difficulties with fine-needle aspiration cytology and the unusual pathological findings in this case.

Abstract Background We previously reported that a standardized pharmacist check of medical orders related to the administration criteria of anticancer drugs prior to preparation of injectable anticancer drugs was useful for reducing drug wastage after mixing. To further reduce anticancer drug wastage after preparation, we added a pharmacist check of patients' infection-related condition to the previous protocol and assessed the effectiveness of the modified protocol for reducing injectable anticancer drug wastage. Methods In addition to the administration criteria of anticancer drugs, patients’ infection-related condition, which was based on a body temperature ≥ 37.5 °C or elevated C-reactive protein (CRP) or white blood cell (WBC) count from baseline, was added to pharmacists’ checklist of items used previously to prepare injectable anticancer drugs. We retrospectively compared the number, type and cost of anticancer drugs discarded after preparation and the reasons for discarding these drugs between pre- and post-protocol modification. Results The rate at which anticancer drugs were discarded after preparation was significantly reduced after introducing the modified protocol compared to the original protocol (0.288% [18/6253] vs. 0.095% [6/6331], P = 0.013). Furthermore, the number of cases for which mixed anticancer agents were discarded because of infection decreased from 11 (fever: n = 8; elevated CRP or WBC: n = 3) to one (elevated CRP: n = 1) a year. Conclusions In addition to the standard administration criteria of anticancer drugs, checking patients’ infection-related condition, defined by a body temperature ≥ 37.5 °C or elevated CRP or WBC from baseline, before mixing by the pharmacist is useful for reducing anticancer drug wastage after preparation.

The characteristic of inverted singlet-triplet excited states, in which the lowest singlet excited state (S _1 ) is lower than the lowest triplet state (T _1 ) in energy, was observed in a dialkylamine-substituted pentaazaphenalene derivative, 5AP-N(C12) _2 . The transient photoluminescence measurements showed that the reverse intersystem crossing has virtually zero activation energy, whereas the intersystem crossing is proceeded by a thermal activation process. T _1 was located energetically above S _1 with a negative energy gap between S _1 and T _1 (Δ E _ST ) of −37 meV. Fluorescence and phosphorescence spectra also confirmed the negative Δ E _ST of −46 to −32 meV.

Abstract The diagnosis of bile duct tumors can be difficult at times. A transpapillary bile duct biopsy findings with endoscopic retrograde cholangiopancreatography sometimes contradict diagnostic imaging findings. In bile duct tumors, inflammatory polyps in the extrahepatic bile duct are relatively rare with extrahepatic cholangitis. The disease's clinical relevance, including its natural history and prognosis, is not always clear. We show here a rare case of an inflammatory polyp in the common bile duct. A 69‐year‐old woman with abdominal pain was diagnosed with cholangitis. The findings of contrast‐enhanced computed tomography and magnetic resonance cholangiopancreatography suggested that she had extrahepatic cholangiocarcinoma. The examination and therapy of cholangitis were performed by endoscopic retrograde cholangiopancreatography. The cholangiography revealed a suspected tumor in the hilar bile duct with some common bile duct stones. Then, after endoscopic sphincterotomy to remove tiny common bile duct stones, further detailed examinations were performed at the same time using an oral cholangioscope revealed a papillary raised lesion with a somewhat white surface in the bile duct; a biopsy was conducted on the same spot, and epithelial cells with mild atypia appeared in the shape of a papilla. Since the malignant tumor or the intraductal papillary neoplasm of the bile duct could not be ruled out, extrahepatic bile duct resection was conducted with the patient's informed consent. Bile duct inflammatory polyp was the histopathological diagnosis.

Abstract Background Cutibacterium modestum is one of the five species of the genus Cutibacterium. While C. acnes has been reported as an important pathogen in bone and joint infections, the clinical characteristics of C. modestum infections remain unclear. Moreover, thus far, there has been no clinical case report regarding C. modestum infections. Case presentation An 82-year-old man with a history of repeated trigger point injections for lumbago at the L4 level presented with fever and an exacerbation of lumbago. Physical examination indicated knocking pain at the L4–L5 levels; magnetic resonance imaging showed irregular bone destruction of the L4 vertebral body, and low T1 and high T2 intensity lesions at the L4–L5 intervertebral disc. Two sets of blood cultures (two aerobic and two anaerobic) were performed. Intravenous cefazolin was administered, considering the common pathogens of vertebral osteomyelitis, such as Staphylococcus aureus. The patient’s condition did not improve; thereafter, anaerobic culture bottles revealed Gram-positive rods on day 11 of incubation. There was no evidence of infective endocarditis upon transthoracic echocardiography. Needle aspiration from the L4–L5 intervertebral disc was performed on day 13 that also showed the presence of Gram-positive rods. The patient was diagnosed with vertebral osteomyelitis caused by C. modestum using a combination of characteristic peak analysis with matrix-assisted laser desorption ionization (MALDI), microbial biochemistry examinations, and 16S rRNA gene sequencing from the blood and pus cultures. He was successfully treated with alternative intravenous ampicillin, followed by oral amoxicillin for 10 weeks, according to the tests for ampicillin susceptibility, with a minimum inhibitory concentration of 0.016 μg/mL using E-test® under aerobic conditions. Conclusions Cutibacterium modestum is a microorganism that is difficult to identify. A combination of characteristic peaks with MALDI, appropriate microbial biochemical examinations, and 16S rRNA gene sequencing may serve as an efficient guide for the identification of C. modestum.

Background: Bronchoalveolar lavage (BAL) has widely been used to manage respiratory diseases including respiratory infections. The aim of this study was to evaluate the diagnostic yield of BAL for detecting nontuberculous Mycobacterium (NTM). Methods: We retrospectively reviewed the records of 54 patients who underwent bronchoscopy due to suspected NTM pulmonary disease. Positive culture results of respiratory specimens were defined as NTM pulmonary disease. For BAL, two or three aliquots of 50 mL (total 100 or 150 mL) of sterile normal saline were instilled through bronchoscope. Results: NTM was detected in 31 of 54 (57.4%) patients. The detection rates were not different between the patients who underwent bronchoscopy with BAL (24 of 39, 61.5%) and those without (7 of 15, 46.7%) (P = 0.437). BAL fluid was mostly neutrophil dominant in both positive and negative NTM culture groups. In the subgroup analysis of 33 patients who underwent both the BAL and anti- glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody measurements, 12 of 19 (63.2%) positive Mycobacterium avium complex (MAC) culture patients and 8 of 14 (57.1%) negative MAC culture patients were positive for anti-GPL-core IgA antibody (seropositive) (P = 0.991). There was no severe complication related to BAL. Conclusions: The diagnostic yield of BAL with ≥100 mL sterile saline was not superior to that of bronchial wash or sputum aspiration in patients with suspected NTM pulmonary disease. Patients with seropositive but negative culture results for MAC suggest pseudonegative for pulmonary MAC disease.

Chronic pancreatitis (CP) is pathologically characterized by the loss of exocrine pancreatic parenchyma, irregular fibrosis, cellular infiltration, and ductal abnormalities. Diagnosing CP objectively is difficult because standard diagnostic criteria are insufficient. The change of parenchymal hardness is the key factor for the diagnosis and understanding of the severity of CP. The ultrasonography (US) or endoscopic ultrasonography (EUS) elastography have been used to diagnose pancreatic diseases. Both strain elastography (SE) and shear wave elastography are specific diagnostic techniques for measuring tissue hardness. Most previous studies were conducted with SE. There are three methods of interpreting SE; the method of recognizing the patterns in SE distribution images in the region of interest, the method of using strain ratio to compare the hardness of adipose tissue or connective tissue with that of the lesion, and the method of evaluating the hardness distribution of a target by histogram analysis. These former two methods have been used primarily for neoplastic diseases, and histograms analysis has been used to assess hardness distribution in the evaluation of CP. Since the hardness of the pancreas increases with aging, it is necessary to consider the age in the diagnosis of pancreatic disorders using US or EUS elastography.

Fusobacterium nucleatum rarely causes vertebral osteomyelitis or liver abscesses, and no reports exist of it concurrently causing vertebral osteomyelitis and pyogenic liver abscess. A 58-year-old woman with a history of periodontitis presented with worsening lumbago, left lower leg pain, numbness, and fever for a week. Physical examination indicated knocking pain at the L2–L3 levels with a psoas sign on the left side. A magnetic resonance image showed L2–S1 vertebral osteomyelitis and intervertebral discitis, with a left psoas major muscle abscess. Vertebral osteomyelitis caused by Staphylococcus aureus was suspected; blood cultures were obtained, and intravenous cefazolin was administered. Computed tomography, which was performed to detect disseminated foci, revealed a multilocular liver abscess. On day 4 of incubation, the anaerobic blood culture bottles were positive for characteristic filamentous gram-negative rods. The empiric antimicrobial therapy was changed to ampicillin/sulbactam. The isolate was identified as F. nucleatum based on 16S rRNA gene sequencing. The liver abscess was drained on day 12. Based on the antimicrobial susceptibility test results, the patient was treated with intravenous ampicillin/sulbactam for 4 weeks followed by oral amoxicillin/clavulanate for an additional 8 weeks and remained disease-free at the 1-year follow-up. Clinicians should consider F. nucleatum as the causative organism for vertebral osteomyelitis presenting with asymptomatic pyogenic liver abscess. The gold standard for identifying and diagnosing F. nucleatum infections is 16S rRNA gene sequencing, and gram staining helps determine appropriate antimicrobials.

Abstract Background Spontaneous regression of thymic carcinoma is extremely rare. We report a case of a resected thymic carcinoma with preoperative spontaneous regression in a 67-year-old woman. Case presentation The patient presented with low-grade fever and anterior chest pain. Chest computed tomography (CT) showed a 55 × 43 mm exophytic heterogeneously enhancing mass showing some areas of necrosis. Chest CT done one day preoperatively revealed that the tumor had rapidly shrunk for one month. Surgical resection was performed to obtain a definitive diagnosis and achieve complete resection, yielding a postoperative diagnosis of thymic carcinoma. The patient survived without signs of recurrence for 12 months postoperatively. Conclusions Mediastinal tumors with necrosis demonstrating spontaneous regression should include thymic carcinomas in the differential diagnosis.

Abstract Background Adult cases of retroperitoneal isolated enteric duplication cyst (IEDC) are rare, with only 17 case reports in the relevant literature. We herein present a case, which was characterized by changes in intra-cystic density on computed tomography (CT), which was safely resected by laparoscopic surgery. Case presentation The patient was a 60-year-old male who received abdominal CT to investigate the cause of increased serum CA19-9 levels. CT revealed a unilocular cystic mass located in the lower right retroperitoneum. The size increased from 5 to 10 cm in three and a half years and the CT value decreased from 101 Hounsfield Units (HU) to 20 HU. We performed laparoscopic surgical resection, because the possibility that the enlargement of the lesion represented malignant transformation could not be denied. The large cystic mass firmly adhered to the appendix and its mesentery via the retroperitoneum, the appendix was resected en bloc with the cystic lesion. Microscopically, it had no communication with the appendix, and had an intestinal wall structure of muscularis mucosae and muscularis propria. The final pathological diagnosis was IEDC in the retroperitoneal space. There was no histological evidence of malignancy. Conclusion When we encounter a retroperitoneal cystic lesion, we should consider the possibility of malignancy to determine the treatment strategy and perform a careful operation without breaking the cyst wall, irrespective of the preoperative diagnosis.

Abstract Background Although the automatic diagnosis of fractures using artificial intelligence (AI) has recently been reported to be more accurate than those by orthopedics specialists, big data with at least 1000 images or more are required for deep learning of the convolutional neural network (CNN) to improve diagnostic accuracy. The aim of this study was to develop an AI system capable of diagnosing distal radius fractures with high accuracy even when learning with relatively small data by learning to use bi-planar X-rays images. Methods VGG16, a learned image recognition model, was used as the CNN. It was modified into a network with two output layers to identify the fractures in plain X-ray images. We augmented 369 plain X-ray anteroposterior images and 360 lateral images of distal radius fractures, as well as 129 anteroposterior images and 125 lateral images of normal wrists to conduct training and diagnostic tests. Similarly, diagnostic tests for fractures of the styloid process of the ulna were conducted using 189 plain X-ray anteroposterior images of fractures and 302 images of the normal styloid process. The distal radius fracture is determined by entering an anteroposterior image of the wrist for testing into the trained AI. If it identifies a fracture, it is diagnosed as the same. However, if the anteroposterior image is determined as normal, the lateral image of the same patient is entered. If a fracture is identified, the final diagnosis is fracture; if the lateral image is identified as normal, the final diagnosis is normal. Results The diagnostic accuracy of distal radius fractures and fractures of the styloid process of the ulna were 98.0 ± 1.6% and 91.1 ± 2.5%, respectively. The areas under the receiver operating characteristic curve were 0.991 {n = 540; 95% confidence interval (CI), 0.984–0.999} and 0.956 (n = 450; 95% CI 0.938–0.973). Conclusions Our method resulted in a good diagnostic rate, even when using a relatively small amount of data.

Abstract Background Trans-jejunal nutrition via a post-pyloric enteral feeding tube has a low risk of aspiration or reflux; however, placement of the tube using the blind method can be difficult. Assistive devices, such as fluoroscopy or endoscopy, are useful but may not be suitable for patients with hemodynamic instability or severe respiratory failure. The aim of this study was to explore factors associated with first-pass success in the blind placement of post-pyloric enteral feeding tubes in critically ill patients. Methods Data were obtained retrospectively from the medical records of adult patients who had a post-pyloric enteral feeding tube placed in the intensive care unit between January 1, 2012, and December 31, 2018. Logistic regression analysis was performed to assess the association between first-pass success and the independent variables. For logistic regression analysis, the following 13 variables were defined as independent variables: age, sex, height, fluid balance from baseline, use of sedatives, body position during the procedure, use of cardiac assist devices, use of prokinetic agents, presence or absence of intestinal peristalsis, postoperative cardiovascular surgery, use of renal replacement therapy, serum albumin levels, and position of the greater curvature of the stomach in relation to spinal levels L1 − L2. Results Data obtained from 442 patients were analyzed. The first-pass success rate was 42.8% (n = 189). Logistic regression analysis demonstrated that the position of the greater curvature of the stomach cephalad to L1 − L2 was only associated with successful placement (odds ratio for first-pass success, 0.62; 95% confidence interval: 0.40 − 0.95). Conclusions In critically ill patients, the position of the greater curvature of the stomach caudal to L1 − L2 may be associated with a lower first-pass success rate of the blind method for post-pyloric enteral feeding tube placement. Further studies are needed to verify our results because the position of the stomach was estimated by radiographs after enteral feeding tube placement. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN000036549; April 20, 2019).

Abstract We examined whether blowing hot air above body temperature under work clothing may suppress core temperature. Nine Japanese men engaged in two 30-min bicycle ergometer sessions at a workload of 40% VO2max at 40 °C and 50% relative humidity. The experiment was conducted without wearing any cooling apparatus (CON), wearing a cooling vest that circulated 10.0 °C water (VEST), and wearing a fan-attached jacket that transferred ambient air underneath the jacket at a rate of 30 L/s (FAN). The VEST and FAN conditions suppressed the increases of rectal temperature (CON, VEST, FAN; 38.01 ± 0.19 °C, 37.72 ± 0.12 °C (p = 0.0076), 37.54 ± 0.19 °C (p = 0.0023), respectively), esophageal temperature (38.22 ± 0.30 °C, 37.55 ± 0.18 °C (p = 0.0039), 37.54 ± 0.21 °C (p = 0.0039), respectively), and heart rate (157.3 ± 9.8 bpm, 136.9 ± 8.9 bpm, (p = 0.0042), 137.5 ± 6.5 bpm (p = 0.0023), respectively). Two conditions also reduced the estimated amount of sweating and improved various subjective evaluations. Even in the 40 °C and 50% relative humidity environment, we may recommend wearing a fan-attached jacket because the heat dissipation through evaporation exceeded the heat convection from the hot ambient air.

Facial paralysis results in the decline in the generation of facial expressions and is attributed to several causes. Intractable facial paralysis has a poor prognosis, and new treatments are required. Facial paralysis results in the decline in the generation of facial expressions and is attributed to several causes. Reactive oxygen species can inhibit peripheral nerve regeneration after injury. Therefore, the administration of an appropriate antioxidant can promote nerve regeneration. Silicon (Si)-based agents can react with water to generate antioxidant hydrogen. Oral administration of Si-based agents can effectively alleviate symptoms of disease models associated with oxidative stress. Thus, we orally administered a Si-based agent to a facial paralysis model mice to investigate whether promotion of nerve regeneration occurred. The combined administration of methylcobalamin (MeCbl) with the Si-based agent was also investigated. The Si-based agent improved the clinical score evaluation of facial paralysis. Electroneuronography and immunostaining showed that the Si-based agent promoted myelination and recovery of facial nerve function. Furthermore, in the drug-administered group, oxidative stress associated with facial nerve injury was reduced more than that in the non-administered group. The clinical score evaluation, neuroregeneration effect, and reduction of oxidative stress were improved in the combination group compared to the single administration group. The Si-based agent could rapidly improve the disappearance of facial expressions by promoting myelin sheath formation and alleviating oxidative stress. Combination therapy with a Si-based agent and MeCbl should improve the prognosis and treatment of intractable facial paralysis.

In a shale gas and oil reservoir, hydrocarbon fluids are stored in organic nanopores with sizes on the order of ∼1–100 nm. The adsorption, selectivity, and phase behavior of hydrocarbons in the nanopores are crucial for estimating the gas-in-place and predicting the productivity. In this study, to understand the characteristics of the phase behavior of multicomponent hydrocarbon systems in shale reservoirs, the phase behavior of a CH4/n-C4H10 binary mixture in graphite nanopores was investigated by Grand Canonical Monte Carlo (GCMC) molecular simulation. The method for determining the dew-point pressure and bubble-point pressure in the nanopores was explored. The condensation phenomenon was observed owing to the difference in the adsorption selectivities of the hydrocarbon molecules on the nanopore surfaces, and hence the dew-point pressure (and bubble-point pressure) of hydrocarbon mixtures in the nanopores significantly shifted. The GCMC simulations reproduced both the higher and lower bubble-point pressures in nanopores in previous studies. This work highlights the crucial role of the selectivity in the phase behavior of hydrocarbons in nanopores.

Abstract Background Rhabdomyomas comprise the majority of cardiac tumors in fetuses and are found in association with tuberous sclerosis complex. More than 90% of fetuses and neonates with multiple cardiac rhabdomyomas have signs of tuberous sclerosis complex. However, solitary cardiac rhabdomyoma cases are largely unrelated to tuberous sclerosis complex. Here, we report a case involving multiple cardiac rhabdomyomas not associated with tuberous sclerosis complex in a dizygotic twin. Case presentation A 36-year-old Japanese woman was diagnosed with a dizygotic twin pregnancy in the first trimester. Consistent with dizygosity, the fetal sex was discordant (male and female). At 27 weeks of gestation, hydrops and multiple echogenic cardiac masses were noted in the male baby, with the largest mass measuring 34 × 30 mm. The female fetus appeared normal. The cardiac masses enlarged gradually with the progression of the hydrops. At 32 weeks of gestation, intrauterine death of the male fetus was confirmed. The next day, autopsy of the male fetus was performed after cesarean section. Three well-demarcated white-tan-colored nodules were formed in the ventricular walls and interventricular septum, with the largest nodule (40 × 30 mm) in the left ventricular wall. Histologically, these lesions were diagnosed as rhabdomyomas. Conclusions We encountered a case involving multiple cardiac rhabdomyomas arising in one of dizygotic twin fetuses. Unlike most reported cases of multiple cardiac rhabdomyomas, this case was not accompanied by tuberous sclerosis complex. To the best of our knowledge, this is the first case report of multiple cardiac rhabdomyomas that developed in only one of dizygotic twins in the English literature.

Abstract Background The collection of weighed food records (WFR) is a gold standard for dietary assessment. We propose using the 24-h recall method combined with a portable camera and a food atlas (24hR-camera). This combination overcomes the disadvantages of the 24-h dietary recall method. Our study examined the validity of the 24hR-camera method against WFR by comparing the results. Methods Study subjects were 30 Japanese males, aged 31–58 years, who rarely cook and reside in the Tokyo metropolitan area. For validation, we compared the estimated food intake (24hR-camera method) and weighed food intake (WFR method). The 24hR-camera method uses digital photographs of all food consumed during a day, taken by the subjects, and a 24-h recall questionnaire conducted by a registered dietitian, who estimates food intake by comparing the participant’s photographs with food atlas photographs. The WFR method involves a registered dietitian weighing each food item prepared for the subject to consume and any leftovers. Food intake was calculated for each food group and nutrient using the 24hR-camera vs. weighed methods. Results Correlation coefficients between the estimated vs. weighed food intake were 0.7 or higher in most food groups but were low in food groups, such as oils, fats, condiments, and spices. The estimated intake of vegetables was significantly lower for the 24hR-camera method compared to the WFR method. For other food groups, the percentages of the mean difference between estimated vs. weighed food intake were -22.1% to 5.5%, with no significant differences between the methods (except for algae, which had a very low estimated intake). The correlation coefficients between the two methods were 0.774 for energy, and 0.855, 0.769, and 0.763 for the macronutrients, proteins, lipids, and carbohydrates, respectively, demonstrating high correlation coefficients: greater than 0.75. The correlation coefficients between the estimated vs. weighed for salt equivalents and potassium intake were 0.583 and 0.560, respectively, but no significant differences in intake were observed. Conclusions The 24hR-camera method satisfactorily estimated the intake of energy and macronutrients (except salt equivalents and potassium) in Japanese males and was confirmed as a useful method for dietary assessment.

Abstract Endobronchial resection using a bronchoscope is often selected as treatment for carcinoid tumors located in the central airways. However, massive bleeding is one of the most serious complications during bronchoscopic surgery. Here, we report the case of a 77‐year‐old female with a typical carcinoid tumor located in the right truncus intermedius who underwent bronchial artery embolization (BAE) one day before endobronchial intervention using a flexible bronchoscope. The tumor was successfully resected without bleeding. BAE prior to endobronchial resection of carcinoid tumors may be useful for reducing the risk of bleeding.

Omecamtiv mecarbil (OM) is a novel inotropic agent for heart failure with systolic dysfunction. OM prolongs the actomyosin attachment duration, which enhances thin filament cooperative activation and accordingly promotes the binding of neighboring myosin to actin. In the present study, we investigated the effects of OM on the steady-state contractile properties in skinned porcine left ventricular (PLV) and atrial (PLA) muscles. OM increased Ca2+ sensitivity in a concentration-dependent manner in PLV, by left shifting the mid-point (pCa50) of the force-pCa curve (ΔpCa50) by ∼0.16 and ∼0.33 pCa units at 0.5 and 1.0 μM, respectively. The Ca2+-sensitizing effect was likewise observed in PLA, but less pronounced with ΔpCa50 values of ∼0.08 and ∼0.22 pCa units at 0.5 and 1.0 μM, respectively. The Ca2+-sensitizing effect of OM (1.0 μM) was attenuated under enhanced thin filament cooperative activation in both PLV and PLA; this attenuation occurred directly via treatment with fast skeletal troponin (ΔpCa50: ∼0.16 and ∼0.10 pCa units in PLV and PLA, respectively) and indirectly by increasing the number of strongly bound cross-bridges in the presence of 3 mM MgADP (ΔpCa50: ∼0.21 and ∼0.08 pCa units in PLV and PLA, respectively). It is likely that this attenuation of the Ca2+-sensitizing effect of OM is due to a decrease in the number of “recruitable” cross-bridges that can potentially produce active force. When cross-bridge detachment was accelerated in the presence of 20 mM inorganic phosphate, the Ca2+-sensitizing effect of OM (1.0 μM) was markedly decreased in both types of preparations (ΔpCa50: ∼0.09 and ∼0.03 pCa units in PLV and PLA, respectively). The present findings suggest that the positive inotropy of OM is more markedly exerted in the ventricle than in the atrium, which results from the strongly bound cross-bridge-dependent allosteric activation of thin filaments.

BackgroundThe causes of brain death include cerebral herniation and brainstem ischemia. Neuroendocrine failure or a series of autonomic nervous system disorders are clinically recognized in the transition to brain death among patients with critical brain injuries. An accurate evaluation of these physiologic instabilities and biomarkers is essential to assess the severity and prognosis of pediatric brain injury as well as to initiate supportive care. This case report presents a detailed evaluation of the autonomic nervous system and endocrine function during the transition to brain death in infantile hypoxic-ischemic brain injury by analyzing the heart rate variability and endocrine status.Case PresentationA 1-year-old previously healthy boy went into cardiac arrest after choking on a toy at home. Although spontaneous circulation returned 60 min after cardiopulmonary resuscitation, no cerebral activity or brainstem reflexes were observed after 18 hospital days. The heart rate variability was assessed by analyzing the generic electrocardiogram data. Rapid spikes or drops in the total power of the heart rate variability, accompanied by a cortisol surge, as well as an alternating surge of high- and low-frequency domain variables were detected in the process of brain death.ConclusionThe heart rate variability assessment combined with endocrine provides a better understanding of the clinical course of patients undergoing brain death. It accurately detects the loss of brainstem function, which allows physicians to provide the appropriate supportive care.

Purpose: Everolimus-induced diabetes mellitus (DM) outcomes include everolimus-resistant tumors and poor hyperglycemia outcomes, which lead to various other negative clinical outcomes. This study aimed to evaluate the effect of associations between concomitant drug treatment and time to DM event occurrence (onset or exacerbation) on the outcomes of everolimus-induced DM in patients with cancer. Methods: Data from the Japanese Adverse Drug Event Report database (JADER) were used, and patient drug use, time of DM event occurrence, and DM outcomes were determined from patient records. Associations between concomitant drug groups with everolimus and DM event occurrence were then evaluated for patients with both good and poor DM outcomes. Results: Top ten groups used concomitantly were drugs for the treatment of hypertension (HT), controlled DM, constipation, hypothyroidism, kidney disease, insomnia, hyperlipidemia, hyperuricemia, anemia, and gastritis. Among them, only HT, controlled DM, and hyperlipidemia were associated with DM event occurrence. These three drug groups were examined by the outcome of everolimus concomitant usage and revealed a significantly shorter time to DM event occurrence for patients with poor outcomes than for those with good outcomes (p = 0.015) among patients without a concomitant drug for DM. Each of these three drug groups was analyzed on patients who were concomitantly administered with one of each drug group with everolimus and revealed a significantly shorter time to DM event occurrence for patients with poor outcomes than for those with good outcomes in patients who received concomitant HT drugs (p = 0.006). Moreover, among the four HT drug categories, calcium channel blockers were significantly associated with poor outcomes (odds ratio, 2.18 [1.09–4.34], p = 0.028). Conclusion: To prevent everolimus-induced poor DM outcomes, early DM detection and treatment are necessary, and the effect of the concomitant drug should be considered before initiating everolimus treatment.

Abstract Background Endoscopic papillectomy of duodenal papillary tumors (PT) is indicated for adenomas or well-differentiated adenocarcinomas that do not involve the sphincter of Oddi. However, there is currently no reliable pre-operative method to diagnose the infiltration in the sphincter of Oddi.’ Insulin-like growth factor 2 mRNA protein 3 (IMP3) staining is reportedly associated with advanced disease stage and clinical outcomes in many carcinomas. The aim of this retrospective study was to investigate the ability of diagnosing sphincter of Oddi involvement in PT and predicting the prognoses using IMP3 immunohistochemistry. Methods Twenty-five resected specimens from patients with PT and 24 biopsy specimens from the same patients excluding one were immunostained for IMP3. The percentage of positive cells in the tumor was evaluated and compared with the final pathological diagnosis and prognosis. Results The final pathological diagnoses were adenoma in 5 patients and adenocarcinoma in 20 patients (no sphincter of Oddi involvement in 5 and involvement in 15). The ability to diagnose sphincter of Oddi involvement based on the percentage of IMP3-positive cells in resected specimens and tissue biopsies was the area under the curve 0.8 and 0.78, respectively, of the receiver operating characteristic curve, and the accuracies were 80.0% and 75.0% (cutoff value: 10%), respectively. Moreover, patients with an IMP3-positive cell rate of ≥ 10% had a significantly worse prognosis (log-rank test P = 0.01). Conclusion IMP3 immunostaining of resected and biopsy specimens from PT patients enables the diagnosis of sphincter of Oddi involvement objectively and is also effective in predicting the prognosis.

Hexagonal manganese oxides RMnO_{3} (R=Y, Ho–Lu, Sc, and In) show intriguing topological ferroelectric domain walls with variable conductivity, leading to domain wall engineering. Despite the numerous experimental studies on these polar nanoscale structures, controlling ferroelectric domains has not been sufficiently investigated. Here, we reveal the unprecedented coexistence of polar-nonpolar nanoscale domains that can be formed by substituting titanium ions in HoMnO_{3}. Unusual polar nanoscale domains are embedded in nonpolar domains with different crystallographic symmetry. This polar-nonpolar coexisting structure is naturally assembled by adjusting the lattice length during a solid-state reaction process. Furthermore, this comprehensive study reveals that the reversible microstructural change with a nonpolar-polar transition is strongly correlated with the oxygen storage properties in Ho(Mn,Ti)O_{3+δ}. The present results provide important insight into the nanoscale polar-nonpolar domain coexistence in functional rare-earth manganese oxides, RMnO_{3}.

Background and Objectives: Teicoplanin (TEIC) is an effective drug for patients with febrile neutropenia (FN); however, it has been reported that these patients may have increased TEIC clearance compared with patients who do not have FN. The purpose of this study was to study therapeutic drug monitoring in patients with FN when the TEIC dosing design was based on the population mean method. Materials and Methods: Thirty-nine FN patients with hematological malignancy were included in the study. To calculate the predicted blood concentration of TEIC, we used the two population pharmacokinetic (population PK) parameters (parameters 1 and 2) reported by Nakayama et al. and parameter 3, which is a modification of the population PK of Nakayama et al. We calculated the mean prediction error (ME), an indicator of prediction bias, and the mean absolute prediction error (MAE), an indicator of accuracy. Furthermore, the percentage of predicted TEIC blood concentration within 25% and 50% of the measured TEIC blood concentration was calculated. Results: The ME values were −0.54, −0.25, and −0.30 and the MAE values were 2.29, 2.19, and 2.22 for parameters 1, 2, and 3, respectively. For all of the three parameters, the ME values were calculated as minus values, and the predicted concentrations tended to be biased toward smaller values relative to the measured concentrations. Patients with serum creatinine (Scr) < 0.6 mg/dL and neutrophil counts < 100/μL had greater ME and MAE values and a smaller percentage of predicted TEIC blood concentration within 25% of measured TEIC blood concentrations compared with other patients. Conclusions: In patients with FN, the accuracy of predicting TEIC blood concentrations was good, with no significant differences between each parameter. However, patients with a Scr < 0.6 mg/dL and a neutrophil count < 100/μL showed slightly inferior prediction accuracy.

Abstract Mussels, which occupy important positions in marine ecosystems, attach tightly to underwater substrates using a proteinaceous holdfast known as the byssus, which is tough, durable, and resistant to enzymatic degradation. Although various byssal proteins have been identified, the mechanisms by which it achieves such durability are unknown. Here we report comprehensive identification of genes involved in byssus formation through whole-genome and foot-specific transcriptomic analyses of the green mussel, Perna viridis. Interestingly, proteins encoded by highly expressed genes include proteinase inhibitors and defense proteins, including lysozyme and lectins, in addition to structural proteins and protein modification enzymes that probably catalyze polymerization and insolubilization. This assemblage of structural and protective molecules constitutes a multi-pronged strategy to render the byssus highly resistant to environmental insults.