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Background: The use of life-sustaining treatment (LST) in the final stage of life is a major policy concern due to increased costs, while its intensity does not correlate with quality. Previous reports have shown declining trends in LST use in Japan. However, regional practice variations remain unclear. This study aims to describe regional variations in LST use before death among the oldest old in Japan. Methods: A descriptive study was conducted among patients aged 85 years or older who passed away between April 2013 and March 2014. The study utilized health insurance claims from Japan’s National Database (NDB) to examine the use of cardiopulmonary resuscitation (CPR), mechanical ventilation (MV), and admission to the acute care ward (ACW) in the last 7 days of life. Results: Among 224,391 patients, the proportion of patients receiving LST varied by region. CPR ranged from 8.6% (Chubu) to 12.9% (Shikoku), MV ranged from 7.1% (Chubu) to 12.3% (Shikoku), and admission to ACW ranged from 4.5% (Chubu) to 10.1% (Kyushu-Okinawa). The adjusted odds ratios (AOR) for regional variation compared with Kanto were as follows: CPR (in Shikoku, AOR 1.85; 95% confidence interval [CI], 1.73–1.98), MV (in Shikoku, AOR 1.75; 95% CI, 1.63–1.87), and ACW admission (in Kyushu-Okinawa, AOR 1.69; 95% CI, 1.52–1.88). Conclusion: The study presents descriptive information regarding regional differences in the utilization of LST for the oldest old in Japan. Further research is necessary to identify the factors that contribute to these variations and to address the challenge of improving the quality of end-of-life care.

Abstract Despite recent advances in cryo-electron microscopy and artificial intelligence-based model predictions, a significant fraction of structure determinations by macromolecular crystallography still requires experimental phasing, usually by means of single-wavelength anomalous diffraction (SAD) techniques. Most synchrotron beamlines provide highly brilliant beams of X-rays of between 0.7 and 2 Å wavelength. Use of longer wavelengths to access the absorption edges of biologically important lighter atoms such as calcium, potassium, chlorine, sulfur and phosphorus for native-SAD phasing is attractive but technically highly challenging. The long-wavelength beamline I23 at Diamond Light Source overcomes these limitations and extends the accessible wavelength range to λ = 5.9 Å. Here we report 22 macromolecular structures solved in this extended wavelength range, using anomalous scattering from a range of elements which demonstrate the routine feasibility of lighter atom phasing. We suggest that, in light of its advantages, long-wavelength crystallography is a compelling option for experimental phasing.

To study the effects of drugs on embryo/fetal development (EFD), developmental and reproductive toxicity studies in zebrafish (Danio rerio) embryos is expected to be an accepted alternative method to animal studies using mammals. However, there is a lack of clarity in the relationship between the concentration of developmental toxicity agents in whole embryos or larvae (Ce) and that in aqueous solution (Cw), and also between the amount of drug exposure required to cause developmental toxicity in zebrafish embryos or larvae and that required in mammals. Here, we measured Ce for developmental toxicity agents every 24 h starting at 24 h post fertilization (hpf). We found a high correlation (R2: 0.87–0.96) between log [Ce/Cw] and the n-octanol–water distribution coefficient at pH 7 (logD) of each drug at all time points up to 120 hpf. We used this relationship to estimate the Ce values of the 21 positive-control reference drugs listed in ICH guidelines on reproductive and developmental toxicity studies (ICH S5). We then calculated the area under the Ce–time curve in zebrafish (zAUC) for each drug from the regression equation between log [Ce/Cw] and logD and compared it with the AUC at the no-observed-adverse-effect level in rats and rabbits and at the effective dose in humans described in ICH S5. The log of the calculated zAUC for the 14 drugs identified as positive in the zebrafish developmental toxicity test was relatively highly positively correlated with the log [AUC] for rats, rabbits, and humans. These findings provide important and positive information on the applicability of the zebrafish embryo developmental toxicity test as an alternative method of EFD testing. (267 words)

ObjectiveCystoid macular edema (CME) in retinitis pigmentosa (RP) is an important complication causing visual dysfunction. We investigated the effect of CME on photoreceptors in RP patients with previous or current CME, using an adaptive optics (AO) fundus camera.MethodsWe retrospectively observed the CME and ellipsoid zone (EZ) length (average of horizontal and vertical sections) by optical coherence tomography. The density and regularity of the arrangement of photoreceptor cells (Voronoi analysis) were examined at four points around 1.5° from superior to inferior and temporal to nasal. We also performed a multivariate analysis using CME duration, central macular thickness and transversal length of CME.ResultsWe evaluated 18 patients with previous or current CME (18 eyes; age, 48.7 ± 15.6 years) and 24 patients without previous or current CME (24 eyes; age, 46.0 ± 14.5 years). There were no significant differences in age, logMAR visual acuity, or EZ length. In groups with and without CME, cell density was 11967 ± 3148 and 16239 ± 2935 cells/mm2, and sequence regularity was 85.5 ± 3.4% and 88.5 ± 2.8%, respectively; both parameters were significantly different. The correlation between photoreceptor density and age was more negative in group with CME. The CME group tended toward greater reductions in duration of CME.ConclusionComplications of CME in RP patients may lead to a decrease in photoreceptor density and regularity. Additionally, a longer duration of CME may result in a greater reduction in photoreceptor density.

Abstract Background The recently developed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine has a short history of use and further information is needed regarding its efficacy, especially in immunocompromised conditions, such as plasma cell dyscrasia (PCD). Methods We retrospectively measured serum SARS‐CoV‐2 antibodies against the spike protein (S‐IgG) after the second and third mRNA vaccine doses (doses 2 and 3, respectively) in 109 patients with PCD. We evaluated the proportion of patients with an adequate humoral response (defined as S‐IgG titers ≥300 antibody units/mL). Results Although active anti‐myeloma treatments prior to vaccination had a significantly negative impact on adequate humoral response, specific drug subclasses including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies were not negatively associated, except for B‐cell maturation antigen‐targeted therapy. Dose 3 (booster vaccination) led to significantly higher S‐IgG titers and more patients acquired an adequate humoral response. Furthermore, evaluation of vaccine‐induced cellular immune response in patients using T‐spot Discovery SARS‐CoV‐2 kit, revealed an enhanced cellular immune response after Dose 3. Conclusions This study highlighted the significance of booster SARS‐CoV‐2 mRNA vaccination in patients with PCD with respect to humoral and cellular immunity. Moreover, this study highlighted the potential impact of certain drug subclasses on vaccine‐induced humoral immune response.

Purpose: Novel therapeutic options, such as regenerative medicine and gene therapy, are now emerging as viable treatment options for patients with severe visual impairments, such as retinitis pigmentosa (RP). Gradable assessment of patients’ visual function is essential to consider treatment options and to evaluate treatment outcomes; however, evaluation of visual function in patients with advanced low vision is often challenging because of patients’ poor and sometimes unpredictable responses. In this study, we attempted to accurately assess visual capabilities and disease stage in patients with RP with a visual acuity (VA) of ≤ 0.01. Design: Retrospective analysis of visual function indicators, including VA, retinal thickness, full-field stimulus testing (FST), and chromatic pupillometry. Subjects: Overall, 43 patients (84 eyes) with advanced RP with a VA of ≤ 0.01 visited Kobe City Eye Hospital from 2019 to 2021. Methods: Hierarchical (multilevel) Bayesian modeling was used to estimate individual eye’s pupil response and FST threshold, taking into account the ambiguity and randomness often observed in patients with ultralow vision. Using the estimated ability obtained from each test, the correlation between each test and retinal thickness was further analyzed to make a comprehensive assessment of the data. Main Outcome Measures: Visual acuity, retinal thickness, FST threshold, and pupil diameter change to different light stimuli. Results: Full-field stimulus testing and pupillometry measurements were moderately correlated with VA but exhibited a wide range of values within the same VA groups. Full-field stimulus testing was not correlated with central retinal thickness at counting fingers/hand motion VA range and seemed to reflect overall remaining photoreceptor function, including peripheral retina. Pupillometry may be able to distinguish between different levels of inner retinal function. Conclusions: The combination of pupillometry and FST allowed for graded evaluation of visual function within patients grouped in the same VA groups in patients with advanced RP with ultralow vision. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP), proposed in a recent NIH consensus overview, is a rare precursor entity of malignant peripheral nerve sheath tumor (MPNST) in neurofibromatosis type 1 (NF1) patients. Only one report on imaging findings of ANNUBP is available. Herein, we present the case of a 19-year-old female, diagnosed with a mediastinal tumor by chance, who visited to our hospital. She had café-au-lait spots on her trunk and a past history of resected neurofibroma. Her family also had café-au-lait spots; therefore, an NF1-induced tumor was strongly suspected. MRI revealed a paravertebral mass of 7.5 cm in size consisting of an inner rim with low T2 signal intensity and an outer rim with high T2 intensity, which was similar to a target sign, adjacent to the pulmonary veins; the center of the tumor was well enhanced by gadolinium, and the peripheral region was myxoid and slightly enhanced. FDG-PET showed high FDG uptake, SUVmax of 8.5, although the peripheral region represented low FDG accumulation. CT-guided needle biopsy was repeated because of the suspicion of an MPNST, which resulted in the histopathological diagnosis of ANNUBP. Marginal tumor resection was performed, and the final post-resection histopathological diagnosis was ANNUBP transformed from neurofibroma; the region of ANNUBP lost p16 immunostaining, although it was retained in the peripheral region of the neurofibroma. There has been no recurrence or metastasis 1 year after treatment. In conclusion, ANNUBP could be represented as a well-enhanced homogeneous mass on MRI and a high FDG accumulated region on FDG PET/CT, as seen in MPNST, in NF1 patients.

Key Clinical Message SMARCA4‐deficient thoracic carcinoma is a malignant tumor that may present as cancer of unknown primary. This tumor is refractory and requires a novel approach. In addition to identifying therapeutic targets, multigene panel testing can reveal novel genetic mutations, leading to more pathologically relevant diagnoses and appropriate tumor care. Abstract SMARCA4‐deficient undifferentiated tumors are characterized by SMARCA4 inactivation. We present a case of a 74‐year‐old man with an undifferentiated tumor and a novel SMARCA4 mutation detected using multigene panel testing. The tumor was multiagent and refractory to three chemotherapy lines. The test results helped guide appropriate medical management.

Abstract Background Epithelioid hemangioendothelioma (EHE) is a rare and slow-growing malignant vascular neoplasm composed of epithelioid endothelial cells within a distinctive myxohyaline stroma. It most commonly involves somatic soft tissue, lungs, liver and bone. Herein, we describe a case of EHE arising in the axillary region. Case presentation A 61-year-old man was under observation for multiple hepatic hemangiomas. Fluorodeoxyglucose–positron emission tomography/computed tomography showed specific uptake in a right axillary tumor. The patient was referred to our department for further investigation of the axillary tumor. An elastic-soft and poorly mobile tumor was palpable in the right axilla. Contrast-enhanced computed tomography showed a right axillary tumor and enlarged hepatic hemangiomas. In addition, multiple nodules in both lungs, a left renal angiomyolipoma, and left adrenal adenoma were revealed. Ultrasonography showed masses in both lobes of the thyroid gland, and a 30-mm lobulated hypoechoic mass in the axilla with well-defined and rough borders, showing internal heterogeneity. Fine-needle aspiration cytology was performed on the thyroid and axillary tumors: the thyroid tumor was class V, raising suspicion of papillary thyroid cancer (PTC); the left superior internal jugular node was class V, raising suspicion of metastasis of PTC; and the axillary tumor was class III, raising suspicion of a mesenchymal tumor with few epithelioid cells. The multiple lung nodules were diagnosed as metastatic tumors derived from thyroid cancer. We diagnosed these diseases as PTC of T1b(m)N1bM1(lung) Stage IVB and a right axillary tumor of unclear origin. However, it was assumed to be a primary mesenchymal tumor or a lymph node metastasis from lung cancer or occult breast cancer. We performed total thyroidectomy, left cervical lymph node dissection, and right axillary tumor excision. Histopathologic examination revealed the thyroid tumor as a PTC and the axillary tumor as an EHE. The EHE showed nuclear atypia, necrosis and high mitotic figures. Hence, it was considered to be a high-risk EHE. Conclusions We experienced a rare primary subcutaneous axillary EHE with metastatic thyroid cancer in the lung. Since our case was classified as a high-risk EHE, a close follow-up would be appropriate.

Background: Although eosinophilic granulomatosis with polyangiitis (EGPA) has been considered as a single disease entity belonging to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, several studies have suggested that in addition to the mechanisms associated with ANCA, those associated with eosinophils play a vital role in tissue damage. Nevertheless, the morphological bases underlying eosinophil-associated lesions have not been completely elucidated. Methods: We investigated the electron microscopic findings of sural nerve biopsy specimens obtained from 18 patients with EGPA by focusing on the behavior of eosinophils, particularly the mode of secretion. Results: Eosinophils tended to be located at sites close to endothelial cells within the lumina of epineurial small vessels. Attachment of eosinophils to endothelial cells was observed, particularly at the junction between neighboring endothelial cells, and some of these eosinophils appeared to escape from the vascular lumen to migrate into the extravascular interstitium. Furthermore, we observed eosinophil degranulation via piecemeal degranulation and cytolysis. Degranulating eosinophils were identified in both intravascular and extravascular compartments. Some of the small vessels appeared to be occluded by numerous eosinophils, and eosinophils attached by platelets were also observed, suggesting that coagulopathy occurs in EGPA. Conclusions: Both extravascular and intravascular eosinophils can induce tissue damage unrelated to classical necrotizing vasculitis associated with ANCA in patients with EGPA. Further research is necessary to elucidate the molecular basis of the induction of these fine structural changes, which will contribute to the development of targeted therapies based on specific mechanisms of eosinophil-related diseases.

Objective: Japan's national-level healthcare insurance claims database (NDB) is a collective database that contains the entire information on healthcare services being provided to all citizens. However, existing anonymized identifiers (ID1 and ID2) have a poor capability of tracing patients' claims in the database, hindering longitudinal analyses. This study presents a virtual patient identifier (vPID), which we have developed on top of these existing identifiers, to improve the patient traceability. Methods: vPID is a new composite identifier that intensively consolidates ID1 and ID2 co-occurring in an identical claim to allow to collect claims of each patient even though its ID1 or ID2 may change due to life events or clerical errors. We conducted a verification test with prefecture-level datasets of healthcare insurance claims and enrollee history records, which allowed us to compare vPID with the ground truth, in terms of an identifiability score (indicating a capability of distinguishing a patient's claims from another patient's claims) and a traceability score (indicating a capability of collecting claims of an identical patient). Results: The verification test has clarified that vPID offers significantly higher traceability scores (0.994, Mie; 0.997, Gifu) than ID1 (0.863, Mie; 0.884, Gifu) and ID2 (0.602, Mie; 0.839, Gifu), and comparable (0.996, Mie) and lower (0.979, Gifu) identifiability scores. Discussion: vPID is seemingly useful for a wide spectrum of analytic studies unless they focus on sensitive cases to the design limitation of vPID, such as patients experiencing marriage and job change, simultaneously, and same-sex twin children. Conclusion: vPID successfully improves patient traceability, providing an opportunity for longitudinal analyses that used to be practically impossible for NDB. Further exploration is also necessary, in particular, for mitigating identification errors.

Introduction: Minimal change disease (MCD), a common cause of primary nephrotic syndrome that accounts for 10%–15% of all primary nephrotic syndrome cases in adults, is frequently associated with malignant lymphoma. However, studies on MCD associated with prostate cancer are scarce. Case Presentation: A 73-year-old male with prostate cancer was referred to our department with hypoalbuminemia and severe proteinuria while waiting for prostatectomy. We diagnosed the patient with nephrotic syndrome and performed a renal biopsy. Renal pathological findings were consistent with those of MCD. The clinical course suggested an association between prostate cancer and MCD as our patient achieved complete remission of MCD after receiving androgen deprivation and radiation therapy for prostate cancer without the use of glucocorticoids or other immunosuppressants. Discussion: Although MCD can be associated with solid tumors, MCD associated with prostate cancer is very rare. The current case is the first to directly raise the possibility that secondary MCD may develop due to prostate cancer in some patients.

Abstract The retinal pigment epithelium (RPE) is essential for the survival and function of retinal photoreceptor cells. RPE dysfunction causes various retinal diseases including age-related macular degeneration (AMD). Clinical studies on ES/iPS cell-derived RPE transplantation for RPE dysfunction-triggered diseases are currently underway. Quantification of the diseased RPE area is important to evaluate disease progression or the therapeutic effect of RPE transplantation. However, there are no standard protocols. To address this issue, we developed a 2-step software that enables objective and efficient quantification of RPE-disease area changes by analyzing the early-phase hyperfluorescent area in fluorescein angiography (FA) images. We extracted the Abnormal region. This extraction was based on deep learning-based discrimination. We scored the binarized extracted area using an automated program. Our program’s performance for the same eye from the serial image captures was within 3.1 ± 7.8% error. In progressive AMD, the trend was consistent with human assessment, even when FA images from two different visits were compared. This method was applicable to quantifying RPE-disease area changes over time, evaluating iPSC-RPE transplantation images, and a disease other than AMD. Our program may contribute to the assessment of the clinical course of RPE-disease areas in routine clinics and reduce the workload of researchers.

We aim to graphically analyze the depth of conceptual understanding behind the Force Concept Inventory (FCI) responses of students, focusing on three questions (questions 1, 15, and 28). In our study, we created and implemented subquestions to clarify and quantify the students’ reasoning steps in reaching their responses to the original FCI questions. We used alluvial diagrams to visualize the responses of students on the subquestions and original FCI questions, representing the transition rates across the question options as flows. The flows represent common patterns of consistency and inconsistency in the students’ conceptual understandings across the original FCI question and the subquestions. By combining subquestions and alluvial diagrams as we did, we are able to efficiently analyze the depth of understanding for a given situation and to visualize the existence of a specific misconception. For example, we found that even among those who correctly answered FCI question 15 about Newton’s third law, many students incorrectly answered a corresponding subquestion asking about whether Newton’s third law holds at the end of the interaction between the two objects. This misconception turned out to be fairly robust, as these same students had a similar answering pattern for question 28. Alluvial diagrams can be used for a broad range of applications, including analysis of multiple-tier tests, testlets (e.g., FCI questions 8 through 11), tests for representational consistency (e.g., a representational variant of the FCI), and so on.

Fat-forming variant of solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm. Here we report the case of a 33-year-old woman who developed pain and muscle weakness from the posterior aspect of the right hip to lower extremity. Imaging examinations revealed a mass with fatty components and hypervascular solid components filling the sacral spinal canal and sacral foramen. The sacral mass was resected and histological examination of the specimens revealed patternless proliferation of short spindle-shaped cells with staghorn blood vessels. A number of mature adipocyte-like cells were also observed. The tumor cells were positive for STAT6 and the nuclei of the adipocytes were also positive, which was diagnostic for fat-forming SFT.

Introduction Intravesical Bacillus Calmette–Guerin immunotherapy is known to prevent recurrence of bladder cancer, but it can cause tuberculosis infections as an adverse event. Case presentation A 75‐year‐old man visited our hospital due to hematuria. The patient was diagnosed with bladder cancer and underwent transurethral resection of the bladder tumor. Postoperatively, the patient received Bacillus Calmette–Guerin immunotherapy. One year later, we performed transurethral surgery and prostate biopsy because of cystoscopic findings showing nodulous lesions in the bladder and an elevated serum prostate‐specific antigen level. The patient presented with high fever and malaise since the surgery. After careful examination, the patient was diagnosed with miliary tuberculosis caused by Mycobacterium bovis. The pathology of the bladder and prostate revealed acid‐fast bacilli collection by Ziehl–Neelsen staining. Conclusion The surgery exacerbated the local infection into a systemic infection. The risk of developing miliary tuberculosis should be considered at transurethral surgery or prostate biopsy in patients after intravesical Bacillus Calmette–Guerin immunotherapy.

BackgroundTelehealth using telephones or online communication is being promoted as a policy initiative in several countries. However, there is a lack of research on telehealth utilization in a country such as Japan that offers free access to medical care and regulates telehealth provision—particularly with respect to COVID-19. ObjectiveThe present study aimed to clarify telehealth utilization, the characteristics of patients and medical institutions using telehealth, and the changes to telehealth in Japan in order to support the formulation of policy strategies for telehealth provision. MethodsUsing a medical administrative claim database of the National Health Insurance and Advanced Elderly Medical Service System in Mie Prefecture, we investigated patients who used telehealth from January 2017 to September 2021. We examined telehealth utilization with respect to both patients and medical institutions, and we determined their characteristics. Using April 2020 as the reference time point for COVID-19, we conducted an interrupted time-series analysis (ITSA) to assess changes in the monthly proportion of telehealth users to beneficiaries. ResultsThe number of telehealth users before the reference time point was 13,618, and after the reference time point, it was 28,853. Several diseases and conditions were associated with an increase in telehealth utilization. Telehealth consultations were mostly conducted by telephone and for prescriptions. The ITSA results showed a sharp increase in the proportion of telehealth use to beneficiaries after the reference time point (rate ratio 2.97; 95% CI 2.14-2.31). However, no apparent change in the trend of increasing or decreasing telehealth use was evident after the reference time point (rate ratio 1.00; 95% CI 1.00-1.01). ConclusionsWe observed a sharp increase in telehealth utilization after April 2020, but no change in the trend of telehealth use was evident. We identified changes in the characteristics of patients and providers using telehealth.

The brain is sensitive to oxygen deprivation. Here, the authors show in experimental animals that sensitivity to hypoxia is inversely related to the level of sulfide:quinone oxidoreductast (SQOR) and the capacity to catabolize sulfide in the brain.

Induced differentiation is one of the most experience- and skill-dependent experimental processes in regenerative medicine, and establishing optimal conditions often takes years. We developed a robotic AI system with a batch Bayesian optimization algorithm that autonomously induces the differentiation of induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells. From 200 million possible parameter combinations, the system performed cell culture in 143 different conditions in 111 days, resulting in 88% better iPSC-RPE production than that obtained by the pre-optimized culture in terms of the pigmentation scores. Our work demonstrates that the use of autonomous robotic AI systems drastically accelerates systematic and unbiased exploration of experimental search space, suggesting immense use in medicine and research.

Improving the wear resistance of polymer-based materials can lead to high energy efficiency of transport machineries owing to the higher strength-to-weight ratio. Oxidized wood-utilized synthesized copper-based particles (OWCu) was incorporated into epoxy resin to investigate its effect on the wear resistance of OWCu-incorporated epoxy with the steel counterpart using a ball-on-plate tribometer. OWCu was mainly composed of CuO with a small amount of graphitic carbon, and the average particle size was approximately 0.5 μm. A higher wear resistance was observed for the OWCu-incorporated epoxy at more than 0.6 mass% compared to the neat epoxy. The mechanism for the improvement of the wear resistance property was discussed, and it was revealed that the surface roughness of the steel counterpart was maintained at a low level for the OWCu-incorporated epoxy, which played a dominant role in reducing the wear of the OWCu-incorporated epoxy. The polishing effect of OWCu could reduce the surface roughness of the steel counterpart in the friction process. In addition, at higher concentrations of more than 5.0 mass%, OWCu adhered to the steel surface, which decreased the wear of the steel surface. OWCu is a promising material to enhance the wear resistance of polymer-based materials, especially with low elongation.

Carbon nanomaterials have been studied for their promising tribological properties under boundary lubrication. However, the behavior of carbon nanomaterials upon entering narrow friction interfaces under boundary lubrication is poorly understood. In this study, to clarify how graphene oxide (GO), which is one of the carbon nanomaterials, enters and works on a friction interface under boundary lubrication, in situ observations of a friction interface between an SUJ2 ball and soda glass-lime disk in a GO water dispersion, with a load of 1 N, were conducted using optical microscopy. Isolated dispersed GO accumulated only in front of the contact areas. GO accumulations formed, grew, and peeled off due to the friction. Although the GO accumulations were significantly unstable, they functioned as friction reduction and anti-wear. We firstly found that the unstable GO lubricating accumulations that formed in front of the contact areas were able to widen between the ball and the disk similar to a wedge; this wedge effect would cause a decrease in friction and wear. Unlike the wedge effect under hydrodynamic lubrication, the GO accumulations that functioned as the wedge stayed on the ball surface.

Copper based particles were synthesized by a wood-powder-template-based process. Wood powders mixed with an aqueous cooper salt solution were heated under N2 gas flow, and then, the mixture of the charcoal powder and copper particles were heated in air to remove charcoal. Finally, oxidized wood-derived copper particles (OWCu) of less than 1 μm were synthesized. Wood powders acted as the template and limited the sizes of the copper particles. In addition, the tribological properties of OWCu in synthetic oil were investigated using a pin-on-plate reciprocating tribometer. Our results revealed that 0.5 mass% OWCu reduced both the friction coefficient (max 45%) and wear volume (max 39%) of SUJ2 lubricated by PAO4. The best reduction effect was obtained for OWCu synthesized at 400°C under N2 gas flow, which had the smallest average particle size, where the coverage of the OWCu layer on the wear track was the largest. These facts suggest that the particle size reduction of OWCu can increase the coverage and improve the friction coefficient and wear volume reduction effects of the lubricant. Control of the wood-powder-template-based synthesized particles to the optimal size for the roughness of the sliding surface would help achieve better tribological performance.

Graphene oxide (GO) and oxidized wood-derived nanocarbon (oWNC) were dispersed in an epoxy resin to improve the mechanical and tribological properties of an epoxy resin. Mechanical properties of the GO/epoxy (GO/EP) and oWNC/epoxy composites (oWNC/EP) were investigated by tensile tests and nano-indentation. Under dry, water, and oil lubrication conditions, friction coefficients and wear volumes of these composites were measured. GO has single-layered structure. oWNC has chain-like nanostructures, and the nanochains are aggregated. GO and oWNCs have same surface chemical composition due to the same oxidation treatment. Thus, in this study, the structure and morphology dependences of the nanocarbons in mechanical and tribological properties will be appeared when the nanocarbons were used as the additives in the resin. The tensile strength, tensile modulus, and hardness increased by 20%, 63%, and 35% in maximum by the addition of GO and oWNC to the epoxy resin, respectively. Moreover, the wear resistance of GO/EP and oWNC/EP was enhanced compared to that of a neat epoxy. The reduction rates of the wear volume for 5.0 mass% GO/EP and 1.0 mass% oWNC/EP achieved to 91% and 67%, respectively. Comparing GO and oWNC, oWNC effectively reduced the friction coefficient and wear at a lower concentration. The improvement of tribological properties after the addition of the oxidized nanocarbons can be attributed to the increase in the hardness and lubricity of the composites.

Objectives: To evaluate condition-specific antibiotic prescription rates and the appropriateness of antibiotic use in outpatient settings in Japan. Methods: Using Japan’s national administrative claims database, all outpatient visits with infectious disease diagnoses were linked to reimbursed oral antibiotic prescriptions. Prescription rates stratified by age, sex, prefecture, and antibiotic category were determined for each infectious disease diagnosis. The proportions of any antibiotic prescription to all infectious disease visits and the proportions of first-line antibiotic prescriptions to all antibiotic prescriptions were calculated for each infectious disease diagnosis. Results: Of the 659 million infectious disease visits between April 2012 and March 2015, antibiotics were prescribed in 266 million visits (704 prescriptions per 1000 population per year). Third-generation cephalosporins, macrolides, and quinolones accounted for 85.9% of all antibiotic prescriptions. Fifty-six percent of antibiotic prescriptions were directed toward infections for which antibiotics are generally not indicated. The diagnoses with frequent antibiotic prescription were bronchitis (184 prescriptions per 1000 population per year), viral upper respiratory infections (166), pharyngitis (104), sinusitis (52), and gastrointestinal infection (41), for which 58.3%, 40.6%, 58.9%, 53.9%, and 26.1% of visits antibiotics were prescribed, respectively. First-line antibiotics were rarely prescribed for pharyngitis (8.8%) and sinusitis (9.8%). More antibiotics were prescribed for children aged 0–9 years, adult women, and patients living in western Japan. Conclusions: Antibiotic prescription rates are high in Japan. Acute respiratory or gastrointestinal infections, which received the majority of the antibiotics generally not indicated, should be the main targets of antimicrobial stewardship intervention. Keywords: National administrative claims database, Big data, Antibiotic, Antimicrobial stewardship

The pharmacological and toxicological effects of active metabolites of enzymes including cytochrome P450 (CYP) are important. While it has been believed for a long time that thalidomide causes characteristic limb malformation only in rabbits and primates including humans, the involvement of their CYP3A subtypes (CYP3As) has been suggested. Recently, however, it was reported that zebrafish were sensitive to thalidomide, showing defects of pectoral fins, homologous organs of forelimbs in mammals, as well as other deformities. In this study, we prepared human CYP3A7 (hCYP3A7)-expressing zebrafish (F0) using a transposon system. Thalidomide caused pectoral fin defects and other malformations including pericardial edema in hCYP3A7-expressing embryos/larvae but not in wild-type and hCYP1A1-expressing embryos/larvae. Thalidomide also reduced the expression of fibroblast growth factor 8 in pectoral fin buds in only hCYP3A7-expressing embryos/larvae. The results suggest the involvement of human-type CYP3A in thalidomide teratogenicity.

Background: Driven by the rapid aging of the population, Japan introduced public long-term care insurance to reinforce healthcare services for the elderly in 2000. Precisely predicting future demand for long-term care services helps authorities to plan and manage their healthcare resources and citizens to prevent their health status deterioration. Methods: This paper presents our novel study for developing an effective model to predict individual-level future long-term care demand using previous healthcare insurance claims data. We designed two discriminative models and subsequently trained and validated the models using three learning algorithms with medical and long-term care insurance claims and enrollment records, which were provided by 170 regional public insurers in Gifu, Japan. Results: The prediction model based on multiclass classification and gradient-boosting decision tree achieved practically high accuracy (weighted average of Precision, 0.872; Recall, 0.878; and F-measure, 0.873) for up to 12 months after the previous claims. The top important feature variables were indicators of current health status (e.g., current eligibility levels and age), risk factors to worsen future healthcare status (e.g., dementia), and preventive care services for improving future healthcare status (e.g., training and rehabilitation). Conclusions: The intensive validation tests have indicated that the developed prediction method holds high robustness, even though it yields relatively lower accuracy for specific patient groups with health conditions that are hard to distinguish.

In this study, a novel method was developed for in situ scanning electron microscopy (SEM) observations of friction interfaces, from a top view, using a Si3N4 thin film (SiN film), which has high electron transmission ability, and a microtribometer. Nanodiamond (ND) aggregates were adsorbed on the back surface of the SiN film. A JIS-SUS304 ball, on which surface ND aggregates were adsorbed and tribofilms were already formed, contacted and slid with the back surface of the SiN film. An SEM electron beam went through the SiN film, and generated secondary electrons from the ball surface contacting the back surface of the SiN film and the adsorbed ND aggregates. Thereafter, the generated secondary electrons from the ball surface penetrated again through the SiN film and reached the SEM electron detector. In other words, the contacting ball surface and the adsorbed ND aggregates were successfully imaged through the SiN film. Energy dispersive X-ray spectroscopy analyses of the friction interfaces were also accomplished. Moreover, in situ SEM observations of friction interfaces under boundary lubrication, using poly-alpha olefin (PAO) oil with graphene oxide aggregates and lithium grease with MoS2 particles, were successfully accomplished. The PAO oil and lithium grease had electron transmission ability, and the friction interfaces were imaged by SEM as seen with an optical microscope.

Abstract Introduction The use of optical coherence tomography (OCT) images is increasing in the medical treatment of age-related macular degeneration (AMD), and thus, the amount of data requiring analysis is increasing. Advances in machine-learning techniques may facilitate processing of large amounts of medical image data. Among deep-learning methods, convolution neural networks (CNNs) show superior image recognition ability. This study aimed to build deep-learning models that could distinguish AMD from healthy OCT scans and to distinguish AMD with and without exudative changes without using a segmentation algorithm. Methods This was a cross-sectional observational clinical study. A total of 1621 spectral domain (SD)-OCT images of patients with AMD and a healthy control group were studied. The first CNN model was trained and validated using 1382 AMD images and 239 normal images. The second transfer-learning model was trained and validated with 721 AMD images with exudative changes and 661 AMD images without any exudate. The attention area of the CNN was described as a heat map by class activation mapping (CAM). In the second model, which classified images into AMD with or without exudative changes, we compared the learning stabilization of models using or not using transfer learning. Results Using the first CNN model, we could classify AMD and normal OCT images with 100% sensitivity, 91.8% specificity, and 99.0% accuracy. In the second, transfer-learning model, we could classify AMD as having or not having exudative changes, with 98.4% sensitivity, 88.3% specificity, and 93.9% accuracy. CAM successfully described the heat-map area on the OCT images. Including the transfer-learning model in the second model resulted in faster stabilization than when the transfer-learning model was not included. Conclusion Two computational deep-learning models were developed and evaluated here; both models showed good performance. Automation of the interpretation process by using deep-learning models can save time and improve efficiency. Trial Registration No15073.

Abstract It is expected that a large amount of data related to diabetes and other chronic diseases will be generated. However, databases constructed without standardized data item sets can be limited in their usefulness. To address this, the Collaborative Committee of Clinical Informatization in Diabetes Mellitus was established in 2011 by the Japan Diabetes Society and Japan Association for Medical Informatics. The committee has developed core item sets and self‐management item sets for diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease in collaboration with the Japanese Society of Hypertension, Japan Atherosclerosis Society, Japanese Society of Nephrology, and Japanese Society of Laboratory Medicine, as well as a mapping table that aligns the self‐management item sets with the Japanese standardized codes for laboratory testing. The committee also determined detailed specifications for implementing the four self‐management item sets in personal health record (PHR) applications to facilitate risk stratification, the generation of alerts using information and communications technology systems, the avoidance of data input errors, and the generation of reminders to input the self‐management item set data. The approach developed by the committee may be useful for combining databases for various purposes (such as for clinical studies, patient education, and electronic medical record systems) and for facilitating collaboration between PHR administrators.

Native single-wavelength anomalous dispersion (SAD) is an attractive experimental phasing technique as it exploits weak anomalous signals from intrinsic light scatterers (Z < 20). The anomalous signal of sulfur in particular, is enhanced at long wavelengths, however the absorption of diffracted X-rays owing to the crystal, the sample support and air affects the recorded intensities. Thereby, the optimal measurable anomalous signals primarily depend on the counterplay of the absorption and the anomalous scattering factor at a given X-ray wavelength. Here, the benefit of using a wavelength of 2.7 over 1.9 Å is demonstrated for native-SAD phasing on a 266 kDa multiprotein-ligand tubulin complex (T2R-TTL) and is applied in the structure determination of an 86 kDa helicase Sen1 protein at beamline BL-1A of the KEK Photon Factory, Japan. Furthermore, X-ray absorption at long wavelengths was controlled by shaping a lysozyme crystal into spheres of defined thicknesses using a deep-UV laser, and a systematic comparison between wavelengths of 2.7 and 3.3 Å is reported for native SAD. The potential of laser-shaping technology and other challenges for an optimized native-SAD experiment at wavelengths >3 Å are discussed.

Background The study was conducted to evaluate the clinical and computed tomography (CT) findings of non‐small cell lung cancer (NSCLC) patients to distinguish between ALK gene rearrangement, EGFR mutation, and non‐ALK/EGFR (no genetic abnormalities). Methods We enrolled 201 patients with primary NSCLC who had undergone molecular testing for both ALK gene rearrangement and EGFR mutation. The clinical features and CT findings of the main lesion and associated pulmonary abnormalities were investigated. Results Female gender (P = 0.0043 vs. non‐ALK/EGFR), young age (P = 0.0156 vs. EGFR), and a light or never smoking history (P = 0.0039 vs. non‐ALK/EGFR) were significant clinical characteristics of NSCLC with ALK gene rearrangement. The significant CT characteristics compared to NSCLC with EGFR mutation were a large mass (P = 0.0155), solid mass (P = 0.0048), and no air bronchogram (P = 0.0148). A central location (P = 0.0322) and lymphadenopathy (P = 0.0353) were also more frequently observed. Coexisting emphysema was significantly less frequent in NSCLC patients with ALK gene rearrangement (P = 0.0135) than non‐ALK/EGFR. Conclusions NSCLC with ALK gene rearrangement was more likely to develop in younger women with a light or never smoking history. The characteristic CT findings of NSCLC with ALK gene rearrangement were a large solid mass, less air bronchogram, a central location, and lymphadenopathy.

Liposomes have been attracted attention, because liposomes can mimic the lipid bilayer membrane of cells. Scientists apply liposomes for drug delivery systems (DDSs) and for artificial cells. Hence, the handling of liposomes is very important. In particular, it is difficult to control the adsorption of the liposome onto the target selectively and the release of the drug by its own rupture. Therefore, scientists are looking for the way to carefully monitor the behavior of liposomes from adsorption to rupture in deep.We integrated quartz crystal microbalance dissipation (QCM–D) and localized surface plasmon resonance (LSPR) into a single sensor and monitored the signals from the sensor on the adsorption and rupture of liposome. The integrated sensor detected resonance frequency and dissipation from QCM-D, and wavelength shifts from LSPR simultaneously. The integrated sensor successfully monitored conformational changes of liposomes in real time upon exposure to the surfactant, Triton X-100. The data clearly revealed liposome adsorption and deformation, and disruption of membrane integrity by normalizing three signals, resonance frequency, resonance resistance and wavelength shift. In fact, we found that normalized signals were divided into 5 steps through the experiment: liposome adsorption, liposome deformation slightly, liposome conjugated with micelles of surfactant, liposome disruption and lipid bilayer covered on the surface. These results indicate that our device provides a powerful tool to gain deeper insights into biomolecular interactions, expanding numerous applications such as monitoring of conformational changes in proteins, oligonucleotides, viruses, bacteria, vesicles, and cells.

Cases. Case 1 was a 58-year-old man who presented with an incidentally detected, slowly growing mass in the right hypochondrium area. An imaging study showed the mass arising from the 11th rib, with ill-defined margins and cortical destruction. Differential diagnoses included chondrosarcoma and metastatic malignant tumor. Open biopsy was associated with moderate bleeding (300 mL) despite small incision. Microscopic findings showed numerous irregular, dilated, and thin-walled vessels, consistent with the diagnosis of hemangioma of bone, and en bloc excision was performed with no surgical complication. Case 2 was a 49-year-old man who presented with an incidentally detected 4th rib mass with calcification on computed tomography scan. Chondrosarcoma was suspected according to imaging features. An open biopsy was considered to have a risk of tumor seeding because the tumor was located behind the scapula. En bloc excision of the tumor without biopsy was performed. The pathological findings were consistent with hemangioma of bone. Conclusion. We reported two cases of rare hemangioma arising from the rib, which mimicked chondrosarcoma. The preoperative diagnosis was challenging, both clinically and radiologically. Because biopsy for hemangioma of the rib is associated with a bleeding risk, the en bloc excision without biopsy can be a practical treatment option.

Background. Angiomatoid fibrous histiocytoma (AFH) is a rare intermediate malignant tumor that arises mainly in soft tissues, especially in the superficial extremities of patients younger than 30 years. There have been a few reports of AFH arising from sites other than soft tissue, including bone, and unusual site and age make it difficult to diagnose this rare tumor. Case Presentation. Here, we present a case of a 54-year-old man who was examined for chest pain, and computed tomography (CT) incidentally detected a bone tumor at the scapula with destruction of cortical bone and invasion into soft tissue. Magnetic resonance imaging revealed multiple cystic components with fluid-fluid levels. FDG-PET showed uptake at the axillary lymph node. The CT-guided needle biopsy revealed spindle cell sarcoma on histopathology. After neoadjuvant chemotherapy, a scapulectomy was performed. The final postresection histopathological diagnosis was the same as the preoperative diagnosis, and no obvious chemotherapeutic effect was observed. Next-generation sequencing of RNA isolated from paraffin-embedded tumor tissue revealed that these lesions harbored the EWSR1-CREB1 fusion gene, and the tumor was diagnosed as AFH. C-reactive protein level, which was elevated preoperatively, decreased after the operation, and there was no recurrence or metastasis 5 years after the treatment. Conclusion. The diagnosis of AFH is difficult when the tumor has an atypical presentation. Comprehensive genomic analysis, especially RNA sequencing, is efficient in diagnosing this rare tumor. Moreover, magnetic resonance imaging findings identical to AFH in soft tissue, the presence of paraneoplastic symptoms such as elevated inflammatory markers, and lymph node swelling were clues towards suspecting this tumor.

Cellulose nanofibers (CNFs) are synthesized by unraveling cellulose made from wood. CNFs have attracted significant attention among biomass materials owing to their excellent mechanical properties and wide range of applications. This study aims to elucidate the effects of CNFs as a lubricating additive. In order to accomplish this, CNFs were dispersed in water at densities of 0.02.1.0 mass%, and friction tests were performed using a ball-on-plate friction tester with a reciprocating motion configuration. Stainless steel (JIS-SUS304) and polyoxymethylene (POM) were used as sliding plates, while various materials were used for sliding balls. On both the SUS304 and POM plates, friction reductions were observed by adding only a small amount of CNFs (0.02 mass%). Although wear on the SUS304 plate reduced by 0.02 mass%, the water dispersion of CNFs was not distinct; it was observed only at densities of CNFs that were more than 0.2 mass%. On the POM plate, wear was induced by adding 0.02 mass% of CNF water dispersion. Adverse effects may arise with the addition of more than 0.2 mass% CNF. A distinctive feature observed in the water dispersion lubrication of CNFs was that a tribofilm is not formed due to the chemically inert nature of CNFs. It appears highly probable that in the water dispersion lubrication of CNFs, the physical effects of these fibers are much stronger than their chemical effects. These effects include rolling and/or sliding, which occurred in fullerene and carbon nanotubes.

This paper describes the role of ambient pressure in self-heating torrefaction of livestock manure. We explored the initiating temperatures required to cause self-heating of wet dairy cattle manure at different ambient pressures (0.1, 0.4, 0.7, and 1.0 MPa). Then, we conducted proximate, elemental, and calorific analyses of biochar torrefied at 210, 250, and 290°C. The results showed that self-heating was induced at 155°C or higher for 0.1 MPa and at 115°C or lower for 0.4 MPa or higher. The decrease of the initiating temperature at elevated pressure was due not only to more oxygen, but also to the retention of moisture that can promote chemical oxidation of manure. Biochar yields decreased with increasing torrefaction temperature and pressure, and the yield difference at 0.1 and 1.0 MPa was more substantial at lower temperatures: a 29.8, 16.4, and 9.4% difference at 210, 250, and 290°C, respectively. Proximate and elemental analyses showed that elevated pressure promotes devolatilization, deoxygenation, and coalification compared to atmospheric pressure; its impact, however, was less at higher temperatures as the torrefaction temperature became more dominant. Calorific analysis revealed that elevated pressure can increase the higher heating value (HHV) on a dry and ash-free basis at 210°C because of the increase in carbon content, but its impact is limited at 250 and 290°C. Meanwhile, the HHV on a dry basis exhibited the opposite trend due primarily to an enlargement of ash content. The present study revealed that ambient pressure considerably affects the initiating temperature of self-heating and the chemical properties of biochar at a low torrefaction temperature.

Background. Chordomas are rare malignant bone tumors preferentially forming in neuraxial bones. Chondroid chordoma is a subtype of chordoma. Chordomas reportedly present as synchronous multiple lesions upon initial diagnosis. However, it remains unknown whether these lesions are multicentric or metastatic multiple chordoma tumors. Case Presentation. Here, we present the case of a 57-year-old woman with multiple chordomas at the clivus, C6, and T12 upon initial presentation. Sequential surgeries and radiotherapy were performed for these lesions, and postoperative histological diagnosis revealed that all lesions were chondroid chordomas. Next-generation sequencing revealed that these lesions harbored a common somatic mutation in epidermal growth factor receptor (EGFR), c.3617A>C, which is not considered a pathogenic chordoma mutation, thus indicating that these lesions were not multicentric but rather multiple metastatic tumors. Subsequent multiple metastases to the lung and appendicular and axial bones were detected 15 months after the initial surgery. Recurrent lesions at the clivus progressed despite EGFR-targeted therapy, surgery, and radiotherapy. Conclusion. The present evidence indicates that multiple chordomas in this case were caused by multiple metastases rather than multicentric lesions. Multiple presentations of chordoma imply systemic dissemination of tumor cells, and novel efficient systemic therapy is required to treat this disease.

This paper presents improvements made to a computerized adaptive testing (CAT)-based version of the FCI (FCI-CAT) in regards to test security and test efficiency. First, we will discuss measures to enhance test security by controlling for item overexposure, decreasing the risk that respondents may (i) memorize the content of a pretest for use on the post-test or (ii) share information about the items with their classmates who take the assessment later. Second, we will discuss measures to enhance test efficiency, so that a shorter test length can yield a desired accuracy and precision of the measurement. Specifically, we utilized collateral information in the form of a pretest proficiency estimate of each respondent for selecting items and estimating respondent proficiency level in the post-test. To shorten the total testing time further, we also allowed the test lengths to be different for the pre- and post-test. To analyze how these improvements affect the accuracy and precision (which we measure in terms of root-mean-square error) of Cohen’s d, we conducted a Monte Carlo simulation and a post hoc simulation. Then, we calculated the minimal test length of the FCI-CAT whose accuracy and precision are equivalent to that of the paper-and-pencil version of the FCI. Consequently, we obtained the following three findings: (i) By using collateral information, we can achieve the accuracy and precision of the full-length FCI with fewer items via the FCI-CAT. (ii) For a class size of 40, we can control for test security while still reducing the sum of the pre- and post-test lengths of the FCI-CAT to a total of 33 items (17 items on the pretest and 16 items on the post-test), thereby reducing the testing time to 55%. (iii) If one’s goal is to maximize test efficiency, the pretest length should be slightly larger than the post-test length. On the other hand, if the goal is to maximize test security, the pretest length should be smaller and the post-test length should be larger. If one desires a balance of these two goals, it would be reasonable to choose equal pre- and post-test lengths.

Abstract Dust and water vapor are important constituents in the Martian atmosphere, exerting significant influence on the heat balance of the atmosphere and surface. We have developed a method to retrieve optical and physical properties of Martian dust from spectral intensities of direct and scattered solar radiation to be measured using a multi-wavelength environmental camera onboard a Mars lander. Martian dust is assumed to be composed of silicate-like substrate and hematite-like inclusion, having spheroidal shape with a monomodal gamma size distribution. Error analysis based on simulated data reveals that appropriate combinations of three bands centered at 450, 550, and 675 nm wavelengths and 4 scattering angles of 3°, 10°, 50°, and 120° lead to good retrieval of four dust parameters, namely, aerosol optical depth, effective radius and variance of size distribution, and volume mixing ratio of hematite. Retrieval error increases when some of the observational parameters such as color ratio or aureole are omitted from the retrieval. Also, the capability of retrieving total column water vapor is examined through observations of direct and scattered solar radiation intensities at 925, 935, and 972 nm. The simulation and error analysis presented here will be useful for designing an environmental camera that can elucidate the dust and water vapor properties in a future Mars lander mission.

Abstract. We retrospectively evaluated 48 essential thrombocythemia (ET) patients who were treated in our institute (male/female, 14/34, median age, 61.5 years). In 14 patients treated with anagrelide (ANA), the degree of platelet count reduction (median, −56.6%) was strongly correlated with increase of mean platelet volume (MPV) (median, +11.7%) (R = 0.777). This correlation was not observed in ET patients treated with hydroxycarbamide alone (R = 0.245). The change in size of platelets strongly suggested that ANA affected the final process of platelet production. Thus, we hypothesized that ANA modifies the process by which platelets are released from proplatelets. To verify the association in an in vitro setting, we compared MEG-01 cells treated with PMA ± ANA. The number of platelet-like particles (PLPs) was decreased (P

Phosphaturic mesenchymal tumors (PMTs) that cause tumor-induced osteomalacia (TIO) occur commonly in the bone with a small and nonaggressive appearance. Here, we report the case of a 67-year-old man with disseminated PMT in the humerus after a pathological fracture. Liquid nitrogen was used as an adjuvant therapy after curettage of the tumor, and the frozen autograft, using a pedicle freezing method, conserved the function of the shoulder joint. To our knowledge, this is the first case of a disseminated PMT in the bone that was treated with a frozen autograft, and this treatment method may be effective for cases in which curettage for PMT in the bone would be inevitably inadequate.

As a method to shorten the test time of the Force Concept Inventory (FCI), we suggest the use of computerized adaptive testing (CAT). CAT is the process of administering a test on a computer, with items (i.e., questions) selected based upon the responses of the examinee to prior items. In so doing, the test length can be significantly shortened. As a step to develop a CAT-based version of the FCI (FCI-CAT), we examined the optimal test length of the FCI-CAT such that accuracy and precision [which we measure in terms of bias, standard error, and root-mean-square error (RMSE)] of Cohen’s d would be comparable to that of the full FCI for a given class size. First, we estimated the item parameters of the FCI items based on the three-parameter logistic model of item response theory, which are used in the algorithm of CAT. For this estimation, we used 2882 responses of Japanese university students. Second, we conducted a Monte Carlo simulation to analyze how the bias, standard error, and RMSE of Cohen’s d depend upon the test length. Third, we conducted a post hoc simulation to examine the consistency of the Monte Carlo results with what would have been obtained using empirical responses. For this comparison, we used 86 pairs of pre- and post- test responses of Japanese university students. As a result, we found that for a class size of 40, we may reduce the test length of the FCI-CAT to 15–19 items, thereby reducing the test time of the FCI to 50%–63%, with an accompanying decrease in accuracy and precision of only 5%–10%. The results of the Monte Carlo study and the post hoc simulation were consistent, which supports the adequacy of our Monte Carlo study and its relevance in terms of administering the FCI-CAT in real classrooms.

Zebrafish are used widely in biomedical, toxicological, and developmental research, but information on their xenobiotic metabolism is limited. Here, we characterized the expression of 14 xenobiotic cytochrome P450 (CYP) subtypes in whole embryos and larvae of zebrafish (4 to 144 h post-fertilization (hpf)) and the metabolic activities of several representative human CYP substrates. The 14 CYPs showed various changes in expression patterns during development. Many CYP transcripts abruptly increased at about 96 hpf, when the hepatic outgrowth progresses; however, the expression of some cyp1s (1b1, 1c1, 1c2, 1d1) and cyp2r1 peaked at 48 or 72 hpf, before full liver development. Whole-mount in situ hybridization revealed cyp2y3, 2r1, and 3a65 transcripts in larvae at 55 hpf after exposure to rifampicin, phenobarbital, or 2,3,7,8-tetrachlorodibenzo-p-dioxin from 30 hpf onward. Marked conversions of diclofenac to 4′-hydroxydiclofenac and 5-hydroxydiclofenac, and of caffeine to 1,7-dimethylxanthine, were detected as early as 24 or 50 hpf. The rate of metabolism to 4’-hydroxydiclofenac was more marked at 48 and 72 hpf than at 120 hpf, after the liver had become almost fully developed. These findings reveal the expression of various CYPs involved in chemical metabolism in developing zebrafish, even before full liver development.

In Indonesia, there is a need to improve the efficiency of damage assessments of the agricultural insurance system for paddy rice producers affected by floods, droughts, pests, and diseases. In this study, we develop a method to estimate the transplanting date required for damage assessments of paddy rice fields. The study area is the Cihea irrigation district in West Java, Republic of Indonesia. Backscattering coefficients of VH polarization measured by a synthetic aperture radar onboard the Sentinel-1 satellite were used for the estimations. We investigated the accuracy of the estimations of the proposed method by smoothing out the time-series data, applying a speckle filter, and by signal synthesis of the surrounding fields. It was found that these variations effectively improved the estimation accuracy. To further improve the estimation accuracy, the data for all incident angles were used after correcting the incident angle dependence of the backscattering coefficients for three types of data with different incident angles (32°, 41°, and 45°) obtained in the study area. The estimated transplanting date for each field in the test site was compared with the transplanting date obtained through interviews. The standard deviations of the estimation errors for the four cropping periods from March 2018 to February 2020 were found to be ~5–6 days, and the percentages of estimation errors in transplanting dates within 5, 10, and 15 days were estimated to be 69%, 92%, and 97%, respectively. It was confirmed that a sufficiently reliable transplanting date estimation can be obtained ~10–15 days after transplantation.

A large number of studies have been conducted on organic carbon (OC) variation in mangrove ecosystems. However, few have examined its relationship with soil quality and stratigraphic condition. Mangrove OC characteristics would be explicitly understood if those two parameters were taken into account. The aim of this study was to examine mangrove OC characteristics qualitatively and quantitatively after distinguishing mangrove OC from other OC. Geological survey revealed that the underground of a mangrove ecosystem was composed of three layers: a top layer of mangrove origin and two underlying sublayers of geologic origin. The underlying sublayers were formed from different materials, as shown by X-ray fluorescence analysis. Despite a large thickness exceeding 700 cm in contrast to the 100 cm thickness of the mangrove mud layer, the sublayers had much lower OC stock. Mangrove mud layer formation started from the time of mangrove colonization, which dated back to between 1330 and 1820 14C years BP, and OC stock in the mangrove mud layer was more than half of the total OC stock in the underground layers, which had been accumulating since 7200 14C years BP. pH and redox potential (Eh) of the surface soils varied depending on vegetation type. In the surface soils, pH correlated to C% (r = −0.66, p < 0.01). C/N ratios varied widely from 3.9 to 34.3, indicating that mangrove OC had various sources. The pH and Eh gradients were important factors affecting the OC stock and the mobility/uptake of chemical elements in the mangrove mud layer. Humic acids extracted from the mangrove mud layer had relatively high aliphatic contents, in contrast with the carboxylic acid rich sublayers, indicating that humification has not yet progressed in mangrove soil.

We report an extremely rare case of urothelial carcinoma (UC) of the urinary bladder with diverse histological differentiation into squamous, glandular, and plasmacytoid components. A 65-year-old man presented with gross hematuria. Cystoscopy showed a papillary-growing tumor with a wide-based stalk on the left wall of the urinary bladder. Based on the clinical diagnosis of locally invasive bladder cancer, the patient underwent radical cystectomy. Histological examination of the cystectomy specimen revealed UC with histological differentiation into multiple tumor subtypes. The tumor was composed of squamous cell carcinoma with marked keratinization, adenocarcinoma characterized by tall columnar cells with scattered goblet cells, conventional high-grade invasive UC and UC in situ, and plasmacytoid UC composed of discohesive cancer cells with eccentric nuclei and eosinophilic cytoplasm that diffusely infiltrated the bladder wall through the serosal surface. Immunohistochemically, the loss of membranous E-cadherin expression was noted only in the plasmacytoid UC component. The patient developed local recurrences 2 months postoperatively and died of the disease 6 months postoperatively. It is critical to correctly diagnose the histological variants of UC to predict a patient's prognosis and to determine the optimal treatment.

The spectral intensity of direct and scattered solar radiation is of fundamental importance for various studies in civil engineering, agriculture, solar power generation, and radiation budget estimation. In this paper, we describe a ground-based, wide-spectral-range sensor that can be used for measuring spectral intensities both in the visible and near-infrared spectral regions. The measurements are conducted either with artificial light sources or direct/scattered solar radiation. The measured spectra yields information on the absorption features of atmospheric gases such as nitrogen dioxide (NO2), carbon dioxide (CO2) and water vapor, as well as aerosol optical properties in the atmosphere. Relatively weak absorption of nitrogen dioxide is measured with the technique of differential optical absorption spectroscopy (DOAS), whereas aerosol, carbon dioxide, and water vapor amounts are measured by matching the observed spectra with simulated ones. Both High Resolution Transmission (HITRAN) and Moderate Resolution Atmospheric Transmission (MODTRAN) database/codes are used to derive column amounts of absorbing molecular species and to characterize aerosol optical properties.

Smoothed particle hydrodynamics (SPH) is a particle method for analyzing physical problems. But this method has numerical problems when treating multilayer problems and free surface. In this report we propose equations to treat multilayer heat conduction problems and normalized equations to avoid the edge effect which is caused by the lack of particles at the free surface. Numerical results, in the case of 1 layer heat conduction model has good agreement with results of difference method. Numerical results in the case of 2 layer heat conduction model, where the ratio of heat conductivity of 2 layer is changed from 5 to 50 shows that normalized equations are effective to treat multilayer heat conduction problems.

We report a case of acute myeloid leukemia (AML) with two cytogenetically unrelated clones. The patient was a 45-year-old male who was diagnosed with acute monoblastic leukemia (AMoL). Initial G-band analysis showed 51,XY,+6,+8,inv(9)(p12q13)c,+11,+13,+19[12]/52,idem,+Y[8], but G-band analysis after induction therapy showed 45,XY,-7,inv(9)(p12q13)c[19]/46,XY,inv(9)(p12q13)c[1]. Retrospective FISH analysis revealed a cryptic monosomy 7 clone in the initial AML sample. The clone with multiple trisomies was eliminated after induction therapy and never recurred, but a clone with monosomy 7 was still detected in myelodysplastic marrow with a normal blast percentage. Both clones were successfully eliminated after related peripheral blood stem cell transplantation, but the patient died of relapsed AML with monosomy 7. We concluded that one clone was de novo AMoL with chromosome 6, 8, 11, 13, and 19 trisomy and that the other was acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) with chromosome 7 monosomy showing different responses to chemotherapy. Simultaneous onset of cytogenetically unrelated hematological malignancies that each have a different disease status is a rare phenomenon but is important to diagnose for a correct understanding of the disease status and for establishing an appropriate treatment strategy.