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Background: This study aimed to investigate the diagnostic performance of combined computed tomography (CT) and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for predicting histologic invasiveness of pure ground-glass nodules (pGGNs). Methods: The study analyzed 91 patients who underwent resection of pGGNs and examined the correlation of pathologic invasiveness with preoperative CT and FDG PET findings. Results: Overall, 24, 36, and 31 patients had adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAD), respectively. Compared with AIS and MIA, IAD was significantly correlated with larger CT size (P = .001), maximum CT value (P = .026), and high maximum standardized uptake value (SUVmax; P < .001). Multivariable logistic analyses revealed that CT size (odds ratio [OR], 3.848; P = .019) and SUVmax (OR, 4.968; P = .009) were independent predictors of histologic invasiveness. Receiver operating characteristic curve analysis revealed that a cutoff CT size value of 18 mm predicted histologic invasiveness with a sensitivity and specificity of 65% and 80%, respectively; similarly, a cutoff SUVmax value of 1.5 predicted histologic invasiveness with a sensitivity and specificity of 61% and 90%, respectively. Of 20 lesions with CT size ≥18 mm and SUVmax ≥1.5, 16 (80%) were IAD. Of 54 lesions with CT size

Abstract A young patient diagnosed with advanced colon cancer and liver metastasis was found to have familial adenomatous polyposis (FAP) through comprehensive genomic analysis. Whole-genome array comparative genomic hybridization (aCGH) revealed germline deletions at chromosome 5q22.1-22.2 encompassing the entire APC gene. The patient and her son exhibited mild intellectual disability without developmental delay. This case highlights the need for further exploration of the characteristics associated with whole APC deletions. aCGH is a valuable tool for studying FAP and provides a detailed analysis of large deletions.

Objective: With the development of diagnostic imaging, a new clinical entity called reversible cerebral vasoconstriction syndrome (RCVS), which is considered to be a cause of secondary headache, has emerged. We herein present two cases of RCVS with different patterns of clinical progression. Case report: Case 1 occurred during labor, whereas case 2 occurred after delivery. Neither case presnted thunderclap headache at the onset of symptoms. Hypertensive disorders of pregnancy did not occur during the pregnancy or the puerperium in either case. Neurological symptoms following mild headache (Case 1: coma; Case 2: paralysis of the right extremities) were observed. Conclusion: Even when a patient has no risk factors for RCVS and had no severe headache, it is important not to miss any of the neurological symptoms. Magnetic resonance imaging (MRI) strongly supports the diagnosis, even during pregnancy. In addition, the diagnosis should always be reviewed while excluding eclampsia.

A current-perpendicular-to-plane giant magnetoresistive (CPP-GMR) device with a half-metallic electrode is one of the most promising candidates of next-generation read head for hard disk drive. In this study, we fabricate [001]-oriented polycrystalline CPP-GMR devices with the normal ferromagnet (NFM) CoFe/half-metallic ferromagnet (HMFM) Co2FeGa0.5Ge0.5 (CFGG) bilayer electrodes to enhance the magnetoresistance (MR) ratio by large interfacial spin-dependent scattering at the NFM/HMFM interface. The CoFe/CFGG bilayer electrode provides the additional large interfacial spin-dependent scattering and achieves high MR ratio of 22.7% with the CoFe(4.5 nm)/CFGG(2.5 nm) bilayer electrodes, which is almost three(two) times larger than the MR ratio with the single CoFe(CFGG) (7 nm) electrodes. The bias voltage dependent study revealed an additional advantage of increasing the output voltage |ΔV| by using the CoFe/CFGG bilayer due to the improvement of the endurance against spin-transfer torque under high bias current. A maximum output voltage [Formula: see text] of 6.5 mV was obtained with the CoFe(5.5 nm)/CFGG(1.5 nm) electrodes, which is the highest ever reported in the CPP-GMR devices with a uniform metallic spacer including high-quality epitaxial devices.

Background: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. Methods: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. Results: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. Conclusions: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.

Abstract Background Several methods have been reported for detecting resistance genes or phenotypic testing on the day of positive blood culture in Escherichia coli or Klebsiella pneumoniae bacteremia. However, some facilities have not introduced these methods because of costs or other reasons. Toyota Kosei Hospital introduced cefpodoxime (CPDX) rapid screening on May 7, 2018, to enable early detection of third-generation cephalosporin resistance. In this study, we aimed to evaluate the effects of intervention with an Antimicrobial Stewardship Team using CPDX rapid screening. Methods Cefotaxime (CTX)-resistant E. coli or K. pneumoniae bacteremia cases were selected retrospectively and divided into two groups: the pre-CPDX screening (June 1, 2015, to May 6, 2018) and CPDX screening groups (July 7, 2018, to August 31, 2021). The primary outcome was the proportion of cases in which modifications were made to the administration of susceptible antimicrobial agents within 24 h of blood culture-positive reports. Results Overall, 63 patients in the pre-CPDX screening group and 84 patients in the CPDX screening group were eligible for analysis. The proportion of patients who modified to susceptible antimicrobial agents within 24 h of blood culture-positive reports was significantly increased in the CPDX screening group compared to that in the pre-CPDX screening group (6.3% vs. 22.6%, p = 0.010). Conclusion The results demonstrated that in CTX-resistant E. coli or K. pneumoniae bacteremia, CPDX rapid screening increased the proportion of early initiation of appropriate antimicrobial agents.

Abstract Background Staying at home during the dying process is important for many patients; and palliative care units (PCUs) can help facilitate home death. This study compared patient survival between those who were discharged to home from a palliative care unit and those who were not, and aimed to identify the factors associated with home death after the discharge. Methods This retrospective cohort study used a database of patients admitted to a palliative care unit at Kouseiren Takaoka Hospital in Japan. All consecutive patients admitted to the hospital’s PCU between October 2016 and March 2020 were enrolled. Patient survival and factors potentially associated with survival and place of death were obtained. A total of 443 patients with cancer were analyzed, and 167 patients were discharged to home and 276 were not. Results Propensity score matching analyses revealed that median survival time was significantly longer in patients who were discharged to home than those who were not (57 vs. 27 days, P

Introduction Intravesical Bacillus Calmette–Guérin immunotherapy is an effective treatment for non‐muscle‐invasive bladder cancer, which is occasionally associated with side effects and complications. The incidence of significant renal complications after intravesical Bacillus Calmette–Guérin immunotherapy is less than 2%. We report a case of renal granuloma after intravesical Bacillus Calmette–Guérin immunotherapy for bladder cancer, which radiologically resembled a papillary renal cell carcinoma. Case presentation A 65‐year‐old man, who had a medical history of urothelial carcinoma and received intravesical Bacillus Calmette–Guérin therapy, was referred to our Urology Department with a right renal tumor. Imaging findings suggested papillary renal cell carcinoma. Robot‐assisted partial nephrectomy was performed, and the histopathological examination revealed epithelioid cell granuloma, which were considered to be Bacillus Calmette–Guérin‐related renal granuloma. Conclusion Bacillus Calmette–Guérin‐related renal granuloma mimicking papillary renal cell carcinoma have been reported. We should consider the possibility of renal granulomas when encountering image abnormalities for patients treated with intravesical Bacillus Calmette–Guérin therapy.

Abstract The Aira caldera, located in southern Kyushu, Japan, originally formed 100 ka, and its current shape reflects the more recent 30 ka caldera-forming eruptions (hereafter, called the AT eruptions). This study aimed to delineate the detailed two-dimensional (2D) seismic velocity structure of the Aira caldera down to approximately 15 km, by means of the travel-time tomography analysis of the seismic profile across the caldera acquired in 2017 and 2018. A substantial structural difference in thickness in the subsurface low-velocity areas in the Aira caldera between the eastern and western sides, suggest that the Aira caldera comprises at least two calderas, identified as the AT and Wakamiko calderas. The most interesting feature of the caldera structure is the existence of a substantial high-velocity zone (HVZ) with a velocity of more than 6.8 km/s at depths of about 6–11 km beneath the central area of the AT caldera. Because no high ratio of P- to S-wave velocity zones in the depth range were detected from the previous three-dimensional velocity model beneath the AT caldera region, we infer that the HVZ is not an active magma reservoir but comprises a solidified and cool remnant. In addition, a poorly resolved low-velocity zone around 15 km in depth suggests the existence of a deep active magma reservoir. By superimposing the distribution of the known pressure sources derived from the observed ground inflation and the volcanic earthquake distribution onto the 2D velocity model, the magma transportation path in the crust was imaged. This image suggested that the HVZ plays an important role in magma transportation in the upper crust. Moreover, we estimated that the AT magma reservoir in the 30 ka Aira caldera-forming eruptions has the total volume of 490 km3 DRE and is distributed in a depth range of 4–11 km. Graphical Abstract

This paper reports the result of an investigation of a hypothesis that the melting polar ice of Earth flowing down to the equatorial region causes volcano eruptions. We assumed a cube inside the spherical body of Earth, formulated a 3-dimensional inertia tensor of the cube, and then simulated the redistribution of the mass that is to be caused by the movement of melted ice on the Earth’s surface. Such mass distribution changes the inertia tensor of the cube. Then, the cube’s rotation inside Earth was simulated by multiplying the Euler angle matrix by the inertia tensor. Then, changes in the energy intensity and the angular momentum of the cube were calculated as coefficients of Hamiltonian equations of motion, which are made of the inertia tensor and sine and cosine curves of the rotation angles. The calculations show that the melted ice increases Earth’s internal energy intensity and angular momentum, possibly increasing volcano eruptions.

Abstract Topological integrated circuits are integrated-circuit realizations of topological systems. Here we show an experimental demonstration by taking the case of the Kitaev topological superconductor model. An integrated-circuit implementation enables us to realize high resonant frequency as high as 13GHz. We explicitly observe the spatial profile of a topological edge state. In particular, the topological interface state between a topological segment and a trivial segment is the Majorana-like state. We construct a switchable structure in the integrated circuit, which enables us to control the position of a Majorana-like interface state arbitrarily along a chain. Our results contribute to the development of topological electronics with high frequency integrated circuits.

More than 100 laboratories in the World Health Organization Global Measles and Rubella Laboratory Network (GMRLN) perform nucleic acid-based methods for case confirmation of measles or rubella infections and/or strain surveillance (genotyping). The quality of laboratory data is critical to ensure that diagnostic results and country reports to regional verification committees are based on accurate data. A molecular External Quality Assurance (mEQA) program was initiated by the US-CDC in 2014 to evaluate the performance of laboratories in the network. The inclusion of testing for measles and rubella viruses, with a focus on detection and genotyping, plus the diversity of assays and platforms employed required a flexible and comprehensive proficiency testing program. A stepwise introduction of new evaluation criteria gradually increased the stringency of the proficiency testing program, while giving laboratories time to implement the required changes. The mEQA program plays an important role in many processes in the GMRLN, including informing plans for the training of laboratory staff, access to reagents, and the submission of sequence data to global databases. The EQA program for Local Public Health Institutes in Japan is described as an example for national mEQA programs. As more laboratories initiate molecular testing, the mEQA will need to continue to expand and to adapt to the changing landscape for molecular testing.

Abstract Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn’s disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P

Abstract The carbon to nitrogen (CN) ratio of phytoplankton connects the carbon and nitrogen cycles in the ocean. Any variation in this ratio under climate change will alter the amount of carbon fixed by photosynthesis, and ultimately the amount sequestered in the ocean. However, a consistent mechanistic explanation remains lacking for observed species‐specific variations in phytoplankton CN ratios. We show that acclimation to ambient environmental conditions explains the observed variation of phytoplankton CN ratios by incorporating phytoplankton acclimation theory based on a resource allocation trade‐off between carbon vs. nitrogen acquisition capacity into a three‐dimensional marine ecosystem model. Inter‐specific differences in CN ratio and its sensitivity are caused by inter‐specific differences in Droop's minimum nitrogen cell quota. Our model, constrained by observed phytoplankton parameters, shows that the global mean phytoplankton CN ratio is greater than the canonical Redfield ratio, as suggested previously based on regional in situ observations.

BackgroundRobots offer many unique opportunities for helping individuals with autism spectrum disorders (ASD). Determining the optimal motion of robots when interacting with individuals with ASD is important for achieving more natural human-robot interactions and for exploiting the full potential of robotic interventions. Most prior studies have used supervised machine learning (ML) of user behavioral data to enable robot perception of affective states (i.e., arousal and valence) and engagement. It has previously been suggested that including personal demographic information in the identification of individuals with ASD is important for developing an automated system to perceive individual affective states and engagement. In this study, we hypothesized that assessing self-administered questionnaire data would contribute to the development of an automated estimation of the affective state and engagement when individuals with ASD are interviewed by an Android robot, which will be linked to implementing long-term interventions and maintaining the motivation of participants.MethodsParticipants sat across a table from an android robot that played the role of the interviewer. Each participant underwent a mock job interview. Twenty-five participants with ASD (males 22, females 3, average chronological age = 22.8, average IQ = 94.04) completed the experiment. We collected multimodal data (i.e., audio, motion, gaze, and self-administered questionnaire data) to train a model to correctly classify the state of individuals with ASD when interviewed by an android robot. We demonstrated the technical feasibility of using ML to enable robot perception of affect and engagement of individuals with ASD based on multimodal data.ResultsFor arousal and engagement, the area under the curve (AUC) values of the model estimates and expert coding were relatively high. Overall, the AUC values of arousal, valence, and engagement were improved by including self-administered questionnaire data in the classification.DiscussionThese findings support the hypothesis that assessing self-administered questionnaire data contributes to the development of an automated estimation of an individual’s affective state and engagement. Given the efficacy of including self-administered questionnaire data, future studies should confirm the effectiveness of such long-term intervention with a robot to maintain participants’ motivation based on the proposed method of emotion estimation.

Objectives: We evaluated the effectiveness of the Lao People's Democratic Republic's measles-rubella immunization program using the seroprevalence from two cross-sectional surveys. Methods: The nationwide surveys occurred in 2014 and 2019 using a multistage cluster sampling, both requiring samples from 2184 individuals from 52 randomly selected villages. Immunoglobulin G titers, measured using enzyme-linked immunosorbent assay, were considered positive at ≥120 mIU/ml (measles) and ≥10 IU/ml (rubella). We calculated the vaccination-related reduction in the force of rubella infection and the number of congenital rubella syndrome cases averted in 2019. Results: We collected 2135 (women: 55.2%, mean age: 23.2 years) and 2001 (52.7%, 23.1 years) samples in 2014 and 2019, respectively. During 2014-2019, immunoglobulin G prevalence increased from 83.9% (95% confidence interval [CI]: 83.8-84.0) to 98.3% (97.7-98.8) for measles and from 75.4% (75.3-75.5) to 87.8% (86.4-89.2) for rubella. The most plausible reduction in the average force of rubella infection was 100% (95% CI: 28-100) since vaccination started, averting 78 (95% CI: 42-128) congenital rubella syndrome cases in 2019. Conclusion: This is the first population-based study for measles and rubella at two different time points in developing countries. Measles and rubella seroprevalence increased significantly during 2014-2019, greatly exceeding the immunity thresholds for their elimination.

Abstract Background The effectiveness of local therapy has been reported in patients with oligo‐recurrence of non‐small cell lung cancer (NSCLC), a metachronous recurrence with a limited number of recurrences, which can be treated with local therapy. Conversely, remarkable progress has been made in systemic therapy for NSCLC with the advent of molecular targeted therapy. In particular, epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) are very effective in the treatment of EGFR‐mutated NSCLC. There is currently no consensus on treatment for oligo‐recurrence of EGFR‐mutated NSCLC. Methods From 2004 to 2014, 811 patients underwent complete resection for NSCLC at Kitasato University Hospital and, of these, 244 patients developed recurrence. Oligo‐recurrence was defined as the presence of two or less recurrent lesions, and 34 patients presented with EGFR‐mutated oligo‐recurrence. Results We retrospectively examined and compared the effects of EGFR‐TKIs with those of radical local therapy in patients with oligo‐recurrent EGFR‐mutated NSCLC. The five‐year post‐recurrence survival (PRS) rates of patients with EGFR‐mutated oligo‐recurrence who received radical local therapy (n = 23) and those who did not (n = 11) were 59.4 and 45.5%, respectively (p = 0.777). Multivariate analysis revealed no favorable prognostic factors associated with prolonged PRS, and radical local therapies did not improve PRS in patients with oligo‐recurrence (p = 0.551). Conclusion Radical local therapy did not affect PRS in patients with oligo‐recurrent EGFR‐mutated NSCLC. Even in cases of oligo‐recurrence, the administration of local therapy in patients with EGFR‐mutated NSCLC might be carefully considered.

Introduction Metastasectomy of oligometastatic prostate cancer has the potential to contribute to improving prognosis. We report on a case of metastasectomy of solitary liver tumor after radical prostatectomy. Case presentation An 80‐year‐old man underwent radical prostatectomy for prostate cancer, followed by radiotherapy after the operation because of increased serum prostate‐specific antigen levels of 0.529 ng/mL. Levels increased further to 0.997 ng/mL even after salvage therapy. The patient then received androgen deprivation therapy. Levels remained stable for 3 years, but rapidly increased to 19.781 ng/mL in the following 6 months. Abdominal computed tomography revealed a solitary liver tumor, and no metastasis to other sites was identified. The patient underwent liver segmentectomy. Microscopic examination of excised specimens revealed prostate cancer cells. Five years after surgery, serum prostate‐specific antigen maintained to the lowest level so far. Conclusion Metastasectomy might be a beneficial therapeutic option to improve the prognosis for solitary metastasis from prostate cancer.

Abstract Pathogenic variants of HECW2 have been reported in cases of neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL; OMIM #617268). A novel HECW2 variant (NM_001348768.2:c.4343 T > C,p.Leu1448Ser) was identified in an NDHSAL infant with severe cardiac comorbidities. The patient presented with fetal tachyarrhythmia and hydrops and was postnatally diagnosed with long QT syndrome. This study provides evidence that HECW2 pathogenic variants can cause long QT syndrome along with neurodevelopmental disorders.

Primary pleural angiosarcoma (PPA) is a rare and clinically fatal pleural tumor originating from vascular endothelial cells. Herein, we presented the case of a 73-year-old man who was referred to our emergency room with complaints of right chest and back pain for a few days. Chest computed tomography revealed massive pleural effusion and a large mass in the right chest cavity. Thoracoscopic examination demonstrated a large hemorrhagic tumor on the parietal pleura whose pathological analysis indicated PPA. The patient received immunotherapy combined with nivolumab and ipilimumab. A cycle of nivolumab and ipilimumab improved his hemorrhagic anemia and reduced the pleural effusion and tumor size. This treatment outcome suggests that nivolumab and ipilimumab comprise a vital treatment option for PPA.

Abstract The X-linked human glutamate receptor subunit 3 (GRIA3) gene (MIM *305915, Xq25) encodes ionotropic α amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptor subunit 3, which mediates postsynaptic neurotransmission. Variants in this gene can cause a variety of neurological disorders, primarily reported in male patients. Here, we report a female patient with developmental and epileptic encephalopathy who carries the novel de novo GRIA3 variant NM_007325.5: c.1982T > C: p.Met661Thr.

We developed an autonomous and efficient system for synthesising ferromagnetic materials with large magnetocrystalline anisotropy by integrating theoretical, informatics, and experimental approaches. By combining the first-principles calculation of the magnetic anisotropy with Bayesian optimisation, we virtually screened candidate materials, comprising four elements and four-layer periods, from various magnetic multilayers. We employed the expected improvement as the acquisition function and Matern52 as the kernel function, to develop a robust machine learning model. We fabricated the top three predicted magnetic materials under laboratory conditions by monoatomic layer deposition and evaluated their magnetic anisotropy using a superconducting quantum interference device (SQUID). Ultimately, we demonstrated that [Fe/Co/Fe/Ni]13 is a novel ferromagnetic material whose magnetic anisotropy exceeds that of L10-FeNi- and L10-FeCo-type alloys. Furthermore, the origin of the perpendicular magnetic anisotropy was derived from the spin-conserving as well as the spin-flip terms. We determined that Bayesian optimisation offers promising configurability features in terms of the electronic structure that extend beyond the empirical knowledge and human intuition.

IntroductionSocial skills training (SST) is used to help individuals with autism spectrum conditions (ASC) better understand the perspectives of others and social interactions, develop empathy skills, and learn how to engage with others socially. However, many individuals with ASC cannot easily sustain high motivation and concentration during such an intervention when it is administered by humans. We developed a social skills training program using multiple humanoid robots (STUH), including an android robot, that aimed to enable individuals with ASC to become familiar with the perspectives of others and improve their sociability and empathy skills. The objective of the present study was to investigate the effectiveness of STUH for these individuals.MethodsIn STUH, we prepared 50 social exercises that consisted of conversations and behavioral interactions between an android robot and a simple humanoid robot. We prepared another humanoid robot that featured a cartoon-like and mechanical design, which played the role of host. In the first half-session of STUH, participants worked on the exercise from the perspective of an outsider. In the second half-session of STUH, they simulated experience by using robots as their avatars. The intervention associated with STUH was conducted for five days in total. We conducted an analysis of variance (ANOVA) featuring the intervention time point as the independent variable to examine changes in each score on the sociability index items.ResultsIn total, 14 individuals with ASC participated in the study. The results of multiple comparison tests using the Bonferroni method indicated that all sociability index items improved between preintervention and follow-up. Our program enabled the participants to become familiar with the perspectives of others and improve their sociability.DiscussionGiven the promising results of this study, future studies featuring long-term follow-up should be conducted to draw definitive conclusions about the efficacy of our training system.

We demonstrated the effectiveness of the machine learning method combined with first-principles calculations for the enhancement of the anomalous Nernst effect (ANE) of multilayers. The composition ratio of CoNi homogeneous alloy superlattices was optimized by Bayesian optimization so as to maximize the transverse thermoelectric conductivity (αxy). The nonintuitive optimal composition with a large αxy of ∼10 A K−1 m−1 was identified through the two-step Bayesian optimization using rough and fine candidate pools. The Berry curvature and band dispersion analyses revealed that αxy is enhanced by the appearance of the flat band near the Fermi level due to the multilayer formation. The magnitude of the energy derivative of the anomalous Hall conductivity increases owing to the large Berry curvature near the flat band along the R-M high symmetry line, which emerges only in the optimized superlattice, leading to the αxy enhancement. The effective method verified here will broaden the choices of ANE materials to more complex systems and, therefore, lead to the development of transverse thermoelectric conversion technologies.

Abstract Background Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable limited‐disease (LD) small cell lung cancer (SCLC), which has remained unchanged for over two decades. Based on a previous study that confirmed the non‐inferiority of amrubicin (AMR) plus cisplatin (AP) when compared with EP for extensive‐disease (ED) SCLC, we have previously conducted a phase I study assessing AP with concurrent TRT (2 Gy/time, once daily, 50 Gy in total) for LD‐SCLC therapy. Our findings revealed that AP with concurrent TRT could prolong overall survival to 39.5 months with manageable toxicities. Therefore, we plan to conduct a phase I study to investigate and determine the effect of AP combined with AHTRT, recommended dose (RD), maximum tolerated dose (MTD), and dose‐limiting toxicity (DLT) of AP in patients with LD‐SCLC. Methods Treatment‐naive patients with LD‐SCLC, age between 20 and 75 years, who had a performance status of 0 or 1 and adequate organ functions will be enrolled. For chemotherapy, cisplatin 60 mg/m2/day (day 1) and AMR (day 1 to 3) will be administered with AHTRT (1.5 Gy/time, twice daily, 45 Gy in total). The initial AMR dose is set to 25 mg/m2/day. RD and MTD will be determined by evaluating toxicities. Discussion Based on our previous study, the initial dose of AMR 25 mg/m2 is expected to be tolerated and acceptable. Here, we aim to determine whether treatment with AP and concurrent AHTRT would be an optimal choice with manageable toxicities for LD‐SCLC.

Abstract Background Olanzapine has been shown to have an additive effect on the three-drug antiemetic therapy consisting of aprepitant, palonosetron, and dexamethasone, in a highly emetogenic cisplatin-containing chemotherapy. Although olanzapine may be more economical than aprepitant or palonosetron, an adequate cost-efficacy analysis has not been conducted. Methods We conducted a cost-utility analysis to evaluate the cost-effectiveness of olanzapine use in four-drug antiemetic therapy among Japanese patients. We simulated model patients treated with highly emetogenic cisplatin-containing chemotherapy and developed a decision-analytical model of patients receiving triple antiemetic therapy with or without olanzapine in an inpatient setting. The cost and probabilities of each treatment were calculated from the perspective of the Japanese healthcare payer. The probabilities, utility value, and other costs were obtained from published sources. One-way and probabilistic sensitivity analyses were conducted to examine the influence of each parameter on the model and the robustness of a base-case analysis. Threshold analysis was conducted to determine the cost of olanzapine that would make the incremental cost-effectiveness ratio (ICER) equivalent to the threshold ICER). The threshold incremental cost-effectiveness ratio was set at 5 million Japanese Yen (JPY) per quality-adjusted life-year (QALY) gained. Results The cost was 10,238 JPY in the olanzapine regimen and 9719 JPY in the non-olanzapine regimen. The QALY gained were 0.01065 QALYs and 0.01029 QALYs in the olanzapine and non-olanzapine regimen, respectively. The incremental cost of the olanzapine regimen relative to the non-olanzapine regimen was 519 JPY, and the incremental QALYs were 0.00036 QALY, resulting in an ICER of 1,428,675 JPY per QALY gained. In the one-way sensitivity analysis, the results were most sensitive to the utility value of incomplete control. The probabilistic sensitivity analysis revealed the probability that the ICER was below the willingness-to-pay, and the incremental QALYs was positive was 96.2%. The calculated cost of olanzapine per 5 mg that would make the incremental cost-effectiveness ratio equivalent to the threshold incremental cost-effectiveness ratio was calculated to be 475 JPY. Conclusions Olanzapine was cost-effective in the four-drug antiemetic therapy for Japanese patients treated with highly emetogenic cisplatin-containing chemotherapy.

Abstract Background In Japan, dilatation & curettage (D&C) has been performed under general anesthesia as a surgery for an early pregnancy miscarriage for a long time. In 2016, manual vacuum aspiration (MVA) under general anesthesia was introduced at our hospital and has been used as a surgical treatment for first-trimester pregnancy miscarriage, with its utility to date being reported here. In July 2018, our hospital introduced the MVA procedure under local anesthesia. In this study, we evaluated the efficacy and safety of MVA under general and local anesthesia in first-trimester pregnancy miscarriage surgery in Japanese women. Methods In this retrospective observational cohort study, we enrolled 322 pregnant women at less than 12 weeks of gestation, who underwent MVA surgery under local anesthesia (n = 166) or conventional general anesthesia (n = 156). The duration of surgery, blood loss volume, quantity of anesthesia, presence or absence of retained products of conception, and clinical complications were evaluated. In addition, the intraoperative pain and treatment satisfaction were assessed using the visual analog scale (VAS). Results The duration of surgery was significantly shorter in the local anesthesia group. No significant differences were observed between both groups in terms of the blood loss volume and incidence of retained products of conception. In addition, no serious complications were observed in either group. No significant differences were noted between the two groups in the VAS scores for pain and treatment satisfaction. Conclusions In this retrospective study, the use of MVA under local anesthesia for early pregnancy miscarriage surgery was found to be equally safe and effective when performed under conventional general anesthesia. This technique allowed the achievement of appropriate pain control with excellent patient satisfaction.

Abstract Background Wisconsin syndrome is a congenital anomaly caused by a 3q interstitial deletion. It is associated with characteristic facies and developmental delays. Only 33 cases with a deletion estimated to be in the associated region 3q25 have been reported. Case report We present the case of a 5-year-old Japanese girl with a 3q24q25.2 deletion. Her facial features corresponded to the Wisconsin syndrome phenotype, and she exhibited brain volume laterality, which has not been reported previously. Conclusion The clinical features of our case may contribute to narrowing down the list of candidate genes of Wisconsin syndrome.

Abstract Bystander cardiopulmonary resuscitation (BCPR), early defibrillation and timely treatment by emergency medical services (EMS) can double the chance of survival from out-of-hospital sudden cardiac arrest (OHCA). We investigated the effect of the COVID-19 pandemic on the pre-hospital chain of survival. We searched five bibliographical databases for articles that compared prehospital OHCA care processes during and before the COVID-19 pandemic. Random effects meta-analyses were conducted, and meta-regression with mixed-effect models and subgroup analyses were conducted where appropriate. The search yielded 966 articles; 20 articles were included in our analysis. OHCA at home was more common during the pandemic (OR 1.38, 95% CI 1.11–1.71, p = 0.0069). BCPR did not differ during and before the COVID-19 pandemic (OR 0.94, 95% CI 0.80–1.11, p = 0.4631), although bystander defibrillation was significantly lower during the COVID-19 pandemic (OR 0.65, 95% CI 0.48–0.88, p = 0.0107). EMS call-to-arrival time was significantly higher during the COVID-19 pandemic (SMD 0.27, 95% CI 0.13–0.40, p = 0.0006). Resuscitation duration did not differ significantly between pandemic and pre-pandemic timeframes. The COVID-19 pandemic significantly affected prehospital processes for OHCA. These findings may inform future interventions, particularly to consider interventions to increase BCPR and improve the pre-hospital chain of survival.

Abstract Background Micropapillary adenocarcinoma has a poor prognostic histological pattern. Additionally, preoperative detection of lymph node metastases by preoperative examination is difficult in some patients with micropapillary adenocarcinoma, and postoperative upstage may occur. However, clinicopathological features of patients with micropapillary adenocarcinoma with nodal upstage have not been established, therefore this study aimed to identify the factors associated with potential lymph node metastases during preoperative examination to ensure effective surgical procedures. Methods Between January 2011 and December 2020, 1029 patients received complete resection for primary non‐small‐cell lung cancer by lobectomy or more extensive resection with systematic lymph node dissection at this institution. One hundred and thirty‐one patients diagnosed with adenocarcinoma with micropapillary component were included in this study. The clinicopathological features of patients with nodal upstage whose postoperative N stage was more advanced than the preoperative N stage were examined. Results Forty patients had nodal upstage after resection. 18F‐fluorodeoxyglucose (FDG) positron emission tomography‐computed tomography (PET‐CT) revealed that a maximum standardized uptake value (SUVmax) ≥5 for the primary lesion was significantly associated with postoperative nodal upstage. There were no significant differences in terms of sex, age, smoking history, surgical procedure, and diabetes. Among 38 patients with nodal upstage, 23 patients had no significant preoperative lymphadenopathy and showed no abnormal FDG uptake in the lymph nodes on 18F‐FDG‐PET‐CT, respectively. Conclusions Lymph node metastases were suspected in patients preoperatively diagnosed with micropapillary adenocarcinoma with FDG SUVmax ≥5 for the primary tumor. Therefore, standard surgical resection and careful lymph node dissection should be performed for such patients.

BackgroundThis study aimed to develop an efficient interview sheet during pregnancy and screening tool to identify pregnant women needing social support at obstetric institutions. Moreover, we investigate the perinatal factors associated with the Edinburgh postnatal depression scale (EPDS).MethodsThis prospective cohort study was conducted at three medical institutions that commonly encounter cases with social issues. Pregnant women were assessed using an interview sheet at the first visit (n = 678), at approximately 28 weeks gestation (n = 495), 36 weeks gestation (n = 296), and the postpartum period (n = 822). We investigated the important items identified on the new screening questionnaire (NEW interview sheets) for women needing social support. The items on the interview sheet were scored by multiple linear regression analysis, and the cutoff values were calculated using the receiver operating characteristic curve. The association between perinatal factors and EPDS was assessed using multiple logistic regression analyses.ResultsThe study included 166 cases for which all NEW interview sheets for all periods were available. NEW interview sheets and stepwise screening tools during the first and second trimester were developed in which 2.5% of pregnant women were identified as requiring social support, respectively. The factors associated with EPDS ≧ 9 were “Women who felt confused/troubled or did not feel anything to be pregnant” (adjusted odds ratio [aOR]: 6.51, 95% confidence interval [CI]: 1.62–26.15), “Maternal mental disorder” (aOR 4.38; CI 1.06–18.10), “Consultation request at first visit” (aOR 3.22; CI 1.09–9.45), and “Women who have difficulty or anxiety about pregnancy during the second trimester” (aOR 3.14; CI 1.29–7.67).ConclusionsWe created the NEW interview sheets and screening tools during the first and the second trimester. Future studies are needed to validate these screening tools.

The northeastern coast of Japan suffered a massive tsunami in 2011, a natural disaster which ‘reset’ the coastal ecosystem when it destroyed much of the original sealife and scoured the seabed. This has presented an opportunity to learn more about the load on coastal ecosystems exerted by human exploitation such as aquaculture rafts and areas of anchored and float-suspended ropes. We surveyed the coastal environment in Matsushima Bay for approximately four years following the year after the occurrence of the 2011 tsunami. Phytoplankton abundance increased with increasing water temperature. Nutrient concentrations were high at the exit of a small branch of the Ofuna-iri Canal (entering the southwestern inner part of the bay at Shiogama) but no significant differences in nutrient concentrations were observed at other stations, so it is considered that the aquaculture installations in Matsushima Bay currently have no significant effect on observed nutrient concentrations. The composition of eukaryotes in the surface seawater varied with the year and the season, but there were no clear differences between sampling stations. The lack of any differences in nutrient concentrations or eukaryote assemblages between areas with or without aquaculture installations is considered to be a result of efficient seawater exchange, despite the presence of many small islets separating Matsushima Bay from the open ocean. In addition, the aquaculture installations at present number less than half of the maximum number before the tsunami, so the bay is by no means overexploited by aquaculture. It is concluded that the current aquaculture installations have no major negative impact on the environment in Matsushima Bay.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has significantly influenced epidemiology, yet its impact on out-of-hospital cardiac arrest (OHCA) remains unclear. We aimed to evaluate the impact of the pandemic on the incidence and case fatality rate (CFR) of OHCA. We also evaluated the impact on intermediate outcomes and clinical characteristics. Methods PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases were searched from inception to May 3, 2021. Studies were included if they compared OHCA processes and outcomes between the pandemic and historical control time periods. Meta-analyses were performed for primary outcomes [annual incidence, mortality, and case fatality rate (CFR)], secondary outcomes [field termination of resuscitation (TOR), return of spontaneous circulation (ROSC), survival to hospital admission, and survival to hospital discharge], and clinical characteristics (shockable rhythm and etiologies). This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021253879). Results The COVID-19 pandemic was associated with a 39.5% increase in pooled annual OHCA incidence (p

ABSTRACT The lipid composition of the host cell membrane is one of the key determinants of the entry of enveloped viruses into cells. To elucidate the detailed mechanisms behind the cell entry of rubella virus (RuV), one of the enveloped viruses, we searched for host factors involved in such entry by using CRISPR/Cas9 genome-wide knockout screening, and we found sphingomyelin synthase 1 (SMS1), encoded by the SGMS1 gene, as a candidate. RuV growth was strictly suppressed in SGMS1-knockout cells and was completely recovered by the overexpression of enzymatically active SMS1 and partially recovered by that of SMS2, another member of the SMS family, but not by that of enzymatically inactive SMS1. An entry assay using pseudotyped vesicular stomatitis virus possessing RuV envelope proteins revealed that sphingomyelin generated by SMSs is crucial for at least RuV entry. In SGMS1-knockout cells, lipid mixing between the RuV envelope membrane and the membrane of host cells occurred, but entry of the RuV genome from the viral particles into the cytoplasm was strongly inhibited. This indicates that sphingomyelin produced by SMSs is essential for the formation of membrane pores after hemifusion occurs during RuV entry. IMPORTANCE Infection with rubella virus during pregnancy causes congenital rubella syndrome in infants. Despite its importance in public health, the detailed mechanisms of rubella virus cell entry have only recently become somewhat clearer. The E1 protein of rubella virus is classified as a class II fusion protein based on its structural similarity, but it has the unique feature that its activity is dependent on calcium ion binding in the fusion loops. In this study, we found another unique feature, as cellular sphingomyelin plays a critical role in the penetration of the nucleocapsid into the cytoplasm after hemifusion by rubella virus. This provides important insight into the entry mechanism of rubella virus. This study also presents a model of hemifusion arrest during cell entry by an intact virus, providing a useful tool for analyzing membrane fusion, a biologically important phenomenon.