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This study proposes a receiving-end voltage compensation method employing a phase-specific reactive power control strategy with a neutral-point-clamped (NPC) inverter in a three-phase four-wire distribution system. The principle of the proposed receiving end voltage compensation method is explained. Further, the proposed control strategy can solve the problems of the three-phase, four-wire distribution system, which are an increase in the neutral-line current and the unbalanced voltage. Computer simulation is performed to confirm the validity of the proposed method. The simulation results indicate the receiving-end voltages can be compensated using the proposed method.

Abstract Neuroblastoma (NB) is one of the most lethal childhood cancers due to its propensity to become treatment resistant. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicate these two contrasting scenarios and show branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.

Abstract The present paper provides an overview of an online module for formative assessment of summary writing skills for second language (L2) introductory academic writing instruction in Japan and presents initial empirical results on how Japanese undergraduate students’ summary writing performance changed with a series of automated summary content feedback delivered in the module. A key feature of this module was the provision of fine-grained feedback delivered as scaffolding during revisions in terms of two key aspects of summary content: main idea representation and paraphrasing. Participants were 64 Japanese undergraduate engineering majors in introductory academic writing courses at a private university in Tokyo. The students completed two summary writing tasks provided through the online module. Results of a multivariate analysis of variance showed significant improvement of the content analytic score on revision on the initial summary task, and that this improved performance level was retained on a transfer task. The language use analytic score also improved significantly on the transfer task. Detailed analyses of learner-produced summaries based on descriptive statistics further suggested that the learners made substantively meaningful changes concerning main idea coverage and verbatim copying of the source text while still meeting the length requirement, although the results differed somewhat across the source texts assigned. Despite some study limitations, these results provide initial support for immediate content feedback provision for the development of basic summary writing skills.

An 89-year-old woman presented with a 6-year history of occasional episodes of impaired consciousness that were relieved by ingestion of a snack. Three months before presenting to our hospital, she had been hospitalized in a local hospital with subdural hematoma caused by a head contusion, where previously unrecognized hypoglycemia was discovered. Fasting plasma glucose concentration was 37 mg/dL, with a relatively high serum level of insulin (34.9 μU/mL). Computed tomography showed a 14 mm hyperenhancing tumor in the tail of the pancreas and she was referred to our hospital for further investigation. A prolonged fasting test revealed the plasma glucose concentration reduced to 43 mg/dL (2.4 mmol/L) at 8 h after the last meal. Serum insulin, proinsulin, and C-peptide concentrations were 21.1 μU/mL, 16.9 pmol/L, and 2.72 ng/mL, respectively. Subsequent intravenous administration of 1 mg of glucagon increased the plasma glucose concentration to 76 mg/dL (4.2 mmol/L). Moreover, the insulin-to-C-peptide molar ratio was 0.14. These data indicated the presence of insulinoma. Interestingly, serum anti-insulin antibodies were elevated (21.1 U/mL), although she had no history of taking exogenous insulin injection, alpha lipoic acid, or sulfhydryl group-containing agents. Human leukocyte antigen (HLA) typing revealed HLA-DRB1*0407 and HLA-DRB1*1405 alleles. Treatment with diazoxide prevented hypoglycemia, but was discontinued due to weight gain and leg edema. Elevated serum anti-insulin antibodies persisted almost 1 year after the diagnosis of insulinoma. We present a rare case of insulinoma concomitant with serum anti-insulin antibodies.

The intestinal absorption of essential nutrients, especially those not readily biosynthesized, is a critical physiological process for maintaining homeostasis. Numerous studies have indicated that intestinal absorption is mediated by various membrane transporters. Citrate, a crucial bioactive compound produced as an intermediate in the Krebs cycle, is absorbed in the small intestine through carrier-mediated systems because of its high hydrophilicity. While the luminal absorption of citrate is mediated by Na+-dicarboxylate cotransporter 1 (NaDC1/SLC13A2), the mechanism governing the release of the transported citrate into the bloodstream remains unknown. Here, we explored the transporters responsible for intestinal citrate absorption at the basolateral membrane, focusing on highly expressed orphan transporters in the small intestine as candidates. Consequently, SLC35G1, originally identified as a partner of stromal interaction molecule 1, a cell surface transmembrane glycoprotein, was found to play a role in the intestinal absorption of citrate at the basolateral membrane. Furthermore, our results revealed that SLC35G1-mediated citrate transport was diminished by chloride ions at physiologically relevant extracellular concentrations. This suggests that SLC35G1, to our best knowledge, is the first transporter identified to be extremely sensitive to chloride ions among those functioning on the basolateral membrane of intestinal epithelial cells. This study provides valuable insights into the intestinal absorption of citrate and significantly contributes to elucidating the poorly understood molecular basis of the intestinal absorption system.

Abstract Plants are valuable resources for drug discovery as they produce diverse bioactive compounds. However, the chemical diversity makes it difficult to predict the biological activity of plant extracts via conventional chemometric methods. In this research, we propose a new computational model that integrates chemical composition data with structure-based chemical ontology. For a model validation, two training datasets were prepared from literature on antibacterial essential oils to classify active/inactive oils. Random forest classifiers constructed from the data showed improved prediction performance in both test datasets. Prior feature selection using hierarchical information criterion further improved the performance. Furthermore, an antibacterial assay using a standard strain of Staphylococcus aureus revealed that the classifier correctly predicted the activity of commercially available oils with an accuracy of 83% (= 10/12). The results of this study indicate that machine learning of chemical composition data integrated with chemical ontology can be a highly efficient approach for exploring bioactive plant extracts.

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

Background. Accurate preoperative evaluation of renal function in living kidney donor candidates (LKDCs) is crucial to prevent kidney failure after nephrectomy. We examined the performance of various estimated glomerular filtration rate (eGFR) equations, including the new chronic kidney disease epidemiology collaboration (CKD-EPI) equation in LKDCs. Methods. We analyzed 752 LKDCs who were assessed for measured GFR by inulin clearance as part of routine pretransplant examination from 2006 to 2020. CKD-EPI2012 from cystatin C (CKD-EPI12cys), CKD-EPI2021 from creatinine (CKD-EPI21cr), CKD-EPI21cr-cys, Japanese modified (JPN) eGFRcr, and JPN eGFRcys were compared in determining the suitability for LKDCs. Results. CKD-EPI12cys had the lowest absolute and relative biases, with higher P30 and P10, followed by JPN eGFRcys, CKD-EPI21cr, and CKD-EPI21cr-cys. The root mean square error was least for CKD-EPI12cys, then JPN eGFRcys, CKD-EPI21cr-cys, CKD-EPI21cr, and JPN eGFRcr. CKD-EPI21cr, CKD-EPI12cys, and CKD-EPI21cr-cys estimated GFR higher, whereas JPN eGFRcr estimated GFR lower. At the threshold of 90 mL/min/1.73 m2, CKD-EPI21cr had the highest percentage of misclassification at 37.37%, whereas JPN eGFRcr had the lowest percentage of misclassification at 6.91%. Using the age-adapted approach, JPN eGFRcr had the lowest percentage of misclassification into overestimation at 7.31%. All eGFR had >5.0%, and CKD-EPI21cr had the highest percentage of misclassification at 21.94%. Conversely, CKD-EPI21cr-cys had the lowest percentage of misclassification into underestimation at 3.19%, both at the threshold of 90 mL/min/1.73 m2 and the age-adapted approach. JPN eGFRcr had the highest percentage at 33.38% and 40.69%, respectively. Conclusions. In evaluating the renal function of Japanese LKDCs, the new CKD-EPI equation had a lower rate of underestimation but a relatively high rate of overestimation. New GFR estimation formulas are needed to be tailored to each ethnic group to enhance the accuracy and reliability of donor selection processes.

Coronavirus disease 2019 (COVID-19) causes a systemic inflammatory response and a temporary immunosuppression of hosts. Several reports have showed that reactivation of herpes simplex virus type 1 (HSV-1) is strongly associated with COVID-19. We present a case of a 66-year-old female, who developed HSV-1 encephalitis, showing impaired consciousness and typical MRI findings such as hyperintense lesions in the temporal lobe, insular cortices, bilateral medial frontal lobe on diffusion-weighted imaging, 7 days after the onset of COVID-19 symptoms. The number of cases of encephalitis in patients with COVID-19 is increasing. However, there has been limited reports of HSV-1 encephalitis following COVID-19, especially for cases with an interval of 7 days or less from the onset of COVID-19 symptoms to the onset of HSV-1 encephalitis. Our case highlights the importance of considering HSV-1 encephalitis in the differential when managing a patient with COVID-19-associated neurologic complications, even if it is in the early stages of COVID-19.

Abstract This technical report explains details on the results of the investigation to build a subsurface structural model and a selection of earthquake data at the target site of the blind prediction exercise for “The 6th International Association of Seismology and Physics of the Earth’s Interior/International Association of Earthquake Engineering International Symposium on the Effect of Surface Geology on Seismic Motion (ESG6).” The selection process of the target site in the Kumamoto Plain, Japan, in ESG6 was explained with a historical review of the blind prediction tests in the previous ESG conferences. We have collected existing subsurface structural and earthquake data and conducted geophysical and geotechnical surveys in and around the target site to generate important velocity structure and the earthquake data used in the blind test. Microtremor data were obtained in triangular arrays ranging in side lengths from 1 to 962 m, and active surface wave data were derived along a 36-m line at the site. These data were provided for the prediction of a subsurface structural model in the first step of the blind prediction exercise. We also conducted a velocity logging in a borehole to a bottom depth of 39 m at the site and laboratory tests of soil samples from the borehole. We constructed a velocity profile of the shallow and deep sedimentary layers from a combination of the geophysical and geotechnical data at the site, and validated it by comparing the characteristics of the ground motion data from the moderate event. This “preferred velocity model” was provided as a standard model to the participants in the second and third steps of the blind prediction test to predict the earthquake ground motions of a moderate event and the mainshock of the 2016 Kumamoto earthquake. Graphical Abstract

Introduction: Trastuzumab deruxtecan (T-Dxd) has been approved for the treatment of HER2-positive gastric cancer. However, there are only a limited number of cases of gastric cancer where a long-term complete response (CR) has been maintained. Consequently, we report a case of gastric cancer in which long-term CR was maintained. Case Presentation: A woman in her late 60s underwent a gastrointestinal endoscopy, which revealed a type 2 lesion with ulceration in the lesser curvature of the vestibule, and a biopsy, which revealed an adenocarcinoma. Computed tomography (CT) revealed wall thickening of the gastric antecubital region, metastatic liver tumor, and extra-regional lymph node metastasis; a diagnosis of T4a, N3a, M1 (H, LYN), and cStage IVB (HER2 3+) was confirmed. Trastuzumab, oxaliplatin, and S-1 were administered initially. After 9 months, ascites appeared, and progressive disease was diagnosed. Paclitaxel and ramucirumab were started as second-line treatments but discontinued owing to neutropenia and increasing ascites. Third-line treatment with T-Dxd was initiated, and 11 months later, CT showed the disappearance of metastases. Even after 31 months, the CR was maintained. Conclusion: To the best of our knowledge, this is one of the few cases in which long-term CR was maintained with third-line T-Dxd treatment. Treatment strategies for patients with gastric cancer to achieve long-term CR require careful consideration.

Abstract The on-site P-wave earthquake early warning (EEW) based on the site-specific ratios of S-waves to P-waves has been applied to large-sized offshore earthquakes, and the efficiency of the method has been validated. However, the method requires the P-waves including earthquake ground motions radiated from a large slip area while avoiding the inclusion of S-waves. In this study, we investigated the applicability of the on-site P-wave EEW method for ground motions near an earthquake source fault region, using strong-motion data observed during the 2016 Kumamoto earthquake sequence in Japan. At first, we examined the appropriate time-window length following the arrival of the P-waves. As a result, P-waves with a time-window length of 2.56 s after the arrival at most strong-motion stations were required at least to predict appropriately S-waves for the 2016 Kumamoto earthquake sequence, including the large-sized earthquakes. On the other hand, in the case of the large-sized earthquake as the mainshock (Mj 7.3), the method can predict within a brief time of 0.5 to 2 s in the operational use that strong ground motions exceeding a certain threshold (e.g., acceleration of 150 cm/s2) will come. Moreover, we found that the method was not strongly affected by the non-linearity of soil deposits due to strong ground motions during the 2016 Kumamoto earthquake sequence. The variability of the relationship between P- and S-waves at the seismic bedrock influenced by the source and path effects is larger than the variability of the relationships between P-/S-waves at the seismic bedrock and at the ground surface by the site effects, and therefore, it hides the effect of the non-linearity of soil deposits. Graphical Abstract

In the originally published article [...]

ABSTRACT We aimed to assess the frequency of acute kidney injury (AKI) in different areas under the concentration–time curve (AUC) values of vancomycin (VAN) using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. This multicenter retrospective observational study was conducted in eight hospitals. We retrospectively analyzed the data of patients who had received VAN in an intensive care unit (ICU) between January 2020 and December 2022. The primary outcome was the incidence of AKI. Patients were classified into three groups according to the AUC24–48h at the initial therapeutic drug monitoring (TDM) as follows:

We aimed to investigate the clinical value of allograft biopsy performed long after renal transplantation. We retrospectively evaluated 99 allograft biopsies in recipients with transplantation vintages of 10 years or longer. Mixed-effects model showed that 1-year estimated glomerular filtration rate (eGFR) slopes after biopsy were significantly greater than those before biopsy [−3.13, −4.42 mL/min/1.73 m2/year, p = 0.01]. Renal biopsy changed the treatment strategies in more than half of the patients. Improvement in eGFR slopes was pronounced in 51 patients with treatment modification based on the biopsy results [2.27 (95% confidence interval (CI): 0.66, 3.89) mL/min/1.73 m2/year], whereas no improvement was observed in those without [0.33 (95% CI: −1.05, 1.71) mL/min/1.73 m2/year, Pinteraction = 0.001]. Among the treatment modifications, enhancement of immunosuppression (IS) led to the most remarkable improvement in eGFR slope. Patients with g scores ≥2 were more likely to receive IS enhancement than those with g scores = 0 [odds ratio; 15.0 (95% CI: 1.65, 136)]. Patients with active glomerulitis (g ≥ 1) without chronicity (cg ≤ 1) showed the most significant improvement in eGFR slope. Given the prevalence of active glomerulitis (g ≥ 1, 21%), which is responsive to treatment even long after transplantation, and the observed magnitude of eGFR slope improvement, renal biopsy can indeed improve allograft prognosis.

Tauopathy is known to be a major pathognomonic finding in important neurodegenerative diseases such as progressive supranuclear palsy (PSP) and corticobasal degeneration. However, the mechanism by which tauopathy is triggered remains to be elucidated. We previously identified the point mutation c.11596C > G, p.Pro3866Ala in the Bassoon gene (BSN) in a Japanese family with PSP-like syndrome. We showed that mutated BSN may have been involved in its own insolubilization and tau accumulation. Furthermore, BSN mutations have also been related to various neurological diseases. In order to further investigate the pathophysiology of BSN mutation in detail, it is essential to study it in mouse models. We generated a mouse model with the mouse Bassoon p.P3882A mutation, which corresponds to the human BSN p.P3866A mutation, knock-in (KI) and we performed systematic behavioral and histological analyses. Behavioral analyses revealed impaired working memory in a Y-maze test at 3 months of age and decreased locomotor activity in the home cage at 3 and 12 months of age in KI mice compared to those in wild-type mice. Although no obvious structural abnormalities were observed at 3 months of age, immunohistochemical studies showed elevation of Bsn immunoreactivity in the hippocampus and neuronal loss without tau accumulation in the substantia nigra at 12 months of age in KI mice. Although our mice model did not show progressive cognitive dysfunction and locomotor disorder like PSP-like syndrome, dopaminergic neuronal loss was observed in the substantia nigra in 12-month-old KI mice. It is possible that BSN mutation may result in dopaminergic neuronal loss without locomotor symptoms due to the early disease stage. Thus, further clinical course can induce cognitive dysfunction and locomotor symptoms.

Realizing smooth traffic flow is important for achieving carbon neutrality. Adaptive traffic signal control, which considers traffic conditions, has thus attracted attention. However, it is difficult to ensure optimal vehicle flow throughout a large city using existing control methods because of their heavy computational load. Here, we propose a control method called AMPIC (Adaptive Model Predictive Ising Controller) that guarantees both scalability and optimality. The proposed method employs model predictive control to solve an optimal control problem at each control interval with explicit consideration of a predictive model of vehicle flow. This optimal control problem is transformed into a combinatorial optimization problem with binary variables that is equivalent to the Ising problem. This transformation allows us to use Ising solvers, which have been widely studied and are expected to offer fast and efficient optimization performance. The method works adaptively according to traffic conditions such as the structure of the road network and feedback from observation of the traffic system. We performed numerical experiments using a microscopic traffic simulator for a realistic city road network. Compared to the classical pattern control method, the results show that AMPIC increases the vehicle cruising speed by 13%, reduces the waiting vehicle ratio to 60%, and lowers the CO 2emissions to only 25% of the original level. The model predictive approach with a long prediction horizon thus effectively improves control performance. Systematic parametric studies on model cities indicate that the proposed method realizes smoother traffic flows for large city road networks. Among Ising solvers, D-Wave’s quantum annealing is shown to find near-optimal solutions at a reasonable computational cost.

Abstract Background The substantial heterogeneity of clinical presentations in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia still requires robust chest computed tomography analysis to identify high-risk patients. While extension of ground-glass opacity and consolidation from peripheral to central lung fields on chest computed tomography (CT) might be associated with severely ill conditions, quantification of the central-peripheral distribution of ground glass opacity and consolidation in assessments of SARS-CoV-2 pneumonia remains unestablished. This study aimed to examine whether the central-peripheral distributions of ground glass opacity and consolidation were associated with severe outcomes in patients with SARS-CoV-2 pneumonia independent of the whole-lung extents of these abnormal shadows. Methods This multicenter retrospective cohort included hospitalized patients with SARS-CoV-2 pneumonia between January 2020 and August 2021. An artificial intelligence-based image analysis technology was used to segment abnormal shadows, including ground glass opacity and consolidation. The area ratio of ground glass opacity and consolidation to the whole lung (GGO%, CON%) and the ratio of ground glass opacity and consolidation areas in the central lungs to those in the peripheral lungs (GGO(C/P)) and (CON(C/P)) were automatically calculated. Severe outcome was defined as in-hospital death or requirement for endotracheal intubation. Results Of 512 enrolled patients, the severe outcome was observed in 77 patients. GGO% and CON% were higher in patients with severe outcomes than in those without. Multivariable logistic models showed that GGO(C/P), but not CON(C/P), was associated with the severe outcome independent of age, sex, comorbidities, GGO%, and CON%. Conclusion In addition to GGO% and CON% in the whole lung, the higher the ratio of ground glass opacity in the central regions to that in the peripheral regions was, the more severe the outcomes in patients with SARS-CoV-2 pneumonia were. The proposed method might be useful to reproducibly quantify the extension of ground glass opacity from peripheral to central lungs and to estimate prognosis.

Abstract So-called Z-scheme systems permit overall water splitting using narrow-bandgap photocatalysts. To boost the performance of such systems, it is necessary to enhance the intrinsic activities of the hydrogen evolution photocatalyst and oxygen evolution photocatalyst, promote electron transfer from the oxygen evolution photocatalyst to the hydrogen evolution photocatalyst, and suppress back reactions. The present work develop a high-performance oxysulfide photocatalyst, Sm2Ti2O5S2, as an hydrogen evolution photocatalyst for use in a Z-scheme overall water splitting system in combination with BiVO4 as the oxygen evolution photocatalyst and reduced graphene oxide as the solid-state electron mediator. After surface modifications of the photocatalysts to promote charge separation and redox reactions, this system is able to split water into hydrogen and oxygen for more than 100 hours with a solar-to-hydrogen energy conversion efficiency of 0.22%. In contrast to many existing photocatalytic systems, the water splitting activity of the present system is only minimally reduced by increasing the background pressure to 90 kPa. These results suggest characteristics suitable for applications under practical operating conditions.

The development of quantum annealing has stimulated interest in solving NP-hard problems, including various industrial problems, such as quadratic unconstrained binary optimization (QUBO), with specialized solvers. This study focuses on the rectangle packing problem (RPP), which is an NP-hard problem applicable to industrial applications. The objective of this problem is to place given items in a minimum area without overlap. Naive QUBO representations, such as a direct binary encoding of locations, could require a large number of bits, which limits the problem size, hindering the acquisition of the optimal solution. To circumvent this difficulty, we employ the concept of sequence pairs to efficiently represent the locations of items. We also propose a strategy that uses multiple sampling solutions obtained with a QUBO solver, where we employ new constraints on the number of the rectangles contributing to the placement area for restricting the search space to smoothly bridge the QUBO formulation of the sequence pair and the minimization of area of rectangle placement. We estimate an approximate curve for the optimum number of rectangles contributing to the placement area. Then, we add the penalty term concerning the deviation from the estimated optimal value on the objective function. In numerical experiments with instances with 4 to 10 rectangles, we demonstrate that the proposed sampling-based strategy can efficiently find feasible solutions. This strategy would be useful for dealing with more complex problems, such as rectangle orientation and three-dimensional problems, with a relatively small number of bits using sequence pairs.

Abstract Background Von Willebrand factor (VWF) and factor VIII (FVIII) complex play a pivotal role in hemostasis. A deficiency or defect of VWF causes von Willebrand disease (VWD). Recombinant (r)VWF product has proved to be effective for hemostatic treatment of VWD, but limited information is available on their role in moderating thrombus formation under flow condition. We aimed to assess thrombus formation in the presence of rVWF combined with rFVIII or pegylated-extended half-life rFVIII (peg-EHL-rFVIII) in VWD whole blood under high shear flow. Methods Perfusion chamber experiments under high shear (2,500 s− 1) combined with immunostaining were performed using patient’s whole blood with type 1 VWD, mixed with rVWF (Vonvendi®; 1.6 IU/mL), rFVIII or peg-EHL-rFVIII (Advate® or Adynovate®; 1.0 IU/mL), or both. Similar experiments were also conducted with clinical medical devices (T-TAS®). Results The addition of rFVIII did not augment thrombus formation assessed by surface coverage (SC) and thrombus height (TH), whereas rVWF enhanced these parameters (SC 19.1 ± 1.1% vs. 30.1 ± 4.1%, TH 2.2 ± 0.14 μm vs. 3.6 ± 0.40 μm, respectively). The co-presence of rVWF/rFVIII was comparable to plasma-derived VWF/FVIII (Confact®, VWF:FVIII ratio = 1.6:1.0) for increasing thrombogenicity in SC (32.5 ± 4.3% vs. 38.7 ± 5.5%) and in TH (5.0 ± 0.60 μm vs. 5.5 ± 0.64 μm), respectively. The pre-incubation time with rVWF and rFVIII appeared to have a little effect on the size of thrombus. Peg-EHL-rFVIII mediated thrombus formation to similar extent as rFVIII in the co-presence of rVWF. Similar results were obtained even with T-TAS. Immunostaining demonstrated that rFVIII and peg-EHL-rFVIII were similarly co-localized with rVWF in formed thrombi, indicating that pegylation did not interfere with molecular complexes. Conclusion The effects of high-level rVWF and peg-EHL-rFVIII on thrombus formation were comparable to conventional therapeutic products in a patient’s whole blood with VWD under high shear flow.

Abstract Essential oils contain a variety of volatile metabolites, and are expected to be utilized in wide fields such as antimicrobials, insect repellents and herbicides. However, it is difficult to foresee the effect of oil combinations because hundreds of compounds can be involved in synergistic and antagonistic interactions. In this research, it was developed and evaluated a machine learning method to classify types of (synergistic/antagonistic/no) antibacterial interaction between essential oils. Graph embedding was employed to capture structural features of the interaction network from literature data, and was found to improve in silico predicting performances to classify synergistic interactions. Furthermore, in vitro antibacterial assay against a standard strain of Staphylococcus aureus revealed that four essential oil pairs (Origanum compactum—Trachyspermum ammi, Cymbopogon citratus—Thujopsis dolabrata, Cinnamomum verum—Cymbopogon citratus and Trachyspermum ammi—Zingiber officinale) exhibited synergistic interaction as predicted. These results indicate that graph embedding approach can efficiently find synergistic interactions between antibacterial essential oils.

Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 μU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 μU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery.

Cystoid macular edema (CME) is a rare side effect associated with chemotherapy. Although the development of CME has been reported to occur following treatment with taxane drugs, such as nanoparticle albumin-bound paclitaxel (Nab-PTX), the occurrence of CME with treatment with atezolizumab has not yet been reported. Here, we report the case of a 49-year-old woman who developed CME 19 months into chemotherapy with Nab-PTX and atezolizumab. Improvement was not achieved with steroid injections into the Tenon’s sac, and Nab-PTX and atezolizumab treatments were ceased. One month later, there was subjective improvement in her symptoms. Although many reports have indicated that cessation of chemotherapy has successfully improved CME, a specific treatment for CME has not yet been established. Clinicians should be aware of the ophthalmologic side effects and offer immediate treatment if symptoms develop.

Abstract Background The diagnosis of Parkinson’s disease (PD) and evaluation of its symptoms require in-person clinical examination. Remote evaluation of PD symptoms is desirable, especially during a pandemic such as the coronavirus disease 2019 pandemic. One potential method to remotely evaluate PD motor impairments is video-based analysis. In this study, we aimed to assess the feasibility of predicting the Unified Parkinson’s Disease Rating Scale (UPDRS) score from gait videos using a convolutional neural network (CNN) model. Methods We retrospectively obtained 737 consecutive gait videos of 74 patients with PD and their corresponding neurologist-rated UPDRS scores. We utilized a CNN model for predicting the total UPDRS part III score and four subscores of axial symptoms (items 27, 28, 29, and 30), bradykinesia (items 23, 24, 25, 26, and 31), rigidity (item 22) and tremor (items 20 and 21). We trained the model on 80% of the gait videos and used 10% of the videos as a validation dataset. We evaluated the predictive performance of the trained model by comparing the model-predicted score with the neurologist-rated score for the remaining 10% of videos (test dataset). We calculated the coefficient of determination (R 2) between those scores to evaluate the model’s goodness of fit. Results In the test dataset, the R 2 values between the model-predicted and neurologist-rated values for the total UPDRS part III score and subscores of axial symptoms, bradykinesia, rigidity, and tremor were 0.59, 0.77, 0.56, 0.46, and 0.0, respectively. The performance was relatively low for videos from patients with severe symptoms. Conclusions Despite the low predictive performance of the model for the total UPDRS part III score, it demonstrated relatively high performance in predicting subscores of axial symptoms. The model approximately predicted the total UPDRS part III scores of patients with moderate symptoms, but the performance was low for patients with severe symptoms owing to limited data. A larger dataset is needed to improve the model’s performance in clinical settings.

Abstract A numerical investigation of surface wave propagation in the surface wave exploration of river embankments is implemented using 3D shallow soil models with different subsurface shapes and S-wave velocities. The focus is on the effects of surface and subsurface irregularities on the propagation and dispersion characteristics of Rayleigh waves generated by a surface source and observed at points along the crest of the embankment. Rayleigh wave dispersion curves observed along the embankment crest are found to be contaminated by reflected waves, with the amount of contamination affected more by the position of the velocity boundary at the bottom edge of the embankment than the surface topography. When the velocity boundary is close to the ground surface, especially at the toe of the slope, the effect of reflected waves is sufficiently large to generate biases in the phase velocity estimates. Graphical Abstract

Abstract Background Effective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis. Methods We performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated. Results Profilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study. Conclusion PFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.

Abstract In this study, we compared observations and predictions submitted by participants for blind prediction experiments for ground motions using aftershocks, foreshock, and mainshock of the 2016 Kumamoto earthquake sequence, Japan, to improve our understanding of the quality of state-of-the-art methods on the reproducibility of the effects of surface geology on seismic motions. In the blind predictions, 1D, 2D, and 3D methods, Green’s function methods, spectral ratio approaches, and other approaches were applied. As for PGA/PGV, acceleration/velocity duration, Fourier spectrum, pseudo-velocity response spectrum, and site amplification factors, the observed values are mostly within the range of average ± σ of all the predictions in the case of weak and strong ground motions. The results of the mean absolute percentage errors for these indices show that the applied methods can predict weak and strong ground motions for the three components in the range of one-half to twice the observations. The average goodness-of-fit (GOF) scores for weak and strong ground motions indicate either a very good fit (6.5–8) or a good fit (4.5–6.5) for the three components. Finally, examples of the categorized methods are quite limited; however, results indicate that the predictions by all the categorized methods can adequately reproduce weak and strong ground motions within either a very good or good fit. Although we could not find a significant difference in the results from the categorized methods, scores by the 2D and 3D methods in the frequency range of 0.5–1 and 1–2 Hz for all the blind predictions are higher than the scores by the other methods. The GOF score for the part after the S-wave by the 2D and 3D methods is higher than that by the 1D method. This supports that the predictions by the 2D and 3D methods due to the accounting of the proper geometry could reproduce the basin-induced and/or basin-transduced surface waves excited by the basin-edge effect more than the 1D method using the earthquake record observed at the reference site. Graphical Abstract

Introduction: Gastrointestinal duplications are rare congenital anomalies that can occur anywhere throughout the intestinal tract. However, gastric duplication is very rare. A case of gastric duplication with uncommon complications, hypergastrinemia and duodenal ulcer, is described. Case report: The patient was an 11-year-old girl who presented with epigastric pain and non-bilious vomiting. The patient had a history of recurrent duodenal ulcers. Gastrin levels when the patient first presented with a duodenal ulcer at 8 years of age had reached 730 pg/mL. Computed tomography (CT) showed a cyst outside the pyloric antrum after remission of the duodenal ulcer, and it was suspected to be gastric duplication. For recurrence of the duodenal ulcer, the patient had been treated with histamine 2 receptor blockade for 3 years. At 11 years of age, the patient had stopped the medication and presented with gastric pain and vomiting. CT showed an enlarged gastric cyst and an obstructed pylorus. The patient was then referred to our hospital, and a laparotomy was performed to resect the cyst. Histological examination revealed positive staining for gastrin in the cyst wall mucosa, which is consistent with gastric duplication. Postoperative serum gastrin levels decreased, suggesting that gastric duplication had caused the hypergastrinemia. Conclusion: A case of gastric duplication was presented. Gastric duplication should be considered when treating patients with cystic disease of the pyloric region. In addition, hypergastrinemia may occur due to duplicated intestine near the pylorus, which may cause a duodenal ulcer.

Abstract: Objective: Stress fractures (SF), menstrual dysfunction (MD), and eating disorders (ED) in young athletes are important issues. We conducted this study to determine the frequency of SF, MD, and ED experienced by high school track and field athletes in Japan and to understand the factors associated with them. Materials and Methods: A cross-sectional study of 1199 high level high school track and field athletes (608 males and 591 females) who participated in a selective training camp held by the Japan Association of Athletics Federations. Results: Approximately one in four male and female athletes self-reported SF. Moreover, we identified the length of the practice time per week and the event (sprinting, middle-distance, jumping, and combined) as relevant factors. Approximately one in three female athletes self-reported MD history, with those participating in long-distance events experiencing it significantly more frequently than those participants in sprinting, throwing, and jumping events. Furthermore, we identified ED history and long-distance events as MD history-related factors. ED history was self-reported at low frequency without gender difference, and long-distance was significantly more frequently reported than sprinting and jumping. Conclusions: About a quarter of Japanese high school track and field athletes experience SF, and about a third of the females experience MD. The association of these with athletic events, training time, and ED should be considered.

BackgroundThere are different types of transcatheter mitral valve repair (TMVr) currently in clinical use, including leaflet approximation, annular cinching, and restoration of the chordal apparatus of the mitral valve (MV). While the concomitant combination (COMBO) therapy of mitral transcatheter edge-to-edge repair (M-TEER) with another TMVr concept has been proven feasible, potentially offering patient-tailored treatment for severe mitral regurgitation (MR), a comparison with M-TEER alone has not been made.AimsTo evaluate the procedural and clinical outcome of COMBO therapies compared with M-TEER alone.MethodsWe included consecutive patients undergoing COMBO and M-TEER between March 2015 and April 2018 at our Heart Valve Center, while excluding patients presenting a case of redo or with previous MV surgery. Procedural outcomes and all-cause mortality were compared between COMBO therapy vs. M-TEER alone.ResultsA total of 357 patients (mean age 78.9 ± 7.0 years, 53.2% male, M-TEER n = 322, COMBO n = 35; COMBO: MitraClip and the Carillon mitral contour system n = 26, MitraClip and Cardioband n = 5, and MitraClip and NeoChord n = 4) were analyzed. Patients with COMBO therapy had larger left chamber sizes, a lower left ventricular systolic ejection fraction (LVEF; COMBO: 37.4 ± 13.8%, M-TEER: 47.9 ± 14.3%, p

In order to break through limits of conventional MRAMs, MTJs with strain-induced magnetic anisotropy were intensively tested as SOT-MRAM cells. Small critical switching-current of 10–25 μA and switching-voltage of about 0.055 V, and almost no retention energy dependence of them were predicted and confirmed by experiments. Finally, high write efficiency of 1750 kBT/V (4.1 kBT/μA) and high write-power efficiency of 100 [kBT/(μA·V)] were obtained.

The cartilage-conduction pathway was recently proposed as a third auditory pathway; however, middle-ear vibrations have not yet been investigated in vivo. We aimed to measure the ossicles and bone vibration upon cartilage-conduction stimulation with a non-contact laser Doppler vibrometer. We recruited adult patients with normal ear structures who underwent cochlear implant surgery at our hospital between April 2020 and December 2022. For sound input, a cartilage-conduction transducer, custom-made by RION Corporation (Tokyo, Japan), was fixed to the surface of the tragus and connected to an audiometer to regulate the output. A posterior tympanotomy was performed and a laser beam was directed through the cavity to measure the vibration of the ossicles, cochlear promontory, and posterior wall of the external auditory canal. Five participants (three men, mean age: 56.4 years) were included. The mean hearing loss on the operative side was 96.3 dB HL in one patient, and that of the other patients was off-scale. The vibrations were measured at a sound input of 1 kHz and 60 dB. We observed vibrations of all three structures, demonstrating the existence of cartilage-conduction pathways in vivo. These results may help uncover the mechanisms of the cartilage-conduction pathway in the future.

Objective To measure muscle activity before and after robot-assisted gait training (RAGT) in patients with stroke and examine the differences in muscle activity changes compared with conventional gait training (CGT). Methods Thirty patients with stroke (RAGT group, n=17; CGT group, n=13) participated in the study. All patients underwent RAGT using a footpad locomotion interface or CGT for 20 minutes for a total of 20 sessions. Outcome measures were lower-limb muscle activity and gait speed. Measurements were performed before the start of the intervention and after the end of the 4-week intervention. Results The RAGT group showed increased muscle activity in the gastrocnemius, whereas the CGT group showed high muscle activity in the rectus femoris. In the terminal stance of the gait cycle, the gastrocnemius, the increase in muscle activity was significantly higher in the RAGT group than in the CGT group. Conclusion The results suggest that RAGT with end-effector type is more effective than CGT to increase the gastrocnemius muscle activity.

Abstract 1D velocity profiles at a strong motion station in the northern part of the Kumamoto plain, Japan, were submitted in Step-1 of the blind prediction exercise of strong ground motions in the sixth international symposium on effects of surface geology on seismic motion (ESG6). Individual participants were requested to estimate a 1D S-wave velocity profile of sedimentary layers from the given data obtained by microtremor array explorations and surface-wave explorations at the site. This paper reports the target site, methods used by the individual participants, and the submitted results. More than half of the participants estimated the phase velocities of the Rayleigh-wave in the frequency range from 0.53 to 29.8 Hz. The statistical analysis of the phase velocity dispersion curves indicates that the standard deviation was below 40 m/s at the frequencies above 3.4 Hz, and it was below 20 m/s above 20 Hz. The S-wave velocity profiles are also similar to a depth of 20 m. The standard deviation was below 45 m/s. The average S-wave velocity in the top 30 m from the surface is 207.3 ± 60.7 m/s for the submitted profiles. The large variation is related to the introduction of the near-surface low velocity layers. The large variation of the S-wave velocities was found in the deep part. The average S-wave velocity at a depth of 1500 m was 2674 m/s with the standard deviation of 786 m/s. We compared 1D amplifications for the submitted profiles. Common peaks can be identified at 0.3–0.4 Hz and 1–2 Hz, excluding two teams. However, the amplifications vary much in the frequency range higher than 4 Hz. Through the experiment, it was found that the dispersion curves and the shallow S-wave velocity structures are estimated with a low standard deviation among the participants. Further development of the techniques for deep S-wave velocity profiling was found to be required. Graphical Abstract

Abstract Streptozotocin (STZ), an anti-cancer drug that is primarily used to treat neuroendocrine tumors (NETs) in clinical settings, is incorporated into pancreatic β-cells or proximal tubular epithelial cells through the glucose transporter, GLUT2. However, its cytotoxic effects on kidney cells have been underestimated and the underlying mechanisms remain unclear. We herein demonstrated that DNA damage and subsequent p53 signaling were responsible for the development of STZ-induced tubular epithelial injury. We detected tubular epithelial DNA damage in NET patients treated with STZ. Unbiased transcriptomics of STZ-treated tubular epithelial cells in vitro showed the activation of the p53 signaling pathway. STZ induced DNA damage and activated p53 signaling in vivo in a dose-dependent manner, resulting in reduced membrane transporters. The pharmacological inhibition of p53 and sodium-glucose transporter 2 (SGLT2) mitigated STZ-induced epithelial injury. However, the cytotoxic effects of STZ on pancreatic β-cells were preserved in SGLT2 inhibitor-treated mice. The present results demonstrate the proximal tubular-specific cytotoxicity of STZ and the underlying mechanisms in vivo. Since the cytotoxic effects of STZ against β-cells were not impaired by dapagliflozin, pretreatment with an SGLT2 inhibitor has potential as a preventative remedy for kidney injury in NET patients treated with STZ.

Oxidative stress (OS) affects men’s health and impairs spermatogenesis. Micronutrient antioxidants are available for male infertility as complemental support; however, their efficacy remains debatable. This study aimed to investigate whether antioxidants can help to reduce sperm OS and improve semen analysis and quality. We included 171 male partners of couples planning to undergo assisted reproductive technology (ART). Male partners, aged 29–41 years, of couples intending to conceive were self-selected to take daily antioxidants (n = 84) containing folic acid and zinc, or not to take antioxidants (n = 52) for 6 months. We analyzed the alterations in serum oxidant levels, sperm parameters, OS, and deoxyribonucleic acid fragmentation after 3 and 6 months. Additionally, implantation, clinical pregnancy, and miscarriage rates after vitrified–warmed embryo transfer were compared between those taking antioxidants and those not taking them after 6 months. In men with high static oxidation–reduction potential (sORP), we observed a significant improvement in sperm concentration and sORP. The high-quality blastocyst rate tended to increase, and implantation and clinical pregnancy rates also significantly increased after 6 months of intervention. The micronutrient antioxidants could improve sperm function by reducing OS and improving ART outcomes. Therefore, micronutrient antioxidants may be a viable treatment option for male infertility.

Abstract Super-resolving the coarse outputs of global climate simulations, termed downscaling, is crucial in making political and social decisions on systems requiring long-term climate change projections. Existing fast super-resolution techniques, however, have yet to preserve the spatially correlated nature of climatological data, which is particularly important when we address systems with spatial expanse, such as the development of transportation infrastructure. Herein, we show an adversarial network-based machine learning enables us to correctly reconstruct the inter-regional spatial correlations in downscaling with high magnification of up to 50 while maintaining pixel-wise statistical consistency. Direct comparison with the measured meteorological data of temperature and precipitation distributions reveals that integrating climatologically important physical information improves the downscaling performance, which prompts us to call this approach $$\pi$$ π SRGAN (Physics Informed Super-Resolution Generative Adversarial Network). The proposed method has a potential application to the inter-regionally consistent assessment of the climate change impact. Additionally, we present the outcomes of another variant of the deep generative model-based downscaling approach in which the low-resolution precipitation field is substituted with the pressure field, referred to as $$\psi$$ ψ SRGAN (Precipitation Source Inaccessible SRGAN). Remarkably, this method demonstrates unexpectedly good downscaling performance for the precipitation field.

Abstract S-net is a large-scale ocean bottom (OB) network in the Japan Trench area, consisting of inline-type 150 observatories equipped with seismometers and pressure gauges. Among them, 41 observatories have been buried about one meter beneath the seafloors in the shallow water regions (water depth

The use of quantum annealers in black-box optimization to obtain the desired properties of a product with a small number of trials has attracted attention. However, the application of this technique to engineering design problems has been limited. Here, we demonstrate the applicability of black-box optimization with a quantum annealer to the design of electric circuit systems, focusing on $\pi $ -type noise filters as an example. We develop a framework that uses quantum annealing to find the optimal location of electrical components and conductor paths connecting the components, and confirm that the learning process appropriately works over a number of trials to efficiently search for a design with high performance. The results show the potential applicability of quantum annealing to design problems of electric circuit systems.

Abstract Background In Brugada syndrome (BrS), the arrhythmogenic substrate is suggested to be located in the epicardial surface of the right ventricle outflow tract. Postmortem examinations of BrS described epicardial and interstitial fibrosis, the causes of which remain unclear. Case presentation We present a family in whom the proband is a case of aborted sudden cardiac death from ventricular fibrillation (VF) without spontaneous Brugada-type electrocardiogram, and his mother underwent pacemaker implantation due to sick sinus syndrome. The proband showed recurrent acute pericarditis two consecutive years before the VF episode. These events occurred twice in mid-spring, the same season when the lethal arrhythmia occurred. Conclusions This case suggests a possibility in the pathogenesis of epicardial fibrosis of BrS that the RVOT lesions induced by SCN5A mutations have not only fibrotic characteristics but also in some patients, inflammatory characteristics which may be manifested as repeated mild pericarditis or occult pericarditis.

Background: Information regarding the outcomes of transcatheter aortic valve replacement (TAVR) in men is limited. This study aimed to investigate short- to mid-term outcomes and prognostic predictors in this population. Method and Results: The data of 519 men were analyzed from 1,693 consecutive patients with symptomatic severe aortic stenosis who underwent TAVR at six hospitals between April 2010 and July 2020. The primary endpoint was all-cause mortality at 30 days after TAVR. The mean age and Society of Thoracic Surgeons (STS) score were 83.7 ± 5.9 years and 6.3 ± 4.7%, respectively. Overall, 23.5% of patients consumed alcohol with a frequency of > 1 drinks/week, and 12.1% consumed alcohol with a frequency of > 8 drinks/week, while 66.1% were former smokers and 4.2% were current smokers. Mortality at 30 days was 0.8%. During the median follow-up period of 448 days, the estimated survival rates at 1 year post-TAVR was 90.7 ± 1.4%. In multivariate analysis, the serum albumin level [hazard ratio (HR): 2.20, 95% confidence interval (CI):1.36–3.62, p = 0.001], atrial fibrillation (HR: 1.79, 95% CI: 1.13–2.82, p = 0.012), and STS score (HR: 1.33, 95% CI: 1.06–1.67, p = 0.015) were independently associated with all-cause mortality following TAVR. Adjusted hazard ratios of current smoking, heavy drinking, and presence of cancer were 1.05 (95% CI: 0.36–2.98),1.37 (95% CI: 0.75–2.48), and 1.13 (95% CI: 0.75–2.48), respectively. Conclusion: Our study demonstrated that serum albumin levels, atrial fibrillation, and STS score were independently associated with all-cause mortality following TAVR in men.

Cytokine storm caused by the overproduction of inflammatory interleukin (IL)-6 plays a central role in the development of acute inflammation. The extremely rare disease, TAFRO syndrome, progresses quickly. Renal dysfunction, fever, reticulin fibrosis, anasarca, thrombocytopenia, and organomegaly with pathological findings such as idiopathic multicentric Castleman disease are all characteristics of TAFRO syndrome. Interstitial pneumonia (IP), which is not characteristic of this disease, is probably a complication of the inflammatory process. An 88-year-old man presented with a 3-day history of fever, dry cough, and progressive dyspnea. After he was first treated with antibiotics, he was transferred to our hospital because he showed no improvement. Data showed hemoglobin Hb 90.00 (SI) (9.0 g/dL); leukocyte count WBC 23 × 109/L (SI) [23,000/μL (neutrophils 87.5%, lymphocytes 2.5%, blast cells 0%)]; hemoglobin 90 g/L (9.0 g/dL); platelet count 101.00 × 109/L (10 100/μL); lactate dehydrogenase 4.78 μkat/L (286 U/L); serum albumin 25.00 g/L (2.5 g/dL); blood urea nitrogen 18.17 μmol/L (50.9 mg/dL); creatinine 285.53 μmol/L (3.23 mg/dL); C-reactive protein 161.50 mg/L (16.15 mg/dL); IL-61830 pg/mL; and surfactant protein D level 26.6 ng/mL. Findings from computed tomography indicated increased ground-glass opacities without traction bronchiectasis consistent with acute IP. The diagnosis was leukocytosis and progressive kidney injury. After bone marrow aspiration caused by persistent pancytopenia, mild reticulin fibrosis was identified. Because of the high IL-6 concentration, which revealed small atrophic follicles with regressed germinal centers surrounded by several lymphocytes, right inguinal lymph node biopsy was performed. Two minor and three major criteria led to diagnosis of TAFRO syndrome. Administrations of antibiotic therapy and methylprednisolone pulse therapy were ineffective. After rapid progress of respiratory failure, the patient died on day 30 of hospitalization. Autopsy of lung tissues showed diffuse alveolar damage with hyaline membranes. Based on these findings, we diagnosed acute exacerbation of IP associated with TAFRO syndrome due to IL-6 overproduction-associated cytokine storm.

BackgroundPosttraumatic stress disorder (PTSD) can be a source of significant social and daily distress in autism spectrum disorder (ASD). Compared to typically developed (TD) individuals, people with ASD are at an increased risk of adverse childhood experiences (ACEs), which can result in abnormal neuronal development. However, whether or how ACEs influence abnormal neural development and PTSD symptoms in ASD has not been fully elucidated.MethodsThirty-nine TD individuals and 41 individuals with ASD underwent T1-weighted magnetic resonance imaging and neurite orientation dispersion and density imaging (NODDI), with axonal and dendritic densities assessed in terms of the orientation dispersion index and neurite density index (NDI), respectively. Voxel-based analyses were performed to explore the brain regions associated with PTSD symptoms, and the relationships between the severity of ACEs and PTSD symptoms and NODDI parameters in the extracted brain regions were examined.ResultsThere was a significant positive association between PTSD symptom severity and NDI in the bilateral supplementary motor area; right superior frontal, left supramarginal, and right superior temporal gyrus; and right precuneus in the ASD group, but not in the TD group. ACE severity was significantly associated with NDI in the right superior frontal and left supramarginal gyrus and right precuneus in the ASD group. Moreover, NDI in the right precuneus mainly predicted the severity of PTSD symptoms in the ASD group, but not the TD group.ConclusionThese results suggest that ACE-associated higher neurite density is of clinical importance in the pathophysiology of PTSD symptoms in ASD.

Estimating governing equations from observed time-series data is crucial for understanding dynamical systems. From the perspective of system comprehension, the demand for accurate estimation and interpretable results has been particularly emphasized. Herein, we propose a novel data-driven method for estimating the governing equations of dynamical systems based on machine learning with high accuracy and interpretability. The proposed method enhances the estimation accuracy for dynamical systems using sparse modeling by incorporating physical constraints derived from Hamiltonian mechanics. Unlike conventional approaches used for estimating governing equations for dynamical systems, we employ a sparse representation of Hamiltonian, allowing for the estimation. Using noisy observational data, the proposed method demonstrates a capability to achieve accurate parameter estimation and extraction of essential nonlinear terms. In addition, it is shown that estimations based on energy conservation principles exhibit superior accuracy in long-term predictions. These results collectively indicate that the proposed method accurately estimates dynamical systems while maintaining interpretability.

Abstract Aims/Introduction The importance of low‐density lipoprotein cholesterol (LDL‐C) in the primary prevention of cardiovascular disease has recently been reported in the population aged ≥75 years with hypercholesterolemia. Therefore, the current status of LDL‐C management for primary prevention of coronary artery disease in patients aged ≥75 years with type 2 diabetes mellitus was investigated. Materials and Methods A total of 124 patients aged ≥75 years who had type 2 diabetes mellitus, but no coronary artery disease, were investigated. The patients' background characteristics, LDL‐C, glycemic status, ankle‐brachial index and cardio‐ankle vascular index were compared between patients taking and not taking LDL‐C‐lowering agents, such as hydroxymethylglutaryl‐CoA reductase inhibitors (statins) and ezetimibe. The details of the antihyperlipidemic and antidiabetic agents used in the present study were also examined. Results LDL‐C was significantly lower in patients taking LDL‐C‐lowering agents (LDLCLT[+]) than in patients not taking them (LDLCLT[−]), although LDL‐C was maintained