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Traumatic brain injury (TBI) has been found to be associated with certain peripheral organ injuries; however, a few studies have explored the chronological influences of TBI on multiple organs and the systemic effects of therapeutic interventions. Particularly, high-mobility group box 1 (HMGB1) is a potential therapeutic target for TBI; however, its effects on peripheral organs remain unclear. Therefore, this study aimed to determine whether severe TBI can lead to multiple organ injury and how HMGB1 inhibition affects peripheral organs. This study used a weight drop-induced TBI mouse model and found that severe TBI can trigger short-lived systemic inflammation, in the lungs and liver, but not in the kidneys, regardless of the severity of the injury. TBI led to an increase in circulating HMGB1 and enhanced gene expressions of its receptors in every organ. Anti-HMGB1 antibody treatment reduced neuroinflammation but increased inflammation in peripheral organs. This study also found that HMGB1 inhibition appears to have a beneficial role in early neuroinflammation but could lead to detrimental effects on peripheral organs through decreased peripheral immune suppression. This study provides novel insights into the chronological changes in multiple organs due to TBI and the unique roles of HMGB1 between the brain and other organs. [ABSTRACT FROM AUTHOR]

The analysis of cells frozen within the International Space Station (ISS) will provide crucial insights into the impact of the space environment on cellular functions and properties. The objective of this study was to develop a method for cryopreserving blood cells under the specific constraints of the ISS. In a ground experiment, mouse blood was directly mixed with a cryoprotectant and gradually frozen at −80 °C. Thawing the frozen blood sample resulted in the successful recovery of viable mononuclear cells when using a mixed solution of dimethylsulfoxide and hydroxyethyl starch as a cryoprotectant. In addition, we developed new freezing cases to minimize storage space utilization within the ISS freezer. Finally, we confirmed the recovery of major mononuclear immune cell subsets from the cryopreserved blood cells through a high dimensional analysis of flow cytometric data using 13 cell surface markers. Consequently, this ground study lays the foundation for the cryopreservation of viable blood cells on the ISS, enabling their analysis upon return to Earth. The application of this method in ISS studies will contribute to understanding the impact of space environments on human cells. Moreover, this method may find application in the cryopreservation of blood cells in situations where research facilities are inadequate. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to conduct a bibliometric analysis of trends in the description items within the literature published from 2019 to 2021 with "maxillary sinus septum" in the title or subtitle. Methods: Electronic data from PubMed (MEDLINE), Google Scholar, and ScienceDirect were searched from 2019 to 2021. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) to select 21 of 243 articles and examined their studies. Statistical calculations from data recorded by the authors were performed using the Chi-square, Mann–Whitney, and independent tests. Significance was set at P < 0.05. Results: The number of articles decreased annually. The highest number of publications was from Asia (64.3%), accounting for 71.4% of publications. The features of the septum were described for eight items, with one septum (70.14%) mentioned significantly more frequently, followed by on one side (65.89%) or the right side (62.22%). Location was mentioned significantly more frequently in the middle (55.22%) and for those aged 45 years and older (50.38%). No significant differences were observed in prevalence, age, height, or width between sexes; the patients' ages ranged from 18 to 90 years. Septa were significantly more prevalent in dentulous (45.38%) and partially edentulous (48.58%) patients, with significantly more patients exhibiting buccopalatal orientation (82.39%). Conclusions: This study focused primarily on anatomical features using CBCT examination, and analyses of male–female differences and the origin of the sinus septum are necessary for the future. [ABSTRACT FROM AUTHOR]

In this study, we enhance our previously proposed modeling approach, which combines wavelet transform and linear regression and utilizes Fourier transform infrared spectroscopy spectra, to simultaneously estimate the concentrations of two comonomers in binary copolymerization reactions. The advanced multi-output models were evaluated using reaction systems involving methyl methacrylate against two styrene-based and three methacrylate-based monomers with the help of quantum chemical calculations for peak interpretation. The multi-output model surpassed individual concentration prediction models in prediction accuracy for the shared comonomer of methyl methacrylate across the data sets, with identified peaks uniquely associated with the comonomer. [ABSTRACT FROM AUTHOR]

With mathematical rigor, we demonstrate that electron–phonon interactions enhance the stability of charge density waves in low-temperature phases of many-electron systems. Our proof method involves an appropriate application of the Pirogov–Sinai theory to electron–phonon systems. Combining our findings with existing results, we obtain rigorous information regarding the low-temperature phase diagram for half-filled electron–phonon systems. [ABSTRACT FROM AUTHOR]

Autophagy is primarily activated by cellular stress, such as starvation or mitochondrial damage. However, stress-independent autophagy is activated by unclear mechanisms in several cell types, such as thymic epithelial cells (TECs). Here we report that the mitochondrial protein, C15ORF48, is a critical inducer of stress-independent autophagy. Mechanistically, C15ORF48 reduces the mitochondrial membrane potential and lowers intracellular ATP levels, thereby activating AMP-activated protein kinase and its downstream Unc-51-like kinase 1. Interestingly, C15ORF48-dependent induction of autophagy upregulates intracellular glutathione levels, promoting cell survival by reducing oxidative stress. Mice deficient in C15orf48 show a reduction in stress-independent autophagy in TECs, but not in typical starvation-induced autophagy in skeletal muscles. Moreover, C15orf48–/– mice develop autoimmunity, which is consistent with the fact that the stress-independent autophagy in TECs is crucial for the thymic self-tolerance. These results suggest that C15ORF48 induces stress-independent autophagy, thereby regulating oxidative stress and self-tolerance. Stress-independent autophagy is less understood than stress-induced autophagy and is important for thymic self-tolerance. Here the authors show that a mitochondrial protein C15ORF48 is important for stress-independent autophagy and alters glutathione metabolism and C15orf48 knockout mice develop autoimmunity and changes to thymic epithelial cells. [ABSTRACT FROM AUTHOR]

We propose a method to explore the flavor structure of quarks and leptons with reinforcement learning. As a concrete model, we utilize a basic value-based algorithm for models with U(1) flavor symmetry. By training neural networks on the U(1) charges of quarks and leptons, the agent finds 21 models to be consistent with experimentally measured masses and mixing angles of quarks and leptons. In particular, an intrinsic value of normal ordering tends to be larger than that of inverted ordering, and the normal ordering is well fitted with the current experimental data in contrast to the inverted ordering. A specific value of effective mass for the neutrinoless double beta decay and a sizable leptonic CP violation induced by an angular component of flavon field are predicted by autonomous behavior of the agent. Our finding results indicate that the reinforcement learning can be a new method for understanding the flavor structure. [ABSTRACT FROM AUTHOR]

To clarify the differences and similarities in the cytokine profiles of macrophage activating syndrome (MAS) between systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD). The study participants included 9 patients with MAS-SLE, 22 with non-MAS-SLE, 9 with MAS-AOSD, and 13 with non-MAS-AOSD. Serum cytokine levels were measured using a multiplex bead assay. Cytokine levels were compared between patients with SLE and AOSD with/without MAS. Moreover, cytokine patterns were examined using principal component analysis (PCA) and cluster analysis. IL-6, IL-8, IL-18, and TNF-α levels were elevated in patients with SLE and AOSD. IFN-α levels were elevated in SLE, whereas IL-1β and IL-18 levels were elevated in AOSD. In SLE, IFN-α and IL-10 levels were higher in MAS than in non-MAS and controls. PCA revealed distinctive cytokine patterns in SLE and AOSD, SLE with IFN-α and IP-10, AOSD with IL-1β, IL-6, and IL-18, and enhanced cytokine production in MAS. PCA and cluster analysis showed no differences in cytokine patterns between the MAS and non-MAS groups. However, serum ferritin levels were correlated with IFN-α levels in SLE. Cytokine profiles differed between SLE and AOSD but not between MAS and non-MAS. MAS is induced by the enhancement of underlying cytokine abnormalities rather than by MAS-specific cytokine profiles. Type I IFN may be involved in MAS development in patients with SLE. [ABSTRACT FROM AUTHOR]

To determine the efficacy of SARS-CoV-2 mRNA vaccination for allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, we measured antibody titer serially in 92 allo-HSCT patients. Among the evaluable 87 patients, median age at vaccination was 53 years (range, 18–75). The average time between allo-HSCT and vaccination was 3.3 years (range, 0.5–15.7). One month after the second dose, 70 patients (80.5%) had a positive response, whereas 17 patients (19.5%) had a negative response (< 20 U/mL). Only patients older than 44 years had a negative response. Low IgM level was the only significant predictor of vaccine failure in elderly patients. When antibody response before and after the third vaccination was examined in 47 patients, antibodies increased significantly from a median of 18.3 U/mL to 312.6 U/mL (P < 0.01). The median antibody titer after the third vaccination of healthy individuals (n = 203) was 426.4 U/mL, which was comparable to that of patients (P = 0.2). The antibody titer after the third mRNA vaccination increased even in patients whose first two mRNA vaccinations failed. These findings suggest that allo-HSCT recipients should receive the mRNA vaccine regularly. [ABSTRACT FROM AUTHOR]

This cross-sectional study of 136 patients with chronic obstructive pulmonary disease (COPD) investigated the mechanism underlying overlap syndrome, defined as coexisting COPD and obstructive sleep apnea (OSA). OSA was defined as a respiratory event index (REI) ≥ 5 events/h, determined using type-3 portable monitors. The mean REI was 12.8 events/h. Most participants (60.1%) had mild OSA (REI: 5–15 events/h). The REI was positively correlated with forced expiratory volume in one second (%FEV1) (r = 0.33, p < 0.001), body mass index (BMI) (r = 0.24, p = 0.005), and fat-free mass index (r = 0.31, p = 0.005), and negatively correlated with residual volume divided by total lung capacity (r = −0.27, p = 0.003). Receiver-operating characteristic curve analysis revealed an optimal BMI cutoff of 21.96 kg/m2 for predicting moderate/severe OSA. A BMI ≥ 21.96 kg/m2 was associated with OSA among participants with %FEV1 ≥ 50%, but not those with %FEV1 < 50%. This study revealed an interaction between airflow limitation and hyperinflation, nutritional status, and OSA. [ABSTRACT FROM AUTHOR]

The effectiveness and safety of trimethoprim/sulfamethoxazole (TMP/SMX) desensitization therapy is insufficiently evaluated in hematological diseases. From 2002 to 2019, we retrospectively analyzed 112 patients with hematological diseases who underwent desensitization therapy after TMP/SMX prophylaxis withdrawal due to adverse events. They orally started TMP/SMX at 0.4 mg/2 mg, which was then increased daily to 80 mg/400 mg for 5 or 9 days. Eighty-eight patients (79%) had complete desensitization, and the major reason for failure was rash seen in 21 cases (19%). The cause of desensitization and reasons for failure matched in 22 cases (92%). Pneumocystis pneumonia was not observed throughout the study. In the failure group, the number of eosinophils and alanine aminotransferase (ALT) levels were significantly increased after desensitization. In particular in the failure group, the slight increase in eosinophils was seen through the beginning to halfway during desensitization (36/μL (0–900/μL) and 48/μL (0–2560/μL), respectively, p = 0.025). These data show that TMP/SMX desensitization therapy is effective and safe in hematological diseases. The recurrence of adverse events could help predict desensitization success. [ABSTRACT FROM AUTHOR]

Objectives: Standardised uptake value ratio (SUVR) is usually obtained by dividing the SUV of the region of interest (ROI) by that of the cerebellar cortex. Cerebellar cortex is not a valid reference in cases where amyloid β deposition or lesions are present. Only few studies have evaluated the use of other regions as references. We compared the validity of the pons and corpus callosum as reference regions for the quantitative evaluation of brain positron emission tomography (PET) using 11C-PiB compared to the cerebellar cortex. Methods: We retrospectively evaluated data from 86 subjects with or without Alzheimer's disease (AD). All subjects underwent magnetic resonance imaging, PET imaging, and cognitive function testing. For the quantitative analysis, three-dimensional ROIs were automatically placed, and SUV and SUVR were obtained. We compared these values between AD and healthy control (HC) groups. Results: SUVR data obtained using the pons and corpus callosum as reference regions strongly correlated with that using the cerebellar cortex. The sensitivity and specificity were high when either the pons or corpus callosum was used as the reference region. However, the SUV values of the corpus callosum were different between AD and HC (p < 0.01). Conclusions: Our data suggest that the pons and corpus callosum might be valid reference regions. [ABSTRACT FROM AUTHOR]

Background: Little is known about the natural history of comatose patients with brain injury, as in many countries most of these patients die in the context of withdrawal of life-sustaining therapies (WLSTs). The accuracy of predicting recovery that is used to guide goals-of-care decisions is uncertain. We examined long-term outcomes of patients with ischemic or hemorrhagic stroke predicted by experienced clinicians to have no chance of meaningful recovery in Japan, where WLST in patients with isolated neurological disease is uncommon. Methods: We retrospectively reviewed the medical records of all patients admitted with acute ischemic stroke, intracerebral hemorrhage, or nontraumatic subarachnoid hemorrhage between January 2018 and December 2020 to a neurocritical care unit at Toda Medical Group Asaka Medical Center in Saitama, Japan. We screened for patients who were predicted by the attending physician on postinjury day 1–4 to have no chance of meaningful recovery. Primary outcome measures were disposition at hospital discharge and the ability to follow commands and functional outcomes measured by the Glasgow Outcome Scale-Extended (GOS-E), which was assessed 6 months after injury. Results: From 860 screened patients, we identified 40 patients (14 with acute ischemic stroke, 19 with intracerebral hemorrhage, and 7 with subarachnoid hemorrhage) who were predicted to have no chance of meaningful recovery. Median age was 77 years (interquartile range 64–85), 53% (n = 21) were women, and 80% (n = 32) had no functional deficits prior to hospitalization. Six months after injury, 17 patients were dead, 14 lived in a long-term care hospital, 3 lived at home, 2 lived in a rehabilitation center, and 2 lived in a nursing home. Three patients reliably followed commands, two were in a vegetative state (GOS-E 2), four fully depended on others and required constant assistance (GOS-E 3), one could be left alone independently for 8 h per day but remained dependent (GOS-E 4), and one was independent and able to return to work-like activities (GOS-E 5). Conclusions: In the absence of WLST, almost half of the patients predicted shortly after the injury to have no chance of meaningful recovery were dead 6 months after the injury. A small minority of patients had good functional recovery, highlighting the need for more accurate neurological prognostication. [ABSTRACT FROM AUTHOR]

Activity cliffs (AC) are formed by pairs of structural analogues that are active against the same target but have a large difference in potency. While much of our knowledge about ACs has originated from the analysis and comparison of compounds and activity data, several studies have reported AC predictions over the past decade. Different from typical compound classification tasks, AC predictions must be carried out at the level of compound pairs representing ACs or nonACs. Most AC predictions reported so far have focused on individual methods or comparisons of two or three approaches and only investigated a few compound activity classes (from 2 to 10). Although promising prediction accuracy has been reported in most cases, different system set-ups, AC definitions, methods, and calculation conditions were used, precluding direct comparisons of these studies. Therefore, we have carried out a large-scale AC prediction campaign across 100 activity classes comparing machine learning methods of greatly varying complexity, ranging from pair-based nearest neighbor classifiers and decision tree or kernel methods to deep neural networks. The results of our systematic predictions revealed the level of accuracy that can be expected for AC predictions across many different compound classes. In addition, prediction accuracy did not scale with methodological complexity but was significantly influenced by memorization of compounds shared by different ACs or nonACs. In many instances, limited training data were sufficient for building accurate models using different methods and there was no detectable advantage of deep learning over simpler approaches for AC prediction. On a global scale, support vector machine models performed best, by only small margins compared to others including simple nearest neighbor classifiers. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Stability of charge density waves in electron-phonon systems" published in the Journal of Statistical Physics. The notice includes two corrections that were overlooked during the refinement of the manuscript. The first correction addresses an error in the definition of the staggered density, and the second correction modifies Theorem 1.1, which is a corollary of the main theorem of the paper. The corrections provide accurate and updated information for readers conducting research on this topic. The text discusses staggered densities and magnetic order in a specific system. It states that no magnetic order exists in the system, and provides equations and graphs to support this claim. The text also mentions the exponential decay of the two-point correlation function for local observables. The author declares no financial interests, and the publisher remains neutral. No datasets were generated or analyzed in the study. [Extracted from the article]

In June 2020, the Japanese government approved boron neutron capture therapy for the treatment of head and neck cancer. The treatment is usually performed in a single fraction, with the neutron irradiation time being approximately 30–60 min. As neutrons scatter in air and loses its intensity, it is preferable to bring the patient as close to the beam port as possible to shorten the irradiation time. However, this can be a challenge, especially for patients with head and neck cancer, as the shoulders are an obstacle to a clean positioning. In this study, a novel neutron collimation system for an accelerator based neutron source was designed to allow for a more comfortable treatment, without compromising the irradiation time. Experimental measurements confirmed the simulation results and showed the new collimator can reduce the irradiation time by approximately 60% (under the same condition where the distance between the source and the patient surface was kept the same). The dose delivered to the surrounding healthy tissue was reduced with the new collimator, showing a 25% decrease in the D50 of the mucosal membrane. Overall, the use of the newly designed collimator will allow for a more comfortable treatment of the head and neck region, reduce the treatment time, and reduce the dose delivered to the surrounding healthy tissue. [ABSTRACT FROM AUTHOR]

Introduction: The effectiveness of modern ceramic bearings has been well established in reducing the osteolysis associated with wear of the bearing surfaces in total hip arthroplasty (THA). However, there are limited mid- to long-term follow-up data for complications associated with ceramic bearings. Materials and methods: This case series analyzed 124 consecutive primary uncemented THAs in 108 patients with a mean age of 61 years using alumina ceramic-on-alumina ceramic bearing couples. Seventy THAs (56%) were evaluated at a minimum 14 years of follow-up; the mean follow-up period was 16 ± 1 years (14–20 years). Kaplan–Meier survivorship was determined with revision surgery for any reason as the end point. Complications were recorded focusing on osteolysis, ceramic fracture, and abnormal sounds until the final follow-up. Clinical data were scored according to the Merle d'Aubigne and Postel hip score at 14 years after THA. Results: The survivorship was 93.5% (95% CI 86.7–97.0%) at 14-years postoperatively. Five patients (4.0%) underwent revision surgery due to instability or infection before 1-year postoperatively. Two patients (1.6%) underwent revision surgery due to ceramic liner fracture at 9- and 12-years postoperatively, respectively. There was no radiographic evidence of osteolysis. A total of 27 complications occurred: dislocations (n = 7/124), squeaking sounds (n = 3/124), clicking sounds (n = 6/124), ceramic liner fractures (n = 2/124), periprosthetic fractures (n = 4/124), deep infections (n = 2/124), transient sciatic nerve palsy (n = 2/124), and femoral stem breakage (n = 1/124). The Merle d'Aubigne and Postel hip score was 16.8 ± 1.4 points. Conclusions: The survivorship analysis demonstrates the uncemented THA using alumina ceramic bearings may provide favorable clinical outcome and can offer minimal wear at a minimum 14-year follow-up. Revision surgery was mostly required due to instability and infection in the short-term, and implant breakage in the mid- to long-term. [ABSTRACT FROM AUTHOR]

Key message: This study describes biological functions of the bHLH transcription factor RERJ1 involved in the jasmonate response and the related defense-associated metabolic pathways in rice, with particular focus on deciphering the regulatory mechanisms underlying stress-induced volatile emission and herbivory resistance. RERJ1 is rapidly and drastically induced by wounding and jasmonate treatment but its biological function remains unknown as yet. Here we provide evidence of the biological function of RERJ1 in plant defense, specifically in response to herbivory and pathogen attack, and offer insights into the RERJ1-mediated regulation of metabolic pathways of specialized defense compounds, such as monoterpene linalool, in possible collaboration with OsMYC2—a well-known master regulator in jasmonate signaling. In rice (Oryza sativa L.), the basic helix–loop–helix (bHLH) family transcription factor RERJ1 is induced under environmental stresses, such as wounding and drought, which are closely linked to jasmonate (JA) accumulation. Here, we investigated the biological function of RERJ1 in response to biotic stresses, such as herbivory and pathogen infection, using an RERJ1-defective mutant. Transcriptome analysis of the rerj1-Tos17 mutant revealed that RERJ1 regulated the expression of a typical family of conserved JA-responsive genes (e.g., terpene synthases, proteinase inhibitors, and jasmonate ZIM domain proteins). Upon exposure to armyworm attack, the rerj1-Tos17 mutant exhibited more severe damage than the wildtype, and significant weight gain of the larvae fed on the mutant was observed. Upon Xanthomonas oryzae infection, the rerj1-Tos17 mutant developed more severe symptoms than the wildtype. Among RERJ1-regulated terpene synthases, linalool synthase expression was markedly disrupted and linalool emission after wounding was significantly decreased in the rerj1-Tos17 mutant. RERJ1 appears to interact with OsMYC2—a master regulator of JA signaling—and many OsJAZ proteins, although no obvious epistatic interaction was detected between them at the transcriptional level. These results indicate that RERJ1 is involved in the transcriptional induction of JA-mediated stress-responsive genes via physical association with OsMYC2 and mediates defense against herbivory and bacterial infection through JA signaling. [ABSTRACT FROM AUTHOR]

Sudden infant death syndrome (SIDS) remains a leading cause of infant death in high-income countries. Supporting models for categorization of sudden unexpected infant death into SIDS/non-SIDS could reduce mortality. Therefore, we aimed to develop such a tool utilizing forensic data, but the reduced number of SIDS cases renders this task inherently difficult. To overcome this, we constructed Bayesian network models according to diagnoses performed by expert pathologists and created conditional probability tables in a proof-of-concept study. In the diagnostic support model, the data of 64 sudden unexpected infant death cases was employed as the training dataset, and 16 known-risk factors, including age at death and co-sleeping, were added. In the validation study, which included 8 new cases, the models reproduced experts' diagnoses in 4 or 5 of the 6 SIDS cases. Next, to confirm the effectiveness of this approach for onset prediction, the data from 41 SIDS cases was employed. The model predicted that the risk of SIDS in 0- to 2-month-old infants exposed to passive smoking and co-sleeping is eightfold higher than that in the general infant population, which is comparable with previously published findings. The Bayesian approach could be a promising tool for constructing SIDS prevention models. [ABSTRACT FROM AUTHOR]

Purpose: Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for advanced esophageal squamous cell carcinoma (ESCC) in Japan. Computed tomography (CT) is usually used to assess the therapeutic effect of NAC; however, there are no reliable criteria for predicting pathological response or patient prognosis. Methods: We included 84 patients who underwent esophagectomy between January 2009 and December 2018 and retrospectively reviewed their CT scans performed before and after NAC. The reduction rate of the largest tumor area (TA), long diameter (LD), and short diameter (SD) were measured on a transverse CT image. The pathological response and cutoff values were calculated using the receiver operating characteristic curve, and the most suitable ones for determining the effect were examined. Results: The areas under the curve for predicting responders to NAC based on the reduction rate of the TA, LD, and SD were 0.755, 0.761, and 0.781, respectively. The optimal cutoff value of the SD reduction rate for predicting responders to NAC was 22%. An SD reduction ≥ 22% was an independent prognostic factor for overall survival in univariate (p = 0.005, hazard ratio [HR] = 2.755) and multivariate analyses (p = 0.030 HR 2.690). Furthermore, an SD reduction of ≥ 22% was also an independent prognostic factor for relapse-free survival in the univariate (p = 0.007, HR = 2.491) and multivariate analyses (p = 0.007, HR = 0.030). Conclusions: The reduction rate of the tumor SD is a simple predictor of pathological response and patient prognosis. [ABSTRACT FROM AUTHOR]

The retrospective evaluation of virtual screening approaches and activity prediction models are important for methodological development. However, for fair comparison, evaluation data sets must be carefully prepared. In this research, we compiled structure–activity–relationship matrix-based data sets for 15 biological targets along with many diverse inactive compounds, assuming the early stage of structure–activity–relationship progression. To use a large number of diverse inactive compounds and a limited number of active compounds, similarity profiles (SPs) are proposed as a set of molecular descriptors. Using these highly imbalanced data sets, we evaluated various approaches including SPs, under-sampling, support vector machine (SVM), and message passing neural networks. We found that for the under-sampling approaches, cluster-based sampling is better than random sampling. For virtual screening, SPs with inactive reference compounds and the under-sampling SVM also perform well. For classification, SPs with many inactive references performed as well as the under-sampling SVM trained on a balanced data set. Although the performance of SPs and the under-sampling SVM were comparable, SPs with many inactive references were preferable for selecting structurally distinct compounds from the active training compounds. [ABSTRACT FROM AUTHOR]

Chronic myocarditis is a prolonged inflammatory condition in the myocardium and its histological manifestation is defined by the presence of an inflammatory infiltrate. Chronic myocarditis has not been well known and its treatment of chronic myocarditis has not been established. Primary outcome of this study was to assess the efficacy of immunomodulatory treatment in addition to conventional treatment, and secondary outcomes were to clarity the prognosis of natural history of chronic myocarditis and incidence of chronic myocarditis in patients with dilated cardiomyopathy (DCM). We searched for studies in Medline, Embase, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi published between January 1946 and June 2020. Sixteen studies met the inclusion criteria. A meta-analysis revealed that patients receiving immunomodulatory treatment showed an improvement in left ventricular ejection fraction after immunomodulatory treatment compared to the control group (hazard ratio, 16.65; confidence interval, 4.55–28.74; p = 0.007). Five-year survival rate of the patients with inflammatory DCM (iDCM) and DCM was 52.7–70.3% and 51.9–91.1%, respectively. Moreover, 51.5%–62.7% of patients with DCM met the criteria of iDCM. Our systematic review revealed that patients with chronic myocarditis had poor prognosis and immunomodulatory treatment was significantly effective in addition to conventional treatment. [ABSTRACT FROM AUTHOR]

We propose an abstract framework describing energy-renormalized Hamiltonians in terms of local algebras. Within the framework, we examine the positivity improvingness of the semigroup generated by the renormalized Hamiltonian. As examples, we discuss the renormalized Nelson Hamiltonian and the renormalized Nelson Hamiltonian at fixed total momentum. The characteristic features of our approach are as follows: (i) in contrast with the probabilistic approach in the Schrödinger representation, our method works well in the Fock representation and (ii) the method covers the massless case. [ABSTRACT FROM AUTHOR]

Conferring drought resistant traits to crops is one of the major aims of current breeding programs in response to global climate changes. We previously showed that exogenous application of acetic acid to roots of various plants could induce increased survivability under subsequent drought stress conditions, but details of the metabolism of exogenously applied acetic acid, and the nature of signals induced by its application, have not been unveiled. In this study, we show that rice rapidly induces jasmonate signaling upon application of acetic acid, resulting in physiological changes similar to those seen under drought. The major metabolite of the exogenously applied acetic acid in xylem sap was determined as glutamine—a common and abundant component of xylem sap—indicating that acetic acid is not the direct agent inducing the observed physiological responses in shoots. Expression of drought-responsive genes in shoot under subsequent drought conditions was attenuated by acetic acid treatment. These data suggest that acetic acid activates root-to-shoot jasmonate signals that partially overlap with those induced by drought, thereby conferring an acclimated state on shoots prior to subsequent drought. [ABSTRACT FROM AUTHOR]

Biomass may ignite due to biological oxidation and chemical oxidation. If this phenomenon (spontaneous ignition) is controlled, it would be possible to produce biochar at a lower cost without the need for an external heat resource. We investigated if self-heating could be controlled by using sawdust and bark chips. When sawdust and bark chips were used under controlled conditions, the bark chips temperature increased to the torrefaction temperature. The ash content of bark chips was ~ 2%d.b. higher than that of sawdust; consequently, the inorganic substances contained in the bark chips might affect the self-heating. Self-heating was suppressed when inorganic substances were removed by washing with water. Therefore, the inorganic substances in the biomass might have affected self-heating. The inorganic element contents of the bark chips were measured by inductively coupled plasma optical emission spectrometry before and after washing. The potassium content of the bark chips was reduced remarkably by washing, and there was a possible influence of potassium on self-heating. Finally, the effect of moisture content on self-heating was investigated to obtain stable reactivity. Thus, at a moisture content of 40%w.b., a steady self-heating behavior may be realized. [ABSTRACT FROM AUTHOR]

Quantitative structure–activity relationship (QSAR) and quantitative structure–property relationship (QSPR) models predict biological activity and molecular property based on the numerical relationship between chemical structures and activity (property) values. Molecular representations are of importance in QSAR/QSPR analysis. Topological information of molecular structures is usually utilized (2D representations) for this purpose. However, conformational information seems important because molecules are in the three-dimensional space. As a three-dimensional molecular representation applicable to diverse compounds, similarity between a test molecule and a set of reference molecules has been previously proposed. This 3D representation was found to be effective on virtual screening for early enrichment of active compounds. In this study, we introduced the 3D representation into QSAR/QSPR modeling (regression tasks). Furthermore, we investigated relative merits of 3D representations over 2D in terms of the diversity of training data sets. For the prediction task of quantum mechanics-based properties, the 3D representations were superior to 2D. For predicting activity of small molecules against specific biological targets, no consistent trend was observed in the difference of performance using the two types of representations, irrespective of the diversity of training data sets. [ABSTRACT FROM AUTHOR]

Purpose: Recent large-scale clinical studies have shown that preoperative renal insufficiency is associated with an increased risk of postoperative complications after esophagectomy; however, it remains unclear whether asymptomatic renal dysfunction affects the postoperative course after esophagectomy. Methods: The subjects of this retrospective study were 177 patients who underwent esophagectomy between May, 2009 and December, 2018. Renal function was evaluated based on the pretreatment estimated glomerular filtration rate (eGFR). Patients were divided into two groups according to the eGFR cut-off value of 55 ml/min per 1.73 m2. Results: There were 17 patients in the low eGFR group and 160 patients in the normal group eGFR group. The rate of severe complications was significantly higher in the low eGFR than in the normal eGFR group. A low eGFR was the only significant complication risk factor identified; however, there were no marked differences in mortality or survival between the low and normal eGFR groups. Conclusion: Our findings demonstrate that pretreatment asymptomatic renal dysfunction may be a significant risk factor for severe morbidity after esophagectomy. [ABSTRACT FROM AUTHOR]

We prove that the Aizenman–Lieb theorem on ferromagnetism in the Hubbard model holds true even if the electron–phonon interactions and the electron–photon interactions are taken into account. Our proof is based on path integral representations of the partition functions. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare retrospectively the rates of renal morbidity and mortality in surgical patients receiving 6% HES 130/0.4 to those receiving albumin. Methods: From a Japanese nationwide medical database between 2014 and 2016, we identified adults who received HES 130/0.4 (HES group) or albumin (albumin group) as a single colloid solution on the day of surgery. After propensity score matching, the two groups were analyzed with χ2 or Mann Whitney U test. The primary outcome was the incidence of acute kidney injury (AKI). Secondary outcomes included the incidence of renal-replacement therapy, hospital length of stay, in-hospital 30-day mortality, the use of vasoactive agents, and the fluid requirement on the day of surgery. Results: Of 76,048 patients in the database, propensity score matching identified 289 matched pairs. There was no statistically significant difference in the incidence of AKI between the HES and the albumin group (15.2% vs. 20.8%, respectively: P = 0.08). The secondary outcomes did not differ between groups except the following. Median hospital stay was 5 days shorter in the HES group (18 vs. 23 days; P < 0.001), and the median net fluid requirement on the day of surgery was 15 mL/kg lower in the HES group (140 vs. 155 mL/kg, respectively; P = 0.01). Conclusions: Postoperative renal morbidity and mortality did not differ between patients receiving HES 130/0.4 and those receiving albumin. HES 130/0.4 was associated with shorter hospital stay and less fluid requirement compared to albumin. These findings support the use of 6% HES 130/0.4 for perioperative volume replacement as an alternative to albumin. Trial registration: UMIN000027896 and the date of registration was June 30, 2017 at https://www.umin.ac.jp/ctr/index-j.html. [ABSTRACT FROM AUTHOR]

Purpose: Limited gastrectomy has been generally performed in clinical T1N0 gastric cancer. The aim of this study was to identify risk factors for stage underestimation in clinical T1N0 gastric cancer. Methods: This study reviewed the medical records of 566 patients who underwent gastrectomy for clinical T1N0 gastric cancer. Results: The tumor stage was underestimated in 122 (21.6%) patients. The relapse-free survival rate was significantly lower in the patients with pathological stage II (P = 0.021) and III (P < 0.001) disease than in those with pathological stage IA disease. In the multivariate analysis, a location in the upper third of the stomach, tumor size of ≥ 30 mm, undifferentiated adenocarcinoma and clinical tumor depth of SM were identified as independent risk factors for pathological stages II and III. The rate of pathological stages II and III was 0% in the patients with no risk factors, 3% in those with 1 risk factor, 10.5% in those with 2 risk factors, 19.8% in those with 3 risk factors and 50% in those with 4 risk factors. Conclusions: Location, tumor size, undifferentiated adenocarcinoma and clinical tumor depth were independent risk factors for pathological stages II and III in clinical T1N0 gastric cancer. [ABSTRACT FROM AUTHOR]

Left ventricular noncompaction (LVNC) is a hereditary cardiomyopathy and is associated with high morbidity and mortality. However, the role and significance of school screening for LVNC have not been fully elucidated. In this multicenter, retrospective cohort study, a total of 105 children with LVNC were included from 2000 to 2017. At the initial presentation, 44 patients (41.9%) were diagnosed by school screening. One (1.0%) patient underwent heart transplantation and four (3.8%) patients died during the study. Electrocardiogram data showed a high prevalence of fragmented QRS (33.4%) and J wave (15.7%). Treatments were needed in eight (18.2%) patients who were detected by school screening. The multivariable proportional hazards model showed T-wave abnormality on electrocardiogram in first graders was independent risk factors for major adverse cardiac events (odds ratio 4.94, p value = 0.0007). Moreover, dilation of the left atrium on chest X-ray and low ejection fraction on echocardiogram at the initial treatment were independent risk factors for treatment (odds ratio 1.7 × 107 and 22.3, p = 0.0362 and 0.0028, respectively). This study is the first report focusing on school screening in a large pediatric cohort with LVNC. With the use of abnormalities in electrocardiogram, school screening may be a good detector of and predictor for LVNC. [ABSTRACT FROM AUTHOR]

The purpose of the present paper is to analyze correlation structures of the ground states of the Schrödinger operator. We construct Griffiths inequalities for the ground state expectations by applying operator-theoretic correlation inequalities. As an example of such an application, we study the ground state properties of Schrödinger operators. [ABSTRACT FROM AUTHOR]

Background: Cullin4A (CUL4A), which is a component of E3 ubiquitin ligase, is implicated in many cellular events. Although the altered expression of CUL4A has been reported in several human cancers, the role of CUL4A in esophageal cancer remains unknown. Methods: We investigated the CUL4A expression in primary esophageal squamous cell carcinoma (ESCC) tissue specimens from 120 patients by immunohistochemistry and explored its clinical relevance and prognostic value. Furthermore, the effect of the expression of CUL4A on cancer cell proliferation was analyzed in vitro using an siRNA silencing technique. Results: The higher expression of CUL4A was significantly associated with a deeper depth of tumor invasion (P < 0.001) and the presence of venous invasion (P = 0.014). The disease-specific survival (DSS) rate in patients with tumors that showed high CUL4A expression levels was significantly lower than that in patients whose tumors showed low CUL4A expression levels (P = 0.001). Importantly, the CUL4A status was identified as an independent prognostic factor for DSS (P = 0.045). Our results suggested that the CUL4A expression has significant prognostic value in ESCC. Furthermore, CUL4A gene silencing significantly inhibited the proliferation of ESCC cells in vitro. In addition, the knockdown of the CUL4A expression induced G1 phase arrest and increased the p21 and p27 protein levels. Conclusions: CUL4A might play an important role in regulating the proliferation of ESCC cells and promoting the development of postoperative recurrence. [ABSTRACT FROM AUTHOR]

Purpose: Fluid therapy focused on glycocalyx (GCX) protection in hemorrhagic shock is a current focus of research. Hydroxyethyl starch (HES) solution is commonly used for fluid resuscitation; however, its effects on the GCX remain unclear. The primary aim of this study was to explore the protective effect of HES130 in maintaining GCX thickness and reducing plasma syndecan-1 expression. Methods: An acute hemorrhage murine model with the dorsal skin chambers was used to measure GCX thickness and to evaluate vascular permeability. Groups of mice were treated with normal saline (NS), albumin (NS-A), HES130 (NS-V), or no exsanguination or infusion (C). We measured syndecan-1 plasma concentrations, performed blood gas analysis, and analyzed the 7-day cumulative mortality. Results: GCX thickness in NS mice was significantly reduced compared to that in group C, but no other groups showed a difference compared to group C. The plasma concentration of syndecan-1 was significantly higher in NS mice than in group C. There were no significant differences in the fluorescence intensity of dextran in the interstitial space. HES70 leakage was suppressed in NS-V mice compared to those in other groups. HES70 was localized to the inner vessel wall in C, NS, and NS-A mice, but not in group NS-V. Blood gas analysis indicated that pH and lactate showed the greatest improvements in NS-V mice. The 7-day cumulative mortality rate was the highest in group NS. Conclusion: Resuscitation with HES130 protected the GCX and suppressed vascular permeability of HES70 during early stages of acute massive hemorrhage. [ABSTRACT FROM AUTHOR]

We explored new cytotoxic C19-diterpenoid alkaloid, lipojesaconitine (1), from rhizoma of Aconitum japonicum Thunb. subsp. subcuneatum (Nakai) Kadota. Two additional non-cytotoxic new C19-diterpenoid alkaloids, 10-hydroxychasmanine (2) and 3-hydroxykaracoline (3), together with eight known C19- and C20-diterpenoid alkaloids (4−11) were also isolated. Their structures were elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and MS (HRMS). Six known diterpenoid alkaloids, foresticine (5), neolinine (6), aconicarchamine A (7), 9-hydroxynominine (8), kobusine (9), and torokonine (10), were isolated for the first time from A. japonicum subsp. subcuneatum. Alkaloid 1 showed cytotoxicity with IC50 values ranging from 6.0 to 7.3 µM against four human tumor cell lines, except a multidrug-resistant subline, suggesting that 1 was likely exported by P-glycoprotein. [ABSTRACT FROM AUTHOR]

Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) is an enzyme that converts cholesterol to cholesteryl esters. A recent in vivo study reported that inhibiting ACAT1 enzyme activity upregulates the membrane cholesterol levels of T cells, enhancing their cytotoxic function. In the present study, we investigated whether the presence of the ACAT1 single nucleotide polymorphism rs11545566 in transplant donors affected the risk of graft-versus-host disease (GVHD) in 116 adult patients who underwent bone marrow transplantation from human leukocyte antigen-identical sibling donors, and who received GVHD prophylaxis with short-term methotrexate and cyclosporine. The frequencies of the AA, AG, and GG genotypes in the donors were 31%, 45%, and 24%, respectively. The cumulative incidences of grade II-IV acute GVHD on day 100 in patients whose donors had AA vs. non-AA genotypes were 6% and 18%, respectively, and those of extensive chronic GVHD at 2 years were 7% and 32%, respectively. Multivariate analyses demonstrated that donor rs11545566 non-AA genotypes showed a trend toward a higher incidence of grade II-IV acute GVHD (P = 0.079), and were significantly associated with a higher incidence of extensive chronic GVHD (P = 0.021). These results suggest that donor ACAT1 rs11545566 genotype may be predictive of GVHD. [ABSTRACT FROM AUTHOR]

The environment experienced during spaceflight may impact the immune system and the thymus appears to undergo atrophy during spaceflight. However, molecular aspects of this thymic atrophy remain to be elucidated. In this study, we analysed the thymi of mice on board the international space station (ISS) for approximately 1 month. Thymic size was significantly reduced after spaceflight. Notably, exposure of mice to 1 × g using centrifugation cages in the ISS significantly mitigated the reduction in thymic size. Although spaceflight caused thymic atrophy, the global thymic structure was not largely changed. However, RNA sequencing analysis of the thymus showed significantly reduced expression of cell cycle-regulating genes in two independent spaceflight samples. These reductions were partially countered by 1 × g exposure during the space flights. Thus, our data suggest that spaceflight leads to reduced proliferation of thymic cells, thereby reducing the size of the thymus, and exposure to 1 × g might alleviate the impairment of thymus homeostasis induced by spaceflight. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the change in skeletal muscle mass and evaluate the prognostic impact of sarcopenia on esophageal cancer (EC) patients Methods: The subjects of this retrospective study were 90 EC patients who were treated with neoadjuvant chemotherapy (NAC) and subsequent esophagectomy. The skeletal muscle index (SMI) was defined according to computed tomography (CT) imaging of the total cross-sectional muscle tissue, measured at the third lumbar level using a volume analyzer before NAC and surgery. The SMI was calculated by normalization according to height, and skeletal muscle loss (SML) was defined as (pre-NAC SMI value − preoperative SMI value) × 100/pre-NAC SMI. Results: Sarcopenia was evident in 72 (80.0%) patients before NAC and 77 (85.6%) patients before NAC and surgery. The SMI value was decreased in 28 (68.9%) patients and the median SML was 3.3%. The 3-year overall survival rate was 68.9% in the low SML group and 0% in the high SML group (P < 0.001). Sarcopenia before NAC or surgery was not significantly associated with overall survival. Multivariable analysis identified high SML as an independent prognostic factor. Conclusions: These results suggest that skeletal muscle loss is associated with a worse long-term outcome for EC patients treated with NAC. [ABSTRACT FROM AUTHOR]

We construct a model-independent framework describing stabilities of ferromagnetism in strongly correlated electron systems; Our description relies on the operator theoretic correlation inequalities. Within the new framework, we reinterpret the Marshall–Lieb–Mattis theorem and Lieb's theorem; in addition, from the new perspective, we prove that Lieb's theorem still holds true even if the electron–phonon and electron–photon interactions are taken into account. We also examine the Nagaoka–Thouless theorem and its stabilities. These examples verify the effectiveness of our new viewpoint. [ABSTRACT FROM AUTHOR]

In this work, computational compound screening strategies on the basis of two- and three-dimensional (2D and 3D) molecular representations were investigated including similarity searching and support vector machine (SVM) ranking. Calculations based on topological fingerprints and molecular shape queries and features were compared. A unique aspect of the analysis setting apart from previous comparisons of 2D and 3D virtual screening approaches has been the design of compound reference, training, and test data sets with controlled incremental increases in intra-set structural diversity and different categories of structural relationships between reference/training and test sets. The use of these data sets made it possible to assess the relative performance of 2D and 3D screening strategies under increasingly challenging conditions ultimately leading to the use of training and test sets with essentially unrelated structures. The results showed that 3D similarity searching had little advantage over 2D searching in identifying active compounds with remote structural relationships. However, 3D SVM models trained on the basis of shape features were superior to other approaches (including 2D SVM) when the detection of structure–activity relationships became increasingly challenging. Such 3D SVM methods has thus far only been little investigated in virtual screening, proving a wealth of opportunities for further analyses. [ABSTRACT FROM AUTHOR]

Olfactory adaptation is an important process that allows the individual to adjust to changes in the environment. This process has been proposed to be aberrant in individuals with autism spectrum disorders (ASD). However, few studies have examined olfactory adaptation in children with ASD. We examined olfactory adaptation in children with ASD and typically developing (TD) children using a pulse ejection system, which resolved problems associated with previous laboratory-based olfactory psychophysical studies. Nine children with ASD and nine TD children participated in this study and all participants completed the entire experiment. Using this system, we found that the TD group showed greater adaptation than the ASD group. Our results provide a better understanding of olfactory adaptation in children with ASD. [ABSTRACT FROM AUTHOR]

Purpose: Narrow thoracic inlet might be associated with increased incidence of cervical anastomotic leakage (AL) after esophagectomy with retrosternal reconstruction. We retrospectively evaluated the relationship of the length from the suprasternal notch to the trachea (LST) and AL using computed tomography. Methods: In this retrospective study including 121 patients with esophageal cancer who underwent subtotal esophagectomy with retrosternal reconstruction between 2008 and 2016, clinicopathological characteristics, including the LST, surgical procedures, and perioperative outcomes, were compared between the AL and non-AL groups. Results: AL occurred in 19 of the 121 patients (15.7%). There were no associations between AL development and age, sex, body mass index, tumor location, TNM stage, histological type, surgical approach, or type of the anastomotic procedure. Surgery duration was longer in the AL group than in the non-AL group (p = 0.004). Other surgical factors such as intra-operative blood loss and anastomotic technique were not associated with AL. LST was significantly shorter in the AL group than in the non-AL group (p < 0.001). Multivariate analysis revealed that LST was a significant predictor of AL (p < 0.001). Conclusion: LST is a simple and useful predictor of AL after esophagectomy with retrosternal reconstruction. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the prognostic value of the fibrinogen-to-platelet ratio (FPR) as an inflammatory and coagulative index by examining its clinicopathologic and prognostic efficiency in patients with gastric cancer (GC).Methods: The subjects of this retrospective study were 182 GC patients whose FPR was measured preoperatively between January, 2001 and December, 2006. The FPR was defined as the plasma fibrinogen divided by the platelet counts.Results: Patients aged ≥ 65 years and with venous invasion had a significantly higher FPR (p = 0.02 and p < 0.01, respectively) than those aged < 65 years and without venous invasion. We found a correlation between the FPR and all recurrences (p < 0.01). Patients with a low FPR had significantly better overall survival (OS) and relapse-free survival (RFS) rates than patients with a high FPR (p = 0.001 for both). Furthermore, the FPR was an independent predictor of OS and RFS (p = 0.02 and 0.001, respectively), but the fibrinogen level was not. In a subgroup analysis, the FPR was a significant prognostic factor for OS and RFS in patients with pathological stages II/III disease and in patients aged < 65 years.Conclusion: The FPR can be calculated easily and is more useful than the fibrinogen level for predicting the prognosis of GC patients. Patients with a high FPR, particularly those with undifferentiated tumors, those with pStage II/III disease, and those aged < 65 years, require more intensive chemotherapy. [ABSTRACT FROM AUTHOR]

The advantages of using a tele-operated robot to facilitate otherwise difficult verbal disclosure of thoughts and concerns was examined. In a field study, individuals with autism spectrum disorder, who often face obstacles in social interaction, were provided daily-life-guidance by a robot tele-operated by their caregiver. In cases in which the robot was operated remotely or from the same room, subjects were able to disclose concerns to the robot that they had not previously disclosed to their caregiver. Furthermore, under the latter case the improved communicability was maintained through subsequent conversation with the operator. In a separate laboratory experiment involving participants not judged to be on the autism spectrum, it was observed that the participants were silent longer during conversation via a robot than in face-to-face conversation. The enhanced length of silence in the first setting can be considered to be an index for good counseling of a subject. Furthermore, the enhanced length of silence was maintained in subsequent face-to-face conversation with a robot operator in the same room, which appears to be consistent with the results of the field experiment. The findings encourage future applications in therapeutic conversation approaches such as counseling for providing clients with environments that facilitate the disclosure of concerns. [ABSTRACT FROM AUTHOR]