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An efficient one-step synthesis of diarylacetic acids was successfully performed by electrochemical direct carboxylation of diarylmethanol compounds in DMSO. Constant-current electrolysis of diarylmethanol species in DMSO using a one-compartment cell equipped with a Pt cathode and a Mg anode in the presence of carbon dioxide induced reductive C(sp3)−O bond cleavage at the benzylic position in diarylmethanol compounds and subsequent fixation of carbon dioxide to produce diarylacetic acids in good yield. This protocol provides a novel and simple approach to diarylacetic acids from diarylmethanol species and carbon dioxide without transformation of the hydroxy group into appropriate leaving groups, such as halides and esters including carbonates.

Abstract Background Prostate cancer is a common cancer among men worldwide that has a very poor prognosis, especially when it progresses to metastatic castration-resistant prostate cancer (mCRPC). Therefore, novel therapeutic agents for mCRPC are urgently required. Because prostate-specific membrane antigen (PSMA) is overexpressed in mCRPC, targeted alpha therapy (TAT) for PSMA is a promising treatment for mCRPC. Astatine-211 (211At) is a versatile α-emitting radionuclide that can be produced using a cyclotron. Therefore, 211At-labeled PSMA compounds could be useful for TAT; however, 211At-labeled compounds are unstable against deastatination in vivo. In this study, to develop in vivo stable 211At-labeled PSMA derivatives, we designed and synthesized 211At-labeled PSMA derivatives using a neopentyl glycol (NpG) structure that can stably retain 211At in vivo. We also evaluated their biodistribution in normal and tumor-bearing mice. Results We designed and synthesized 211At-labeled PSMA derivatives containing two glutamic acid (Glu) linkers between the NpG structure and asymmetric urea (NpG-L-PSMA ((L-Glu)2 linker used) and NpG-D-PSMA ((D-Glu)2 linker used)). First, we evaluated the characteristics of 125I-labeled NpG derivatives because 125I was readily available. [125I]I-NpG-L-PSMA and [125I]I-NpG-D-PSMA showed low accumulation in the stomach and thyroid, indicating their high in vivo stability against deiodination. [125I]I-NpG-L-PSMA was excreted in urine as hydrophilic radiometabolites in addition to the intact form. Meanwhile, [125I]I-NpG-D-PSMA was excreted in urine in an intact form. In both cases, no radioactivity was observed in the free iodine fraction. [125I]I-NpG-D-PSMA showed higher tumor accumulation than [125I]I-NpG-L-PSMA. We then developed 211At-labeled PSMA using the NpG-D-PSMA structure. [211At]At-NpG-D-PSMA showed low accumulation in the stomach and thyroid in normal mice, indicating its high stability against deastatination in vivo. Moreover, [211At]At-NpG-D-PSMA showed high accumulation in tumor similar to that of [125I]I-NpG-D-PSMA. Conclusions [211At]At-NpG-D-PSMA showed high in vivo stability against deastatination and high tumor accumulation. [211At]At-NpG-D-PSMA should be considered as a potential new TAT for mCRPC.

Abstract Aim Postmortem brain research is necessary for elucidating the pathology of schizophrenia; an increasing number of studies require a combination of suitable tissue samples preserved at multiple brain banks. In this study, we examined whether a comparative study of protein expression levels can be conducted using postmortem brain samples preserved in different facilities. Methods We compared the demographic factors of postmortem brain samples preserved in two institutions and measured and compared the expression levels of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and glial fibrillary acidic protein (GFAP) in the prefrontal cortex and superior temporal gyrus. GAPDH is generally used as a loading control for western blotting, and GFAP is considered as an astrocyte marker in the brain. Results We found significant differences between the two institutions in postmortem interval, age at death, and preservation time. To reduce the effects of these differences on our measurements, the parameters were set as covariates in our analyses of covariance. Subsequently, no differences in GAPDH and GFAP expression were found between institutions. Conclusions When studies are conducted using brain samples preserved in different brain banks, differences in demographic factors should be carefully considered and taken into account by statistical methods to minimize their impact as much as possible. Since there was no significant difference in the protein expression levels of GAPDH and GFAP in either region between the two institutions that preserved the postmortem brains, we concluded that it is possible to perform protein quantitative analysis assuming that there is no effect of difference between two institutions.

Key Clinical Message Recently, hypoxia‐inducible factor prolyl hydroxylase (HIF‐PH) inhibitors have been used for renal anemia, but side effects have also been reported. We report on the association of central hypothyroidism and cholesterol with roxadustat. Based on this case and previous reports, we believe that patients receiving roxadustat should have their thyroid function and cholesterol levels checked regularly.

Abstract Aim The etiology of bipolar disorder (BD) remains unknown; however, lipid abnormalities in BD have received increasing attention in recent years. In this study, we examined the expression levels of enzyme proteins associated with the metabolic pathway of phosphoinositides (PIs) and their downstream effectors, protein kinase B (Akt1) and glycogen synthase kinase 3β (GSK3β), which have been assumed to be the targets of mood stabilizers such as lithium, in the postmortem brains of patients with BD. Methods The protein expression levels of phosphatidylinositol 4‐phosphate 5‐kinase type‐1 gamma (PIP5K1C), phosphatidylinositol 4‐kinase alpha (PIK4CA), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), Akt1, and GSK3β were measured using enzyme‐linked immunosorbent assays and multiplex fluorescent bead‐based immunoassays in the prefrontal cortex (PFC). Specifically, PTEN, Akt1, GSK3β, and PIP5K1C were measured in seven BD patients and 48 controls. Additionally, PIK4CA was analyzed in 10 cases and 34 controls. Results PTEN expression levels were markedly decreased in the PFCs of patients with BD, whereas those of Akt and GSK3β were prominently elevated. Moreover, patients medicated with lithium exhibited higher Akt1 expression levels and lower PTEN expression levels in comparison with the untreated group. Conclusion Our results suggest that the expression levels of Akt1/GSK3β and its upstream regulator PTEN are considerably altered.

Introduction Combination therapies of immune checkpoint and tyrosine kinase inhibitors for end‐stage kidney disease and patients on hemodialysis need careful consideration as few case reports provide suitable management decisions. Case presentation A 70‐year‐old man who had undergone hemodialysis for 6 years due to nephrosclerosis. Avelumab plus axitinib combination therapy was performed for repeated lung metastasis, and a complete response was achieved without major side effects. Conclusion A complete response was achieved after Ave plus Axi combination therapy for clear cell renal cell carcinoma in a patient undergoing dialysis. This suggests that Ave plus Axi combination therapy may be safe and effective for dialysis patients.

Introduction Renal autotransplantation is considered a surgical procedure for extensive ureteral defects. Herein, we report a case of severe ureteral injury repaired by laparoscopic nephrectomy and renal autotransplantation with an iliac vein patch using bovine pericardium. Case presentation A 56‐year‐old woman who had previously undergone gynecological surgery complained of right‐sided abdominal pain. She was then later diagnosed with a right middle ureteral injury with a 5‐cm long defect. We performed retroperitoneal laparoscopic nephrectomy and renal autotransplantation. As the iliac vein was fragile, venous patching using bovine pericardium was performed. The patient's renal function was well preserved after surgery. Conclusion Laparoscopic nephrectomy and renal autotransplantation is an effective method for repairing severe ureteral injury with the preservation of renal function. A venous patch using bovine pericardium might be considered as a replacement for a fragile vein.

The site of enterohepatic Helicobacter colonization/infection in humans is still unknown. We report microbiologically and histopathologically confirmed H. fennelliae localization in the large intestine in an immunocompromised patient in Japan. This case contributes to better understanding of the life cycle of enterohepatic Helicobacter species.

Background Considering concerns about conventional toe grip strength, we devised a method to measure toe pressure strength in the standing position, which is close to the actual motion. This study examined the association between toe pressure strength in the standing position and walking speed among older adults. Methods This cross-sectional study included 150 community-dwelling older adults (81±8 years, 73% female) who participated in the physical fitness test. We analyzed the correlation between the participants’ maximum walking speed and physical function. Furthermore, we performed regression analysis with the maximum walking speed as the dependent variable to examine the association with toe pressure strength in the standing position. We also examined the association between maximum walking speed and toe pressure strength in the standing position by introducing a covariate. Results Correlation analysis revealed a significant positive correlation between maximum walking speed and toe pressure strength in the standing position, with a moderate effect size (r=0.48, p

This study examines how local employees gain information and make sense of new expatriates' roles and responsibilities in multinational corporations by applying Weick's sensemaking theory. Data were collected through semi-structured interviews of 17 local employees working for a Japan-based automotive manufacturing company in a Midwestern U.S. city. Results revealed that local employees extracted cues from their environment to make sense of expatriates' roles and responsibilities by communicating directly with others, observing expatriates communicating with others, and applying knowledge from previous experiences with expatriates. In making sense of the information, local employees compared their expectations for expatriates with their experiences and interpreted expatriates' roles and responsibilities negatively when there was a discrepancy between them. This study provides valuable insights into the sensemaking process of local employees as they adapt to expatriates as part of their ongoing socialization process. [ABSTRACT FROM AUTHOR]

BackgroundHeart rate variability (HRV) is believed to possess the potential for disease detection. However, early identification of heart disease remains challenging, as HRV analysis in dogs primarily reflects the advanced stages of the disease.Hypothesis/objectiveThe aim of this study is to compare 24-h HRV with sleep HRV to assess the potential utility of sleep HRV analysis.AnimalsThirty healthy dogs with no echocardiographic abnormalities were included in the study, comprising 23 females and 7 males ranging in age from 2 months to 8 years (mean [standard deviation], 1.4 [1.6]).MethodsThis study employed a cross-sectional study. 24-h HRV and sleep HRV were measured from 48-h Holter recordings. Both linear analysis, a traditional method of heart rate variability analysis, and nonlinear analysis, a novel approach, were conducted. Additionally, circadian rhythm parameters were assessed.ResultsIn frequency analysis of linear analysis, the parasympathetic index nHF was significantly higher during sleep compared to the mean 24-h period (mean sleep HRV [standard deviation] vs. mean 24 h [standard deviation], 95% confidence interval, p value, r-family: 0.24 [0.057] vs. 0.23 [0.045], 0.006–0.031, p = 0.005, r = 0.49). Regarding time domain analysis, the parasympathetic indices SDNN and RMSSD were also significantly higher during sleep (SDNN: 179.7 [66.9] vs. 156.6 [53.2], 14.5–31.7, p

Dampers should be installed at appropriate quantities and locations to control building vibrations against excitations such as earthquakes and wind loads. One of the objectives of the structural optimization problem for damper placement is to minimize the initial cost of damper installation to satisfy various structural constraints under a set of input levels and target performance values. However, it is arbitrary what input levels should be used in the design, and it is also necessary to account for various uncertainties in the inputs and structural properties. This study presents a new method for assessing the robustness of building structures with design variables while simultaneously considering various phases of structural performance criteria and input amplitudes. The proposed robustness index is a multidimensional function that can take into account the influence of different input levels on the structural performance. In this paper, the proposed new robustness index is applied to the robust optimal design of the damper placement, where the damping coefficient of the linear oil damper added to the building is uncertain. The worst resonant seismic motion for the building is investigated based on the critical double impulse method and its equivalent one-cycle sine wave, which is used as the input seismic motion. By applying the equivalent one-cycle sine wave to the structural response analysis with variations in the input velocity amplitude, the proposed robustness index is effective in comprehensively assessing the relationships between the input velocity amplitude of the seismic motion and the upper response limit of the structure under the variation of the damping coefficient of the oil damper. The comprehensive and efficient evaluation of these relationships enables a more detailed assessment of the influence of uncertainties in design variables on structural performance. In the numerical examples, the optimal damper placement for a 12-story building model is discussed based on the robustness and structural performance of both acceleration and story ductility distribution.

Abstract Anadromous salmonids exhibit partial migration, where some individuals within a population migrate down to the ocean through complex interactions between body size and photoperiod. This study aimed to integrate the ontogenetic and seasonal patterns of smoltification, a series of changes for future marine life, in a strain of masu salmon (Oncorhynchus masou). Spring smoltification, as evidenced by the activation of gill Na+,K+-ATPase (NKA), was induced during winter under an advanced photoperiod. In addition, juveniles showed an additional peak in gill NKA activity in August regardless of the photoperiod. When juvenile masu salmon were subjected to feeding manipulations during the first spring/summer, only fish exceeding a fork length of 12 cm exhibited an increased gill NKA activity. We tested whether size-driven smoltification required a long-day period by exposing juveniles to a constant short-day length (9-h light and 15-h dark) from January to November. Juveniles under short-day conditions exceeded 12 cm in June but showed no signs of smoltification. Thus, masu salmon undergo photoperiod-limited, size-driven smoltification during the first summer and size-limited, photoperiod-driven smoltification the following spring. The findings of the present study provide a framework for further elucidation of the physiological mechanisms underlying partial migration in salmonids.

Abstract We report a case of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in a 31‐year‐old man. He had been diagnosed with mild COVID‐19 3 days earlier and presented to the emergency department with altered mental status. Brain magnetic resonance imaging (MRI) showed a high‐intensity area confined to the splenium of the corpus callosum on diffusion‐weighted imaging, which is consistent with MERS. MERS is characterized by a reversible change in the splenium of the corpus callosum. MERS secondary to COVID‐19 has been reported recently. It is important to consider MERS in COVID‐19 patients with impaired consciousness.

Abstract Aims Schizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. There were studies showing that the phospholipid abnormalities in subjects with schizophrenia (Front Biosci, S3, 2011, 153; Schizophr Bull, 48, 2022, 1125; Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933). Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in subjects with schizophrenia (Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933; Schizophr Res, 215, 2020, 493; J Psychiatr Res, 47, 2013, 636; Int J Mol Sci, 22, 2021). For exploring the signaling pathways contributing to the lipid changes in previous study (Sci Rep, 7, 2017, 6), we performed two types of transcriptome analyses in subjects with schizophrenia: an unbiased transcriptome analysis solely based on RNA‐seq data and a correlation analysis between levels of gene expression and lipids. Methods RNA‐Seq analysis was performed in the postmortem prefrontal cortex from 10 subjects with schizophrenia and 5 controls. Correlation analysis between the transcriptome and lipidome from 9 subjects, which are the same samples in the previous lipidomics study (Sci Rep, 7, 2017, 6). Results Extraction of differentially expressed genes (DEGs) and further sequence and functional group analysis revealed changes in gene expression levels in phosphoinositide 3‐kinase (PI3K)‐Akt signaling and the complement system. In addition, a correlation analysis clarified alterations in ether lipid metabolism pathway, which is not found as DEGs in transcriptome analysis alone. Conclusions This study provided results of the integrated analysis of the schizophrenia‐associated transcriptome and lipidome within the PFC and revealed that lipid‐correlated alterations in the transcriptome are enriched in specific pathways including ether lipid metabolism pathway.

Myocardial protection has become an essential adjunctive procedure in veterinary cardiac surgery. Del Nido cardioplegia is a good alternative to the traditional St. Thomas II (ST) cardioplegia in open heart surgery in humans. This study aims to compare intra- and postoperative results between ST cardioplegia and modified del Nido (mDN) cardioplegia in mitral valve surgery in dogs with myxomatous mitral valve disease (MMVD). This retrospective study was conducted using clinical records of 16 MMVD dogs that underwent either ST or mDN cardioplegia. We measured cardiopulmonary bypass (CPB) time, aortic cross-clamp (ACC) time, total operation time, the number of cardioplegia doses, total amount of cardioplegia, required defibrillations, in-hospital mortality and pre- and one-month postoperative echocardiographic variables. CPB (159.4 ± 16.1 vs. 210.1 ± 34.0 min), ACC (101.4 ± 7.0 vs. 136.0 ± 24.8 min) and total operation time (262.3 ± 13.1 vs. 327.0 ± 45.4 min) were significantly shorter in the mDN group (p < 0.05). The number of cardioplegia doses (3.25 ± 0.4 vs. 6.25 ± 1.2) and total amount of cardioplegia (161.3 ± 51.5 vs. 405.0 ± 185.9 mL) in the mDN group were also significantly smaller than the ST group (p < 0.05). No difference was observed in the requirement of defibrillation, in-hospital mortality and pre- and postoperative echocardiographic variables. The utilization of mDN cardioplegia was associated with shorter operative time in mitral valve surgery in dogs.

Background Various functions are involved in prefrailty. However, no studies have examined more relevant functions. Therefore, this study examined the domains of the Kihon Checklist (KCL) associated with prefrailty by comparing them to robustness measures, using the KCL to comprehensively assess life-related functions in community-dwelling older adults. Methods The 194 (mean age, 75±6 years) participants were community-dwelling older adults. Their robustness and preferences were assessed using the Japanese Cardiovascular Health Study criteria. Comprehensive life-related functions were assessed using the KCL, and each physical function was measured. Results The main KCL characteristics associated with robustness and prefrailty were physical function (odds ratio [OR]=1.83; 95% confidence interval [CI], 1.17–2.88), nutritional status (OR=8.16; 95% CI, 2.96–22.48), and depressed mood (OR=3.46; 95% CI, 1.76–6.79). In particular, older adults had difficulty moving, including climbing stairs and getting up from a chair, which suggested a strong fear of falling. The participants also reported psychological characteristics such as low life fulfillment, a low sense of self-usefulness, and a strong sense of boredom. Conclusions Prefrail individuals were characterized by poor physical function and nutritional status, as well as depressive mood. Prefrailty may be prevented or improved by approaches to improve physical function and fear of falling in addition to psychological interventions that encourage activity and a sense of self-usefulness.

Abstract Schizophrenia is a multifactorial disorder, the genetic architecture of which remains unclear. Although many studies have examined the etiology of schizophrenia, the gene sets that contribute to its symptoms have not been fully investigated. In this study, we aimed to identify each gene set associated with corresponding symptoms of schizophrenia using the postmortem brains of 26 patients with schizophrenia and 51 controls. We classified genes expressed in the prefrontal cortex (analyzed by RNA-seq) into several modules by weighted gene co-expression network analysis (WGCNA) and examined the correlation between module expression and clinical characteristics. In addition, we calculated the polygenic risk score (PRS) for schizophrenia from Japanese genome-wide association studies, and investigated the association between the identified gene modules and PRS to evaluate whether genetic background affected gene expression. Finally, we conducted pathway analysis and upstream analysis using Ingenuity Pathway Analysis to clarify the functions and upstream regulators of symptom-related gene modules. As a result, three gene modules generated by WGCNA were significantly correlated with clinical characteristics, and one of these showed a significant association with PRS. Genes belonging to the transcriptional module associated with PRS significantly overlapped with signaling pathways of multiple sclerosis, neuroinflammation, and opioid use, suggesting that these pathways may also be profoundly implicated in schizophrenia. Upstream analysis indicated that genes in the detected module were profoundly regulated by lipopolysaccharides and CREB. This study identified schizophrenia symptom-related gene sets and their upstream regulators, revealing aspects of the pathophysiology of schizophrenia and identifying potential therapeutic targets.

Since the domestication of dogs 10,000 years ago, they have shared their living environment with humans and have co-evolved. The breeding process that dogs have undergone in only a few centuries has led to a significant accumulation of specific genetic alterations that could induce particular diseases in certain breeds. These canine diseases are similar to what is found in humans with several differences; therefore, comparing such diseases occurring in humans and dogs can help discover novel disease mechanisms, pathways, and causal genetic factors. Human angiosarcoma (AS) and canine hemangiosarcoma (HSA), which are sarcomas originating from endothelium, are examples of diseases shared between humans and dogs. They exhibit similar characteristics and clinical behaviors, although with some critical differences resulting from evolution. In this review, we will describe the similarities and differences in terms of clinical and molecular characteristics between human AS and canine HSA, and discuss how these similarities and differences can be applied to advance the treatment of these diseases.

Polydimethylsiloxane (PDMS)-coated macroporous silica (MPSi) particles were developed for the extraction of volatile organic compounds (VOCs) from air samples in thermal desorption-gas chromatographic analysis. The gas sample was collected by a gas sampling pump at 100 mL/min. Different amounts of PDMS coating were prepared, and the fundamental extraction and desorption performances were investigated using even numbered n-alkanes of C8–C28. The extraction efficiency increased by increasing PDMS coating, and the desorption efficiency showed more than 99% at a desorption temperature of 310°C for all the investigated adsorbents. This remarkable desorption performance showed a higher peak area of the analytes than that of the Tenax TA-packed thermal desorption tube, especially for higher molecular weight compounds. Furthermore, an activated carbon particle of Carbopack X was introduced on the latter side of the PDMS-MPSi to extract low-molecular weight compounds. This double-bed-type extraction tube showed a successful determination of a wide range of VOCs. The double-bed-type extraction tube was then applied to the extraction of VOCs related to sick building syndrome (SBS). The results for the extraction and desorption performances of the SBS-related VOCs were well agreed with that of alkanes, and the applicability of the extraction tube to the determination of other types of conventional VOCs were confirmed.

This study examined conversation preferences in workplace meetings via a cross-sectional survey of working adults (N = 217). Dialogue orientations from the argumentation literature were employed in conjunction with a typology of meetings proposed by the authors to examine communication and satisfaction in various types of meetings. Results revealed that three dialogue orientations (negotiation, information-giving, and eristic) predicted meeting satisfaction to a moderate degree. In addition, the use of several dialogue orientations differed depending on meeting type and an individual's supervisory role. We discuss how these results can inform our understanding of dialogue opportunities and constraints during meetings, and recommend ways for improving meetings. These results are discussed in the context of organizational communication, including practical recommendations and theoretical implications. [ABSTRACT FROM AUTHOR]

The mechanisms of angiogenesis in alveolar soft part sarcoma (ASPS) remain to be explored. Here, the authors highlight the role of the ASPSCR1::TFE3 fusion in regulating super-enhancer activity during the angiogenic process in ASPS.

Abstract Vancomycin (VCM) is an antimicrobial that is recommended for therapeutic drug monitoring (TDM) for maintaining the efficacy and safety of treatment. The trough monitoring has been used to guide VCM dosing regimens. However, newer guidelines recommend the use of area under the curve/minimum inhibitory concentration (AUC/MIC)-guided vancomycin dosing, and there is a need for easier and more frequent measurements of VCM concentrations. Therefore, in this study, we developed a simple and rapid analytical method for measuring urinary VCM by combining solid-phase extraction and fluorescence analysis. Urine samples are easier and less invasive than blood samples. In addition to the therapeutic range of blood VCM, this method was also able to measure 0.01–1 mg/mL, which is the concentration range of urinary VCM. The accuracy of 10, 20, and 30 μg/mL VCM solutions were between 93.18 and 109.76%. The relative standard deviation (RSD) of intra-day and inter-day analysis were less than 6.25% and 6.28%, respectively. Since this method does not use large equipment, it is expected to be better suited for clinical use.

BackgroundSchizophrenia (SZ) is a disorder diagnosed by specific symptoms and duration and is highly heterogeneous, clinically and pathologically. Although there are an increasing number of studies on the association between genetic and environmental factors in the development of SZ, the actual distribution of the population with different levels of influence of these factors has not yet been fully elucidated. In this study, we focused on stress as an environmental factor and stratified SZ based on the expression levels of stress-responsive molecules in the postmortem prefrontal cortex.MethodsWe selected the following stress-responsive molecules: interleukin (IL) -1β, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, glucocorticoid receptor, brain-derived neurotrophic factor, synaptophysin, S100 calcium-binding protein B, superoxide dismutase, postsynaptic density protein 95, synuclein, apolipoprotein A1 (ApoA1), ApoA2, and solute carrier family 6 member 4. We performed RNA sequencing in the prefrontal gray matter of 25 SZ cases and 21 healthy controls and conducted a hierarchical cluster analysis of SZ based on the gene expression levels of stress-responsive molecules, which yielded two clusters. After assessing the validity of the clusters, they were designated as the high stress-response SZ group and the low stress-response SZ group, respectively. Ingenuity Pathway Analysis of differentially expressed genes (DEGs) between clusters was performed, and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was conducted on four cases each in the high and low stress-response SZ groups to validate DNA damage.ResultsWe found higher prevalence of family history of SZ in the low stress-response SZ group (0/3 vs. 5/4, p = 0.04). Pathway analysis of DEGs between clusters showed the highest enrichment for DNA double-strand break repair. TUNEL staining showed a trend toward a lower percentage of TUNEL-positive cells in the high stress-response SZ group.ConclusionOur results suggest that there are subgroups of SZ with different degrees of stress impact. Furthermore, the pathophysiology of these subgroups may be associated with DNA damage repair. These results provide new insights into the interactions and heterogeneity between genetic and environmental factors.

Descent deceleration using parachutes is widely used in the aerospace field for scenarios such as weather observation using the descent of high-altitude balloons (radiosondes), re-entry during space sample return, and emergency drone landings. These parachutes are used to protect the aircraft and samples, and to avoid hazards with objects and humans on the ground. However, it is difficult to control the dropping point using parachutes, and there have been concerns regarding accidents caused by insufficient deceleration and adverse environmental effects caused by the disposal of unrecovered objects. To solve these problems, we propose a control method for the aerial recovery of low-speed descent objects using fixed-wing unmanned aerial vehicles (UAVs). Our previous work has shown a flight trajectory generation method that employs updating final-state control (UFSC) to handle variations in the terminal target states until the object is recovered. The frequency-shaped optimal regulator control that enables a return to steady-state flight has also been used after UFSC. However, owing to the characteristics of each control method, the problem of sudden fluctuations in the control input before and after recovery of a descending object remained, and performing aerial recovery using an actual aircraft was predicted to be difficult. In this study, this problem is avoided by switching from UFSC to adaptive nonstationary control (ANC), which has proposed in previous studies. ANC can be applied when the aircraft approaches a descending object, and it can be confirmed that the control input is smooth in a series of trajectory designs until return to steady-state flight.

Abstract Introduction Myxomatous mitral valve degeneration (MMVD) is an acquired heart disease which sometimes result in pulmonary oedema and left atrial rupture. In previous reports, left atrial rupture has been non‐surgically controlled and its prognosis investigated. There is, however, no report concerning surgically treated left atrial rupture with mitral valvuloplasty and follow‐up results. Objectives This report aimed to develop a surgical strategy for a case of left atrial rupture caused by MMVD. Materials and methods Three dogs were presented at a private hospital for surgical treatment of MMVD. All three dogs had a previous history of left atrial rupture due to MMVD. The left atrium rapture was diagnosed from indicating that characteristics of the drained pericardial effusion consistent with blood. Mitral valvuloplasty was performed in all dogs using an extracorporeal circulation machine, and the surgical procedure was modified according to each case. In cases with severe adhesion between the pericardial and left atrial appendage, suturing of the left atrial appendage was performed strategically. Additionally, in cases with severe hypotension caused by left atrial rupture, cardiopulmonary bypass was started as soon as possible during the surgical procedure. Discussion and Conclusion Since the haemodynamics of all dogs had improved, and the owner reported no cardiac‐related clinical signs, all drugs were withdrawn 3 months after surgery. Since left atrial rupture due to MMVD can cause hypotension, cardiopulmonary bypass should be started as soon as possible during the surgical procedure to maintain the blood pressure and suturing of the left atrial appendage should be performed strategically.

Hall-effect measurements were performed in the temperature range of 10-400 K on degenerate n-type polycrystalline InAsxP1-x films deposited on glass substrates by molecular-beam deposition at 240 or 320 °C. For the analysis of the temperature dependence of electrical conductivity of these films, we use a model developed in our preceding paper, which is based on an energy-filtering model with potential fluctuations at grain boundaries, but with refining it so as to be applicable for a non-parabolic conduction band. Using the refined version of our energy-filtering model, the experimental curves of temperature-dependent electrical conductivity are fitted to deduce the mean free path as well as the mean value and the standard deviation of the barrier height. The analysis results show that, in almost of the InAsxP1-x films investigated, the grain-boundary potential barriers fluctuate in height across the Fermi level. Owing to the substantially low potential barrier height, the InAsxP1-x film with x = 0.65 exhibited a high electron mobility of about 250 cm2/(Vs) in spite of the low substrate temperature of 320 °C. [ABSTRACT FROM AUTHOR]

Osteoid osteoma (OO) is a benign osteoblastic tumor characterized by nocturnal pain that responds well to non-steroidal anti-inflammatory drugs. This condition commonly affects adolescents and young adults, and patients between 5 and 24 years of age account for 85% of all OO cases; it occurs very rarely in patients under 5 years old. Tumors often occur in the cortical bone in the diaphysis and metaphysis of the appendicular skeleton and are more common in the lower extremities than upper extremities. Here, we present an extremely rare case of intramedullary OO that arose in the proximal metaphysis of the humerus in a 2-year-old boy, which mimicked subacute osteomyelitis on imaging studies. We also conducted a retrospective literature review and found that the intramedullary location was fairly common in very young patients (

Electrochemical Friedel–Crafts-type amidomethylation was successfully carried out by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborates, such as iPr2NHEtBF4. Constant current electrolysis of 1,3,5-trimethoxybenzene or indoles in DMA containing 0.1 M iPr2NHEtBF4 using an undivided cell equipped with a Pt plate cathode and a Pt wire anode (a quasi-divided cell) resulted in selective formation of N-acyliminium ions of DMA at the anode, which reacted with arenes to give the corresponding amidomethylated products in good to high yields.

BackgroundEvaluating and controlling confounders are necessary when investigating molecular pathogenesis using human postmortem brain tissue. Particularly, tissue pH and RNA integrity number (RIN) are valuable indicators for controlling confounders. However, the influences of these indicators on the expression of each gene in postmortem brain have not been fully investigated. Therefore, we aimed to assess these effects on gene expressions of human brain samples.MethodsWe isolated total RNA from occipital lobes of 13 patients with schizophrenia and measured the RIN and tissue pH. Gene expression was analyzed and gene sets affected by tissue pH and RIN were identified. Moreover, we examined the functions of these genes by enrichment analysis and upstream regulator analysis.ResultsWe identified 2,043 genes (24.7%) whose expressions were highly correlated with pH; 3,004 genes (36.3%) whose expressions were highly correlated with RIN; and 1,293 genes (15.6%) whose expressions were highly correlated with both pH and RIN. Genes commonly affected by tissue pH and RIN were highly associated with energy production and the immune system. In addition, genes uniquely affected by tissue pH were highly associated with the cell cycle, whereas those uniquely affected by RIN were highly associated with RNA processing.ConclusionThe current study elucidated the influence of pH and RIN on gene expression profiling and identified gene sets whose expressions were affected by tissue pH or RIN. These findings would be helpful in the control of confounders for future postmortem brain studies.

Introduction: EGFR tyrosine kinase inhibitors are standard therapeutic agents for patients with advanced NSCLC harboring EGFR mutations. Nevertheless, some patients exhibit primary resistance to EGFR tyrosine kinase inhibitors in the first-line treatment setting. AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is involved in primary resistance to EGFR tyrosine kinase inhibitors in EGFR-mutated NSCLC. Methods: We investigated spatial tumor heterogeneity using autopsy specimens and a patient-derived cell line from a patient with EGFR-mutated NSCLC having primary resistance to erlotinib plus ramucirumab. Results: Quantitative polymerase chain reaction analysis revealed that AXL mRNA expression differed at each metastatic site. In addition, AXL expression levels were likely to be negatively correlated with the effectiveness of erlotinib plus ramucirumab therapy. Analysis of a patient-derived cell line established from the left pleural effusion before initiation of treatment revealed that the combination of EGFR tyrosine kinase inhibitors and an AXL inhibitor remarkably inhibited cell viability and increased cell apoptosis in comparison with EGFR tyrosine kinase inhibitor monotherapy or combination therapy of these inhibitors with ramucirumab. Conclusions: Our observations suggest that AXL expression may play a critical role in the progression of spatial tumor heterogeneity and primary resistance to EGFR tyrosine kinase inhibitors in patients with EGFR-mutated NSCLC.

IntroductionPerinatal women tend to have difficulties with sleep along with autonomic characteristics. This study aimed to identify a machine learning algorithm capable of achieving high accuracy in predicting sleep–wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability (HRV).MethodsNine HRV indicators (features) and sleep–wake conditions of 154 pregnant women were measured for 1 week, from the 23rd to the 32nd weeks of pregnancy. Ten machine learning and three deep learning methods were applied to predict three types of sleep–wake conditions (wake, shallow sleep, and deep sleep). In addition, the prediction of four conditions, in which the wake conditions before and after sleep were differentiated—shallow sleep, deep sleep, and the two types of wake conditions—was also tested.Results and DiscussionIn the test for predicting three types of sleep–wake conditions, most of the algorithms, except for Naïve Bayes, showed higher areas under the curve (AUCs; 0.82–0.88) and accuracy (0.78–0.81). The test using four types of sleep–wake conditions with differentiation between the wake conditions before and after sleep also resulted in successful prediction by the gated recurrent unit with the highest AUC (0.86) and accuracy (0.79). Among the nine features, seven made major contributions to predicting sleep–wake conditions. Among the seven features, “the number of interval differences of successive RR intervals greater than 50 ms (NN50)” and “the proportion dividing NN50 by the total number of RR intervals (pNN50)” were useful to predict sleep–wake conditions unique to pregnancy. These findings suggest alterations in the vagal tone system specific to pregnancy.

Mesenchymal chondrosarcoma affects adolescents and young adults, and most cases usually have the HEY1::NCOA2 fusion gene. However, the functional role of HEY1-NCOA2 in the development and progression of mesenchymal chondrosarcoma remains largely unknown. This study aimed to clarify the functional role of HEY1-NCOA2 in transformation of the cell of origin and induction of typical biphasic morphology of mesenchymal chondrosarcoma. We generated a mouse model for mesenchymal chondrosarcoma by introducing HEY1-NCOA2 into mouse embryonic superficial zone (eSZ) followed by subcutaneous transplantation into nude mice. HEY1-NCOA2 expression in eSZ cells successfully induced subcutaneous tumors in 68.9% of recipients, showing biphasic morphologies and expression of Sox9, a master regulator of chondrogenic differentiation. ChIP sequencing analyses indicated frequent interaction between HEY1-NCOA2 binding peaks and active enhancers. Runx2, which is important for differentiation and proliferation of the chondrocytic lineage, is invariably expressed in mouse mesenchymal chondrosarcoma, and interaction between HEY1-NCOA2 and Runx2 is observed using NCOA2 C-terminal domains. Although Runx2 knockout resulted in significant delay in tumor onset, it also induced aggressive growth of immature small round cells. Runx3, which is also expressed in mesenchymal chondrosarcoma and interacts with HEY1-NCOA2, replaced the DNA-binding property of Runx2 only in part. Treatment with the HDAC inhibitor panobinostat suppressed tumor growth both in vitro and in vivo, abrogating expression of genes downstream of HEY1-NCOA2 and Runx2. In conclusion, HEY1::NCOA2 expression modulates the transcriptional program in chondrogenic differentiation, affecting cartilage-specific transcription factor functions.

Summary: The small GTPase Rab8 plays a vital role in the vesicular trafficking of cargo proteins from the trans-Golgi network to target membranes. Upon reaching its target destination, Rab8 is released from the vesicular membrane into the cytoplasm via guanosine triphosphate (GTP) hydrolysis. The fate of GDP-bound Rab8 released from the destination membranes, however, has not been investigated adequately. In this study, we found that GDP-bound Rab8 subfamily proteins are targeted for immediate degradation, and the pre-emptive quality control machinery is responsible for eliminating these proteins in a nucleotide-specific manner. We provide evidence that components of this quality control machinery have a critical role in vesicular trafficking events, including the formation of primary cilia, a process regulated by the Rab8 subfamily. These results suggest that the protein degradation machinery plays a critical role in the integrity of membrane trafficking by limiting the excessive accumulation of GDP-bound Rab8 subfamily proteins.

Electrochemical carboxylation of benzyl alcohols even in the absence of an electron-withdrawing group on the phenyl ring was successfully carried out by improving our previous electrolysis conditions. Constant current electrolysis of benzyl alcohols including diphenylmethanol in DMSO containing 0.1 mol dm−3 Bu4NBF4 in the presence of carbon dioxide using an undivided cell equipped with a platinum plate cathode and a magnesium rod anode at room temperature resulted in direct substitution of a hydroxyl group by a carboxyl group at the benzylic position to give the corresponding arylacetic acids including diphenylacetic acid in moderate to good yields. Although the effect of DMSO as a solvent is still unclear, the results indicate the potential for a useful, convenient, and eco-friendly synthetic method for arylacetic acids from benzyl alcohols.

Introduction Aggressive angiomyxoma is a rare mesenchymal tumor in females of reproductive age that occurs in the pelvis and perineal zone with a high risk of local infiltration and recurrence. Male aggressive angiomyxoma in perineal zone is very rare. Case presentation A 63‐year old male presented to our hospital with chief complaint of perineal mass. He was diagnosed with perineal lipoma by needle biopsy 3 years before. Computed tomography revealed a 16 cm perineal tumor without lymph node or distal metastasis. As the tumor had gradually increased, we performed tumor resection. The histological diagnosis of tumor using immunohistochemistry was aggressive angiomyxoma with complete resection. Moreover, expressions of both estrogen and progesterone receptors were recognized. No recurrence was seen 9 months after surgery. Conclusion Male aggressive angiomyxoma is a very rare tumor, which has expressions of female hormone receptors. Hormonal therapy might be effective for perioperative therapy or recurrence.

Abstract Aim Clozapine is currently the only effective drug for treatment‐resistant schizophrenia; nonetheless, its pharmacological mechanism remains unclear, and its administration is limited because of severe adverse effects. By comparing the binding proteins of clozapine and its derivative olanzapine, which is safer but less effective than clozapine, we attempted to clarify the mechanism of action specific to clozapine. Methods First, using the polyproline rod conjugates attached with clozapine or olanzapine, clozapine‐binding proteins in extracts from the cerebra of 7‐week‐old ICR mice were isolated and separated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and analyzed by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) to identify proteins. Second, the effect of clozapine on tubulin polymerization was determined turbidimetrically. Finally, the cellular effects of clozapine were observed in HeLa cells by immunofluorescence microscopy. Results Alpha and β tubulins were the most abundant clozapine‐binding proteins. We also found that clozapine directly binds with α and β tubulin heterodimers to inhibit their polymerization to form microtubules and disturbs the microtubule network, causing mitotic arrest in HeLa cells. Conclusion These results suggest that α and β tubulin heterodimers are targeted by the clozapine and the microtubules are involved in the etiology of schizophrenia.