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Thallium bromide (TlBr) semiconductor detectors are being developed as promising candidates for high-detection-efficiency, high-energy-resolution, and room-temperature gamma-ray spectrometers. This study presents methods for evaluating TlBr crystal quality and carrier transport characteristics using neutron Bragg-dip imaging and the time-of-flight method for pulsed-laser-induced carriers, respectively. Neutron Bragg-dip imaging effectively determines the crystal orientation distribution, revealing crystal imperfections and grain boundaries. Time-of-flight measurements provide a spatial distribution of carrier mobility. In this study, two samples obtained from both the upstream and downstream region in the crystal ingot were evaluated. Although both samples show similar crystal quality, the upstream sample showed high carrier mobility across all areas, whereas the downstream sample exhibits low mobility in some areas. These findings suggest that, at least within the range of carrier mobility currently obtained, the effect of crystal integrity on carrier mobility is less significant than that of impurities. In conclusion, combining neutron Bragg-dip imaging with carrier mobility measurements offers a comprehensive approach to evaluating and improving TlBr detectors., (© 2024. The Author(s).)

Variant annotations are crucial for efficient identification of pathogenic variants. In this study, we retrospectively analyzed the utility of four annotation tools (allele frequency, ClinVar, SpliceAI, and Phenomatcher) in identifying 271 pathogenic single nucleotide and small insertion/deletion variants (SNVs/small indels). Although variant filtering based on allele frequency is essential for narrowing down on candidate variants, we found that 13 de novo pathogenic variants in autosomal dominant or X-linked dominant genes are registered in gnomADv4.0 or 54KJPN, with an allele frequency of less than 0.001%, suggesting that very rare variants in large cohort data can be pathogenic de novo variants. Notably, 38.4% candidate SNVs/small indels are registered in the ClinVar database as pathogenic or likely pathogenic, which highlights the significance of this database. SpliceAI can detect candidate variants affecting RNA splicing, leading to the identification of four variants located 11 to 50 bp away from the exon-intron boundary. Prioritization of candidate genes by proband phenotype using the PhenoMatcher module revealed that approximately 95% of the candidate genes had a maximum PhenoMatch score ≥ 0.6, suggesting the utility of phenotype-based variant prioritization. Our results suggest that a combination of multiple annotation tools and appropriate evaluation can improve the diagnosis of rare diseases., (© 2024. The Author(s).)

This study aimed to elucidate mid- to long-term radiological and respiratory outcomes in patients aged 7-11 years at index surgery with Marfan syndrome and early-onset scoliosis (EOS) in a retrospective multicenter study. Primary outcomes were final thoracic height and final percentage of predicted vital capacity (%VC) at or after 16 years of age. We identified 21 (6 male and 15 female) patients with a mean age of 9.9 years and mean follow-up period of 149.3 months. Fifteen patients underwent primary fusion, whereas six underwent growth-friendly surgery (GFS). The mean preoperative and final T1-T12 heights were 204.0 mm and 248.0 mm, respectively. Final pulmonary function tests were available for 16 patients, and the mean final %VC was 54.0% with 10 patients exhibiting a final %VC < 60%. A significant moderate association was observed between the final T1-T12 height and final %VC. The predicted final T1-T12 height required for a final %VC of 60% was approximately 260 mm. Although most older patients with Marfan syndrome and EOS acquired a considerably large final T1-T12 height, a larger thoracic height was required for satisfactory respiratory function in many cases; hence, GFS may be indicated even in this population., (© 2024. The Author(s).)

Human skin samples for microbiome analysis are traditionally collected using a non-invasive swabbing method. Here, we compared the differences in bacterial community structures on scalp hair and scalps with samples collected using non-invasive swabbing and cutting/removal of scalp hair in 12 individuals. Hair-related samples, such as hair shafts and hair swabs, had significantly higher alpha diversity than scalp swab samples, whereas there were no significant differences between hair shafts and hair swabs. The relative abundances of the three major phyla and five major operational taxonomic units were not significantly different between the hair shaft and hair swab samples. The principal coordinate analysis plots based on weighted UniFrac distances were grouped into two clusters: samples from hair-related areas and scalp swabs, and there were significant differences only between samples from hair-related areas and scalp swabs. In addition, a weighted UniFrac analysis revealed that the sampling site-based category was a statistical category but not a hair sampling method-based category. These results suggest that scalp hair bacteria collected using non-invasive swab sampling were comparable to those collected cutting/removal of scalp hair., (© 2024. The Author(s).)

Spinal deformities, including adolescent idiopathic scoliosis (AIS) and adult spinal deformity (ASD), affect many patients. The measurement of the Cobb angle on coronal radiographs is essential for their diagnosis and treatment planning. To enhance the precision of Cobb angle measurements for both AIS and ASD, we developed three distinct artificial intelligence (AI) algorithms: AIS/ASD-trained AI (trained with both AIS and ASD cases); AIS-trained AI (trained solely on AIS cases); ASD-trained AI (trained solely on ASD cases). We used 1612 whole-spine radiographs, including 1029 AIS and 583 ASD cases with variable postures, as teaching data. We measured the major and two minor curves. To assess the accuracy, we used 285 radiographs (159 AIS and 126 ASD) as a test set and calculated the mean absolute error (MAE) and intraclass correlation coefficient (ICC) between each AI algorithm and the average of manual measurements by four spine experts. The AIS/ASD-trained AI showed the highest accuracy among the three AI algorithms. This result suggested that learning across multiple diseases rather than disease-specific training may be an efficient AI learning method. The presented AI algorithm has the potential to reduce errors in Cobb angle measurements and improve the quality of clinical practice., (© 2024. The Author(s).)

In recent decades, the field of moral psychology has focused on moral judgments based on some moral foundations/categories (e.g., harm/care, fairness/reciprocity, ingroup/loyalty, authority/respect, and purity/sanctity). When discussing the moral categories, however, whether a person judges moral compliance or moral violation has been rarely considered. We examined the extent to which moral judgments are influenced by each other across moral categories and explored whether the framework of judgments for moral violation and compliance would be different. For this purpose, we developed the episodes set for moral and affective behaviors. For each episode, participants evaluated valence, arousal, morality, and the degree of relevance to each of the Haidt's 5 moral foundations. The cluster analysis showed that the moral compliance episodes were divided into three clusters, whereas the moral violation episodes were divided into two clusters. Also, the additional experiment indicated that the clusters might not be stable in time. These findings suggest that people have different framework of judgments for moral compliance and moral violation., (© 2024. The Author(s).)

Hypochlorous acid (HOCl) is an endogenous oxidant and chlorinating agent in mammals that is effective against a broad range of microorganisms. However, the effects of exogenous HOCl on biological processes have not been reported. In this study, the effects of highly purified slightly acidic hypochlorous acid water (HP-HAW) were investigated. After the safety of oral administration of HP-HAW was confirmed, the effects of HP-HAW on glucose homeostasis were assessed in mice. HP-HAW treatment significantly improved blood glucose levels in hyperglycemic condition. Based on the 16S rRNA sequencing, HP-HAW treatment significantly increased the diversity and changed the composition of gut microbiota by decreasing the abundance of genus Romboutsia in mice fed normal chow. In obese mice, HP-HAW administration tended to improve glucose tolerance. HP-HAW also attenuated memory impairments and changes N-methyl-d-aspartate (NMDA) receptor mRNA expression in obese mice. HP-HAW treatment suppressed Il-6 mRNA expression in the hippocampus in type 2 diabetic mice. Overall, these results support HP-HAW as a potential therapeutic agent to improve or prevent glucose tolerance and memory decline via gut microbiota alteration., (© 2024. The Author(s).)

In empirical art research, understanding how viewers judge visual artworks as beautiful is often explored through the study of attributes-specific inherent characteristics or artwork features such as color, complexity, and emotional expressiveness. These attributes form the basis for subjective evaluations, including the judgment of beauty. Building on this conceptual framework, our study examines the beauty judgments of 54 Western artworks made by native Japanese and German speakers, utilizing an extreme randomized trees model-a data-driven machine learning approach-to investigate cross-cultural differences in evaluation behavior. Our analysis of 17 attributes revealed that visual harmony, color variety, valence, and complexity significantly influenced beauty judgments across both cultural cohorts. Notably, preferences for complexity diverged significantly: while the native Japanese speakers found simpler artworks as more beautiful, the native German speakers evaluated more complex artworks as more beautiful. Further cultural distinctions were observed: for the native German speakers, emotional expressiveness was a significant factor, whereas for the native Japanese speakers, attributes such as brushwork, color world, and saturation were more impactful. Our findings illuminate the nuanced role that cultural context plays in shaping aesthetic judgments and demonstrate the utility of machine learning in unravelling these complex dynamics. This research not only advances our understanding of how beauty is judged in visual art-considering self-evaluated attributes-across different cultures but also underscores the potential of machine learning to enhance our comprehension of the aesthetic evaluation of visual artworks., (© 2024. The Author(s).)

Benralizumab, a monoclonal antibody targeting IL-5 receptors, reduces exacerbations and oral corticosteroid requirements for severe, uncontrolled eosinophilic asthma. In Japan, geographic disparities in asthma outcomes suggest differential prescribing and access. This study aimed to quantify regional prescribing variations for benralizumab nationwide. Using Japan's National Database (NDB) of insurance claims (2009-2019), benralizumab standardized claim ratios (SCRs) were calculated for 47 prefectures. Correlations between SCRs and other biologics' SCRs, economic variables like average income, and physician densities were evaluated through univariate analysis and multivariate regressions. Income-related barriers to optimal prescribing were examined. Wide variation emerged in benralizumab SCRs, from 40.1 to 184.2 across prefectures. SCRs strongly correlated with omalizumab (r = 0.61, p < 0.00001) and mepolizumab (r = 0.43, p = 0.0024). Average monthly income also positively correlated with benralizumab SCRs (r = 0.45, p = 0.0016), whereas lifestyle factors were insignificant. Respiratory specialist density modestly correlated with SCRs (r = 0.29, p = 0.047). In multivariate regressions, average income remained the most robust predictor (B = 0.74, p = 0.022). Benralizumab SCRs strongly associate with income metrics more than healthcare infrastructure/population factors. Many regions show low SCRs, constituting apparent prescribing gaps. Access barriers for advanced asthma therapies remain inequitable among Japan's income strata. Addressing affordability alongside specialist allocation can achieve better prescribing quality and asthma outcomes., (© 2024. The Author(s).)

In this study, we present the development of a fine structural human phantom designed specifically for applications in dentistry. This research focused on assessing the viability of applying medical computer vision techniques to the task of segmenting individual teeth within a phantom. Using a virtual cone-beam computed tomography (CBCT) system, we generated over 170,000 training datasets. These datasets were produced by varying the elemental densities and tooth sizes within the human phantom, as well as varying the X-ray spectrum, noise intensity, and projection cutoff intensity in the virtual CBCT system. The deep-learning (DL) based tooth segmentation model was trained using the generated datasets. The results demonstrate an agreement with manual contouring when applied to clinical CBCT data. Specifically, the Dice similarity coefficient exceeded 0.87, indicating the robust performance of the developed segmentation model even when virtual imaging was used. The present results show the practical utility of virtual imaging techniques in dentistry and highlight the potential of medical computer vision for enhancing precision and efficiency in dental imaging processes., (© 2024. The Author(s).)

Adolescent idiopathic scoliosis (AIS) affects approximately 3% of the global population. Recent studies have drawn attention to abnormalities in the dynamics of the CSF as potential contributors. This research aims to employ the Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRI to assess and analyze cerebrospinal fluid (CSF) dynamics in AIS patients. 101 AIS patients underwent Time-SLIP MRI. Images were taken at the mid-cervical and craniocervical junction regions. The sum of the maximum movement distances of CSF on the ventral and dorsal sides of the spinal canal within a single timeframe was defined and measured as Travel Distance (TD). Correlations between TD, age, Cobb angle, and Risser grade were analyzed. TD comparisons were made across Lenke classifications. TD for all patients was a weak correlation with the Cobb angle (r = - 0.16). Comparing TD between Lenke type 1 and 5, type 5 patients display significantly shorter TD (p < 0.05). In Risser5 patients with Lenke type 5 showed a significant negative correlation between Cobb angle and TD (r = - 0.44). Lenke type 5 patients had significantly shorter CSF TD compared to type1, correlating with worsening Cobb angles. Further analysis and exploration are required to understand the mechanism of onset and progression., (© 2024. The Author(s).)

The study aimed to examine the association of expanded adverse childhood experiences (ACEs) with psychological distress in adulthood. The data from nation-wide online cohort was used for analysis. Community dwelling adults in Japan were included. The ACEs was assessed by 15 items of ACE-J, including childhood poverty and school bullying. Severe psychological distress was determined as the score of Kessler 6 over 13. Multivariable logistic regression analysis was conducted, by using sample weighting. A total of 28,617 participants were analyzed. About 75% of Japanese people had one or more ACEs. The prevalence of those with ACEs over 4 was 14.7%. Those with ACEs over 4 showed adjusted odds ratio = 8.18 [95% CI 7.14-9.38] for severe psychological distress. The prevalence of childhood poverty was 29% for 50-64 year old participants and 40% of 65 or older participants. The impact of childhood poverty on psychological distress was less than other ACEs in these age cohorts. Bullying was experienced 21-27% in young generations, but 10% in 65 or older participants. However, the impact on psychological distress in adulthood was relatively high in all age groups. ACEs have impacted mental health for a long time. Future research and practice to reduce ACEs are encouraged., (© 2024. The Author(s).)

Non-alcoholic steatohepatitis (NASH), caused by fat buildup, can lead to liver inflammation and damage. Elucidation of the spatial distribution of fibrotic tissue in the fatty liver in NASH can be immensely useful to understand its pathogenesis. Thus, we developed a novel serial section-3D (SS3D) technique that combines high-resolution image acquisition with 3D construction software, which enabled highly detailed analysis of the mouse liver and extraction and quantification of stained tissues. Moreover, we studied the underexplored mechanism of fibrosis progression in the fatty liver in NASH by subjecting the mice to a high-fat diet (HFD), followed by lipopolysaccharide (LPS) administration. The HFD/LPS (+) group showed extensive fibrosis compared with control; additionally, the area of these fibrotic regions in the HFD/LPS (+) group was almost double that of control using our SS3D technique. LPS administration led to an increase in Tnfα and Il1β mRNA expression and the number of macrophages in the liver. On the other hand, transforming growth factor-β1 (Tgfβ1) mRNA increased in HFD group compared to that of control group without LPS-administration. In addition, COL1A1 levels increased in hepatic stellate cell (HSC)-like XL-2 cells when treated with recombinant TGF-β1, which attenuated with recombinant latency-associated protein (rLAP). This attenuation was rescued with LPS-activated macrophages. Therefore, we demonstrated that fatty liver produced "latent-form" of TGF-β1, which activated by macrophages via inflammatory cytokines such as TNFα and IL1β, resulting in activation of HSCs leading to the production of COL1A1. Moreover, we established the effectiveness of our SS3D technique in creating 3D images of fibrotic tissue, which can be used to study other diseases as well., (© 2024. The Author(s).)

Lumbar spinal alignment is crucial for spine biomechanics and is linked to various spinal pathologies. However, limited research has explored gender-specific differences using CT scans. The objective was to evaluate and compare lumbar spinal alignment between standing and sitting CT in healthy individuals, focusing on gender differences. 24 young and 25 elderly males (M) and females (F) underwent standing and sitting CT scans to assess lumbar spinal alignment. Parameters measured and compared between genders included lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), lordotic angle (LA), foraminal height (FH), and bony boundary area (BBA). Females showed significantly larger changes in SS and PT when transitioning from standing to sitting (p = .044, p = .038). A notable gender difference was also observed in the L4-S LA among the elderly, with females showing a significantly larger decrease in lordotic angle compared to males (- 14.1° vs. - 9.2°, p = .039*). Females consistently exhibited larger FH and BBA values, particularly in lower lumbar segments, which was more prominent in the elderly group (M vs. F: L4/5 BBA 80.1 mm 2 [46.3, 97.8] vs. 109.7 mm 2 [74.4, 121.3], p = .019 in sitting). These findings underline distinct gender-related variations in lumbar alignment and flexibility, with a focus on noteworthy changes in BBA and FH in females. Gender differences in lumbar spinal alignment were evident, with females displaying greater pelvic and sacral mobility. Considering gender-specific characteristics is crucial for assessing spinal alignment and understanding spinal pathologies. These findings contribute to our understanding of lumbar spinal alignment and have implications for gender-specific spinal conditions and treatments., (© 2024. The Author(s).)

The MYO7A gene is known to be responsible for both syndromic hearing loss (Usher syndrome type1B:USH1B) and non-syndromic hearing loss including autosomal dominant and autosomal recessive inheritance (DFNA11, DFNB2). However, the prevalence and detailed clinical features of MYO7A-associated hearing loss across a large population remain unclear. In this study, we conducted next-generation sequencing analysis for a large cohort of 10,042 Japanese hearing loss patients. As a result, 137 patients were identified with MYO7A-associated hearing loss so that the prevalence among Japanese hearing loss patients was 1.36%. We identified 70 disease-causing candidate variants in this study, with 36 of them being novel variants. All variants identified in autosomal dominant cases were missense or in-frame deletion variants. Among the autosomal recessive cases, all patients had at least one missense variant. On the other hand, in patients with Usher syndrome, almost half of the patients carried biallelic null variants (nonsense, splicing, and frameshift variants). Most of the autosomal dominant cases showed late-onset progressive hearing loss. On the other hand, cases with autosomal recessive inheritance or Usher syndrome showed congenital or early-onset hearing loss. The visual symptoms in the Usher syndrome cases developed between age 5-15, and the condition was diagnosed at about 6-15 years of age., (© 2024. The Author(s).)

DNA analysis of large herbivore feces samples collected from seagrass beds at two distant sites (Irabu Island in Miyako Islands and Kushi in Okinawa Island) in the Ryukyu Islands proved that some of these feces were from dugongs, which had been treated in recent studies as extinct in this region since the last stranding of a deceased individual in 2019. In addition, local knowledge of sightings of animals thought to be dugongs and confirmed cases of dugong feeding trails since 2010 were compiled to estimate its recent distribution. This is the first scientific report on the presence of this mammal in the Ryukyu Islands within the last four years, and particularly in the Miyako Islands within the last half-century. As the Ryukyu Islands are known to be the northern limit of the dugong's fragmented distribution in East Asia, conservation efforts are therefore needed., (© 2024. The Author(s).)

We investigate the vibrational and magnetic properties of thin layers of chromium tribromide (CrBr 3 ) with a thickness ranging from three to twenty layers (3-20 L) revealed by the Raman scattering (RS) technique. Systematic dependence of the RS process efficiency on the energy of the laser excitation is explored for four different excitation energies: 1.96 eV, 2.21 eV, 2.41 eV, and 3.06 eV. Our characterization demonstrates that for 12 L CrBr 3 , 3.06 eV excitation could be considered resonant with interband electronic transitions due to the enhanced intensity of the Raman-active scattering resonances and the qualitative change in the Raman spectra. Polarization-resolved RS measurements for 12 L CrBr 3 and first-principles calculations allow us to identify five observable phonon modes characterized by distinct symmetries, classified as the A g and E g modes. The evolution of phonon modes with temperature for a 16 L CrBr 3 encapsulated in hexagonal boron nitride flakes demonstrates alterations of phonon energies and/or linewidths of resonances indicative of a transition between the paramagnetic and ferromagnetic state at Curie temperature ( T C ≈ 50  K). The exploration of the effects of thickness on the phonon energies demonstrated small variations pronounces exclusively for the thinnest layers in the vicinity of 3-5 L. We propose that this observation can be due to the strong localization in the real space of interband electronic excitations, limiting the effects of confinement for resonantly excited Raman modes to atomically thin layers., (© 2024. The Author(s).)

This retrospective cohort study established malnutrition's impact on mortality and neurological recovery of older patients with cervical spinal cord injury (SCI). It included patients aged ≥ 65 years with traumatic cervical SCI treated conservatively or surgically. The Geriatric Nutritional Risk Index was calculated to assess nutritional-related risk. Overall, 789 patients (mean follow-up: 20.1 months) were examined and 47 had major nutritional-related risks on admission. One-year mortality rate, median survival time, neurological recovery, and activities of daily living (ADL) at 1 year post-injury were compared between patients with major nutrition-related risk and matched controls selected using 1:2 propensity score matching to adjust for age, pre-traumatic neurological impairment, and activity. In the Kaplan-Meier analysis, the median survival times were 44.9 and 76.5 months for patients with major nutrition-related risk and matched controls, respectively (p = 0.015). Matched controls had more individuals with a neurological improvement of American Spinal Injury Association Impairment Scale ≥ 1 grade (p = 0.039) and independence in ADL at 1 year post-injury than patients with major nutrition-related risk (p < 0.05). In conclusion, 6% of older patients with cervical SCI had major nutrition-related risks; they showed a significantly higher 1 year mortality rate, shorter survival time, poorer neurological improvement, and lower ADL at 1 year post-injury than matched controls., (© 2024. The Author(s).)

Vertical stacking of different two-dimensional (2D) materials into van der Waals heterostructures exploits the properties of individual materials as well as their interlayer coupling, thereby exhibiting unique electrical and optical properties. Here, we study and investigate a system consisting entirely of different 2D materials for the implementation of electronic devices that are based on quantum mechanical band-to-band tunneling transport such as tunnel diodes and tunnel field-effect transistors. We fabricated and characterized van der Waals heterojunctions based on semiconducting layers of WSe 2 and MoS 2 by employing different gate configurations to analyze the transport properties of the junction. We found that the device dielectric environment is crucial for achieving tunneling transport across the heterojunction by replacing thick oxide dielectrics with thin layers of hexagonal-boronnitride. With the help of additional top gates implemented in different regions of our heterojunction device, it was seen that the tunneling properties as well as the Schottky barriers at the contact interfaces could be tuned efficiently by using layers of graphene as an intermediate contact material., (© 2024. The Author(s).)

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation., (© 2024. The Author(s).)

Interpersonal space (IPS) refers to the area surrounding the body in which we engage in social interactions while maintaining our comfort. Numerous previous studies have reported the psychological and physiological changes associated with the proximity of two people engaged in face-to-face interaction. Currently, there is limited knowledge about how the relative position between two socially intimate individuals affects their psychological and physiological states. This research measured the subjective discomfort and electrocardiographic responses of participants when standing static at various relative positions. The highest discomfort, lowest heart rate, and highest heart rate variability (HRV; parasympathetic activity index) were observed when the friend stood in the face-to-face position. Interestingly, heart rate also decreased when the friend stood on the right side, although HRV did not change. We interpreted the results as suggesting that the presence of a familiar person elicits the electrocardiographic responses associated with an increase in parasympathetic activity., (© 2024. The Author(s).)

Helicobacter pylori (H. pylori) infection is a cause of gastric disorders and is treated mainly by pharmacotherapy with antimicrobial agents. An association has been reported between dental caries and H. pylori infection. As antimicrobial agents are less effective inside dental caries because of impaired blood circulation, the presence of untreated dental caries (decayed teeth) may influence the success of H. pylori eradication treatment. In this cross-sectional study, we examined whether failed eradication of H. pylori was associated with decayed teeth in Japanese adults. Enrolled were 226 participants who received dental checkups among those treated for eradication of H. pylori at Asahi University Hospital between April 2019 and March 2021. Treatment efficacy was assessed by urea breath test. Eradication failed in 38 participants (17%), decayed teeth in 32 participants (14%), and number of 0.34 teeth per participants. Multivariate logistic regression analyses showed that failed eradication of H. pylori was associated with decayed teeth (presence: odds ratio, 2.672; 95% confidence interval, 1.093-6.531) after adjusting for gender, age, and brushing frequency. These results indicate that failed eradication of H. pylori was associated with decayed teeth and suggest that untreated dental caries may impact treatment for eradication of H. pylori., (© 2024. The Author(s).)

In onion thrips Thrips tabaci, reduced sensitivity of the sodium channel caused by several sodium channel mutations have been correlated with pyrethroid resistance. For this study, using mitochondrial cytochrome c oxidase subunit I gene sequences, we examined the phylogenetic relation among a total of 52 thelytokous and arrhenotokous strains with different genotypes of the sodium channel mutations. Then, we used flow cytometry to estimate their ploidy. Results showed that the strains are divisible into three groups: diploid thelytoky, triploid thelytoky, and diploid arrhenotoky. Using 23 whole genome resequencing data obtained from 20 strains out of 52, we examined their genetic relation further using principal component analysis, admixture analysis, and a fixation index. Results showed that diploid and triploid thelytokous groups are further classifiable into two based on the sodium channel mutations harbored by the respective group members (strains). The greatest genetic divergence was observed between thelytokous and arrhenotokous groups with a pair of T929I and K1774N. Nevertheless, they shared a genomic region with virtually no polymorphism around the sodium channel gene loci, suggesting a hard selective sweep. Based on these findings, we discuss the evolutionary origin and distribution of the sodium channel mutations in T. tabaci., (© 2024. The Author(s).)

This study aimed to investigate the feasibility of utilizing noninvasive ocular blood flow measurements as potential indicators of systemic circulation in rabbits experiencing hemorrhagic shock. Using Laser speckle flowgraphy, ocular blood flow indices, relative flow volume (RFV), and mean blur rate in the choroidal area (MBR-CH) were assessed in New Zealand White rabbits (n = 10) subjected to controlled blood removal and return. Hemodynamic parameters and biochemical markers were monitored alongside ocular circulation during blood removal and return phases. Additionally, correlations between ocular parameters and systemic indices were examined. The results indicated that RFV and MBR-CH exhibited significant correlations with renal and intestinal blood flows, with stronger correlations observed during blood removal. Additionally, ocular blood flow changes closely mirrored systemic dynamics, suggesting their potential as real-time indicators of shock progression and recovery. These findings indicate that ocular blood flow measurements may serve as real-time indicators of the systemic circulation status during hemorrhagic shock, offering potential insights into shock management and guiding tailored interventions. Thus, noninvasive ocular blood flow evaluation holds promise as an innovative tool for assessing systemic circulation dynamics during hemorrhagic shock., (© 2024. The Author(s).)

Temperature perception is essential for humans to discern the environment and maintain homeostasis. However, some individuals experience cold hypersensitivity, characterized by a subjective feeling of coldness despite ambient environmental temperatures being normal, the underlying mechanisms of which are unknown. In this study, we aimed to investigate the relationship between subjective cold symptoms and somatic burden or single nucleotide polymorphisms to understand the causes of cold hypersensitivity. We conducted an online questionnaire survey [comprising 30 questions, including past medical history, subjective symptoms of cold hypersensitivity, and the Somatic Symptom Scale-8 (SSS-8)]. Respondents were 1200 Japanese adult female volunteers (age: 20-59 years), recruited between April 21 and May 25, 2022, who were customers of MYCODE, a personal genome service in Japan. Among the 1111 participants, 599 (54%) reported cold hypersensitivity. Higher cold hypersensitivity severity was positively associated with the SSS-8 scores. Additionally, a genome-wide association study for cold hypersensitivity was conducted using array-based genomic data obtained from genetic testing. We identified 11 lead variants showing suggestive associations (P < 1 × 10 -5 ) with cold hypersensitivity, some of which showed a reasonable change in expression in specific tissues in the Genotype-Tissue Expression database. The study findings shed light on the underlying causes of cold hypersensitivity., (© 2024. The Author(s).)

Predicting the transition of kidney function in chronic kidney disease is difficult as specific symptoms are lacking and often overlooked, and progress occurs due to complicating factors. In this study, we applied time-series cluster analysis and a light gradient boosting machine to predict the trajectories of kidney function in non-dialysis dependent chronic kidney disease patients with baseline estimated glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m 2 . Based on 5-year changes in estimated GFR, participants were stratified into groups with similar trajectories by cluster analysis. Next, we applied the light gradient boosting machine algorithm and Shapley addictive explanation to develop a prediction model for clusters and identify important parameters for prediction. Data from 780 participants were available for analysis. Participants were classified into five classes (Class 1: n = 78, mean [± standard deviation] estimated GFR 100 ± 19.3 mL/min/1.73 m 2 ; Class 2: n = 176, 76.0 ± 9.3 mL/min/1.73 m 2 ; Class 3: n = 191, 59.8 ± 5.9 mL/min/1.73 m 2 ; Class 4: n = 261, 52.7 ± 4.6 mL/min/1.73 m 2 ; and Class 5: n = 74, 53.5 ± 12.0 mL/min/1.73 m 2 ). Declines in estimated GFR were 8.9% in Class 1, 12.2% in Class 2, 4.9% in Class 3, 12.0% in Class 4, and 45.1% in Class 5 during the 5-year period. The accuracy of prediction was 0.675, and the top three most important Shapley addictive explanation values were 1.61 for baseline estimated GFR, 0.12 for hemoglobin, and 0.11 for body mass index. The estimated GFR transition of patients with preserved chronic kidney disease mostly depended on baseline estimated GFR, and the borderline for estimated GFR trajectory was nearly 50 mL/min/1.73 m 2 ., (© 2024. The Author(s).)

Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a 7-month-old female patient with severe intellectual disability, epilepsy, and low levels of serum copper and ceruloplasmin. While heterozygous deletion of exons 16 and 17 of the ATP7A gene was detected in the proband, her mother, and her grandmother, only the proband suffered from Menkes disease clinically. Intriguingly, X chromosome inactivation (XCI) analysis demonstrated that the grandmother and the mother showed skewing of XCI toward the allele with the ATP7A deletion and that the proband had extremely skewed XCI toward the normal allele, resulting in exclusive expression of the pathogenic ATP7A mRNA transcripts. Expression bias analysis and recombination mapping of the X chromosome by the combination of whole genome and RNA sequencing demonstrated that meiotic recombination occurred at Xp21-p22 and Xq26-q28. Assuming that a genetic factor on the X chromosome enhanced or suppressed XCI of its allele, the factor must be on either of the two distal regions derived from her grandfather. Although we were unable to fully uncover the molecular mechanism, we concluded that unfavorable switching of skewed XCI caused Menkes disease in the proband., (© 2024. The Author(s).)

The coronavirus disease 2019 (COVID-19) pandemic had severe impact on the outcome of out-of-hospital cardiac arrest (OHCA) patients and the possibility of bystander cardiopulmonary resuscitation (CPR). Previous studies focused only on the short periods of the pandemic and reported a significant increase in the number of infections. In a retrospective cohort study we aimed to compare the outcomes of OHCA patients 1 year before and 1 year after the onset of COVID-19. Data of 519 OHCA patients during the pre-pandemic (January-December 2019; 262 patients) and intra-pandemic (April 2020-March 2021; 257 patients) periods in Yokohama Municipal Hospital, Japan were collected and analysed retrospectively. The study outcomes were the return of spontaneous circulation (ROSC), admission to hospital, survival to discharge, and cerebral performance category at discharge. The intra-pandemic period was associated with decreased bystander CPR (P = 0.004), prolonged transport time (P < 0.001), delayed first adrenaline administration (P < 0.001), and decrease in ROSC (P = 0.023). Logistic regression analysis revealed that the following factors were significantly associated with ROSC: "pandemic", "shockable initial waveform", and "witness presence"., (© 2023. The Author(s).)

Serum heme oxygenase (HO)-1 level has been reported as a clinically reliable diagnostic biomarker for acute exacerbation of interstitial lung disease (ILD); however, its utility for predicting mortality among these patients is unclear. Serum HO-1 levels of patients newly diagnosed with acute exacerbation of ILD were measured at the time of initiating steroid pulse therapy. The relationship between serum HO-1 and various other serum biomarkers, change in HRCT findings, and disease prognosis at 12 weeks after diagnosis of acute exacerbation was evaluated in 51 patients, of whom 17 (33%) had idiopathic pulmonary fibrosis (IPF). Serum HO-1 was higher in patients with acute exacerbation of IPF than in patients with acute exacerbation of other ILDs. Serum HO-1 levels were higher in patients who died within these 12 weeks than in survivors. Among age, sex, comorbidities, IPF diagnosis, HRCT findings, and blood biomarkers, serum HO-1 was a primary predictor of 12-week mortality. In 41 patients who underwent repeat HRCT, serum HO-1 was higher in patients with honeycomb progression than in those without. Serum HO-1 measurement could be useful for evaluating disease mortality and morbidity of patients with acute exacerbation of ILDs., (© 2023. The Author(s).)

Escherichia coli harboring polyketide synthase (pks + E. coli) has been suggested to contribute to colorectal cancer development. Physical activity is strongly associated with lower colorectal cancer risks, but its effects on pks + E. coli remain unclear. The aim of this study was to investigate the association between pks + E. coli prevalence and physical activity. A cross-sectional study was conducted on 222 Japanese adults (27-79-years-old, 73.9% female). Triaxial accelerometers were used to measure light-intensity physical activity, moderate-to-vigorous intensity physical activity, the physical activity level, step-count, and time spent inactive. Fecal samples collected from participants were used to determine the prevalence of pks + E. coli. Multivariate logistic regression analysis and restricted cubic spline curves were used to examine the association between pks + E. coli prevalence and physical activity. The prevalence of pks + E. coli was 26.6% (59/222 participants). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the highest tertile with reference to the lowest tertile of physical activity variables were as follows: light-intensity physical activity (OR 0.63; 95% CI 0.26-1.5), moderate-to-vigorous intensity physical activity (OR 0.85; 95% CI 0.39-1.87), physical activity level (OR 0.69; 95% CI 0.32-1.51), step-count (OR 0.92; 95% CI 0.42-2.00) and time spent inactive (OR 1.30; 95% CI 0.58-2.93). No significant dose-response relationship was found between all physical activity variables and pks + E. coli prevalence. Our findings did not suggest that physical activity has beneficial effects on the prevalence of pks + E. coli. Longitudinal studies targeting a large population are needed to clarify this association., (© 2023. The Author(s).)

Machine learning tools have demonstrated viability in visualizing pain accurately using vital sign data; however, it remains uncertain whether incorporating individual patient baselines could enhance accuracy. This study aimed to investigate improving the accuracy by incorporating deviations from baseline patient vital signs and the concurrence of the predicted artificial intelligence values with the probability of critical care pain observation tool (CPOT) ≥ 3 after fentanyl administration. The study included adult patients in intensive care who underwent multiple pain-related assessments. We employed a random forest model, utilizing arterial pressure, heart rate, respiratory rate, gender, age, and Richmond Agitation-Sedation Scale score as explanatory variables. Pain was measured as the probability of CPOT scores of ≥ 3, and subsequently adjusted based on each patient's baseline. The study included 10,299 patients with 117,190 CPOT assessments. Of these, 3.3% had CPOT scores of ≥ 3. The random forest model demonstrated strong accuracy with an area under the receiver operating characteristic curve of 0.903. Patients treated with fentanyl were grouped based on CPOT score improvement. Those with ≥ 1-h of improvement after fentanyl administration had a significantly lower pain index (P = 0.020). Therefore, incorporating deviations from baseline patient vital signs improved the accuracy of pain visualization using machine learning techniques., (© 2023. Springer Nature Limited.)

Although time-stretch spectroscopy is an emerging ultrafast spectroscopic technique, the applications in industrial fields have been limited due to the low output power caused by undesirable nonlinear effects occurred in a long optical fiber used for pulse chirping. Here, we developed a high-power time-stretch near infrared (NIR) spectrometer utilizing arrayed waveguide gratings (AWGs). The combination of AWGs and short optical fibers allowed large amounts of chromatic dispersion to be applied to broadband supercontinuum pulses without the power limitation imposed by employing the long optical fiber. With the proposed configuration, we achieved chirped pulses with the output power of 60 mW in the 900-1300 nm wavelength region, which is about 10 times higher than conventional time-stretch spectrometers using long optical fibers. With the developed spectrometer, the NIR absorption spectra of a standard material and liquid samples were observed with high accuracy and precision within sub-millisecond measurement time even with four orders of magnitude optical attenuation by a neutral density filter. We also confirmed the quantitative spectral analysis capability of the developed spectrometer for highly scattering samples of an oil emulsion. The qualitative comparison of the measurement precision between the developed spectrometer and the previous time-stretch spectrometer was also conducted., (© 2023. Springer Nature Limited.)

Chronic subdural hematoma (CSDH) often causes neurological deterioration and is treated with hematoma evacuation. This study aimed to assess the feasibility of various machine learning models to preoperatively predict the functional outcome of patients with CSDH. Data were retrospectively collected from patients who underwent CSDH surgery at two institutions: one for internal validation and the other for external validation. The poor functional outcome was defined as a modified Rankin scale score of 3-6 upon hospital discharge. The unfavorable outcome was predicted using four machine learning algorithms on an internal held-out cohort (n = 188): logistic regression, support vector machine (SVM), random forest, and light gradient boosting machine. The prediction performance of these models was also validated in an external cohort (n = 99). The area under the curve of the receiver operating characteristic curve (ROC-AUC) of each machine learning-based model was found to be high in both validations (internal: 0.906-0.925, external: 0.833-0.860). In external validation, the SVM model demonstrated the highest ROC-AUC of 0.860 and accuracy of 0.919. This study revealed the potential of machine learning algorithms in predicting unfavorable outcomes at discharge among patients with CSDH undergoing burr hole surgery., (© 2023. Springer Nature Limited.)

Bacterial aggregation by mixing with polymers is applied as pretreatment to identify pathogens in patients with infectious diseases. However, the detailed interaction between polymers and bacteria has yet to be fully understood. Here, we investigate the interaction between polyallylamine and Escherichia coli by isothermal titration calorimetry. Aggregation was observed at pH 10 and the binding was driven by favorable enthalpic gain such as the electrostatic interaction. Neither aggregation nor the apparent heat of binding was observed at pH 4.0, despite the strong positive charge of polyallylamine. These results suggest that intermolecular repulsive forces of the abundant positive charge of polyallylamine cause an increased loss of conformational entropy by binding. Non-electrostatic interaction plays a critical role for aggregation., (© 2023. Springer Nature Limited.)

This study proposes a convolutional neural network method for automatic vertebrae detection and Cobb angle (CA) measurement on X-ray images for scoliosis. 1021 full-length X-ray images of the whole spine of patients with adolescent idiopathic scoliosis (AIS) were used for training and segmentation. The proposed AI algorithm's results were compared with those of the manual method by six doctors using the intraclass correlation coefficient (ICC). The ICCs recorded by six doctors and AI were excellent or good, with a value of 0.973 for the major curve in the standing position. The mean error between AI and doctors was not affected by the angle size, with AI tending to measure 1.7°-2.2° smaller than that measured by the doctors. The proposed method showed a high correlation with the doctors' measurements, regardless of the CA size, doctors' experience, and patient posture. The proposed method showed excellent reliability, indicating that it is a promising automated method for measuring CA in patients with AIS., (© 2023. Springer Nature Limited.)

Although altered networks inside the hippocampus (hippocampal intra-networks) have been observed in dementia, the evaluation of hippocampal intra-networks using magnetic resonance imaging (MRI) is challenging. We employed conventional structural imaging and incident component analysis (ICA) to investigate the structural covariance of the hippocampal intra-networks. We aimed to assess altered hippocampal intra-networks in patients with mild cognitive impairment (MCI). A cross-sectional study of 2122 participants with 3T MRI (median age 69 years, 60.9% female) were divided into 218 patients with MCI and 1904 cognitively normal older adults (CNOA). By employing 3D T1-weighted imaging, voxels within the hippocampus were entered into the ICA analysis to extract the structural covariance intra-networks within the hippocampus. The ICA extracted 16 intra-networks from the hippocampal structural images, which were divided into two bilateral networks and 14 ipsilateral networks. Of the 16 intra-networks, two (one bilateral network and one ipsilateral networks) were significant predictors of MCI from the CNOA after adjusting for age, sex, education, disease history, and hippocampal volume/total intracranial volume ratio. In conclusion, we found that the relationship between hippocampal intra-networks and MCI was independent from the hippocampal volume. Our results suggest that altered hippocampal intra-networks may reflect a different pathology in MCI from that of brain atrophy., (© 2023. Springer Nature Limited.)

Single-cell-specific delivery of small RNAs, such as short hairpin RNA (shRNA) and small noncoding RNAs, allows us to elucidate the roles of specific upregulation of RNA expression and RNAi-mediated gene suppression in early embryo development. The photoinduced cytosolic dispersion of RNA (PCDR) method that we previously reported can introduce small RNAs into the cytosol of photoirradiated cells and enable RNA delivery into a single-cell in a spatiotemporally specific manner. However, the PCDR method has only been applied to planer cultured cells and not to embryos. This study demonstrated that the PCDR method can be utilized for photo-dependent cytosolic shRNA delivery into a single blastomere and for single blastomere-specific RNA interference in mouse embryos. Our results indicate that PCDR is a promising approach for studying the developmental process of early embryogenesis., (© 2023. Springer Nature Limited.)

Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously reported that a recombinant peptide (RCP) enhances subcutaneous islet engraftment. However, it is impractical for clinical use because RCP must be removed when transplanting islets. We herein investigated whether a novel bioabsorbable gelatin hydrogel nonwoven fabric (GHNF) could improve subcutaneous islet engraftment. A silicon spacer with or without GHNF was implanted into the subcutaneous space of diabetic mice. Syngeneic islets were transplanted into the pretreated space or intraportally (Ipo group). Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, CT angiography and gene expression were evaluated. The cure rate and glucose tolerance of the GHNF group were significantly better than in the control and Ipo groups (p < 0.01, p < 0.05, respectively). In the GHNF group, a limited increase of vWF-positive vessels was detected in the islet capsule, whereas laminin (p < 0.05), collagen III and IV were considerably enhanced. TaqMan arrays revealed a significant upregulation of 19 target genes (including insulin-like growth factor-2) in the pretreated space. GHNF markedly improved the subcutaneous islet transplantation outcomes, likely due to ECM compensation and protection of islet function by various growth factors, rather than enhanced neovascularization., (© 2023. The Author(s).)

Organs-on-chips using cultured cells have been developed and applied for evaluating in vitro biological phenomena. We previously reported an openable artificial intestinal tract system, as an in vitro model of the small intestine, for in vitro drug screening. The intestinal tract device could be transformed using an integrated artificial muscle actuator. An initial flat state was suitable for cell culture, and the transformed tubular structure was used as a fluidic channel for perfusion tests. The previously developed intestinal tract system could be used to evaluate drug absorption by cells through perfusion testing. This study presents an improved artificial intestinal tract system for analysis of drug permeation, in addition to absorption. Permeable filters were integrated into the intestinal tract device. Integration of additional filters into the design of the existing artificial muscle actuator was accomplished by considering device performance and available filter locations. Filter permeability was evaluated by perfusion testing. MDCK-II cells were cultured on the device and visually and electrically evaluated. The openable device, equipped with new functions for further pharmacokinetic analysis, could perform and evaluate drug disposition using cultured cells. We anticipate that the improved, openable organ-on-a-chip device system will contribute to advances in in vitro drug screening technology., (© 2023. The Author(s).)

Non-synesthetes exhibit a tendency to associate specific shapes with particular colors (i.e., circle-red, triangle-yellow, and square-blue). Such color-shape associations (CSAs) could potentially affect the feature binding of colors and shapes, thus resulting in people reporting more binding errors in the case of incongruent, rather than congruent, colored-shape pairs. Individuals with autism spectrum disorder (ASD) exhibit atypical sensory processing and impaired multisensory integration. Here, we examined whether autistic traits (Autism-Spectrum Quotient; AQ) influence the strength of color-shape associations, as evidenced by the occurrence of binding errors in incongruent minus congruent conditions. Participants took part in an experiment designed to reveal binding errors induced by incongruent and congruent colored-shape pairs, and completed the Japanese version of the AQ score. The results revealed a significant correlation between AQ scores and occurrence of binding errors when participants were presented with the circle-red and triangle-yellow CSAs: That is, individuals with higher autistic traits tend to make more binding errors in incongruent minus congruent colored-shape pairs, indicating a stronger binding of circle-red and triangle-yellow associations. These results therefore suggest that autistic traits play a role in forming color-shape associations, shedding light on the nature of both color-shape associations and autistic perception., (© 2023. The Author(s).)

We present an ab initio calculation to understand electronic structures and optical properties of a tungsten carbide WC being a major component of a TiCN-based cermet. The TiCN-based cermet is widely used as a cutting tool, and is discarded as usual after use. On the other hand, cermet itself is also a famous ingredient of a solar absorption film. We found that the WC has a fairly low-energy plasma excitation [Formula: see text] 0.6 eV (2 [Formula: see text]m) and therefore can be a good constituent of a solar selective absorber. The evaluated figure of merit for photothermal conversion is prominently high compared to those of the other materials included in the TiCN-based cermet. The imaginary part of the dielectric function is considerably small around the zero point of the real part of the dielectric function, corresponding to the plasma excitation energy. Therefore, a clear plasma edge appeared, ensuring the high performance of the WC as the solar absorber. This is a fascinating aspect, because the wasted TiCN-based cermet cutting tool can be recycled as the solar absorption film after proper treatments and modifications., (© 2023. The Author(s).)

The increased incidence of obesity in the global population has increased the risk of several chronic inflammation-related diseases, including non-alcoholic steatohepatitis (NASH)-hepatocellular carcinoma (HCC). The progression from NASH to HCC involves a virus-independent liver carcinogenic mechanism; however, we currently lack effective treatment and prevention strategies. Several reports have suggested that fecal volatile organic compounds (VOCs) are strongly associated with NASH-HCC; therefore, we explored the biomarkers involved in its pathogenesis and progression. Fecal samples collected from control and NASH-HCC model STAM mice were subjected to headspace autosampler gas chromatography-electron ionization-mass spectrometry. Non-target profiling analysis identified diacetyl (2,3-butandione) as a fecal VOC that characterizes STAM mice. Although fecal diacetyl levels were correlated with the HCC in STAM mice, diacetyl is known as a cytotoxic/tissue-damaging compound rather than genotoxic or mutagenic; therefore, we examined the effect of bioactivity associated with NASH progression. We observed that diacetyl induced several pro-inflammatory molecules, including tumor necrosis factor-α, cyclooxygenase-2, monocyte chemoattractant protein-1, and transforming growth factor-β, in mouse macrophage RAW264.7 and Kupffer KPU5 cells. Additionally, we observed that diacetyl induced α-smooth muscle actin, one of the hallmarks of fibrosis, in an ex vivo cultured hepatic section, but not in in vitro hepatic stellate TWNT-1 cells. These results suggest that diacetyl would be a potential biomarker of fecal VOC in STAM mice, and its ability to trigger the macrophage-derived inflammation and fibrosis may partly contribute to NASH-HCC carcinogenesis., (© 2023. The Author(s).)

Deep ocean water (DOW) exerts positive effects on the growth of marine organisms, suggesting the presence of unknown component(s) that facilitate their aquaculture. We observed that DOW suppressed plasma cortisol (i.e., a stress marker) concentration in Japanese flounder (Paralichthys olivaceus) reared under high-density condition. RNA-sequencing analysis of flounder brains showed that when compared to surface seawater (SSW)-reared fish, DOW-reared fish had lower expression of hypothalamic (i.e., corticotropin-releasing hormone) and pituitary (i.e., proopiomelanocortin, including adrenocorticotropic hormone) hormone-encoding genes. Moreover, DOW-mediated regulation of gene expression was linked to decreased blood cortisol concentration in DOW-reared fish. Our results indicate that DOW activated osteoblasts in fish scales and facilitated the production of Calcitonin, a hypocalcemic hormone that acts as an analgesic. We then provide evidence that the Calcitonin produced is involved in the regulatory network of genes controlling cortisol secretion. In addition, the indole component kynurenine was identified as the component responsible for osteoblast activation in DOW. Furthermore, kynurenine increased plasma Calcitonin concentrations in flounders reared under high-density condition, while it decreased plasma cortisol concentration. Taken together, we propose that kynurenine in DOW exerts a cortisol-reducing effect in flounders by facilitating Calcitonin production by osteoblasts in the scales., (© 2023. The Author(s).)

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients., (© 2023. The Author(s).)