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Abstract To advance the development of high-strength polycrystalline metallic materials towards achieving carbon neutrality, it is essential to design materials in which the atomic level control of general grain boundaries (GGBs), which govern the material properties, is achieved. However, owing to the complex and diverse structures of GGBs, there have been no reports on interatomic potentials capable of reproducing them. This accuracy is essential for conducting molecular dynamics analyses to derive material design guidelines. In this study, we constructed a machine learning interatomic potential (MLIP) with density functional theory (DFT) accuracy to model the energy, atomic structure, and dynamics of arbitrary grain boundaries (GBs), including GGBs, in α-Fe. Specifically, we employed a training dataset comprising diverse atomic structures generated based on crystal space groups. The GGB accuracy was evaluated by directly comparing with DFT calculations performed on cells cut near GBs from nano-polycrystals, and extrapolation grades of the local atomic environment based on active learning methods for the entire nano-polycrystal. Furthermore, we analyzed the GB energy and atomic structure in α-Fe polycrystals through large-scale molecular dynamics analysis using the constructed MLIP. The average GB energy of α-Fe polycrystals calculated by the constructed MLIP is 1.57 J/m2, exhibiting good agreement with experimental predictions. Our findings demonstrate the methodology for constructing an MLIP capable of representing GGBs with high accuracy, thereby paving the way for materials design based on computational materials science for polycrystalline materials.

Arteriovenous malformation or arteriovenous hemangioma of the maxillary sinus is relatively rare. The coexistence of the 2 lesions in the maxillary sinus is extremely rare. Such lesions may cause severe epistaxis due to arterial bleeding. A 73-year-old woman visited our department for recurrent and severe epistaxis, and a blood transfusion (400 mL) was required owing to the decrease in hemoglobin level (8.0 g/dL). On magnetic resonance imaging, the mass expanding in the right maxillary sinus had mixed high signal intensity on T1 magnetic resonance imaging with heterogeneous enhancement. The angiography showed no dilatation or meandering of the blood vessels of the relevant region and any apparent bleeding sites were not detected. An endoscopic nasal surgery could remove the maxillary sinus mass without preoperative embolization. Pathological examination clarified the coexistence of arteriovenous malformation and arteriovenous hemangioma in the mass. She has never complained of epistaxis for 6 months after the surgery.

Abstract Sweat is an essential protection system for the body, but its failure can result in pathologic conditions, including several skin diseases, such as palmoplantar pustulosis (PPP). As reduced intraepidermal E-cadherin expression in skin lesions was confirmed in PPP skin lesions, a role for interleukin (IL)-1-rich sweat in PPP has been proposed, and IL-1 has been implicated in the altered E-cadherin expression observed in both cultured keratinocytes and mice epidermis. For further investigation, live imaging of sweat perspiration on a mouse toe-pad under two-photon excitation microscopy was performed using a novel fluorescent dye cocktail (which we named JSAC). Finally, intraepidermal vesicle formation which is the main cause of PPP pathogenesis was successfully induced using our "LASER-snipe" technique with JSAC. "LASER-snipe" is a type of laser ablation technique that uses two-photon absorption of fluorescent material to destroy a few acrosyringium cells at a pinpoint location in three-dimensional space of living tissue to cause eccrine sweat leakage. These observatory techniques and this mouse model may be useful not only in live imaging for physiological phenomena in vivo such as PPP pathomechanism investigation, but also for the field of functional physiological morphology.

Background: Although several studies have investigated the accuracy of clinical diagnoses of skin tumors, specific ways to improve diagnostic accuracy have not been identified. This study investigated factors that influence the accuracy of clinical skin tumor diagnostic methods and discusses strategies to improve accuracy. Methods: Study 1 retrospectively analyzed 657 skin tumors excised at our hospital between March 2001 and March 2011. Data were extracted from surgical records to establish a diagnostic template for further research. Study 2 prospectively applied this template to aid clinical diagnosis at four facilities between April 2011 and March 2013. The clinical diagnoses were compared with the histological ones and the concordance was determined. Results: A total of 448 and 209 benign and malignant tumors, respectively, were included in Study 1. The overall diagnostic accuracy was 79.0%. In Study 2, 310 patients were clinically diagnosed using a standardized template, which did not affect the diagnostic accuracy. Age, sex, duration of disease, tumor size and location, skin tone, mobility, stiffness, and years of diagnostic experience did not significantly affect diagnostic accuracy. A high proportion of pathologically malignant tumors were clinically misdiagnosed as benign (16/22; 72%). Other clinical examinations were performed in only 35 cases. Conclusions: Auxiliary diagnostic tools such as dermoscopy and biopsies should be used to accurately diagnose malignant tumors.

Abstract Background Although previous studies have reported general inexperience with the Epley manoeuvre (EM) among general physicians, no report has evaluated the effect of EM on benign paroxysmal positional vertigo (BPPV) in primary care by using point estimates or certainty of evidence. We conducted this systematic review and meta-analysis and clarified the efficacy of EM for BPPV, regardless of primary-care and subspecialty settings. Methods Systematic review and meta-analysis of randomised sham-controlled trials of EM for the treatment of posterior canal BPPV in primary-care and subspecialty settings. A primary-care setting was defined as a practice setting by general practitioners, primary-care doctors, or family doctors. A systematic search was conducted in January 2022 across databases, including Cochrane Central Resister of Controlled Trial, MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. Primary outcomes were the disappearance of subjective symptoms (vertigo), negative findings (Dix–Hallpike test), and all adverse events. We evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. Results Twenty-seven randomised controlled trials were identified. In primary-care settings, EM reduced the subjective symptoms [risk ratio (RR), 3.14; 95% confidence interval (CI), 1.96–5.02]; however, there was no applicable article for all adverse events. In the subspeciality setting, EM reduced the subjective symptoms (RR, 2.42; 95% CI, 1.64–3.56), resulting in an increase in negative findings (RR, 1.81; 95% CI, 1.40–2.34). The evidence exhibited uncertainty about the effect of EM on negative findings in primary-care settings and all adverse events in subspecialty settings. Conclusions Regardless of primary-care and subspecialty settings, EM for BPPV was effective. This study has shown the significance of performing EM for BPPV in primary-care settings. EM for BPPV in a primary-care setting may aid in preventing referrals to higher tertiary care facilities and hospitalisation for follow-up. Trial registration The study was registered in protocols.io (PROTOCOL INTEGER ID: 51,464) on July 11, 2021.

Several factors related to liana abundance have been shown at broad scales, however, the information on factors affecting liana distribution in temperate zones is limited. Climbing types of lianas appear to be associated with interspecific variations of lianas and may be related to the broad-scale distribution and functions of lianas. We aimed to assess the environmental factors related to the abundance of all lianas and those of each climbing type from subtropical to subboreal forests in the Japanese archipelago to better understand the geographical gradient of the liana community.We established six 400 m2 subplots within each of 19 forest plots and recorded the species, stem diameter, and climbing types of lianas with stem diameters ≥ 1 cm. We used generalised linear mixed effects models and model selection based on Akaike's information criterion to examine the effects of climate, soil, and forest structural attributes on liana stem density and basal area.Liana abundance varied substantially among the 19 plots and some forests were characterized by abundant lianas in temperate zones. Twining and root climbers were the major climbing types. Mean annual temperature positively affected the stem density of twining climbers and negatively affected the basal area of root climbers. Maximum snow depth positively affected the stem density of root climbers and negatively affected the basal area of twining climbers. Carbon:nitrogen ratio and dry mass of the soil organic layer had negative effects on the abundance of twining climbers and stem density of both climbers, respectively. Tree basal area positively affected the basal area of root climbers.This study demonstrated the effects of environmental factors, including unique factors such as snow accumulation, on liana distribution at a broad scale from the subtropical to the subboreal zone. Furthermore, the difference between climbing types in distribution may contribute to the gradient of forest ecosystem functions along the environmental factors.

Highly concentrated trehalose induces beneficial senescence-like state in fibroblasts and accelerates the proliferation of keratinocytes and angiogenesis to promote optimal wound repair, demonstrating its therapeutic potential in modulating fibroblast functions.

Background and aim The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after Helicobacter pylori eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after H. pylori eradication. Methods Patients who received H. pylori eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014). Results Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after H. pylori eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after H. pylori eradication. Conclusion Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after H. pylori eradication.KEY MESSAGES Ghrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after H. pylori eradication. Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after H. pylori eradication. Pepsinogen I/II ratios increased immediately after H. pylori eradication and are inappropriate for assessing atrophic gastritis after H. pylori eradication.

Abstract Body-centered-cubic (bcc) transition metals, such as $$\alpha $$ α -Fe and W, cleave along the {100} plane, even though the surface energy is the lowest along the {110} plane. To unravel the mechanism of this odd response, large-scale atomistic simulations of curved cleavage cracks of $$\alpha $$ α -Fe were conducted in association with stress intensity factor analyses of straight crack fronts using an interatomic potential created by an artificial neural network technique. The study provides novel findings: Dislocations are emitted from the crack fronts along the {110} cleavage plane, and this phenomenon explains why the {100} plane can be the cleavage plane. However, the simple straight crack-front analyses did not yield the same conclusion. It is suggested that atomistic modeling, at sufficiently large scales to capture the inherent complexities of materials using highly accurate potentials, is necessary to correctly predict the mechanical strength. The method adopted in this study is generally applicable to the cleavage problem of bcc transition metals and alloys.

Nuclear IL-33 levels are high at the epidermal edges of skin wounds and facilitate wound healing. However, IL-33−mediated regulation of keratinocyte (KC) biology during wound healing remains poorly understood. During skin-wound healing, KC migration and re-epithelialization are mediated predominantly by EGFR signaling activation and depend on the function of signal transducer and activator of transcription 3 (STAT3). We found that migrating KCs at the leading edges of mouse skin wounds exhibited concomitant induction and nuclear colocalization of IL-33 and phosphorylated STAT3. In cultured human KCs, activation of EGFR signaling caused rapid elevation of nuclear IL-33, which directly interacts with phosphorylated STAT3, promoting STAT3 activation. In vitro KC migration and wound-healing assays revealed that high nuclear IL-33 levels were required for KC migration and wound closure. KC mobility associated with a lack of suprabasal epidermal keratins and extracellular matrix degradation mediated by matrix metalloproteinases (MMPs) control cell migration at the intracellular and extracellular levels, respectively. In EGFR-activated KCs, nuclear IL-33 mediated keratin 1 and 10 downregulation and MMP9 upregulation by promoting STAT3 activation and limited MMP1, MMP3, and MMP10 induction by suppressing NF-κB transactivation. Thus, epidermal nuclear IL-33 is involved in KC migration and wound closure by regulating the STAT3 and NF-κB pathways.

The impact of low-dose-rate radiation on genetics is largely unknown, particularly in natural environments. The Fukushima Dai-ich Nuclear Power Plant disaster resulted in the creation of contaminated natural lands. In this study, de novo mutations (DNMs) in germ line cells were surveyed from double-digest RADseq fragments in Japanese cedar and flowering cherry trees exposed to ambient dose rates ranging from 0.08 to 6.86 μGy h−1. These two species are among the most widely cultivated Japanese gymnosperm and angiosperm trees for forestry and horticultural purpose, respectively. For Japanese flowering cherry, open crossings were performed to produce seedlings, and only two candidate DNMs were detected from uncontaminated area. For Japanese cedar, the haploid megagametophytes were used as next generation samples. The use of megagametophytes from open crossing for next generation mutation screening had many advantages such as reducing exposure to radiation in contaminated areas because artificial crossings are not needed and the ease of data analysis owing to the haploid nature of megagametophytes. A direct comparison of the nucleotide sequences of parents and megagametophytes revealed an average of 1.4 candidate DNMs per megagametophyte sample (range: 0–40) after filtering procedures were optimized based on the validation of DNMs via Sanger sequencing. There was no relationship between the observed mutations and the ambient dose rate in the growing area or the concentration of 137Cs in cedar branches. The present results also suggest that mutation rates differ among lineages and that the growing environment has a relatively large influence on these mutation rates. These results suggested there was no significant increase in the mutation rate of the germplasm of Japanese cedar and flowering cherry trees growing in the contaminated areas.

The heartwood color of a major plantation tree Cryptomeria japonica shows high variability among clones and cultivars, and brighter heartwood has higher value in the usage of non-laminated wood such as in traditional construction, which makes heartwood color an important trait in breeding of this species. However, the genetic basis of the interactions between genetics and the environment on heartwood color has been understudied while these are necessary for effective breeding programs in multiple environmental condition. The objectives of the present study were to evaluate the effects of genetics and environments on heartwood color and how they interact in contrasting environments, and to identify genomic regions controlling heartwood color in C. japonica across multiple environments. Heartwood color in terms of L*a*b* color space and spectral reflectance was measured in common gardens established in three contrasting sites. Quantitative trait loci (QTL) that affect heartwood color were identified using previously constructed highly saturated linkage maps. Results found that heartwood color was largely genetically controlled, and genotype-by-environment interaction explained one-third of the total genetic variance of heartwood color. The effect of the environment was small compared to the effect of genetics, whereas environmental effects largely varied among heartwood color traits. QTL analysis identified a large number of QTLs with small to moderate effects (phenotypic variation explained of 6.6% on average). Some of these QTLs were stably expressed in multiple environments or had pleiotropic effects on heartwood color and moisture content. These results indicated that genetic variation in phenotypic plasticity plays an important role in regulating heartwood color and that the identified QTLs would maximize the breeding efficiency of heartwood color in C. japonica in heterogeneous environments.

Since stroke-prone spontaneously hypertensive rats (SHRSP) develop hypertension and stroke without exception, the prevention or reduction of risk by various nutrients was tested on blood pressure and the mortality caused by stroke and cardiovascular diseases (CVD). In addition to sodium (Na) accelerating hypertension and stroke and potassium (K) counteracting the adverse effect of Na, taurine (Tau), rich in seafood, and magnesium (Mg) contained in soy, nuts, grains, etc., were proven to reduce stroke and CVD and improved survival. Therefore, the Cardiovascular Diseases and Alimentary Comparison Study was started in 1985 to explore the association of biomarkers of diet in 24 h urine(24U) with CVD risks, and about 100 males and 100 females aged 48–56 in each of 50 populations were studied until 1995. Linear regression analysis indicated that the 24U Tau/creatinine and Mg/creatinine ratios were inversely associated with body mass index, systolic and diastolic blood pressure, and total cholesterol. In comparison with six Euro-Western regions, 24U Tau and Mg collected from six regions, respectively, in Japan and the Mediterranean countries were significantly higher and were significantly associated with lower CVD risks. Diets rich in Tau and Mg were concluded to be contributory to the prevention of CVD in SHRSP and humans.

Obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) are characterized by the concepts of lipo- and glucotoxicity. NAFLD is characterized by the accumulation of different lipidic species within the hepatocytes. Bile acids (BA), derived from cholesterol, and conjugated and stored in the gallbladder, help the absorption/processing of lipids, and modulate host inflammatory responses and gut microbiota (GM) composition. The latter is the new “actor” that links the GI tract and liver in NAFLD pathogenesis. In fact, the discovery and mechanistic characterization of hepatic and intestinal farnesoid X receptor (FXR) shed new light on the gut–liver axis. We conducted a search on the main medical databases for original articles, reviews, meta-analyses of randomized clinical trials, and case series using the following keywords, their acronyms, and their associations: farnesoid X receptor, bile acids metabolism, gut microbiota, dysbiosis, and liver steatosis. Findings on the synthesis, metabolism, and conjugation processes of BAs, and their action on FXR, change the understanding of NAFLD physiopathology. In detail, BAs act as ligands to several FXRs with GM modulation. On the other hand, the BAs pool is modulated by GM, thus, regulating FXRs functioning in the frame of liver fat deposition and fibrosis development. In conclusion, BAs passed from their role of simple lipid absorption and metabolism agents to messengers between the gut and liver, modulated by GM.

Anal cystic lesions are extremely rare. From October 2011 to August 2023, 3 (0.12%) of the 2498 anal surgery cases performed in our hospital had cystic lesions. They were 38, 56, and 69 years old, all male, and cystic lesions were located anterior to the anus. The cysts were elastic and soft, and the preoperative diagnosis was thrombosed external hemorrhoids or cysts, but histopathologic examination revealed epidermal cysts in two cases and teratoma in one case. Teratomas in the anus show similar histological features to tailgut cysts and retrorectal cyst-hamartomas, and are thought to be rare cysts caused by the remnants of cloaca. They are usually located in the retrorectal space; cases located in the perianal region are extremely rare, and only four cases including ours have been reported in Japan. We present each case and report a case of teratoma in the anal region with a review of the literature. [ABSTRACT FROM AUTHOR]

Atomic stress, utilized in molecular mechanics and molecular dynamics, is valuable in analyzing complex phenomena such as heat transfer, crack propagation and void growth. However, traditional modeling techniques designed for large-scale systems may lack the precision achievable through first-principles calculations. To overcome this limitation, we propose an approach based on artificial neural network (ANN) potentials to compute atomic stress. A crucial aspect of this method is the use of central force decomposition to derive the atomic stress tensor of the ANN potential, ensuring compliance with the balance between linear and angular momentum. By comparing atomic stress calculations for surface systems in Fe and Al using the ANN and embedded-atom (EAM) potentials, we demonstrate that the ANN potential accurately reproduces the stress oscillations near the surface layer predicted by first-principles calculations. This scheme allows us to evaluate atomic stress with nearly the same accuracy as first-principles calculations, even in large-scale models with complex geometries and defect structures. [ABSTRACT FROM AUTHOR]

We report a case where tranexamic acid, which is an antifibrinolytic agent, was used to effectively treat bleeding tendency in a patient with immunoglobulin light chain (AL) amyloidosis. A male patient in his 80s without a history of bleeding disorders was admitted to our hospital for the examination of bleeding tendency and was diagnosed with a bleeding disorder due to AL amyloidosis. Blood tests revealed elevated plasmin-α2- plasmin inhibitor complex levels, suggesting fibrinolytic activation. Managing the bleeding was difficult; however, we suspected fibrinolytic activation associated with AL amyloidosis and initiated treatment with oral tranexamic acid, which markedly improved the bleeding disorder and abnormalities of the fibrinolytic system. Therefore, in cases of bleeding due to fibrinolytic activation of AL amyloidosis, tranexamic acid administration can be an effective treatment. [ABSTRACT FROM AUTHOR]

Abstract Background & aims Body weight is one of the essential indicators of nutritional status, and body weight management is vital in nutritional care. In addition, low body mass index (BMI) was included as a phenotypic criterion in the Global Leadership Initiative on Malnutrition (GLIM) criteria. Furthermore, low BMI has been used in grading the severity of malnutrition (moderate or severe malnutrition) in the GLIM criteria. A recent cross-sectional study reported that muscle mass of the quadriceps in older inpatients with severely low BMI is less than those of older inpatients with moderately low BMI and non-low BMI. However, the longitudinal relationship between body weight and muscle mass of the quadriceps in older inpatients in each BMI category according to the GLIM criteria remains unclear. This study aimed to examine the longitudinal relationship between body weight and muscle mass of the quadriceps in older inpatients in each BMI category according to the GLIM criteria. Methods This retrospective cohort study included 179 older inpatients (aged ≥ 70 years) (median [IQR] age: 84.0 [79.0–89.0]). The period of this study was between January 2017 and March 2020. In accordance with the cut-off value of a low BMI for patients aged ≥ 70 years in the Asian population according to the GLIM criteria, the participants were divided into the following three groups: the severely low BMI group (