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In this study, we systematically investigated the anomalous Nernst effect in perpendicularly magnetized amorphous TbFeCo thin films with various compositions. It was found that the magnitude of the off diagonal thermopower (ODT), which corresponds to the anomalous Nernst effect, can be uniformly explained with respect to the Tb content regardless of the concentration above or below the compensation composition. The maximum ODT of 1.3 μ V/K and the thermoelectric conductivity of 1.59 A/mK at room temperature were obtained, which is more significant than other perpendicular magnetic anisotropy thin films to achieve a large Nernst voltage for roll-type thermoelectric devices. By considering the thermoelectric tensor, Mott's equation, and the scaling law, it was shown both experimentally and theoretically that the magnitudes of the first and second terms contributing to the anomalous Nernst effect are comparable. It was also found that the ODT of TbFeCo thin films is twice or more significant than the product of the Seebeck coefficient and the Hall angle. Furthermore, amorphous metals and Mn-alloys with a large Berry curvature are located above the relation that the ODT is twice the product of the Seebeck coefficient and the Hall angle, which means that amorphous metals are expected to enhance the ANE. [ABSTRACT FROM AUTHOR]

The article discusses the use of l‐asparaginase (l‐Asp) monotherapy in treating acute fulminant chronic active Epstein–Barr virus infection, a life-threatening condition. Two rare cases of patients with high EBV-DNA levels and organ dysfunction were successfully treated with l‐Asp, leading to the initiation of hematopoietic stem cell transplantation (HSCT). The study found that l‐Asp may be an effective bridging therapy to reduce tumor burden before HSCT in such cases, as CAEBV tumor cells have low levels of asparagine synthetase, potentially contributing to the drug's effectiveness. [Extracted from the article]

Langerhans cell histiocytosis is a rare neoplastic disorder characterized by the proliferation of Langerhans cells and often accompanied by eosinophil infiltration. Charcot-Leyden crystals, composed of galectin 10, are occasionally observed in Langerhans cell histiocytosis; however, histological images are rarely reported. We herein present a patient with Langerhans cell histiocytosis with Charcot-Leyden crystals and hexagonal crystals by describing the histologic and immunohistochemical features of a lymph node. A unique distribution of Charcot-Leyden crystals and hexagonal crystals was observed in this patient, shedding light on their possible formation process of the latter. We discuss the biological significance of eosinophilic abscesses in Langerhans cell histiocytosis and propose that these crystals may be linked to extracellular trap-cell death (ETosis). This example challenges the conventional characterization of "necrosis" in Langerhans cell histiocytosis and underscores the importance of recognizing ETosis as a potential mechanism involved in the pathogenesis of Langerhans cell histiocytosis. Further studies are underway to validate significance of these findings in a larger cohort of Langerhans cell histiocytosis patients. [ABSTRACT FROM AUTHOR]

Loss of vegetable texture after freezing represents a crucial challenge that demands attention and is influenced by various factors, such as cultivar, maturity, and harvest time. Therefore, understanding the factors significantly impacting texture after freezing is imperative. Our previous study revealed a correlation between the temperature at harvest and the firmness of frozen broccoli. However, the specific mechanisms contributing to the decreased firmness of frozen broccoli remain unclear. Therefore, this study aimed to elucidate the mechanism underlying the decreased firmness of frozen broccoli at low temperatures through field experiments. Two broccoli cultivars were selected for the study and harvested under three distinct conditions: spring, winter, and late winter. Among the frozen-thawed samples, those harvested in spring exhibited the highest breaking stress, followed by those from winter and late winter harvests. Analysis of pectin composition revealed that samples from winter and late winter harvests displayed weaker cell wall adhesion compared to spring samples, which could promote tissue breakdown via ice crystal formation. Moreover, the low water-holding capacity of late winter samples could inhibit the restoration of frozen-thawed samples to their original state, consequently leading to significant texture deterioration after freezing. The examination of tissue structure after freeze-thawing supports these considerations. The findings of this study can help stabilize the firmness of frozen broccoli through adjustments in harvest timing. [ABSTRACT FROM AUTHOR]

The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role of the tRNA epitranscriptome in fine-tuning translation via codon decoding at tissue or cell levels remains incomplete. We analyzed tRNA expression and modifications as well as codon optimality across seven mouse tissues. Our analysis revealed distinct enrichment patterns of tRNA modifications in different tissues. Queuosine (Q) tRNA modification was most enriched in the brain compared to other tissues, while mitochondrial tRNA modifications and tRNA expression were highest in the heart. Using this observation, we synthesized, and delivered in vivo, codon-mutated EGFP for Q-codons, where the C-ending Q-codons were replaced with U-ending codons. The protein levels of mutant EGFP were downregulated in liver, which is poor in Q, while in brain EGFP, levels did not change. These data show that understanding tRNA modification enrichments across tissues is not only essential for understanding codon decoding and bias but can also be utilized for optimizing gene and mRNA therapeutics to be more tissue-, cell-, or condition-specific. [ABSTRACT FROM AUTHOR]

Background Mycoplasma genitalium , which causes sexually transmitted diseases, is increasingly resistant to key antibiotics such as macrolides and quinolones, posing a challenge for treatment. Objectives To assess the effectiveness of prolonged sitafloxacin and doxycycline combination therapy as a new alternative treatment strategy for highly drug-resistant M. genitalium strains Methods A prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan, from 1 January 2020 to 31 October 2022. Patients with M. genitalium urogenital or rectal infections and those who did not receive the initial sitafloxacin monotherapy were included. Patients were administered sitafloxacin and doxycycline for 21 days as salvage therapy. M. genitalium isolates were tested for parC , gyrA and 23S rRNA resistance-associated mutations. Results Twenty-seven patients received the combination therapy. All M. genitalium strains available for resistance analysis had parC (24/24) and macrolide resistance-associated (25/25) mutations, and 68% (17/25) had gyrA mutations. The overall cure rate was 77.8%. For strains with concurrent parC and gyrA mutations, the cure rate was 68.8% (P  = 0.053) compared with that for monotherapy (37.5%). Conclusions Prolonged combination therapy is highly effective against M. genitalium strains with concurrent parC and gyrA mutations. Future research should focus on establishing the optimal treatment duration and monitoring the risk of resistance. [ABSTRACT FROM AUTHOR]

Paszkiewicz's conjecture asserts that given a decreasing sequence T_1\ge T_2\ge \dots of positive contractions on a separable infinite-dimensional Hilbert space H, the product S_n=T_nT_{n-1}\cdots T_1 converges in the strong operator topology. In these notes, we give an equivalent, more precise formulation of his conjecture. Moreover, we show that the conjecture is true for the following two cases: (1) 1 is not in the essential spectrum of T_n for some n\in \mathbb {N}. (2) The von Neumann algebra generated by \{T_n\mid n\in \mathbb {N}\} admits a faithful normal tracial state. We also remark that the analogous conjecture for the weak convergence is true. [ABSTRACT FROM AUTHOR]

Wood adhesion is one of the fundamental joint technologies for wood-based materials. We focused on an unprecedented chemical bonding wood adhesion. With the final goal of water-resistant wood adhesion using dicarboxylic acid compounds with straight alkyl chains, this study clarified the difference of adhesiveness between glutaric acid (GA) and citric acid (CA) to explore the direct effects of chemical bonding type adhesion on physical properties. In the prepared wood-based moldings, the structural analysis with 2D-NMR of the interphase between GA or CA and wood surfaces revealed that GA adhesion is cleaner and more reactive than CA adhesion, without any side reactions. GA reacted with the wood powder surface. In addition, the water resistance treatments of the GA-type wood-based molding showed a thickness reversibility that is not observed with CA-adhesion. The results indicate that GA-adhesion is very likely a chemical bonding type of wood adhesion, considering the molding process under high temperature and pressure conditions. The physical properties of the molding were evaluated to determine the adhesion properties. GA-type wood-based molding was tougher and more water-resistant than CA-type wood-based molding. The physical properties were attributed to the side-chain structure of GA. The results indicate that dicarboxylic acid compounds could be superior wood adhesives, and other dicarboxylic acids could be used for wood adhesion and the expression of material properties owing to their various side chain structures. Furthermore, the material properties could be controlled by considering the chemical structure of adhesive compounds in the future. [ABSTRACT FROM AUTHOR]

In Japan, women's participation in society and the overall support they receive lags behind that provided by other countries. Although there are various factors that contribute to this outcome, one may be the assigned roles within the family. The concept of working from home (WFH) received considerable attention over the course of the COVID-19 pandemic. Consequently, this pandemic has led to many husbands WFH, resulting in the emergence of husbands who are also responsible for housework and childcare, as opposed to traditional husbands who are not. In this context, we studied the effects of husbands WFH and clarified the mechanism underlying this change. Semi-structured interviews with six husbands who WFH revealed that WFH changed their allocation of time resources. In particular, husbands spent more time on housework and childcare than commuting work. As a qualitative analysis of interview data, we found the following: learning in balancing housework and childcare and work is emergent. Learning that leads to the recognition and awareness of roles was also emergent. The results of this study suggest that WFH is a key factor that induces learning in husbands’ role recognition. [ABSTRACT FROM AUTHOR]

Super-enhancers (SEs) play an important role in regulating tumor-specific gene expression. JQ1, a Bromodomain-containing protein 4 (BRD4) inhibitor, exerts antitumor effects by disrupting SE-mediated regulation of gene expression. We investigated the anti-adult T-cell leukemia/lymphoma (ATL) effects of JQ1. JQ1 induced apoptosis and inhibited ATL cell proliferation. JQ1 suppressed RUNX1expression through the disruption of SE-mediated gene regulation. In the previous reports, it was shown that IC50s of AI-10-104 and Ro5-3335, RUNX1 inhibitors were 1-10 µM for lymphoblastic leukemia cell lines carrying RUNX1 mutations. In the present study, we demonstrated that IC50s of AI-10-104 and Ro5-3335 were also 1-10 µM or lower for ATL cell lines. Simultaneously, AI-10-104 suppressed MYC proto-oncogene (c-MYC) expression. RUNX1 is a potential therapeutic target for ATL that promotes c-MYC expression. We showed that RUNX1 expression is regulated via SEs in ATL and that RUNX1 may be a novel therapeutic target for ATL. [ABSTRACT FROM AUTHOR]

PURPOSE: Inherited cancer susceptibility is often not suspected in the absence of a significant cancer family history. Pathogenic germline variants in pancreatic cancer are well-studied, and routine genetic testing is recommended in the guidelines. However, data on rare periampullary cancers other than pancreatic cancer are insufficient. We compared the prevalence of germline susceptibility variants in patients with pancreatic cancer and nonpancreatic periampullary cancers. MATERIALS AND METHODS: Six hundred and eight patients who had undergone pancreaticoduodenal resection at a tertiary referral hospital were studied, including 213 with pancreatic ductal adenocarcinoma, 172 with ampullary cancer, 154 with distal common bile duct cancer, and 69 with duodenal adenocarcinoma. Twenty cancer susceptibility and candidate susceptibility genes were sequenced, and variant interpretation was assessed by interrogating ClinVar and PubMed. RESULTS: Pathogenic or likely pathogenic, moderate- to high-penetrant germline variants were identified in 46 patients (7.7%), including a similar percentage of patients with pancreatic (8.5%) and nonpancreatic periampullary cancer (7.1%). Low-penetrant variants were identified in an additional 11 patients (1.8%). Eighty-nine percent of the moderate- to high-penetrant variants involved the major cancer susceptibility genes BRCA2 , ATM , BRCA1 , CDKN2A , MSH2 / MLH1 , and PALB2 ; the remaining 11% involved other cancer susceptibility genes such as BRIP1 , BAP1 , and MSH6. Almost all pathogenic variant carriers had a family history of cancer. CONCLUSION: Patients with pancreatic and nonpancreatic periampullary cancer have a similar prevalence of pathogenic cancer susceptibility variants. Germline susceptibility testing should be considered for patients with any periampullary cancer. [ABSTRACT FROM AUTHOR]

Faltings' annihilator theorem is an important result in local cohomology theory. Recently, Doustimehr and Naghipour generalized the Falitings' annihilator theorem. They proved that if R is a homomorphic image of a Gorenstein ring, then f (M) n = λ (M) n , where f (M) n : = inf { i ∈ ℕ | dim Supp ( t H i (M)) ≥ n for all  t ∈ ℕ } and λ (M) n : = inf { λ R R (M ) | ∈ Spec R  with  dim R / ≥ n }. In this paper, we study the relation between f (M) n and λ (M) n , and prove that if R is an almost Cohen–Macaulay ring, then f (M) n ≥ λ (M) n − cmd R. Using this result, we prove that if R is a homomorphic image of a Cohen–Macaulay ring, then f (M) n = λ (M) n . [ABSTRACT FROM AUTHOR]

Humans often cross their legs unconsciously while sitting, which can lead to health problems such as shifts in the center of gravity, lower back pain, reduced blood circulation, and pelvic distortion. Detecting unconscious leg crossing is important for promoting correct posture. In this study, we investigated the detection of leg-crossing postures using machine learning algorithms applied to data from body pressure distribution sensors. Pressure data were collected over 180 s from four male subjects (25.8 ± 6.29 years old) under three conditions: no leg crossing, right-leg crossing, and left-leg crossing. Seven classifiers, including support vector machine (SVM), random forest (RF), and k-nearest neighbors (k-NN), were evaluated based on accuracy, recall, precision, and specificity. Among the tested methods, k-NN demonstrated the highest classification performance, suggesting it may be the most effective approach for identifying leg-crossing postures in this study. [ABSTRACT FROM AUTHOR]

Cervical cancer is a significant health challenge, yet it can be effectively prevented through early detection. Cytology-based screening is critical for identifying cancerous and precancerous lesions; however, the process is labor-intensive and reliant on trained experts to scan through hundreds of thousands of mostly normal cells. To address these challenges, we propose a novel distribution-augmented approach using contrastive self-supervised learning for detecting abnormal squamous cervical cells from cytological images. Our method utilizes color augmentations to enhance the model's ability to differentiate between normal and high-grade precancerous cells; specifically, high-grade squamous intraepithelial lesions (HSILs) and atypical squamous cells–cannot exclude HSIL (ASC-H). Our model was trained exclusively on normal cervical cell images and achieved high diagnostic accuracy, demonstrating robustness against color distribution shifts. We employed kernel density estimation (KDE) to assess cell type distributions, further facilitating the identification of abnormalities. Our results indicate that our approach improves screening accuracy and reduces the workload for cytopathologists, contributing to more efficient cervical cancer screening programs. [ABSTRACT FROM AUTHOR]

Background: The Japanese icefish (Salangichthys microdon) is a valuable food resource in Japan; however, its freshness rapidly diminishes during transport and cold storage. In this study, the freshness change during chilled (5°C) and super‐chilled (−1 and −2°C) of S. microdon samples collected from Kasumigaura lake in October and December was assessed by observing their surface structure and determining their drip loss, K values, and free amino acid content. Results: The results revealed that more wrinkles formed on the surface of S. microdon samples with increasing storage time. More drip loss occurred in fall than in winter. Higher K values and increased degradation of muscle proteins were observed in winter. Moreover, their free amino acid content increased with storage time at all temperatures. Conclusion: This study suggested that seasonal differences and storage temperature should be considered in selecting the appropriate fishing, handling, and storage methods to maintain the freshness and quality of S. microdon. [ABSTRACT FROM AUTHOR]

Water is a unique and abundant substance in biological and chemical systems. Considering its importance and ubiquity, numerous water models have been developed to reproduce various properties of bulk water in molecular simulations. Therefore, selecting an appropriate water model suitable for the properties of interest is crucial for computational studies of water systems. The four-point Optimal Point Charge (OPC) and three-point OPC (OPC3) water models were developed in 2014 and 2016, respectively. These models reproduce numerous properties of bulk water with high accuracy, such as density, dielectric constant, heat of vaporization, self-diffusion coefficient, and surface tension. In this study, we evaluated the shear viscosities of the OPC and OPC3 water models at various temperatures ranging from 273 to 373 K using the Green–Kubo formalism to assess their performance. The evaluated viscosities of both models were very close to each other at all the examined temperatures. At temperatures above 310 K, the calculated shear viscosities were in excellent agreement with the experimental results. However, at lower temperatures, the water models systematically underestimated the shear viscosity, with the calculated values at 273 and 298 K being 20% and 10% lower than the experimental values, respectively. Despite this limitation, the OPC and OPC3 water models outperformed other widely used water models. [ABSTRACT FROM AUTHOR]

This article explores the critical role of the Japan Federation of Publishing Workers’ Unions (JFPWU) in countering historical denialism in Japan through social movement unionism (SMU). As historical denialism – including the Holocaust, Nanking Massacre, and existence of ‘comfort women’ – grew globally, the JFPWU uniquely mobilized against right-wing narratives, particularly those advanced by the Japanese Society for History Textbook Reform (Tsukuru-kai). Since the 1950s, the JFPWU’s involvement in the textbook movement has evolved from defending the freedom of speech and opposing state censorship to directly challenging historical revisionism in education. Analyzing publicly available reports and JFPWU members’ writings, this paper traces the JFPWU’s strategic shifts across the following three periods: its foundational role in postwar textbook controversies, its engagement in the Ienaga trials against government-imposed textbook screenings, and its active opposition to the Tsukuru-kai’s nationalist textbooks since the late 1990s. This paper elucidates how SMU has allowed the JFPWU to transcend traditional union activities, and form alliances with scholars and civic organizations to advocate historical accuracy and democratic principles. By examining the JFPWU’s sustained commitment to SMU, labor unions’ crucial role in driving social movements is exemplified alongside the challenges of revitalizing labor movements within Japan’s contemporary landscape. [ABSTRACT FROM AUTHOR]

Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition, and its accuracy may be influenced by various factors, including bladder filling. This study aims to investigate the impact of bladder filling on the accuracy of BIA measurements. An experimental crossover study was conducted with sedentary young adults. The influence of bladder filling on total body water (TBW), fat mass (FM), fat-free mass (FFM), and basal metabolic rate (BMR) was assessed. Participant in underwear followed an overnight fast. They were instructed to abstain from vigorous physical activity and alcohol for at least 24 h prior to the session. The results obtained from single-frequency and multi-frequency BIA devices were compared. The findings suggest that bladder filling does not affect measured impedance; however, changes in weight following bladder voiding influenced derived BIA results. Specifically, TBW, FM, and BMR values significantly reduced after voiding (p < 0.05). Furthermore, the study found poor agreement between single-frequency and multi-frequency BIA devices, indicating that they are not interchangeable. Bladder filling does affect BIA measurements, not clinically meaningful. Further research is needed to explore the implications of these findings for clinical practice and research protocols. [ABSTRACT FROM AUTHOR]

A 35-year-old primigravida with a history of adenomyosis enucleation was diagnosed with abnormal fetal position at 25 weeks of gestation. The patient presented with normal vital signs and no symptoms. A cardiotocogram and transabdominal ultrasound revealed a healthy fetus, normal amniotic fluid volume, and no intra-abdominal bleeding. Pelvic magnetic resonance imaging (MRI) indicated a ruptured muscular layer of the uterine fundus, with the fetus completely prolapsed into the abdominal cavity. An emergency cesarean section was performed, during which the fetus was found wrapped within the amniotic membrane in the abdominal cavity. The uterus exhibited extensive tearing along the line of the previous surgical scar; however, no hemorrhage was observed. In this case, despite uterine rupture, blood flow through the umbilical cord from the placenta in the uterus resulted in the survival of the fetus. In addition, MRI was essential in determining the appropriate timing to save the fetus. [ABSTRACT FROM AUTHOR]

We construct Narain conformal field theories (CFTs) from quantum subsystem codes, a more comprehensive class of quantum error-correcting codes than quantum stabilizer codes, for qudit systems of prime dimensions. The resulting code CFTs exhibit a global ℤ2 symmetry, enabling us to perform the ℤ2-gauging to derive their orbifolded and fermionized theories when the symmetry is non-anomalous. We classify a subset of these subsystem code CFTs using weighted oriented graphs and enumerate those with small central charges. Consequently, we identify several bosonic code CFTs self-dual under the ℤ2-orbifold, new supersymmetric code CFTs, and a few fermionic code CFTs with spontaneously broken supersymmetry. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) risk factors for hospitalization and mortality have been reported to be older age, comorbidities, and vaccination status. However, its clinical course and the risk of hospitalization and mortality in patients who received home health care for their predisposing status and diseases remain unclear. This study aimed to determine the characteristics and outcomes of these patients after being infected with the Omicron variant of COVID-19. This retrospective study included 33 patients diagnosed with COVID-19 after we initiated home health care. We classified the patients into 2 groups, that is, hospitalization (n = 7) and non-hospitalization (n = 26), and non-survival (n = 6) and survival (n = 27) and compared their backgrounds. COVID-19 severity was an affecting factor in hospitalization and survival. The nursing care environments and low daily life activities also affected hospitalization but not survival. The proportion of patients with terminal malignancies (50.0% vs 3.7%, p =.017) and the Charlson Comorbidity Index (5.0 vs 2.0, p =.096) were higher in the non-survival than in the survival group. Some patients had urinary tract infections and persistent weight and appetite loss (post COVID-19 syndrome), regardless of this improvement. Serum IL-6 levels were higher in patients with post COVID-19 syndrome than those without symptoms. Optimizing the nursing care environment is essential to continue home health care and lower the hospitalization rate even with SARS-CoV-2 infection. Post COVID-19 syndrome, such as appetite and weight loss, are associated with IL-6-induced inflammation. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal Reflux Disease (GERD) is caused by the reflux of gastric contents into the esophagus and has a 13% global prevalence that is increasing. GERD symptoms negatively impact physical, social, and emotional quality of life. The Frequency Scale for the Symptoms of GERD (FSSG) and the Gastrointestinal Symptom Rating Scale (GSRS) determine the efficacy of treatment but may not correlate with endoscopically estimated esophageal mucosal injury severity. We aimed to probe the correlation between FSSG, GSRS, and esophageal injury severity to evaluate whether these scores can predict GERD severity. Methods: A total of 2962 patients who underwent physical examinations, including upper gastrointestinal endoscopy, at the Kyoto Kuramaguchi Medical Center, Japan, were enrolled in this study. Upper gastrointestinal endoscopy was used to diagnose fundic mucosal atrophy, reflux esophagitis based on the Los Angeles (LA) classification, gastroesophageal flap value function (GEFV) based on Hill's classification, and Barrett's esophagus. Endoscopic diagnoses were examined for correlations with FSSG and GSRS scores. Results: In reflux esophagitis, FSSG and GSRS scores correlated with LA-B and LA-C endoscopic diagnosis but not with LA-M and LA-A endoscopic findings. Multiple regression analysis results were similar. FSSG scores reflected advanced fundic gland mucosal atrophy, while GSRS scores associated with high grade of GEFV. Conclusions: This is the first report to examine the correlation between FSSG and GSRS scores and endoscopic findings in a relatively large patient population. Our findings suggest that these scores can diagnose the severity of reflux esophagitis. [ABSTRACT FROM AUTHOR]

This study proposes a measure that can concurrently evaluate the degree and direction of deviancy from the marginal mean equality (ME) model in square contingency tables with ordered categories. The proposed measure is constructed as the function of the row and column cumulative marginal probabilities. When the ME model does not fit data, we are interested in measuring the degree of deviancy from the ME model, because the model having weaker restrictions than the ME model is only the saturated model. This existing measure, which represents the degree of deviancy from the ME model, does not depend on the probabilities that observations will fall in the main diagonal cells of the table. For the data in which observations are concentrated in the main diagonal cells, the existing measure may overestimate the degree of deviancy from the ME model. The proposed measure can address this issue. This study derives an estimator and an approximate confidence interval for the proposed measure using the delta method. The proposed measure would be utility for comparing degrees of deviancy from the ME model in two datasets. The proposed measure is evaluated the usefulness with the application to real data of clinical trials. [ABSTRACT FROM AUTHOR]

The thermal design of buildings in hot summer and cold winter regions must meet the requirements of thermal insulation in summer and heat preservation in winter. As a vital component of national compulsory education, primary schools must create a good indoor thermal environment for classrooms, which is particularly important for students. Due to the lack of construction standards and limited research on Chinese regions with hot summers and cold winters, policymakers have no comprehensive and efficient approach to creating optimal indoor thermal conditions in primary school classrooms. Therefore, based on the climate conditions of hot summer and cold winter areas, this study conducted field surveys in primary and secondary schools in hot summer and cold winter areas, summarized and analyzed the current situation of the surveyed classrooms and users' subjective evaluation of the indoor thermal environment of classrooms, and summarized the current hot summer and cold winter conditions. Problems in classrooms in primary and secondary schools in the region are clarified, and the research direction of construction strategies is clarified. The study found that most of the school hours in summer and winter were in a poor indoor thermal environment without refrigeration equipment. This study adjusted the school leaving time to 17:20 in summer and 17:00 in winter by adjusting the school leaving time to reduce the time of adverse thermal environment. [ABSTRACT FROM AUTHOR]

Background: Biomarkers to predict the recurrence risk are required to optimize perioperative treatment. Adjuvant chemotherapy for patients with human epidermal growth factor 2-positive (HER2-positive) early breast cancer is decided by pathological responses of neoadjuvant chemotherapy (NAC). However, whether pathological responses are appropriate biomarkers is unclear. Currently, there are several studies using minimal residual disease (MRD) as a predictor of prognosis in solid tumors. However, there is no standard method for detecting MRD. Objectives: This study aimed at prospectively evaluating the relationship between MRD detection and recurrence in Asian patients with HER2-positive early breast cancer. Design: Prospective, observational, single-group, and exploratory. This study will include 60 patients from 2 institutions in Japan and the Philippines. The invasive disease-free survival (IDFS) rates of the MRD-positive and MRD-negative groups are compared in patients with HER2-positive early breast cancer who undergo surgery after receiving NAC. Methods and analysis: Circulating tumor DNA (ctDNA) levels of patients will be evaluated 6 times: before NAC, after NAC, after surgery, and annually after surgery for 3 years. We will analyze the genetic profile of blood and tissue samples using the Todai OncoPanel (TOP) and the methylation level of DNA. The primary endpoint is IDFS. Secondary endpoints include overall survival (OS) and disease-free survival (DFS). Patient enrollment began in June 2022, and new participants are still being recruited. Ethics: This study has been approved by the National Cancer Center Hospital Certified Review Board in March 2022 and has been approved by the Research Ethics Board of the participating center. Discussion: Our findings will contribute to determining whether MRD detection using TOP is useful for predicting the recurrence of HER2-positive early breast cancer. If this is proven, MRD detected by TOP could be used in the future as a biomarker to assist in the de-/escalation of treatment strategies in the next interventional trial, thereby avoiding overtreatment in patients at low risk, and in the addition of intensive treatment modalities for those in patients at high risk. [ABSTRACT FROM AUTHOR]

The correction notice in the Scientific Reports journal addresses errors in the original article regarding the assembly of figures and images. Specifically, Figure 4B and supplementary Figures S4A, S4C, S4B, and S4D contain overlapping images due to errors during preparation and assembly. The corrected figures show the effect of temperature on exosome uptake by cancer cells and the impact of different uptake inhibitors on labeled exosomes. The authors of the article are Sherif E. Emam, Hidenori Ando, Amr S. Abu Lila, Taro Shimizu, Keiichiro Okuhira, Yu Ishima, Mahmoud A. Mahdy, Fakhr-eldin S. Ghazy, Ikuko Sagawa, and Tatsuhiro Ishida. [Extracted from the article]

This study presents a comparative analysis of the accuracy of different methodologies for the design and performance evaluation of thermoelectric generators (TEGs), using analytical, computational numerical, and experimental approaches. TEGs are promising devices for capturing waste energy in industrial processes, converting waste heat into electrical energy and contributing to energy sustainability. However, the efficiency of TEGs is a significant challenge due to their low conversion rates. To address this challenge, three different methodologies were developed and systematically compared. Analytical Model: Developed for the electrical design of thermoelectric micro generators, using theoretical performance data and industrial temperature gradients. This method offers a robust theoretical view but may not capture all practical variables. Computational model in Simulink/MATLAB: Created and validated to consider the variation of the Seebeck coefficient and the internal resistance of thermoelectric modules with temperature. This model provides an accurate simulation of operating conditions but depends on the accuracy of the input parameters. Experimental Multi-string Electrical Arrangement Prototype: This involved the design and construction of a prototype followed by experimental tests to validate its performance. This method provides valuable empirical data but can be limited by the complexity and cost of the experiments. The results show that each methodology has specific advantages and limitations, offering valuable insights for the development of more efficient TEG systems. The comparison of analytical, numerical, and experimental methods revealed differences in accuracy and efficiency, highlighting the importance of an integrated approach to TEG design. This study lays a solid foundation for future research and practical applications in the field of industrial residual energy harvesting. [ABSTRACT FROM AUTHOR]

After half a century from their isolation in 1974, we report the first total syntheses of β‐ and γ‐naphthocyclinones, two dimeric pyranonaphthoquinones featuring an unusual bicyclo[3.2.1]‐octadienone core. The syntheses were achieved with full stereochemical control and functional group management, relying on 1) enantioselective construction of the bicyclic core by Rh‐catalyzed enantioselective 1,4‐addition followed by thiolate‐mediated reductive cyclization, and 2) judicious design of a common chiral, non‐racemic monomer unit that is capable of divergence into the donor and acceptor units, and reunion to construct the bicyclo[3.2.1]octadienone core. [ABSTRACT FROM AUTHOR]

Introduction: In-person cognitive behavioral therapy (CBT) can reduce self-reported anxiety in older adults. However, studies are limited for remote CBT. We assessed the effectiveness of remote CBT in mitigating self-reported anxiety in older adults. Methods: We conducted a systematic review and meta-analysis based on a literature search of PubMed, Embase, PsycInfo, and Cochrane databases up to March 31, 2021, for randomized controlled clinical trials comparing the effectiveness of remote CBT versus non-CBT controls on mitigating self-reported anxiety in older adults. We calculated within-group pre-to-post-treatment standardized mean difference using Cohen's d, obtained the difference between a remote CBT group and a non-CBT control group as our effect size for cross-study comparison, and conducted a random-effects meta-analysis. Changes in scores on self-reported anxiety symptoms (Generalized Anxiety Disorder-7 item Scale, Penn State Worry Questionnaire, or Penn State Worry Questionnaire – Abbreviated), and self-reported depressive symptoms (Patient Health Questionnaire-9 item Scale or Beck Depression Inventory) were primary and secondary outcomes, respectively. Results: Six eligible studies, containing 633 participants with a pooled mean age of 66.6 years, were included in the systematic review and meta-analysis. There was a significant mitigating effect of intervention on self-reported anxiety, favoring remote CBT over non-CBT controls (between-group effect size: −0.63; 95% CI: −0.99 to −0.28). We also found a significant mitigating effect of intervention on self-reported depressive symptoms (between-group effect size: −0.74; 95% CI: −1.24 to −0.25). Discussion: Remote CBT is more effective in reducing self-reported anxiety and depressive symptoms than non-CBT control in older adults. [ABSTRACT FROM AUTHOR]

The Late Oligocene is a period of high penguin diversity, following major changes in the marine environment at the Eocene/Oligocene boundary and prior to the emergence of crown penguins in the Miocene. Historically, a large morphological gap existed between the most crownward Platydyptes among the Oligocene penguins from New Zealand and the Early Miocene stem penguins such as Palaeospheniscus from South America. Here we describe a new species that contributes to filling this gap. Pakudyptes hakataramea gen. et sp. nov. is the earliest tiny penguin, overlapping in size with the little penguin Eudyptula minor. Its distinctive combination of a well-developed proximal end of the humerus and an archaic elbow joint provides clues to the evolution of penguin wings. Phylogenetic analysis indicates that penguin wings evolved rapidly from the Late Oligocene to the Early Miocene, together with the acquisition of morphofunctional and hydrodynamical characteristics that enable the excellent swimming ability of modern penguins. As an indicator of aquatic adaptation, bone microanatomy shows a comparable structure to that of Eudyptula. The appearance of the smallest body size and the evolution of modern wings may have led to the ecological diversity of modern penguins, which confirms the importance of Zealandia in penguin evolution. [ABSTRACT FROM AUTHOR]

Melatonin is synthesized in and secreted from the pineal glands and regulates circadian rhythms. Although melatonin has been reported to modulate the activity of ion channels in several tissues, its effects on pineal ion channels remain unclear. In the present study, the effects of melatonin on voltage-gated K+ (KV) channels, which play a role in regulating the resting membrane potential, were examined in rat pinealocytes. The application of melatonin reduced pineal KV currents in a concentration-dependent manner (IC50 = 309 µM). An expression analysis revealed that KV4.2 channels were highly expressed in rat pineal glands. Melatonin-sensitive currents were abolished by the small interfering RNA knockdown of KV4.2 channels in rat pinealocytes. In human embryonic kidney 293 (HEK293) cells expressing KV4.2 channels, melatonin decreased outward currents (IC50 = 479 µM). Inhibitory effects were mediated by a shift in the voltage dependence of steady-state inactivation in a hyperpolarizing direction. This inhibition was observed even in the presence of 100 nM luzindole, an antagonist of melatonin receptors. Melatonin also blocked the activity of KV4.3, KV1.1, and KV1.5 channels in reconstituted HEK293 cells. The application of 1 mM melatonin caused membrane depolarization in rat pinealocytes. Furthermore, KV4.2 channel inhibition by 5 mM 4-aminopyridine attenuated melatonin secretion induced by 1 µM noradrenaline in rat pineal glands. These results strongly suggest that melatonin directly inhibited KV4.2 channels and caused membrane depolarization in pinealocytes, resulting in a decrease in melatonin secretion through parasympathetic signaling pathway. This mechanism may function as a negative-feedback mechanism of melatonin secretion in pineal glands. [ABSTRACT FROM AUTHOR]

Background: The integration of the Internet into daily life has potential implications for public health, especially in promoting preventive healthcare measures like annual health checkups. This study explores the association between Internet use and the likelihood of participating in these checkups among older Japanese citizens. Methods: Participants aged 65 and older were randomly selected from 37 municipalities in Japan, ensuring they required no long-term care. Out of 24,313 responses to a postal questionnaire, 11,495 participants were deemed eligible for analysis, achieving a valid participation rate of 70.1%. We applied propensity score matching to balance Internet users and non-users, resulting in 6,504 matched cases. Poisson regression analysis was then used to adjust for demographic, socioeconomic, and behavioral variables that could act as potential confounders. Results: Our findings show that 55.1% of participants used the Internet several times a month, and among these, 63.5% had attended an annual health checkup in the preceding year. After adjusting for potential confounders, Internet users were found to be 9% more likely to participate in annual health checkups compared to non-users (95% Confidence Interval: 1.02–1.15). Conclusions: This study concludes that there is a positive association between Internet use and participation in annual health checkups among older individuals in Japan. The results suggest that Internet use may serve as a tool to promote preventive healthcare practices in older populations. However, the study underscores the need for further investigation to understand the underlying mechanisms of this association and to establish a causal relationship. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy has reduced the incidence and mortality of AIDS‐defining malignancies (ADM); however, non–AIDS‐defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. Methods: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. Results: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS‐defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS‐defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T‐cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5‐year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. Conclusions: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS‐defining opportunistic infections after receiving chemotherapy. This retrospective study reports the characteristics and prognosis of malignancies among people living with HIV in Japan. The impact of HIV status at the time of malignant diseases diagnosis was relatively small among patients with non–AIDS‐defining solid tumors, whereas uncontrolled HIV status was associated with poor outcomes among patients with malignant lymphoma. [ABSTRACT FROM AUTHOR]

Aim: To investigate the outcomes of cabozantinib in patients with unresectable hepatocellular carcinoma (uHCC), focusing on dose setting and modification. Methods: We retrospectively analyzed 34 Japanese patients who received cabozantinib for uHCC. Trough concentrations (Ctrough) of cabozantinib were also measured weekly for 6 weeks in the 18 patients. Results: Sixteen patients received ≥40 mg (high‐dose group), and 18 patients received 20 mg (low‐dose group). Dose escalations were performed in 27.8% of the patients in the low‐dose group. Although median duration of the first dose reduction or interruption in the low‐dose group was twice that in the high‐dose group (28 vs. 14 days, p < 0.001), there were no significant differences in the relative dose intensity (RDI) during 6 weeks, progression free survival (PFS), and overall survival (p = 0.162, p = 0.950, p = 0.817, respectively) between the two groups. Patients who received RDI during 6 weeks ≥33.4% showed a trend toward longer median PFS (p = 0.054). Each serum aldolase value during the 6 weeks was significantly correlated with the Ctrough at any point (r = 0.500, p < 0.001). In multivariate analyses, aldolase ≥8.7 U/L within 2 weeks was significantly associated with the very early dose reduction or interruption (odds ratio 20.0, p = 0.002). Conclusions: An initial dose of 20 mg cabozantinib could be a safe option in Japanese patients. The serum aldolase value could be useful for making appropriate dose modifications of cabozantinib. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to statistically compare the rate of torque development normalized by maximal strength (relative RTD) across ankle angles. Additionally, this study was aimed at exploring the correlation coefficients between relative RTD and passive stiffness of the medial gastrocnemius (MG) at different ankle angles. Methods: Twenty-two healthy men and women (age: 31 ± 4 years) performed randomly-ordered explosive isometric plantar flexions at plantarflexed (15°), neutral (0°), and dorsiflexed (− 15°) angles; relative RTD comprised the slope of the time–torque curve normalized to maximal torque. The shear wave velocity (SWV; index of stiffness) of the MG at rest was measured at each angle using ultrasound shear wave elastography. Results: The relative RTD was greater at 15° than − 15° for 0–50, 0–100, and 0–150 ms time-windows and at 15° than 0° for the 0–150 ms time-window (P < 0.05), although peak torque was lower at 15° than 0° and − 15° (P < 0.05). The relative RTD for the 0–50 ms time-window correlated with SWV at − 15° (rs = 0.475, P < 0.05), but not at 15º and 0º. Furthermore, the correlation coefficient of RTD for the 0–100 ms time-window with SWV was significantly greater at − 15° (rs = 0.420) than 0 ° (rs = − 0.109). Conclusions: A greater relative RTD occurs at plantarflexed angles (i.e., the ascending limb of the force–length curve) in the triceps surae, and relative RTD is strongly related to passive MG stiffness at dorsiflexed angles (i.e., longer muscle lengths). [ABSTRACT FROM AUTHOR]

Objective: To identify generalism-related competencies that medical students in Japan should acquire in order to provide comprehensive care for patients. Methods: The team responsible for developing the new 'Generalism' section of the 2022 revision of the Model Core Curriculum for Medical Education in Japan (MCC) consisted of nine members from diverse medical backgrounds across Japan. We adopted pragmatism paradigm and analyzed to identify decision-making processes using a qualitative document analysis. Results: The competency list was presented as a four-tier structure. The first tier of generalism was defined as 'take a multi-systemic view of the patient's problems and consider the patient's psychosocial background in order to provide comprehensive, flexible medical care that responds to the needs of the patient and is not limited to one's own specialty, supporting the achievement of individual and societal well-being.' The second tier was framed in terms of 'perspectives' and constructed of four different domains: 'holistic,' 'community,' 'life,' and 'social.' Conclusion: We identified and defined the competencies required by medical students in Japan to provide comprehensive care for patients. By including these competencies in the MCC, undergraduate medical education will be better placed to respond to anticipated changes in the demand for medical care in Japan. Success factors in our guideline development process include facilitating a collaborative and iterative development process, ensuring that diverse perspectives are integrated, and using practical examples and feedback to refine competencies based on a pragmatic approach. [ABSTRACT FROM AUTHOR]

A constant weight asset allocation is a popular investment strategy and is optimal under a suitable continuous model. We study the tracking error for the target continuous rebalancing strategy by a feasible discrete-in-time rebalancing under a general multi-dimensional Brownian semimartingale model of asset prices. In a high-frequency asymptotic framework, we derive an asymptotically efficient sequence of simple predictable strategies. [ABSTRACT FROM AUTHOR]

Synthesis of 3,8-diaryl-2H-cyclohepta[b]furan-2-ones was accomplished by the one-pot procedure involving sequential iodation and Suzuki–Miyaura coupling reactions. The optical and structural characteristics of 3,8-diaryl-2H-cyclohepta[b]furan-2-ones prepared were scrutinized using UV/Vis spectroscopy, theoretical calculations, and single-crystal X-ray crystallography. The redox properties of the compounds were also evaluated through cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The findings reveal that the introduction of aryl groups at both the 3- and 8-positions significantly influences the electronic properties of the CHFs, resulting in distinct optical and electrochemical characteristics. [ABSTRACT FROM AUTHOR]

Textural deterioration in frozen vegetables is a result of softening after freeze-thawing and is a critical issue to address. In the present study, field experiments were conducted on broccoli using six cultivars of three sizes (i.e., different maturities) in two seasons (spring and winter) to evaluate the relationship between the level of tissue softening caused by the freezing process and composition of pectin, which is a main component of the cell wall. The mechanical properties after freeze-thawing depended more on the growing season than on the cultivar or maturity, i.e., the maximum stress after freeze-thawing of spring broccoli was higher than that of winter broccoli. Between the winter broccoli, the samples harvested at lower temperatures showed more pronounced softening after thawing. For all broccolis, the temperature during harvest was strongly correlated with the maximum compressive stress of frozen broccoli (R = 0.867). Broccoli harvested in winter had a higher ratio of galacturonic acid in water-soluble pectin than that harvested in spring, indicating weakened cell wall adhesion. However, the absence of a substantial correlation between the pectin content and mechanical properties of broccoli, suggests that other factors such as cold-responsive materials are also involved in the tissue softening of frozen broccoli. [ABSTRACT FROM AUTHOR]

Cadmium is a heavy metal that pollutes the environment and foods and is a risk factor for vascular disorders. We have previously demonstrated that pretreatment of vascular endothelial cells with zinc and copper protects the cells against cadmium cytotoxicity. In contrast, cadmium cytotoxicity was potentiated in cells following exposure to lead, thereby indicating that in vascular endothelial cells, cadmium cytotoxicity can be differentially modified by the co-occurrence of other heavy metals. In this study, we revealed that simultaneous treatment or pretreatment with manganese protects vascular endothelial cells against cadmium cytotoxicity. Intracellular accumulation of cadmium was observed to be reduced by simultaneous treatment with manganese, although not by pretreatment. The mRNA expression of metal transporters that regulate the uptake of both cadmium and manganese (ZIP8, ZIP14, and DMT1) remained unaffected by either simultaneous treatment or pretreatment with manganese, and simultaneous treatment with manganese suppressed the cadmium-induced expression of metallothionein but pretreatment with manganese did not exhibit such suppressive effect. Thus, the protection of vascular endothelial cells against cadmium cytotoxicity conferred by simultaneous treatment with manganese is assumed to be partially attributed to a reduction in the intracellular accumulation of cadmium, whereas the effects of pretreatment with manganese are independent of both the reduced intracellular accumulation of cadmium and the induction of metallothionein. These observations accordingly indicate that the protective effects of manganese are mediated via alternative (as yet unidentified) mechanisms. [ABSTRACT FROM AUTHOR]

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm3 to 9.6 mm3, from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM. [ABSTRACT FROM AUTHOR]

Background/Objectives: Recently, pembrolizumab plus 5-fluorouracil and cisplatin (FP), nivolumab plus FP, and nivolumab plus ipilimumab have become the first-line treatments for patients with advanced esophageal cancer. However, the treatment efficacy in primary tumors has not been reported. We assessed the outcomes of these treatments in advanced esophageal cancer, specifically focusing on esophageal dysphagia improvements and the primary tumor response. Methods: This retrospective study was conducted between October 2021 and November 2023. We investigated 23 patients with esophageal cancer and dysphagia who received an immune checkpoint inhibitor (ICI) plus FP or nivolumab plus ipilimumab. Results: The median progression-free survival (PFS) was 10.6 months (95% confidence interval [CI]: 9.0–12.5), and the median overall survival was not reached (95%CI: 13.0–NA). Improvement in dysphagia was observed in 19/23 (82.6%) patients, with a median time to improvement of 26 days (range: 15–77 days) and a median dysphagia PFS of 12.6 months (range: 8.1–NA months). Ten patients experienced immune-related adverse events (irAEs): seven had interstitial pneumonia, and three had thyroid dysfunction, pituitary dysfunction, and rash, respectively. Conclusions: Although there was a high frequency of irAEs, ICI for esophageal cancer achieved high response rates and prolonged survival. The observed improvement in dysphagia suggests the potential efficacy of the treatment against primary tumors. [ABSTRACT FROM AUTHOR]

Background: Acute acquired comitant esotropia caused by prolonged near work, such as the use of digital devices, has been frequently reported in recent years. However, intracranial examination is necessary even for patients with nonparalytic comitant esotropia. Lhermitte–Duclos disease is a rare tumor that grows in layers in the cerebellum. Among those with this disease, cases of esotropia have been reported due to abduction limitation of the eye, but there have been no reports of comitant esotropia. Here, we report the case of a young woman with acute acquired comitant esotropia who was found to have Lhermitte–Duclos disease. Case presentation: A 16-year-old Japanese female patient, whose ethnicity was Asian, was referred to our hospital for acute acquired comitant esotropia. Fundus examination revealed papilledema in both eyes, and magnetic resonance imaging of the head revealed a cerebellar tumor in the right cerebellum with obstructive hydrocephalus. She underwent partial tumor resection, and a histopathological diagnosis of Lhermitte–Duclos disease was obtained. However, comitant esotropia status remained unchanged, and she underwent strabismus surgery. Finally, diplopia disappeared completely. Conclusion: Neurological and intracranial imaging examinations are essential when acute acquired comitant esotropia is observed. Acute acquired comitant esotropia by Lhermitte–Duclos disease did not improve with partial tumor resection and required strabismus surgery, but good surgical results were obtained. [ABSTRACT FROM AUTHOR]

Background: Anamorelin is a selective ghrelin receptor agonist approved for cancer cachexia in Japan. Little is known about predictors of anamorelin efficacy. This study aimed to assess the effect of diabetes on the efficacy and safety of anamorelin in patients with cancer cachexia. Methods: Medical records of patients with advanced non-small-cell lung, gastric, pancreatic, or colorectal cancer who received anamorelin between January 2021 and March 2023 were retrospectively reviewed. The diabetic (DM) group included patients with a confirmed diagnosis of type 2 diabetes mellitus, random plasma glucose of ≥ 200 mg/dL, or hemoglobin A1c of ≥ 6.5%. The maximum body weight gain and adverse events during anamorelin administration were compared between the DM and non-DM groups. Patients with a maximum body weight gain ≥ 0 kg were classified as the responders. Results: Of 103 eligible patients, 31 (30.1%) were assigned to the DM group. The DM group gained less weight (median of −0.53% vs. + 3.00%, p < 0.01) and had fewer responders (45.2% vs. 81.9%, p < 0.01) than the non-DM group. The odds ratio for non-response in the DM group was 6.55 (95% confidential interval 2.37–18.06, p < 0.01), adjusted by age and performance status. The DM group had a higher cumulative incidence of hyperglycaemic adverse events (72.2% vs. 6.3%, p < 0.01) and more discontinuations due to hyperglycaemic adverse events (25.8% vs. 4.2%, p < 0.01) than the non-DM group. Conclusions: Patients with diabetes and cancer cachexia are less likely to gain weight with anamorelin despite a high risk of hyperglycaemic adverse events. [ABSTRACT FROM AUTHOR]

Purpose: This study is to investigate the relationship between long-term changes in the foveal avascular zone (FAZ) and visual function of eyes with macular hole (MH) and compare the relationship between the FAZ of MH eyes and fellow eyes. Methods: This study included 31 patients with unilateral MH who underwent vitrectomy and their fellow eyes. Best-corrected visual acuity (BCVA) and metamorphopsia were measured preoperatively and at 1, 3, 6, and 12 months postoperatively. We evaluated retinal parameters using optical coherence tomography (OCT) and the superficial FAZ using OCT angiography. The FAZ ratio was defined as follows: (preoperative FAZ area of the MH eye)/(FAZ area of the fellow eye). Results: The preoperative FAZ area of MH eyes was 0.42 ± 0.08 mm2, which decreased to 0.24 ± 0.07 mm2 1 month postoperatively (p < 0.001) and slightly increased to 0.25 ± 0.06 mm2 12 months postoperatively (p = 1.000). The FAZ area did not differ significantly from that of fellow eyes (0.39 ± 0.06 mm2, p = 0.281). The FAZ area of MH eyes was not associated with visual function at any time point. The FAZ ratio showed a correlation with the preoperative, 6-month, and 12-month BCVA (r = 0.604, p < 0.001; r = 0.510, p = 0.003; and r = 0.475, p = 0.007, respectively). Conclusions: A larger FAZ in the MH eye than that in the fellow eye is associated with poorer long-term visual acuity. The preoperative comparison of the FAZ of the MH eye with that of the fellow eye may be a biomarker for predicting long-term visual acuity. [ABSTRACT FROM AUTHOR]

This article examines the long-term kidney function of individuals with Lowe syndrome, a genetic disorder characterized by ocular disease, central nervous system disorder, and kidney disease. The study analyzed a large group of pediatric and adult patients with Lowe syndrome and found that all patients had congenital cataracts, CNS involvement, and Fanconi syndrome. The study also investigated the estimated glomerular filtration rate (eGFR) and clinical prognostic factors in these patients. The results indicate that kidney disease is a significant prognostic factor in Lowe syndrome, and further research is necessary to understand the progression of chronic kidney disease in adult patients with this syndrome. Another study analyzed the progression of chronic kidney disease (CKD) in individuals with Lowe syndrome, a rare genetic disorder. The study discovered that CKD progressed rapidly after the age of 10, with 84% of patients developing severe CKD after the age of 20. Nephrocalcinosis and hypercalciuria did not have a significant impact on kidney function. The study also found that age was the only factor significantly associated with kidney function. These findings suggest that the majority of individuals with Lowe syndrome develop end-stage kidney disease by their fourth decade of life. [Extracted from the article]

Cadmium is a heavy metal that pollutes the environment and foods and is a risk factor for vascular disorders. We have previously demonstrated that pretreatment of vascular endothelial cells with zinc and copper protects the cells against cadmium cytotoxicity. In contrast, cadmium cytotoxicity was potentiated in cells following exposure to lead, thereby indicating that in vascular endothelial cells, cadmium cytotoxicity can be differentially modified by the co-occurrence of other heavy metals. In this study, we revealed that simultaneous treatment or pretreatment with manganese protects vascular endothelial cells against cadmium cytotoxicity. Intracellular accumulation of cadmium was observed to be reduced by simultaneous treatment with manganese, although not by pretreatment. The mRNA expression of metal transporters that regulate the uptake of both cadmium and manganese (ZIP8, ZIP14, and DMT1) remained unaffected by either simultaneous treatment or pretreatment with manganese, and simultaneous treatment with manganese suppressed the cadmium-induced expression of metallothionein but pretreatment with manganese did not exhibit such suppressive effect. Thus, the protection of vascular endothelial cells against cadmium cytotoxicity conferred by simultaneous treatment with manganese is assumed to be partially attributed to a reduction in the intracellular accumulation of cadmium, whereas the effects of pretreatment with manganese are independent of both the reduced intracellular accumulation of cadmium and the induction of metallothionein. These observations accordingly indicate that the protective effects of manganese are mediated via alternative (as yet unidentified) mechanisms. [ABSTRACT FROM AUTHOR]

• We injured tibial nerve in heterozygous KCC2-knockout (HT) and wild-type (WT) mice. • Motor dysfunction and decreased ChAT (Ach synthesis) were less severe in HT mice. • EM and immunostaining revealed faster degeneration, regeneration, and myelination. • Nerve injury may induce earlier and longer reduction of the KCC2 in HT mice. • Reduced KCC2 expression may accelerate axonal regeneration via GABA/Gly excitation. Gamma-aminobutyric acid and glycine (GABA/Gly) are predominantly inhibitory neurotransmitters in the mature central nervous system; however, they mediate membrane potential depolarization during development. These differences in actions depend on intracellular Cl- concentrations ([Cl-] i), which are primarily regulated by potassium chloride cotransporter 2 (KCC2). After nerve injury, KCC2 expression markedly decreases and GABA/Gly mediate depolarization. Following nerve regeneration, KCC2 expression recovers and GABA/Gly become inhibitory, suggesting that KCC2 reduction and GABA/Gly excitation may be crucial for axonal regeneration. To directly clarify their involvement in regeneration, we analyzed recovery processes after tibial nerve severance and suturing between heterozygous KCC2 knockout mice (HT), whose KCC2 levels are halved, and their wild-type littermates (WT). Compared with WT mice, the sciatic functional index—indicating lower limb motor function—was significantly higher until 28 days after operation (D28) in HT mice. Furthermore, at D7, many neurofilament-positive fibers were elongated into the distal part of the sutured nerve in HT mice only, and myelinated axonal density was significantly higher at D21 and D28 in HT animals. Electron microscopy and galanin immunohistochemistry indicated a shorter nerve degeneration period in HT mice. Moreover, a less severe decrease in choline acetyltransferase was observed in HT mice. These results suggest that nerve degeneration and regeneration proceed more rapidly in HT mice, resulting in milder motor dysfunction. Via similar microglial activation, nerve surgery may reduce KCC2 levels more rapidly in HT mice, followed by earlier increased [Cl-] i and longer-lasting GABA/Gly excitation. Taken together, reduced KCC2 may accelerate nerve regeneration via GABA/Gly excitation. [ABSTRACT FROM AUTHOR]