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Background: The advantage of intensified myeloablative conditioning (MAC) over standard MAC has not been determined in haematopoietic stem cell transplantation (HSCT) for adult acute lymphoblastic leukemia (ALL) patients., Methods: To evaluate heterogeneous effects of intensified MAC among individuals, we analyzed the registry database of adult ALL patients between 2000 and 2021. After propensity score matching, we applied a machine-learning Bayesian causal forest algorithm to develop a prediction model of individualized treatment effect (ITE) of intensified MAC on reduction in overall mortality at 1 year after HSCT., Results: Among 2440 propensity score-matched patients, our model shows heterogeneity in the association between intensified MAC and 1-year overall mortality. Individuals in the high-benefit group (n = 1220), defined as those with ITEs greater than the median, are more likely to be younger, male, and to have higher refined Disease Risk Index (rDRI), T-cell phenotype, and grafts from related donors than those in the low-benefit group (n = 1220). The high-benefit approach (applying intensified MAC to individuals in the high-benefit group) shows the largest reduction in overall mortality at 1 year (risk difference [95% confidence interval], +5.94 percentage points [0.88 to 10.51], p = 0.011). In contrast, the high-risk approach (targeting patients with high or very high rDRI) does not achieve statistical significance (risk difference [95% confidence interval], +3.85 percentage points [-1.11 to 7.90], p = 0.063)., Conclusions: These findings suggest that the high-benefit approach, targeting patients expected to benefit from intensified MAC, has the capacity to maximize HSCT effectiveness using intensified MAC., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Little is known regarding the diversity patterns of Xylariaceae and Hypoxylaceae (Ascomycota) fungi taking part in the lignin decomposition of leaf litter from different tree species and under different climatic regions. The alpha and beta diversity of Xylariaceae and Hypoxylaceae fungi was investigated on bleached leaf litter from nine subtropical and cool temperate tree species in Japan. A total of 248 fungal isolates, obtained from 480 leaves from the nine tree species, were classified into 43 operational taxonomic units (OTUs) with a 97% similarity threshold and were assigned to nine genera of Xylariaceae and Hypoxylaceae. There was no overlap of fungal OTUs between subtropical and cool temperate trees. The mean number of fungal OTUs was generally higher in subtropical than cool temperate trees, whereas rarefaction curves depicting the numbers of OTU with respect to the number of leaves from which fungi were isolated were less steep in subtropical trees than in cool temperate trees, reflecting the dominance of major OTUs in the subtropical trees and indicating a higher species richness in cool temperate regions. Nonmetric multidimensional scaling showed general overlaps of fungal OTU compositions among tree species in the respective climatic regions, and one-way permutational multivariate analysis of variance indicated that the OTU composition was not significantly different between the tree species. These results suggest a wide host range and some geographic and climatic structures of distribution of these ligninolytic fungi., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© 2024 the Author(s), licensee AIMS Press.)

The Joint Committee for Nationwide Survey on colorectal liver metastasis (CRLM) was established to improve treatment outcomes in patients with CRLM. The aim of this study was to evaluate the transition in the characteristics and treatment strategies of patients with CRLM and to analyze the prognostic factors. The data of 5085 patients newly diagnosed between 2013 and 2017 were compared with those of 3820 patients from 2005 and 2007. In patients who underwent hepatectomy (n = 2759 and 2163), the number of CRLMs was significantly higher and in the 2013-2017 data than in the 2005-2007 data (median 2 vs. 1; p = .005). Overall survival (OS) rates after diagnosis of CRLM after hepatectomy were better in the 2013-2017 data than that in the 2005-2007 data (5-year OS, 62.4% vs. 56.7%, p < .001). Recurrence-free survival (RFS) after hepatectomy was comparable between the groups (5-year RFS, 30.5% vs. 30.7%; p = .068). Multivariate analyses identified age at diagnosis of CRLM ≥70 years, lymph node metastasis of primary lesion, preoperative carbohydrate antigen (CA) 19-9 value >100 U/mL, number of CRLM 2-4, and R2 resection as independent predictors of OS. Synchronous CRLM, concomitant extrahepatic metastasis, lymphatic invasion, lymph node metastasis of primary lesion, preoperative CA19-9 value >100 U/mL, number of CRLM 5-, and nonlaparoscopic approach were selected as that of RFS. Despite having a higher prevalence of advanced stage CRLM in the 2013-2017 patient population compared to the 2005-2007 cohort, prognostic outcomes demonstrably improved in the later period., (© 2024 The Author(s). Journal of Hepato‐Biliary‐Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Objective: Eosinophilic otitis media (EOM) is a chronic eosinophilic inflammatory disease linked to bronchial asthma and nasal polyps. EOM is often accompanied by tympanic membrane perforation. Although the primary treatment, steroid therapy, is generally effective, its efficacy may be limited in advanced cases, particularly those involving significant thickening of the middle ear mucosa. Despite its clinical importance, details regarding the pathogenesis of EOM have not been elucidated. Our study aimed to characterize the microbiome associated with EOM and explore changes with and without tympanic membrane perforation., Methods: We enrolled 27 patients clinically diagnosed with EOM, 25 controls without middle ear infections, and 10 patients with chronic suppurative otitis media (CSOM) [1] [2]. Specimens were collected by swabbing the middle ear, nasopharynx, and external auditory canal (EAC) of subjects in the EOM and control groups, whereas CSOM specimens were collected only from the middle ear. The V3-V4 regions of the 16S ribosomal RNA genes were amplified and subjected to high-throughput sequencing. We evaluated alpha and beta diversity indices between the EOM and control subjects, followed by Linear discriminant analysis Effect Size (LEfSe) analysis to identify potential biomarkers. Additionally, co-occurrence patterns were analyzed to explore the associated microbial interactions. To assess whether similar biomarkers were identified between the EOM and CSOM subjects, LEfSe analysis was conducted for these two groups., Results: Compared with controls, EOM patients were significantly enriched in Nocardioides in the middle ear, nasopharynx, and EAC, highlighting a distinct microbiological feature. Both alpha and beta diversity were significantly reduced in EOM patients with tympanic membrane perforation. When comparing the EOM and CSOM groups, Nocardioides was consistently identified as a significant biomarker for EOM, confirming its distinct association with EOM. In co-occurrence analysis, Nocardioides showed notable positive co-occurrence with several other genera., Conclusion: This study reports the first detailed exploration of the EOM microbiome and identified Nocardioides as a new biomarker. The significant shift in microbial co-occurrence associated with tympanic membrane perforation may contribute to the disease's refractory nature, suggesting new avenues for understanding and managing EOM., (Copyright © 2024. Published by Elsevier B.V.)

The AML-05 study aimed to examine the efficacy and safety of a therapeutic strategy based on risk stratification for low-, intermediate-, or high-risk acute myeloid leukemia (AML) pediatric patients. Allogeneic hematopoietic cell transplantation (allo-HCT) was not indicated for low- or intermediate-risk AML patients in first complete remission. The present retrospective study for the AML-05 study aimed to identify prognostic factors for survival and to determine optimal allo-HCT according to multivariate analysis on overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR), and cumulative incidence of nonrelapse mortality for and between low- and intermediate-risk AML group patients in the AML-05 study who had undergone allo-HCT after its completion and relapse. The unique patient numbers (UPNs) of the AML-05 study were matched with the Transplant Registry Unified Management Program (TRUMP)-registered numbers, and the tied data on the AML-05 study's UPNs and the TRUMP-registered numbers were analyzed. The primary endpoint was 3-yr OS. Among 443 AML patients in the AML-05 study, 79 (32 low-risk AML and 47 intermediate-risk AML) were analyzed. The following statistically favorable prognostic factors were identified by multivariate analysis on the low- and intermediate-risk AML groups, respectively: UCB (OS-hazard ratio [HR], 0.105; 95% CI, 0.011 to 0.941; P = .004 and EFS-HR, 0.065, 95% CI, 0.007 to 0.577, P = .014) and late relapse (OS-HR, 0.212; 95% CI, 0.072 to 0.626; P = .005 and EFS-HR, 0.236; 95% CI, 0.088 to 0.630; P = .004). Three-year OS, 3-yr EFS, and 3-yr CIR were significantly different between the low- and intermediate-risk AML groups. UCB may be a safe and beneficial donor source for low-risk AML patients, while late relapse was a favorable prognostic factor for intermediate-risk AML patients. Intermediate-risk AML patients with late relapse and low-risk AML patients may benefit from allo-HCT after relapse., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Kabuki syndrome (KS) is a rare developmental disorder characterised by multiple congenital anomalies and intellectual disability. UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome), which encodes a histone demethylase, is one of the two major pathogenic risk genes for KS. Although intellectual disability is a key phenotype of KS, the role of UTX in cognitive function remains unclear. Currently, no targeted therapies are available for KS., Aims: This study aimed to investigate how UTX regulates cognition, to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for treatment., Methods: We generated UTX conditional knockout mice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3 (trimethylated histone H3 at lysine 27) demethylation., Results: UTX -knockout mice showed decreased phosphorylation of calcium / calmodulin-dependent protein kinase II, impaired long-term potentiation and deficit in remote contextual fear memory. These effects were reversed by an Food and Drug Administration-approved drug desipramine., Conclusions: Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function, and suggest that desipramine could be a potential treatment for KS., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Oxidative stress damages cochlear hair cells in vitro. However, the effect of systemic inflammation on hearing loss remains unclear. Growing evidence suggests that malnutrition influences the development of hearing loss. In this study, we aimed to investigate the influence of the Glasgow prognostic score (GPS), which is calculated based on systemic inflammatory responses and malnutrition, on auditory threshold increases in patients with cancer., Methods: This single-center retrospective cohort study included patients with cancer who underwent standard pure-tone audiometry (PTA) between November 2014 and May 2023. Patients with complete data in their electronic medical records within 90 days before undergoing standard PTA were included. Multivariate analysis was performed using auditory threshold as the response variable. Covariates, including GPS, were obtained from blood data and physical data before standard PTA. The GPS was classified into three levels based on serum albumin and C-reactive protein levels., Results: Standard PTA was performed 14,868 times in 5,462 patients. Of these, 742 had cancer and 384 met the inclusion criteria. Multivariate analysis revealed that older age, creatinine clearance <60 mL/min, and high GPS significantly increased the auditory threshold at frequencies of 500-8,000 Hz. A history of platinum drug use and male sex increased the auditory threshold at frequencies >4,000 and >2,000 Hz, respectively., Conclusion: The GPS was independently associated with elevated standard PTA thresholds in patients with cancer. These results suggest an association between malnutrition/chronic inflammation and hearing loss and provide new information for planning clinical research on hearing loss prevention., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Researchers have attempted to identify the factors involved in lymph node recurrence in cT1-2N0 tongue squamous cell carcinoma (SCC). However, studies combining histopathological and clinicopathological information in prediction models are limited. We aimed to develop a highly accurate lymph node recurrence prediction model for clinical stage T1-2, N0 (cT1-2N0) tongue SCC by integrating histopathological artificial intelligence (AI) with clinicopathological information. A dataset from 148 patients with cT1-2N0 tongue SCC was divided into training and test sets. The prediction models were constructed using AI-extracted information from whole slide images (WSIs), human-assessed clinicopathological information, and both combined. Weakly supervised learning and machine learning algorithms were used for WSIs and clinicopathological information, respectively. The combination model utilised both algorithms. Highly predictive patches from the model were analysed for histopathological features. In the test set, the areas under the receiver operating characteristic (ROC) curve for the model using WSI, clinicopathological information, and both combined were 0.826, 0.835, and 0.991, respectively. The highest area under the ROC curve was achieved with the model combining WSI and clinicopathological factors. Histopathological feature analysis showed that highly predicted patches extracted from recurrence cases exhibited significantly more tumour cells, inflammatory cells, and muscle content compared with non-recurrence cases. Moreover, patches with mixed inflammatory cells, tumour cells, and muscle were significantly more prevalent in recurrence versus non-recurrence cases. The model integrating AI-extracted histopathological and human-assessed clinicopathological information demonstrated high accuracy in predicting lymph node recurrence in patients with cT1-2N0 tongue SCC., (© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Prognosis for patients undergoing hematopoietic cell transplantation (HCT) has been improving. Short-term survival information, such as crude survival rates that consider deaths immediately after the transplantation, may not be sufficiently useful for assessing long-term survival. Using the data of the Japanese HCT registry, the net survival rate of patients who survived for a given period was determined according to age, disease, and type of transplant. We included a total of 41,716 patients who received their first allogeneic hematopoietic cell transplantation between 1991 and 2015. For each disease, age group, graft source subcategory, net survival was calculated using the Pohar-Perme method, and 5-year conditional net survival (CS) was calculated. Ten-year net survivals of total patient cohort were 41.5% and 47.4% for males and females, respectively. Except for myelodysplastic syndrome, multiple myeloma, and adult T-cell leukemia/lymphoma, 5-year CS for 5-year transplant survivors exceeded 90%. CS was especially high for aplastic anemia, of which was over 100% for children and younger adults receiving cord blood, suggesting that these patients have similar longevity to an equivalent group from the general population. These findings provide useful information for long-term survival, and can serve as benchmark for comparisons among registries, including other cancers., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Histological observation under light microscopy has long been used in human cadaveric studies. However, it can distort the interpretations of findings if not used appropriately; there is no guide for its proper use. The aim of this article is to revisit and discuss the correct use of histology in human cadaveric studies, following discussions with experts in multiple fields of medicine, and to create the first guide for such usage. We reached a consensus with the experts, agreeing that when this principle (structure, quantification, interaction, position: SQIP) is applied to histological observations, the findings will be interpreted correctly. Appropriate use of this recommendation can make human cadaveric studies more accurate and informative. This is the first histology guide for human cadaveric studies., (© 2024 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

The femoral epicondyle is an anatomical bony landmark essential for surgeons and anatomists, but there are discrepancies between the two fields when using this term. In current orthopedic surgery, it commonly denotes the small bony prominence of the femoral condyle. Given the derivation, "epicondyle" should be a region projecting laterally from the articular surface rather than a point. These discrepancies in usage are found not only between the fields but also in the literature. This article reviews the narrative definition of "epicondyle of the femur" in surgery and the evolution of the term in anatomy. The outcomes of the review suggest a relationship between the differing perceptions of the epicondyle and the evolution of the term. In reports of studies related to the epicondyle, it is strongly recommended that the definition of the word is clearly stated, with an understanding of its evolution., (© 2024 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Introduction: Two-stage hepatectomy (TSH) enables patients to undergo surgery for colorectal liver metastasis (CRLM) which one-stage hepatectomy cannot remove. Although the outcome of TSH has been reported, there is no original report from Japan. The aim of this retrospective study was to evaluate the outcome of TSH in Japanese patients with CRLM., Methods: We conducted a retrospective cohort study using the nationwide database that included clinical information of 12,519 patients treated with CRLM between 2005 and 2017 in Japan. The primary outcome measure was overall survival. The second outcome measure was progression-free survival. Fisher's exact test, chi-squared test and Mann-Whitney U test were conducted to examine an intergroup difference. Univariate and multivariate analyses were performed using Cox regression model. Survival analysis was performed by Kaplan-Meier method and log-rank test., Results: Of the database, 53 patients undergoing TSH using portal vein embolization (PVE) were identified and analyzed. Their morbidity and in-hospital mortality rate at the second hepatectomy were 26.4% and 0.0%. The mean observation period was 21.8 months. The estimated 1-, 3- and 5-year overall survival rate were 92.5%, 70.8% and 34.7%. Multivariate analyses showed that more than 10 liver nodules significantly increased the mortality risk by 4.2-fold (95%CI 1.224-14.99, P= 0.023). Survival analysis revealed that repeat hepatectomy for disease progression after TSH was superior to chemotherapy in overall survival (mean: 49.6 vs. 18.7, months, P= 0.004)., Conclusion: In the Japanese cohort, TSH was confirmed to be a safety procedure with acceptable survival outcome. More than 10 liver nodules may be a predictor for unfavorable outcome of patients with CRLM undergoing TSH. Furthermore, repeat hepatectomy can be a salvage treatment for resectable intrahepatic recurrence after TSH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to evaluate the superficial medial collateral ligament distal tibial attachment (sMCL-dTA) morphologically and morphometrically. Seventeen unpaired formalin-fixed cadaveric knees were used. The sMCL was divided into anterior and posterior sections in the paracoronal plane along the midline of the sMCL. The distance from the medial edge of the tibial plateau and the joint line to the proximal margin, center, and distal margin of the sMCL-dTA and the length of the sMCL-dTA were measured in the anterior section, respectively. The sMCL-dTA was histologically observed in the posterior section with hematoxylin and eosin and Masson's trichrome staining. The distance from the medial edge of the tibial plateauto the proximal margin, center, and distal margin of the sMCL-dTA were 38.1 ± 4.2, 49.7 ± 4.4, and 61.5 ± 5.1 mm, respectively. The perpendicular distance from the joint line to the proximal margin, center, and distal margin of the sMCL-dTA were 36.1 ± 4.0, 47.4 ± 4.2, and 59.1 ± 4.8 mm, respectively. The length of the sMCL-dTA was 23.6 ± 3.2 mm. Histologically, the sMCL-dTA was formed by two layers of collagen fibers: the unidirectional fibrous layer and the multidirectional fibrous layer. The respective thicknesses of the two layers both decreased distally. The anatomical location, the length, and the attachment morphology of sMCL-dTA have been clarified using human cadaveric knees. Anatomical data in the present study contribute to the quality of surgery associated with sMCL-dTA., (© 2024 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Background: Postoperative temperature dysregulation affects the length of hospital stay and prognosis. This study evaluated the factors that influence the occurrence of fever in patients after aortic valve replacement surgery., Methods: Eighty-seven consecutive patients who underwent aortic valve replacement surgery were included. Patients' age, sex and body mass index; presence of diabetes mellitus; operation time; blood loss; blood transfusion volume; preoperative and postoperative laboratory findings; presence or absence of oral function management; and fever >38°C were retrospectively analysed through univariate and multiple logistic regression analyses., Results: Among the variables, only diabetes mellitus status was significantly associated with fever ⩾38°C. Postoperatively, patients with diabetes mellitus were significantly less likely to develop fever above 38°C and a fever rising to 38°C., Conclusions: This study shows that the presence of comorbid diabetes mellitus decreases the frequency of developing fever >38°C after aortic valve replacement surgery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

This study aimed to address the prognostic impact of center experience based on the data of 7821 adults with acute myeloid leukemia who underwent allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2019 in Japan, where medical care was provided within a uniform healthcare system. Center experience was defined based on the number of allogeneic HCTs performed for any indication during the study period, by which centers were divided into low-, intermediate-, and high-volume centers. After adjusting for known confounding factors, the risk of overall mortality was lowest for the high-volume centers and highest for the low-volume centers, with the difference between the center categories attributed primarily to the risk of relapse. Patients transplanted at high-volume centers had higher risks of acute and chronic graft-versus-host diseases but without an increased risk of non-relapse mortality (NRM). These findings reveal the presence of a center effect in allogeneic HCT conducted during the past decade in Japan, highlighting the difference in relapse based on center experience. The weaker effect on NRM compared with that on relapse suggests that the transplantation care quality is becoming equalized across the country., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer's disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature., Competing Interests: HH, HS, SH, GS, YT, MT, MI, MS, IH, KH, MH, AN, YM, SO, MM, AU, YK, AM, KN, SK, TS, TI, HN, YG, MR, TT, KY, NT, HK, JI, IN, TK, TT, MD, HN, KT, KS, KN, TT, HF, YS, KY, LR, NH, HM, TY, SW, TA, KT, TN, HK, FH, AH, HH, KT, TT, TK, TK, IG, GC, NA, HH, SK, TK, MH, YH, RM, KO, AH, LB, IY, YH, HK, YM, KI, HK, BK, HO, YY, AT, NK, SG, MI, MN, KM, EO, IO, TS, KY, HA, KT, KI, TS, AK, MF, NU, TK, TT, YY, MI, TH, KI, KN, SH, KE, KH, YT, SN, NS, TY, NU, TY, YK, RO, NS, KS, SH, KO, HM, TF, MT, HS, DS, YI, TI, YK, TY, KS, TM No competing interests declared, SY, NN Employee of Takeda Pharmaceutical Company, Ltd

Background: Physical function and knee kinematics recovery after discoid lateral meniscus (DLM) tear surgery are essential for a better prognosis. However, these alterations remain unclear. Therefore, this study aimed to investigate changes in physical function and knee kinematics following saucerization and DLM tear repair., Methods: We enrolled 16 patients who underwent saucerization and DLM tear repair. Postoperative changes in knee kinematics during gait, and physical function, were evaluated at 3, 6, and 12 months., Results: The peak flexion angle of the operated limb during weight acceptance was significantly higher than that of the contralateral limb at 3 (operated limb: 34.6 ± 8.9°, contralateral limb: 23.7 ± 8.3°; P < 0.01) and 6 months (operated limb: 32.1 ± 9.7°, contralateral limb: 24.6 ± 8.2°; P = 0.03) postoperatively, but not at 12 months (operated limb: 27.1 ± 7.1°, contralateral limb: 23.1 ± 9.5°; P = 0.22) postoperatively. The knee extensor strength of the operated limb was significantly lower than that of the contralateral limb at 3 (operated limb: 1.00 ± 0.59 Nm/kg, contralateral limb: 1.37 ± 0.59 Nm/kg; P = 0.01), 6 (operated limb: 1.22 ± 0.55 Nm/kg, contralateral limb: 1.48 ± 0.60 Nm/kg; P < 0.01), and 12 months (operated limb: 1.39 ± 0.57 Nm/kg, contralateral limb: 1.55 ± 0.64 Nm/kg; P = 0.04) postoperatively., Conclusion: Knee extension deficits and extensor weakness persisted at 6 months after saucerization and repair of DLM tears. Postoperative rehabilitation should be focused on knee extension function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT), negatively impacting quality of life (QoL) and increasing the risk of death. Complexity in cGVHD diagnosis and treatment causes significant variations in cGVHD management strategies across medical centers and physicians despite the existence of published guidelines. Thus, we hypothesized that center volume is associated with cGVHD incidence and outcomes after cGVHD develops. This study aimed to evaluate the effect of center volume on the incidence of cGVHD in patients who underwent HSCT and outcomes in patients with cGVHD. Our retrospective study included 28,786 patients who underwent their first HSCT (overall cohort) and 7664 who developed cGVHD (cGVHD cohort). We categorized institutions into quartiles (very low, low, high, and very high) using the number of HSCTs performed during the study period. We assessed cGVHD incidence in overall cohort and overall survival (OS) in cGVHD cohort. The very high-volume group showed significantly higher cGVHD incidence (adjusted hazard ratio [HR], 1.38; 95% confidence interval [CI]: 1.30 to 1.46) compared to the very low-volume group. However, the cGVHD incidence was similar among very low-, low- and high-volume groups. Low, high, and very high-volume groups showed significantly higher OS with adjusted HRs of 0.83 (95% CI: 0.73 to 0.94), 0.69 (95% CI: 0.61 to 0.79), and 0.68 (95% CI: 0.60 to 0.76), respectively, compared with the very low-volume group. In conclusion, we revealed a higher incidence of cGVHD in the very high-volume group and a poor survival outcome in the very low-volume group in patients with cGVHD., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

One drawback of existing artificial intelligence (AI)-based histopathological prediction models is the lack of interpretability. The objective of this study is to extract p16-positive oropharyngeal squamous cell carcinoma (OPSCC) features in a form that can be interpreted by pathologists using AI model. We constructed a model for predicting p16 expression using a dataset of whole-slide images from 114 OPSCC biopsy cases. We used the clustering-constrained attention-based multiple-instance learning (CLAM) model, a weakly supervised learning approach. To improve performance, we incorporated tumor annotation into the model (Annot-CLAM) and achieved the mean area under the receiver operating characteristic curve of 0.905. Utilizing the image patches on which the model focused, we examined the features of model interest via histopathologic morphological analysis and cycle-consistent adversarial network (CycleGAN) image translation. The histopathologic morphological analysis evaluated the histopathological characteristics of image patches, revealing significant differences in the numbers of nuclei, the perimeters of the nuclei, and the intercellular bridges between p16-negative and p16-positive image patches. By using the CycleGAN-converted images, we confirmed that the sizes and densities of nuclei are significantly converted. This novel approach improves interpretability in histopathological morphology-based AI models and contributes to the advancement of clinically valuable histopathological morphological features., (© 2024. The Author(s).)

There is no global consensus on the surgical technique of cochlear implantation (CI) in ears with an open cavity after canal wall-down (CWD) mastoidectomy. Here, we report CI surgery with an endaural incision for the ears after CWD mastoidectomy. The endaural incision was extended upward to obliterate the open cavity of the temporal fascial flap. The endaural incision was extended downward to close the open cavity inlet. After inserting the implanted electrode, the open cavity was obliterated using a temporal fascial flap, and the cavity was closed at the inlet. We performed this type of CI surgery in four ears in three patients. This extended endaural incision provided an excellent view for pedicling the temporal fascial flap with the superficial temporal artery and for open cavity closure without any serious complications. This technique allowed us to opt for CI surgery of the ears after CWD mastoidectomy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Fukuda et al.)

Acute recurrent pancreatitis (ARP) is a clinical condition characterized by repeated episodes of acute pancreatitis. In this case study, a 62-year-old man was diagnosed with mild pancreatitis five years ago, with alcohol intake initially considered the cause. Since then, he experienced three episodes of pancreatitis despite ceasing alcohol consumption completely. Consequently, the patient was diagnosed with ARP. Various diagnostic and imaging tests were performed to determine the etiology of his condition, including blood tests, magnetic resonance cholangiopancreatography, endoscopic ultrasonography, and contrast-enhanced computed tomography. The results were inconclusive; however, endoscopic retrograde cholangiopancreatography revealed the reflux of bile and pancreatic juice into the alternative ducts, despite the absence of anatomical abnormalities in the biliary tract or pancreatic duct. These findings subsequently led to the diagnosis of biliopancreatic reflux, which activated pancreatic enzymes causing ARP. Endoscopic biliary sphincterotomy was performed to alleviate the patient's symptoms. One year later, the patient remained symptom-free. This case highlights the importance of examining bile and pancreatic juice components before considering endoscopic sphincterotomy in patients with unexplained ARP., (© 2023. Japanese Society of Gastroenterology.)

Cigarette smoking during pregnancy is known to be associated with the incidence of attention-deficit/hyperactive disorder (ADHD). Recent developments in deep learning algorithms enable us to assess the behavioral phenotypes of animal models without cognitive bias during manual analysis. In this study, we established prenatal nicotine exposure (PNE) mice and evaluated their behavioral phenotypes using DeepLabCut and SimBA. We optimized the training parameters of DeepLabCut for pose estimation and succeeded in labeling a single-mouse or two-mouse model with high fidelity during free-moving behavior. We applied the trained network to analyze the behavior of the mice and found that PNE mice exhibited impulsivity and a lessened working memory, which are characteristics of ADHD. PNE mice also showed elevated anxiety and deficits in social interaction, reminiscent of autism spectrum disorder (ASD). We further examined PNE mice by evaluating adult neurogenesis in the hippocampus, which is a pathological hallmark of ASD, and demonstrated that newborn neurons were decreased, specifically in the ventral part of the hippocampus, which is reported to be related to emotional and social behaviors. These results support the hypothesis that PNE is a risk factor for comorbidity with ADHD and ASD in mice.

Cisplatin-induced ototoxicity is caused by reactive oxygen species. It has been recognized that estradiol (E2) regulates redox balance. However, little is known about the protective mechanisms of E2 against cisplatin-induced ototoxicity. In this study, we investigated the effect of E2 on nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated hair cell protection using the organ of Corti isolated from mice. The organ of Corti collected from C57BL/6 mice at 3-5 postnatal days was used in all experiments. The organ of Corti was exposed to 20 μM cisplatin with/without 100 nM E2 to examine the effect of E2 on cisplatin-induced hair cell loss. The mRNA expression of Nrf2 and the phase II detoxification gene after E2 and cisplatin treatment was analyzed using quantitative real-time PCR. E2 significantly reduces cisplatin-induced cochlear hair cell death. In addition, 100 nM E2 increased the mRNA expression of Nrf2 and phase II detoxification genes in the organ of Corti under cisplatin treatment. Our results suggest that E2 activates Nrf2, phase II detoxification enzymes and exerts a protective effect against cisplatin-induced ototoxicity.

CD300A is a member of the CD300 immunoglobulin (Ig)-like receptor family consisting of eight molecules in humans, all of which contain one Ig-like domain in the extracellular portion. Upon binding its ligand phosphatidylserine or phosphatidylethanolamine, CD300A mediates an inhibitory signal through the immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic portion. The CD300 family molecules are highly homologous to each other. In addition, CD300A has a single nucleotide polymorphism (rs2272111), which is a nonsense mutation encoding glutamine (CD300A Q111 ) instead of arginine (CD300A R111 ) at residue 111 in the Ig-like domain of CD300A. In this study, we successfully generated monoclonal antibodies (mAbs) specific to either CD300A R111 or CD300A Q111 or both. These mAbs are useful for the analysis of CD300A genotype by flow cytometry and the development of an antibody drug for the treatment of various diseases.

Considerable evidence of reactive oxygen species (ROS) involvement in cochlear hair cell (HC) loss, leading to acquired sensorineural hearing loss (SNHL), were reported. Cochlear synaptopathy between HCs and spiral ganglion neurons has been gathering attention as a cochlear HC loss precursor not detectable by normal auditory evaluation. However, the molecular mechanisms linking ROS with HC loss, as well as the relationship between ROS and cochlear synaptopathy have not been elucidated. Here, we examined these linkages using NOX4-TG mice, which constitutively produce ROS without stimulation. mRNA levels of Piccolo 1, a major component of the synaptic ribbon (a specialized structure surrounded by synaptic vesicles in HCs), were decreased in postnatal day 6 NOX4-TG mice cochleae compared to those in WT mice; they were also decreased by noise exposure in 2-week-old WT cochleae. As noise exposure induces ROS production, this suggests that the synaptic ribbon is a target of ROS. The level of CtBP2, another synaptic ribbon component, was significantly lower in NOX4-TG cochleae of 1-month-old and 4-month-old mice compared to that in WT mice, although no significant differences were noted at 1.5- and 2-months. The decrease in CtBP2 plateaued in 4-month-old NOX4-TG, while it gradually decreased from 1 to 6 months in WT mice. Furthermore, CtBP2 level in 2-month-old NOX4-TG mice decreased significantly after exposure to cisplatin and noise compared to that in WT mice. These findings suggest that ROS lead to developmental delays and early degeneration of synaptic ribbons, which could be potential targets for novel therapeutics for ROS-induced SNHL., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Cancer in children, adolescents, and young adults (AYAs) although rare, is the leading disease-specific cause of death in Japan. This study aims to investigate cancer incidence and type of treatment hospital among children and AYAs in Japan. Cancer incidence data (2016-2018) for those aged 0-39 years were obtained from the Japanese population-based National Cancer Registry. Cancer types were classified according to the 2017 update of the International Classification of Childhood Cancer (Third Edition), and AYA Site Recode 2020 Revision. Cases were also categorized into three groups: those treated at core hospitals for pediatric cancer treatment (pediatric cancer hospitals [PCHs]), those treated at designated cancer care hospitals, and those treated at nondesignated hospitals. The age-standardized incidence rate was 166.6 (per million-person years) for children (age 0-14 years) and 579.0 for AYAs (age 15-39 years) (including all cancers and benign or uncertain-behavior central nervous system [CNS] tumors). The type of cancer varied with age: hematological malignancies, blastomas, and CNS tumors were common in children under 10 years, malignant bone tumors and soft tissue sarcomas were relatively common in teenagers, and in young adults over 20 years, carcinomas in thyroid, testis, gastrointestinal, female cervix, and breast were common. The proportion of cases treated at PCHs ranged from 20% to 30% for children, 10% or less for AYAs, and differed according to age group and cancer type. Based on this information, the optimal system of cancer care should be discussed., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

CASK -related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including microcephaly with pontine and cerebellar hypoplasia (MICPCH), epilepsy, congenital nystagmus, and neurodevelopmental disorders. Whole-genome sequencing has identified various mutations, including nonsense and missense mutations, from patients with CASK -related disorders, revealing correlations between specific mutations and clinical phenotypes. Notably, missense mutations associated with epilepsy and intellectual disability were found throughout the whole region of the CASK protein, while missense mutations related to microcephaly and MICPCH were restricted in certain domains. To investigate the pathophysiology of CASK -related disorders, research groups have employed diverse methods, including the generation of CASK knockout mice and the supplementation of CASK to rescue the phenotypes. These approaches have yielded valuable insights into the identification of functional domains of the CASK protein associated with a specific phenotype. Additionally, recent advancements in the AI-based prediction of protein structure, such as AlphaFold2, and the application of genome-editing techniques to generate CASK mutant mice carrying missense mutations from patients with CASK -related disorders, allow us to understand the pathophysiology of CASK -related disorders in more depth and to develop novel therapeutic methods for the fundamental treatment of CASK -related disorders.

Objective: The prognostic role of pretreatment C-reactive protein (CRP) has been reported for head and neck cancer. However, little is known about the relationship between the changes in CRP levels during treatment and prognosis. This study aimed to investigate the correlation between CRP elevation during concurrent chemoradiotherapy (CCRT) and survival outcomes., Methods: The medical records of patients with oropharyngeal, hypopharyngeal, and laryngeal cancer treated with CCRT at the University of Tsukuba Hospital and National Hospital Organization Mito Medical Center from April 2014 to December 2019 were retrospectively reviewed. Patients were divided into normal (<0.3 mg/dl) and elevated (≥0.3 mg/dl) CRP groups according to the CRP level after the first cycle of cisplatin. The primary endpoint was progression-free survival (PFS)., Results: A total of 74 patients were enrolled, of whom 36 (49%) showed elevated CRP levels after the first cycle of cisplatin. The 3-year PFS was 83.3% and 61.0% in the normal and elevated CRP groups, respectively, showing significant differences between the two groups., Conclusion: Elevated CRP levels after the first cycle of cisplatin is an objective predictive marker for survival in patient with head and neck squamous cell carcinoma treated with CCRT., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Vestibular schwannomas usually originate in the internal acoustic meatus, and gradually extends into the cerebellopontine cistern. Invasive growth into the petrous bone is extremely rare. We describe a case of a vestibular schwannoma that aggressively extended into the petrous bone and extracranial space. This may have arisen because of an unusually peripheral site of origin on the vestibular nerve.

Purpose: To clarify the utility of the area of residual tumor for patients with esophageal squamous cell cancer treated with neoadjuvant chemotherapy., Methods: We enrolled 186 patients with esophageal squamous cell cancer who underwent surgical resection following neoadjuvant chemotherapy at our hospital. Using digital images, we measured the area of residual tumor at the maximum plane of the specimen and divided the patient into three groups as follows: 0 (area = 0 mm2), low (area = 0-40 mm2), and high (area ≥ 40 mm2). The clinicopathological factors and prognosis were compared among these groups., Results: The median area of the residual tumor was 15.0 mm2　(range 0-1,448.8 mm2). Compared with the 0 and low group, the high group was significantly associated with poorer recurrence-free survival (all P < .001) and overall survival (P < .001 [vs. 0] and P = .017 [vs low]). The area of residual tumor, ypN, tumor regression grade, and lymphovascular invasion were independent predictors of recurrence-free survival. By dividing the patients using a combination of the area of residual tumor and lymphovascular invasion, the high and/or lymphovascular invasion ( +) group displayed significantly poor recurrence-free survival than the 0 group and low/lymphovascular invasion ( -) group. However, there was no significant difference in the recurrence-free survival between the 0 group and low/lymphovascular invasion ( -) group., Conclusion: The area of residual tumor is a promising histopathological prognostic factor for patients with esophageal squamous cell cancer treated with neoadjuvant chemotherapy. Moreover, it is a possible candidate histopathological factor for postoperative chemotherapy selection., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To evaluate proton beam therapy (PBT) in multimodal treatment for locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinus (NPSCC)., Methods: The cases in this study included T3 and T4 NPSCC without distant metastases that were treated at our center using PBT between July 2003 and December 2020. These cases were classified into 3 groups based on resectability and treatment strategy: surgery followed by postoperative PBT (group A); those indicated to be resectable, but the patient refused surgery and received radical PBT (group B); and those declared unresectable based on the extent of the tumor and treated with radical PBT (group C)., Results: The study included 37 cases, with 10, 9 and 18 in groups A, B and C, respectively. The median follow-up period in surviving patients was 4.4 years (range 1.0-12.3 years). The 4-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 58%, 43% and 58% for all patients; 90%, 70% and 80% in group A, 89%, 78% and 89% in group B; and 24%, 11% and 24% in group C. There were significant differences in OS (p = 0.0028) and PFS (p = 0.009) between groups A and C; and in OS (p = 0.0027), PFS (p = 0.0045) and LC (p = 0.0075) between groups B and C., Conclusions: PBT gave favorable outcomes in multimodal treatment for resectable locally advanced NPSCC, including surgery followed by postoperative PBT and radical PBT with concurrent chemotherapy. The prognosis for unresectable NPSCC was extremely poor, and reconsideration of treatment strategies, such as more active use of induction chemotherapy, may improve outcomes., (© 2023. The Author(s).)

The larval parasitoid Diadegma hiraii (Kusigemati) was evaluated as a potential biological control agent of the soybean pod borer, Leguminivora glycinivorella (Matsumura). The timing of adult emergence after overwintering was ascertained, and land-use factors that enhance population density were analyzed. Host cocoons were collected and exposed to different temperatures and photoperiod regimes. Subsequently, the emergence of parasitoid was monitored. Land-use types were categorized into 4 land-use types (Poaceae, Fabaceae, Brassicaceae, and forest). Adult parasitoid emergence was dependent on temperature, but largely unaffected by photoperiod. The estimated emergence time of parasitoid was 3 months before the occurrence of the host, suggesting that the overwintered generation may lay eggs in alternate hosts. Parasitism rate was positively correlated with the area covered by Poaceae plants within a 500-m radius of the soybean field. Based on the results of the overwintering ecology and landscape analysis, D. hiraii probably completes its life cycle in the agroecosystems. The parasitoid's effectiveness as a biological control agent may be influenced by the arrangement of land-use types in the agroecosystems surrounding soybean fields. However, the pest control provided by D. hiraii is limited because of approximately 30% of parasitism rate. Consequently, a combination of this species and cultural control and/or other biological control agents is suggested for sustainable soybean cultivation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large-scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan-Meier method and compared by log-rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5-year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Pharyngocutaneous fistula (PCF), a major complication of total laryngectomy, is caused by pharyngeal repair failure., Objective: Assess the usefulness of endoscopic observation of the pharyngeal suture's healing process for the early detection of PCF development., Methods: Pharyngeal mucosal sutures were endoscopically observed postoperatively in patients who underwent total laryngectomy with primary closure., Results: Postoperatively, a white coat adhered to the pharyngeal mucosal suture of all patients. In most cases, the white coat gradually receded, which was considered to be a normal healing process. Thickening of the white coat and/or dehiscence of surgical wound were interpreted as 'poor healing conditions'. Three cases were judged to have developed poor healing conditions of the pharyngeal mucosal suture and one patient developed PCF. The other two patients did not develop PCF, possibly due to early detection of 'poor healing condition' and conservative approach, such as discontinuation of oral intake., Conclusions: Postoperative poor healing conditions of the pharyngeal mucosal suture may be precursors to PCF development. Endoscopic observation enables early detection of these conditions and may enable the prevention of PCF.

Background: The Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) nomogram was developed to predict disease-free survival in patients with colorectal liver metastases (CRLM) undergoing upfront hepatectomy. However, the utility of the nomogram in patients with resected CRLM remains unknown in the current situation in which treatment strategies are changing with advances in drugs., Methods: Patients in the initial nomogram cohort (n = 727) and validation cohort (n = 2225) were divided into the upfront hepatectomy and preoperative chemotherapy groups. The nomogram was validated by measuring calibration and discrimination in the two cohorts. Calibration curves were plotted, and survival probabilities were compared. Finally, to quantify the discrimination power, we estimated the concordance index (C-index)., Results: In the upfront hepatectomy group, the C-index was 0.63, the suitable cutoff value of the Beppu score was 7, and adjuvant chemotherapy was significantly effective limited to high-risk patients (Beppu score ≥7). The C-index was 0.56 in the preoperative chemotherapy group., Conclusions: The JSHBPS nomogram remains beneficial for patients undergoing upfront hepatectomy in the recent era but is less effective for patients undergoing hepatectomy after chemotherapy. Patients with a Beppu score ≥7 showed high-risk recurrence, and adjuvant chemotherapy should be recommended for these patients., (© 2022 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome is a neurodevelopmental disorder caused by the deficiency of the X-chromosomal gene CASK. However, the molecular mechanisms by which CASK deficiency causes cerebellar hypoplasia in this syndrome remain elusive. In this study, we used CASK knockout (KO) mice as models for MICPCH syndrome and investigated the effect of CASK mutants. Female CASK heterozygote KO mice replicate the progressive cerebellar hypoplasia observed in MICPCH syndrome. CASK KO cultured cerebellar granule (CG) cells show progressive cell death that can be rescued by co-infection with lentivirus expressing wild-type CASK. Rescue experiments with CASK deletion mutants identify that the CaMK, PDZ, and SH3, but not L27 and guanylate kinase domains of CASK are required for the survival of CG cells. We identify missense mutations in the CaMK domain of CASK derived from human patients that fail to rescue the cell death of cultured CASK KO CG cells. Machine learning-based structural analysis using AlphaFold 2.2 predicts that these mutations disrupt the structure of the binding interface with Liprin-α2. These results suggest that the interaction with Liprin-α2 via the CaMK domain of CASK may be involved in the pathophysiology of cerebellar hypoplasia in MICPCH syndrome.

The effects of two possible factors, prevention of pest immigration and enhancement of natural enemies, in suppressing onion thrips, Thrips tabaci L., were estimated in a small-scale experimental system of spring-planted onions intercropped with barley. The population dynamics of the thrips and their potential predatory natural enemies were investigated in four treatments: control (bare ground), insect net barrier, and onion-barley intercropping with or without trimming. We found that intercropping significantly suppressed onion thrips. It is unlikely that this effect was due to the prevention of thrip immigration because they seemed to move over the camouflage and/or physical barriers of the barley and the net barrier surrounding the onions easily. Intercropping with barley significantly increased hoverfly (Syrphidae) larvae numbers on onion leaves, and that of some groups of ground-dwelling predators such as large carnivorous ground beetles (Carabidae), ants (Formicidae), and wolf spiders (Lycosidae). We conclude that the suppression of thrips in this system was associated with the enhancement of hoverfly larvae abundance, mainly Sphaerophoria macrogaster (Thomson) (Syrphidae: Diptera) because they were observed together with thrips on onions and have been reported to predate thrips as well as aphids. Some hoverfly larvae on barley might move to nearby onions to search for new food sources and attack thrips., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The prognosis of pediatric acute myeloid leukemia (AML) has improved via stratification therapy. However, relapse or death occurs in 30%-40% of cases. Novel genetic factors for pediatric AML need to be elucidated to improve prognosis. We detected recurrent internal tandem duplication in upstream binding transcription factor (UBTF-ITD) in 1.2% (6/503) of Japanese pediatric patients with de novo AML. No UBTF-ITD was detected in 175 adult patients with AML or in 65 cell lines that included 15 AML, 39 acute lymphoblastic leukemia, five chronic myeloid leukemia, and six neuroblastoma cell lines. All UBTF-ITDs were found in exon 13 and shared a duplicated region. UBTF-ITD was more frequently detected in patients with trisomy 8, FLT3-ITD, WT1 mutation, and/or high PRDM16 expression (trisomy 8, 3/6; FLT3-ITD, 5/6; WT1 mutation, 2/6; and high PRDM16 expression, 6/6). Gene expression patterns of patients with UBTF-ITD were similar to those of patients with NUP98::NSD1 or FUS::ERG. Survival analysis of the AML-05 cohort revealed that patients with UBTF-ITD had worse outcomes than those without UBTF-ITD (3-year event-free survival, 20% vs. 55%; 3-year overall survival, 40% vs. 74%). Moreover, among the 27 patients with trisomy 8, all three patients with UBTF -ITD had a poor prognosis resulting in early events (relapse or non-complete remission) within 1 year. Our findings suggest that UBTF-ITD may be a novel and significant prognostic factor for pediatric patients with AML., (© 2022 Wiley Periodicals LLC.)

Background Epistaxis is a very common symptom. The occurrence of epistaxis may be affected by dry environments, but there are some differences among previous reports and this view is controversial. Objective We investigated the relationship between the number of epistaxes and daily average relative humidity. Methods Data on patients with epistaxis between March 2011 and February 2021 were collected from two hospitals. The daily average relative humidity was examined, and the change in the number of patients with epistaxis due to humidity was investigated using a generalized linear mixed model. Results A total of 4184 cases of epistaxis were identified. The number of epistaxis cases per day was significantly associated with the daily average relative humidity (p < 0.001). One percent increment in average relative humidity decreases the number of epistaxis cases per day by 1.1%. Conclusion A negative correlation was found to exist between daily average relative humidity and occurrences of epistaxis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Matsumoto et al.)

The impact of human leukocyte antigen (HLA) mismatching at the HLA-A, -B, -C, and -DRB1 loci after unrelated bone marrow transplantation in paediatric patients with haematological malignancies has not been fully examined. Here, we analysed patients with haematological malignancies (all aged ≤15 years; n = 1330) who underwent a first unrelated bone marrow transplantation between 1993 and 2017 in Japan. The results show that although an HLA mismatch was significantly associated with a low relapse rate, it was also associated with higher non-relapse mortality. There was a significant association between HLA mismatch and low overall survival. Locus mismatch analysis revealed that, as in adults, an HLA-C mismatch had a significant negative impact on survival; however, in paediatric patients, an HLA-DRB1 mismatch did not have a negative impact, although these HLA mismatch effects are weakened in recent cases. Taken together, the results suggest that an HLA-matched donor should be the first candidate for paediatric patients; however, for patients without a matched sibling or matched unrelated donor, we can select an unrelated donor with a mismatch at HLA-DRB1 if available., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Background: The most common preventative measure against mumps is vaccination with mumps vaccine. Over 122 countries have implemented mumps vaccine routine immunization programs, mostly via Measles-Mumps-Rubella (MMR) vaccine. In Japan, the unexpectedly high incidence of aseptic meningitis caused by mumps vaccine led to the discontinuation of the MMR national vaccination program in 1993, inadvertently resulting in the re-emergence of mumps. Plans of introducing monovalent mumps vaccine into routine vaccination schedule have become one of the emerging topics in health policy that has warranted the need in evaluating its value for money., Methods: We conducted cost-effectiveness analyses with Markov model and calculated incremental cost-effectiveness ratios (ICERs) of two different vaccination programs (a single-dose program at one-year-old, a two-dose program with second dose uptakes at five) compared to status quo from both payers' and societal perspectives. Transition probabilities and utility weights in estimating quality-adjusted life-year (QALY), and disease treatment costs were either estimated or obtained from literature. Costs per vaccination were assumed at ¥6140 (US$58;1US$ = ¥106)., Results: Both programs reduce disease treatment costs compared to status quo, while the reduction cannot offset vaccination cost. ICER of either program is found to be under ¥5,000,000 (US$47,170)/QALY willingness-to-pay (WTP) threshold from either perspective. Results of probabilistic sensitivity analyses expressed by net monetary benefit indicated that at the WTP threshold, the acceptability is at 92.6% for two-dose vaccination program, 0% for single-dose vaccination program, and 7.4% for current no vaccination program. Two-dose program was optimal among the alternatives. One-way sensitivity analyses revealed that proportion of mumps-related hearing loss among mumps cases and vaccine effectiveness (VE) were key variables in changing the ICERs., Conclusion: Routine vaccination program of single- and two-dose programs were cost-effective from both payers' and societal perspectives. Between the two, the two-dose vaccination program was observed to be more favorable., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)