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Background Ayres Sensory Integration ® (ASI) intervention focuses on developing sensory processing abilities to improve motor coordination, executive functions, participation, and satisfaction in everyday activities. No well-designed research studies have addressed clearly the effectiveness of ASI intervention for children with developmental coordination disorder (DCD) even though ASI intervention was effective for children with autism spectrum disorders. Methods and procedures Seventeen children with DCD (aged 4-8.5 years old) were randomly assigned to either an intervention or a control group. ASI intervention was provided to the intervention group twice a week for 10 weeks. In addition to participants' goals in daily activities, sensory integration abilities and motor coordination were assessed before and after the intervention. Outcomes and results The split-plot factorial design demonstrated significant time × group interaction in the total score (F (1, 15) = 7.651, p = 0.014, partial η 2 = 0.338) and balance score (F (1, 15) = 11.163, p = 0.004, partial η 2  = 0.427) of the Movement Assessment Battery for Children-Second Edition (MABC-2), with significant differences in simple main effects before and after intervention for the intervention group. The post-intervention Goal Attainment Scale (GAS) score showed a significant difference in the time × group interaction (F (1, 15) = 15.662, p = 0.001, partial η 2 = 0.511) and a simple main effect in the intervention group. Conclusions A short-term, intensive ASI intervention improves motor performance, coordination, and daily activities function in children with DCD., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics Committee of Nagasaki University Graduate School of Biomedical Sciences and Ethics Committee of Prefectural University of Hiroshima issued approval 1909120 and 18MH016-01. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This work was supported by the JSPS KAKENHI Grant (Number: JP19K19875). Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Yamanishi et al.)

Background: Children's participation is an important outcome for children, families, and rehabilitation., Objectives: We compared participation patterns (home and community) of 6- to 12-year-old Japanese children with autism and children with typical development (TD) and explored the associations of participation with familial, environmental, and child-related factors., Method: Twenty-five mothers of children with autism and 21 mothers of TD children completed a survey covering their child's participation and environment, family empowerment, autism symptoms, sensory processing, behavior, and demographic characteristics., Results: Children with autism showed restricted home and community participation. Home involvement was associated with family empowerment and the children's age, whereas home frequency was linked to environmental supportiveness and household income., Conclusion: Japanese children with autism need appropriate support to address decreased participation. Occupational therapists may focus on family empowerment and the child's environment to facilitate the home participation of children with autism., 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.

In almost all cancers, the p53 pathway is disabled and cancer cells survive. Hence, it is crucially important to induce cell death independent of p53 in the treatment of cancers. The transcription factor E2F1 is controlled by binding of the tumor suppressor pRB, and induces apoptosis by activating the ARF gene, an upstream activator of p53, when deregulated from pRB by loss of pRB function. Deregulated E2F1 can also induce apoptosis, independent of p53, via other targets such as TAp73 and BIM . We searched for novel E2F1-interacting proteins and identified the RNA helicase DEAD/H box 5 (DDX5), which also functions as a transcriptional coactivator. In contrast to the reported growth-promoting roles of DDX5, we show that DDX5 suppresses cell growth and survival by augmentation of deregulated E2F1 activity. Over-expression of DDX5 enhanced E2F1 induction of tumor suppressor gene expression and cell death. Conversely, shRNA-mediated knockdown of DDX5 compromised both. Moreover, DDX5 modulated E2F1-mediated cell death independent of p53, for which DDX5 also functions as a coactivator. Since p53 function is disabled in almost all cancers, these results underscore the roles of DDX5 in E2F1-mediated induction of cell death, independent of p53, and represent novel aspects for the treatment of p53-disabled cancer cells.

Poly ADP-ribose polymerase inhibitors (PARPi) are first-line maintenance therapy for ovarian cancer and an alternative therapy for several other cancer types. However, PARPi-resistance is rising, and there is currently an unmet need to combat PARPi-resistant tumors. Here, we created an immunocompetent, PARPi-resistant mouse model to test the efficacy of combinatory PARPi and euchromatic histone methyltransferase 1/2 inhibitor (EHMTi) in the treatment of PARPi-resistant ovarian cancer. We discovered that inhibition of EHMT1/2 resensitizes cells to PARPi. Markedly, we show that single EHMTi and combinatory EHMTi/PARPi significantly reduced PARPi-resistant tumor burden and that this reduction is partially dependent on CD8 T cells. Altogether, our results show a low-toxicity drug that effectively treats PARPi-resistant ovarian cancer in an immune-dependent manner, supporting its entry into clinical development and potential incorporation of immunotherapy. Implications: Targeting the epigenome of therapy-resistant ovarian cancer induces an antitumor response mediated in part through an antitumor immune response., (©2024 American Association for Cancer Research.)

Medetomidine, midazolam, and butorphanol (MMB) anesthesia is the preferred choice for rodents but requires excess volume of intramuscular injection in rabbits, which can lead to muscular damage. This study aimed to evaluate a dual-route MMB administration via the intravenous and subcutaneous routes in rabbits. MMB was administered to male Kbs:JW rabbits with an intravenous injection of 0.2 mL/kg followed by a subcutaneous injection of 0.8 mL/kg, totaling 0.2 mg/kg medetomidine, 2.0 mg/kg midazolam, and 2.0 mg/kg butorphanol. We compared the anesthetic effects of this dual-route method with those of intramuscular administration. The dual-route method resulted in a shorter induction time and similar anesthetic duration compared with those of the intramuscular route. While it induced a temporary decrease in body temperature within 30 min post-injection, other vital signs, such as respiration rate, heart rate, and O 2 saturation, remained similar. Notably, unlike intramuscular administration, dual-route administration did not increase tissue injury marker levels. This dual-route MMB administration provided sufficient anesthetic depth during surgery, eliminating pain reflexes. Double-dose administration extended anesthetic duration but resulted in rare fatalities, indicating room for protocol improvement. In conclusion, the novel anesthetic method is preferable for injectable anesthesia in rabbits, providing rapid induction and sufficient anesthetic duration, while potentially minimizing muscle injury. This technique may be beneficial for both laboratory and companion animals and significantly enhance animal welfare in anesthesia by reducing the pain associated with injectable anesthesia.

The transcription factor E2F1 is the principal target of the tumor suppressor pRB. E2F1 promotes cell proliferation by activating growth-promoting genes upon growth stimulation. In contrast, E2F1 contributes to tumor suppression by activating tumor suppressor genes, such as ARF , upon loss of pRB function, a major oncogenic change. The transactivation domain of E2F1 has previously been mapped to the C-terminal region. We show here that the N-terminal region of E2F1 is critical for the activation of tumor suppressor genes. Deletion of the N-terminal region dramatically compromised E2F1 activation of tumor suppressor genes. The N-terminal region showed transactivation ability when fused to the DNA-binding domain of GAL4. A search for novel interacting factors with the N-terminal region, using a yeast two-hybrid system, identified the general transcription factor GTF2H2. Overexpression of GTF2H2 enhanced E2F1 activation of tumor suppressor genes and induction of cell death. Conversely, the knockdown of GTF2H2 compromised both. E2F1 binding enhanced the binding of GTF2H2 to target promoters depending on the integrity of the N-terminal region. Taken together, these results suggest that the N-terminal region of E2F1 contains a novel transactivation domain that mediates the activation of tumor suppressor genes, at least in part, by recruiting GTF2H2.

Introduction: Research supporting the presence of diverse motor impairments, including impaired balance coordination, in children with autism spectrum disorder (ASD) is increasing. The one-legged standing test (OLST) is a popular test of balance. Since machine learning is a powerful technique for learning predictive models from movement data, it can objectively evaluate the processes involved in OLST. This study assesses machine learning's effectiveness in evaluating movement in OLST for predicting high autistic trait., Methods: In this study, 64 boys and 62 girls participated. The participants were instructed to stand on one leg on a pressure sensor while facing the experimenter. The data collected in the experiment were time-series data pertaining to pressure distribution on the sole of the foot and full-body images. A model to identify the participants belonging to High autistic trait group and Low autistic trait group was developed using a support vector machine (SVM) algorithm with 16 explanatory variables. Further, classification models were built for the conventional, proposed, and combined explanatory variable categories. The probabilities of High autistic trait group were calculated using the SVM model., Results: For proposed and combined variables, the accuracy, sensitivity, and specificity scores were 1.000. The variables shoulder, hip, and trunk are important since they explain the balance status of children with high autistic trait. Further, the total Social Responsiveness Scale score positively correlated with the probability of High autistic trait group in each category of explanatory variables., Discussion: Results indicate the effectiveness of evaluating movement in OLST by using movies and machine learning for predicting high autistic trait. In addition, they emphasize the significance of specifically focusing on shoulder and waist movements, which facilitate the efficient predicting high autistic trait. Finally, studies incorporating a broader range of balance cues are necessary to comprehensively determine the effectiveness of utilizing balance ability in predicting high autistic trait., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ohmoto, Terada, Shimizu, Kawahara, Iwanaga and Kumazaki.)

Background: Deltoid muscle detachment and atrophy have been reported to occur after shoulder surgery., Purpose: To investigate the 2-year changes in deltoid muscle structure and function after arthroscopic rotator cuff repair (ARCR) using magnetic resonance imaging (MRI) and electrophysical examination., Study Design: Case series; Level of evidence, 4., Methods: A total of 72 patients (72 shoulders) who underwent ARCR between 2015 and 2020 were enrolled. Whole deltoid muscle volume and regional (anterior, lateral, and posterior) muscle thicknesses were determined on T2-weighted MRI scans of both shoulders taken preoperatively and at 1, 3, 6, 12, and 24 months postoperatively, and their correlations with compound muscle action potentials (CMAPs), shoulder abduction muscle strength, and Constant scores were investigated. Comparison between groups was performed using paired or Student t tests, and the relationship between deltoid muscle volume and various factors was determined using Pearson correlation analysis., Results: The volume of the deltoid muscle on the affected side decreased from 44,369 ± 12,371 mm 3 preoperatively to 38,139 ± 10,615 mm 3 at 1 month postoperatively ( P < .05), representing a 14% decrease. The deltoid muscle volume of the contralateral side also significantly decreased during the same time frame, from 43,278 ± 12,248 to 40,273 ± 11,464 mm 3 ( P < .05), representing a 7% decrease at 1 month postoperatively. Subsequently, the deltoid muscle volume on both sides recovered to preoperative levels at 12 months and was maintained at 24 months. Only the thickness of the anterior part of the deltoid was markedly decreased, from 13.9 ± 3.7 mm preoperatively to 12.0 ± 3.2 mm at 1 month postoperatively ( P < .05), representing a 14% reduction. The CMAP amplitude showed a significant decrease at 1 month postoperatively; however, no significant difference was observed after 12 months when compared with the preoperative values or the values on the contralateral side. Positive correlations were found between deltoid muscle volume and CMAP amplitude at 24 months as well as between deltoid muscle volume and shoulder abduction muscle strength ( R 2 = 0.698; P < .05) and Constant score ( R 2 = 0.133; P < .05)., Conclusion: Our study demonstrated that the early structural and functional decline of the deltoid muscle after ARCR was fully recovered within 1 year, confirming that this procedure does not negatively affect the deltoid muscle., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Angiosarcoma of the bone is very rare, accounting for less than 1% of all malignant bone tumors. We report our experience with an epithelioid hemangiosarcoma arising in the proximal tibia and a review of the literature. The patient, an 85-year-old male, was referred to our institution because of left knee pain that had persisted for five months, and bone radiolucency was observed in the proximal tibia. A bone and prostate biopsy was performed due to a suspicion of prostate cancer and bone metastasis. The positron emission tomography-computed tomography (PET-CT) showed accumulation in the prostate and proximal tibia, and the prostate-specific antigen (PSA) level was high at 14.11 ng/mL. Therefore, we diagnosed the patient with bone metastasis of prostate cancer and performed curettage and cement filling. However, postoperative pathological diagnosis revealed an epithelioid hemangiosarcoma, and we considered amputation. Two months after curettage, the patient underwent transfemoral amputation because of local recurrence. Eight months after amputation, he died due to multiple metastases. Approximately 20% of cases with epithelioid hemangiosarcoma have multiple metastases at the time of initial diagnosis, and it is sometimes difficult to distinguish from bone metastases of cancer because they may be arranged in foci or on cords. There are few reports of effective adjuvant therapy, and the clinical course can be rapid, so early amputation should be considered., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iwanaga et al.)

Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). The trans-activator protein Tax of HTLV-1 plays crucial roles in leukemogenesis by promoting proliferation of virus-infected cells through activation of growth-promoting genes. However, critical target genes are yet to be elucidated. We show here that Tax activates the gene coding for cyclin-dependent kinase 7 (CDK7), the essential component of both CDK-activating kinase (CAK) and general transcription factor TFIIH. CAK and TFIIH play essential roles in cell cycle progression and transcription by activating CDKs and facilitating transcriptional initiation, respectively. Tax induced CDK7 gene expression not only in human T-cell lines but also in normal peripheral blood lymphocytes (PHA-PBLs) along with increased protein expression. Tax stimulated phosphorylation of CDK2 and RNA polymerase II at sites reported to be mediated by CDK7. Tax activated the CDK7 promoter through the NF-κB pathway, which mainly mediates cell growth promotion by Tax. Knockdown of CDK7 expression reduced Tax-mediated induction of target gene expression and cell cycle progression. These results suggest that the CDK7 gene is a crucial target of Tax-mediated trans-activation to promote cell proliferation by activating CDKs and transcription.

Background: Restricted and repetitive behavior (RRB) is a core symptom of autism spectrum disorder (ASD). The structure of RRB subcategories and their relationship with atypical sensory processing in Japan are not well understood. This study examined subcategories of the RRB in Japanese children with ASD and explored their relationship with sensory processing., Methods: A total of 103 children and adolescents with ASD participated in this study, with more than 70% having a co-occurring intellectual disability. First, exploratory factor analysis of the RRB items of the Social Responsiveness Scale second edition (SRS-2) was conducted to identify RRB subcategories. Second, Spearman correlation and multiple regression analysis were run to examine relationships between the RRB subcategories of SRS-2 and subsections of the Short Sensory Profile., Results: Exploratory factor analysis indicated a two factors solution; repetitive sensory and motor behavior and insistence on sameness. Multiple regression analysis suggested that Movement Sensitivity and Auditory Filtering were associated with insistence on sameness. Furthermore, Underresponsive/Seeks Sensation, Visual/Auditory Sensitivity, and diagnosis of intellectual disabilities were associated with repetitive sensory and motor behavior., Conclusions: Findings indicate that RRB subcategories are differently related to sensory processing patterns in children with ASD. These results suggested that RRB subcategories are beneficial to consider the relationship between RRB and sensory processing., Competing Interests: HN was employed by LITALICO Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Noda, Yoneda, Kamogawa, Tanaka, Ide and Iwanaga.)

Chromobox 2 (CBX2), an epigenetic reader and component of polycomb repressor complex 1, is highly expressed in >75% of high-grade serous carcinoma. Increased CBX2 expression is associated with poorer survival, whereas CBX2 knockdown leads to improved chemotherapy sensitivity. In a high-grade serous carcinoma immune-competent murine model, knockdown of CBX2 decreased tumor progression. We sought to explore the impact of modulation of CBX2 on the tumor immune microenvironment (TIME), understanding that the TIME plays a critical role in disease progression and development of therapy resistance. Exploration of existing datasets demonstrated that elevated CBX2 expression significantly correlated with specific immune cell types in the TIME. RNA sequencing and pathway analysis of differentially expressed genes demonstrated immune signature enrichment. Confocal microscopy and co-culture experiments found that modulation of CBX2 leads to increased recruitment and infiltration of macrophages. Flow cytometry of macrophages cultured with CBX2-overexpressing cells showed increased M2-like macrophages and decreased phagocytosis activity. Cbx2 knockdown in the Trp53-null, Brca2-null ID8 syngeneic murine model (ID8 Trp53-/-Brca2-/-) led to decreased tumor progression compared with the control. NanoString immuno-oncology panel analysis suggested that knockdown in Cbx2 shifts immune cell composition, with an increase in macrophages. Multispectral immunohistochemistry (mIHC) further confirmed an increase in macrophage infiltration. Increased CBX2 expression leads to recruitment and polarization of protumor macrophages, and targeting CBX2 may serve to modulate the TIME to enhance the efficacy of immune therapies., Significance: CBX2 expression correlates with the TIME. CBX2 modulation shifts the macrophage population, potentially leading to an immunosuppressive microenvironment, highlighting CBX2 as a target to improve efficacy of immunotherapy., (©2024 The Authors; Published by the American Association for Cancer Research.)

Radial nerve palsy (RNP) is classified as traumatic, non-traumatic, or iatrogenic. The most frequent etiologic agent is the fracture of the humerus of the shaftand distal. We experienced a case of RNP caused by desmoid-type fibromatosis around the radial nerve. The RNP caused by desmoid-type fibromatosis has not been reported in the literature. We present this case here with a review of the RNP literature. The patient is a 16-year-old female, right-hand dominant, who became aware of the difficulty in extending her right little finger without any triggers five months ago. She was also aware of the difficulty in extending the ring finger, and her symptoms gradually worsened. She was referred to our hospital after consulting a home doctor. MRI of the elbow showed a high-intensity occupying lesion on T2-weighted images (T2WI) slightly proximal to the elbow joint. Ultrasonography (US) showed a partial nerve constriction and radial nerve enlargement on the distal side of the constriction. The approach was made from the posterior lateral side of the distal upper arm, and the radial nerve was exposed. There was a 1 cm white tissue strongly adherent on the radial nerve, which was compressing the radial nerve, and it was resected piece by piece. After the resection, the radial nerve was indented. The pathological diagnosis of the resected tissue was fibromatosis. Gradually, she was able to extend her fingers after the surgery and recovered completely in six months., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iwanaga et al.)

Despite the success of poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory double-stranded RNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T-cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi-resistant ovarian tumor growth in vivo, and promotes antitumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer., (©2024 American Association for Cancer Research.)

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes code for growth factors and their receptors, cytokines, cell adhesion molecules, growth signal transducers, transcription factors and cell cycle regulators. We show here that Tax activates the gene coding for coactivator-associated arginine methyltransferase 1 (CARM1), which epigenetically enhances gene expression through methylation of histones. Tax activated the Carm1 gene and increased protein expression, not only in human T-cell lines but also in normal peripheral blood lymphocytes (PHA-PBLs). Tax increased R17-methylated histone H3 on the target gene IL-2Rα , concomitant with increased expression of CARM1. Short hairpin RNA (shRNA)-mediated knockdown of CARM1 decreased Tax-mediated induction of IL-2Rα and Cyclin D2 gene expression, reduced E2F activation and inhibited cell cycle progression. Tax acted via response elements in intron 1 of the Carm1 gene, through the NF-κB pathway. These results suggest that Tax-mediated activation of the Carm1 gene contributes to leukemogenic target-gene expression and cell cycle progression, identifying the first epigenetic target gene for Tax-mediated trans-activation in cell growth promotion.

Participation is important for children's quality of life (QOL). This study aimed to identify participation factors that influence QOL among Japanese children with neurodevelopmental disorders. Ninety-two Japanese parents of children with neurodevelopmental disorders participated in this study. The parents completed the parent version of the Kid- and Kiddo-KINDL health-related QOL questionnaire and the Participation and Environment Measure for Children and Youth. The data were examined using the random forest algorithm to analyze the participation factors that affected the children's QOL. The analyses revealed that school and community environmental factors that affected participation were the most important predictors of QOL among children. As school and community environments can significantly impact the QOL of children with neurodevelopmental disorders, greater focus should be placed on participation in environmental contexts.

Vision is formed by the transmission of light stimuli to the brain through axons extending from photoreceptor cells. Damage to these axons leads to loss of vision. Despite research on neural circuit regeneration through transplantation, achieving precise axon projection remains challenging. To achieve optic nerve regeneration by transplantation, we employed the Drosophila visual system. We previously established a transplantation method for Drosophila utilizing photoreceptor precursor cells extracted from the eye disc. However, little axonal elongation of transplanted cells into the brain, the lamina, was observed. We verified axonal elongation to the lamina by modifying the selection process for transplanted cells. Moreover, we focused on N-cadherin (Ncad), a cell adhesion factor, and Twinstar (Tsr), which has been shown to promote actin reorganization and induce axon elongation in damaged nerves. Overexpression of Ncad and tsr promoted axon elongation to the lamina, along with presynaptic structure formation in the elongating axons. Furthermore, overexpression of Neurexin-1 (Nrx-1), encoding a protein identified as a synaptic organizer, was found to not only promote presynapse formation but also enhance axon elongation. By introducing Ncad, tsr, and Nrx-1, we not only successfully achieved axonal projection of transplanted cells to the brain beyond the retina, but also confirmed the projection of transplanted cells into a deeper ganglion, the medulla. The present study offers valuable insights to realize regeneration through transplantation in a more complex nervous system., (© 2024 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.)

Neurons establish specific synapses based on the adhesive properties of cell-surface proteins while also retaining the ability to form synapses in a relatively non-selective manner. However, comprehensive understanding of the underlying mechanism reconciling these opposing characteristics remains incomplete. Here, we have identified Side-IV/Beat-IIb, members of the Drosophila immunoglobulin superfamily, as a combination of cell-surface recognition molecules inducing synapse formation. The Side-IV/Beat-IIb combination transduces bifurcated signaling with Side-IV's co-receptor, Kirre, and a synaptic scaffold protein, Dsyd-1. Genetic experiments and subcellular protein localization analyses showed the Side-IV/Beat-IIb/Kirre/Dsyd-1 complex to have two essential functions. First, it narrows neuronal binding specificity through Side-IV/Beat-IIb extracellular interactions. Second, it recruits synapse formation factors, Kirre and Dsyd-1, to restrict synaptic loci and inhibit miswiring. This dual function explains how the combinations of cell-surface molecules enable the ranking of preferred interactions among neuronal pairs to achieve synaptic specificity in complex circuits in vivo., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Strategies are critical to promote child participation in important life activities. This study analyzed the participation strategies of the parents of children with neurodevelopmental disorders. Ninety-two Japanese elementary children with neurodevelopmental disorders and their parents were recruited. The parents completed the Participation and Environment Measure for Children and Youth (PEM-CY) questionnaire. Strategy text data obtained from the PEM-CY were analyzed with the co-occurrence network and correspondence analyses. The co-occurrence network analysis showed that the commonality of strategies to enable participation at home, school, and community settings was able to explain the child's characteristics when involved in each setting. The correspondence analysis also suggested the need for specific strategies in each setting. The importance of strategies to improve the attitudinal environment and promote the participation of children with neurodevelopmental disorders was evident. Reducing stigma is important in all environments, especially in the public sphere. In addition, specific strategies are needed in each setting, suggesting the importance of context-specific approaches.

Challenging behavior (CB), the most common example being extreme self-injurious or aggressive/destructive behavior, is often observed as a major behavior issue in individuals with severe intellectual disabilities. This study investigated how CB changed among residents of a facility for people with disabilities before and after it was restructured from a traditional format single room shared by two to three individuals with approximately 20 residents lived together to a format featuring private areas with two rooms per resident and a unitcare system. Twenty-one residents of Care Home A, which was rebuilt in the new care format, were selected. Care staff completed a questionnaire one month before, one month after, and six months after residents moved to the new facility. Scores were compared among each time point. The results revealed significant reductions in residents' aggressive, stereotyped, and targeted behaviors, such as hitting their own head and fecal smearing. The major features of the restructured facility were a living space consisting of two private rooms per resident and a shift to unit care for the entire ward. These new features enabled residents to reduce destructive stimuli and made it easier to understand what to do in each private room.

Importance: An association between sensory processing difficulties and behavioral problems among children has been reported in previous studies. Sleep problems among children can lead to both externalizing and internalizing behavioral problems. However, the relationships between sensory processing and sleep among children are not well understood., Objective: To develop a structural causal model (SCM) predicated on the hypothesis that sensory processing difficulties and sleep problems are closely related among preschoolers and may contribute to behavioral issues., Design: Cross-sectional study., Participants: A total of 168 children ages 3-5 yr who were enrolled in a preschool or an accredited kindergarten (four facilities in total) in a Japanese prefecture participated in the analysis., Outcomes and Measures: After gaining the cooperation of educators, we distributed the following items to the children's parents: an informed consent form, the Short Sensory Profile-Japanese version (SSP-J), the Japanese Sleep Questionnaire for Preschoolers (JSQ-P), and the Child Behavior Checklist for Ages 1.5-5. Through factor analysis of the SSP-J and the JSQ-P, we identified common factors. We developed an SCM using structural equation modeling., Results: Four factors were identified by factor analysis: attention deficit, sensory sensitivity, sleep problems, and restless legs syndrome symptoms. The final structural equation modeling analysis had an acceptable goodness of fit (goodness-of-fit index = .862; root-mean-square error of approximation = .087)., Conclusions and Relevance: The model suggests that sensory sensitivity and sleep difficulties may contribute to behavioral issues among preschoolers. Plain-Language Summary: The results of this study suggest that relationships exist between behavioral problems, sensory processing, and sleep among preschoolers. The authors developed a model that identified four common factors that contribute to behavioral issues among preschoolers: attention deficit, sensory sensitivity, sleep problems, and restless legs syndrome symptoms. Children's behavioral problems are an important consideration for occupational therapy practitioners working with preschoolers. Sensory processing and sleep must be accurately evaluated to address preschoolers' behavioral issues., (Copyright © 2024 by the American Occupational Therapy Association, Inc.)

The transcription factor E2F links the RB pathway to the p53 pathway upon loss of function of pRB, thereby playing a pivotal role in the suppression of tumorigenesis. E2F fulfills a major role in cell proliferation by controlling a variety of growth-associated genes. The activity of E2F is controlled by the tumor suppressor pRB, which binds to E2F and actively suppresses target gene expression, thereby restraining cell proliferation. Signaling pathways originating from growth stimulative and growth suppressive signals converge on pRB (the RB pathway) to regulate E2F activity. In most cancers, the function of pRB is compromised by oncogenic mutations, and E2F activity is enhanced, thereby facilitating cell proliferation to promote tumorigenesis. Upon such events, E2F activates the Arf tumor suppressor gene, leading to activation of the tumor suppressor p53 to protect cells from tumorigenesis. ARF inactivates MDM2, which facilitates degradation of p53 through proteasome by ubiquitination (the p53 pathway). P53 suppresses tumorigenesis by inducing cellular senescence or apoptosis. Hence, in almost all cancers, the p53 pathway is also disabled. Here we will introduce the canonical functions of the RB-E2F-p53 pathway first and then the non-classical functions of each component, which may be relevant to cancer biology.

Background: Osteosarcoma, the most common primary malignant bone tumor in childhood, very rarely occurs in the spine. Criteria of complete tumor resection/stable reconstruction of osteosarcoma and the latest protocol of neoadjuvant chemotherapy of the spine have not been reported because of its rarity, technical difficulties, and its continued severe surgical risk., Case Report: A 11-year-old female complained of back pain for several months and walking disability. The workup discovered a large destructive bone lesion in the thoracic 12 th (Th12) with vertebral body collapse and subluxation, large amount of associated anteroposterior soft tissue components, and narrowing of the spinal canal. Histology at the 1 st decompression and emergent instrumentation surgery revealed giant cell-rich osteosarcoma. Following the 1 st surgery, we performed three cycles of neoadjuvant chemotherapy based on the osteosarcoma 95J (NECO95J) protocol and evaluated efficacy of chemotherapy on the Th12 tumor. The tumor was isolated only to Th12 spine following chemotherapy. Therefore, following vascular embolization of the Th12 tumor, we performed surgical resection by single posterior approach that included total en bloc spondylectomy (TES). She recovered well postoperatively, without motor or sensory deficit and no back pain. Six cycles of postoperative neoadjuvant chemotherapy were administered after the 2 nd surgery and TES. The patient was disease-free at the 8-months clinical and radiological follow-up and showed no neurological involvement at 8-months., Conclusion: We reported a case of pediatric spinal osteosarcoma, the surgical technique of complete tumor resection, and stable reconstruction of spinal osteosarcoma. We also discussed the recent neoadjuvant chemotherapy protocol for osteosarcoma., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)