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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 anti-tumor response mediated in part through an anti-tumor immune response.

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.)

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.

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.)

Studies have proposed that individuals with autism spectrum disorder (ASD) can be divided into several subtypes depending on their sensory features. However, consideration of social communication features is also crucial for configuring ASD subtypes, because social and sensory features are tightly interrelated. In this study, we asked Japanese individuals with ASD to answer the Short Sensory Profile (SSP) and the Social Responsiveness Scale, Second Edition (SRS-2), which measure sensory and social aspects, respectively. Consequent latent profile analysis demonstrated that the participants could be divided into five subgroups: two groups exhibited opposite or inconsistent patterns between the SSP and SRS-2 scores, while the other groups exhibited consistent patterns. Our findings indicate the existence of diverse phenotypes in individuals with ASD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In soft tissue sarcomas, the oncological and functional outcomes between planned excision and unplanned excision with additional wide resection remains controversial. The purpose of this study is to determine the impact of unplanned excision on oncological and functional outcomes., Methods: A retrospective single-center study was performed. Patients with soft tissue sarcoma surgically treated in 2005-2019 were included in this study. A total of 120 patients consisting of planned excision (PE) group (n = 88), and unplanned excision (UE) group (n = 32) were included. Overall-survival (OS), local recurrence-free survival (LRFS), metastasis-free survival (MFS), disease-free survival (DFS), incidence rate of reconstructive surgery and musculoskeletal tumor society (MSTS) score were assessed. Propensity score matching method was used in statistical analysis., Results: The 5-year survival rate of OS, LRFS, MFS, and DFS did not differ between the PE and UE groups, however, rates of reconstructive surgery were higher in the UE group (PE: 48% vs. UE: 84%, p < 0.001). These results did not differ (PE: 41% vs. UE: 82%, p = 0.012) after propensity score matching was performed to align the backgrounds with difference in tumor size and depth. For MSTS score, the total score and "pain" and "emotional acceptance" scores were higher in the PE group before propensity score matching. The "pain" and "emotional acceptance" scores were higher in the PE group after propensity score matching also., Conclusions: Unplanned excision did not deteriorate oncological outcomes, however unplanned excision lead to unnecessary reconstructive surgery. Unplanned excision adversely affected patient-reported outcomes without worsening pure functional outcomes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background/aim: Soft-tissue tumors are difficult to differentiate as benign or malignant. Immune markers, such as the neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and absolute lymphocyte count (ALC) in serum, have been reported to be useful in the diagnosis and predicting prognosis of several malignancies. We investigated the diagnostic value of these immune markers in differentiating soft-tissue tumors., Patients and Methods: A total of 692 patients who underwent biopsy or surgery of soft-tissue tumors were included and divided into benign tumor, low-grade malignancy, or high-grade malignancy groups. Immune markers were calculated from the preoperative blood tests and compared between the groups. A receiver operating curve (ROC) analysis was conducted between the benign disease group and a combination of the groups with malignancy to determine which immune marker had the most diagnostic value., Results: NLR and MLR were significantly different between the three groups with benign disease having the lowest value and high-grade malignancies the highest. Benign disease was also associated with lower PLR and higher ALC. There was no difference between the low- and high-grade malignancies in PLR and ALC. From the ROC analysis, NLR had the highest area under the curve (AUC) value of 0.773 out of the four markers. When limited to small tumors (≤30 mm), NLR had the highest AUC value of 0.729., Conclusion: The NLR showed the highest diagnostic value, although the diagnostic ability was not adequately high to differentiate benign and malignant soft-tissue tumors alone. NLR may serve as diagnostic support in combination with clinical history, physical findings, and tumor-imaging results., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The TFDP1 gene codes for the heterodimeric partner DP1 of the transcription factor E2F. E2F, principal target of the tumor suppressor pRB, plays central roles in cell proliferation by activating a group of growth-related genes. E2F also mediates tumor suppression by activating tumor suppressor genes such as ARF, an upstream activator of the tumor suppressor p53, when deregulated from pRB upon oncogenic changes. Among 8 E2F family members (E2F1∼E2F8), expression of activator E2Fs (E2F1∼E2F3a) is induced at the G1/S boundary of the cell cycle after growth stimulation by E2F itself. However, mechanisms regulating DP1 expression are not known. We show here that over-expression of E2F1 and forced inactivation of pRB, by adenovirus E1a, induced TFDP1 gene expression in human normal fibroblast HFFs, suggesting that the TFDP1 gene is a target of E2F. Serum stimulation of HFFs also induced TFDP1 gene expression, but with different kinetics from that of the CDC6 gene, a typical growth-related E2F target. Both over-expression of E2F1 and serum stimulation activated the TFDP1 promoter. We searched for E2F1-responsive regions by 5' and 3' deletion of the TFDP1 promoter and by introducing point mutations in putative E2F1-responsive elements. Promoter analysis identified several GC-rich elements, mutation of which reduced E2F1-responsiveness but not serum-responsiveness. ChIP assays showed that the GC-rich elements bound deregulated E2F1 but not physiological E2F1 induced by serum stimulation. These results suggest that the TFDP1 gene is a target of deregulated E2F. In addition, knockdown of DP1 expression by shRNA enhanced ARF gene expression, which is specifically induced by deregulated E2F activity, suggesting that activation of the TFDP1 gene by deregulated E2F may function as a failsafe feedback mechanism to suppress deregulated E2F and maintain normal cell growth in the event that DP1 expression is insufficient relative to that of its partner activator E2Fs. a maximum of 6 keywords: E2F, DP1, TFDP1 gene, pRB, gene expression., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: Postpartum depression (PPD) may have negative effects on the parents and lead to impaired cognitive, socioemotional, and behavioral development in their children. The purpose of this study was to examine factors associated with PPD in parents during the first year after delivery., Methods: This study used a self-administered questionnaire. Questionnaires were mailed at 5 days, 3 months, 6 months, and 1 year after delivery, respectively. The particpants were 107 pairs of mothers and fathers. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Data on sense of coherence (SOC), Quality Marriage Index, Social Support Scale, Mother-to-Infant Bonding Scale, and sociodemographic variables were collected. Multiple regression analysis was performed to examine the strength of the association between several variables and the EPDS at each survey period for fathers and mothers, respectively., Results: The prevalence of PPD in the first-year postpartum ranged from 12.1%-23.4% to 7.5%-8.4% for fathers and mothers, respectively. SOC had the strongest impact on EPDS scores for both fathers and mothers at all four survey periods., Conclusions: Our findings suggest that stress coping skills are an important factor affecting PPD throughout the first-year postpartum for both fathers and mothers., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Background: The Polycomb Repressor Complex 1 (PRC1) is an epigenetic regulator of differentiation and development, consisting of multiple subunits including RING1, BMI1, and Chromobox. The composition of PRC1 dictates its function and aberrant expression of specific subunits contributes to several diseases including cancer. Specifically, the reader protein Chromobox2 (CBX2) recognizes the repressive modifications including histone H3 lysine 27 tri-methylation (H3K27me3) and H3 lysine 9 dimethylation (H3K9me2). CBX2 is overexpressed in several cancers compared to the non-transformed cell counterparts, it promotes both cancer progression and chemotherapy resistance. Thus, inhibiting the reader function of CBX2 is an attractive and unique anti-cancer approach., Research Design & Methods: Compared with other CBX family members, CBX2 has a unique A/T-hook DNA binding domain that is juxtaposed to the chromodomain (CD). Using a computational approach, we constructed a homology model of CBX2 encompassing the CD and A/T hook domain. We used the model as a basis for peptide design and identified blocking peptides that are predicted to directly bind the CD and A/T-hook regions of CBX2. These peptides were tested in vitro and in vivo models., Conclusion: The CBX2 blocking peptide significantly inhibited both 2D and 3D growth of ovarian cancer cells, downregulated a CBX2 target gene, and blunted tumor growth in vivo.

The transcription factor E2F, the principal target of the tumor suppressor pRB, plays crucial roles in cell proliferation and tumor suppression. In almost all cancers, pRB function is disabled, and E2F activity is enhanced. To specifically target cancer cells, trials have been undertaken to suppress enhanced E2F activity to restrain cell proliferation or selectively kill cancer cells, utilizing enhanced E2F activity. However, these approaches may also impact normal growing cells, since growth stimulation also inactivates pRB and enhances E2F activity. E2F activated upon the loss of pRB control (deregulated E2F) activates tumor suppressor genes, which are not activated by E2F induced by growth stimulation, inducing cellular senescence or apoptosis to protect cells from tumorigenesis. Deregulated E2F activity is tolerated in cancer cells due to inactivation of the ARF-p53 pathway, thus representing a feature unique to cancer cells. Deregulated E2F activity, which activates tumor suppressor genes, is distinct from enhanced E2F activity, which activates growth-related genes, in that deregulated E2F activity does not depend on the heterodimeric partner DP. Indeed, the ARF promoter, which is specifically activated by deregulated E2F, showed higher cancer-cell specific activity, compared to the E2F1 promoter, which is also activated by E2F induced by growth stimulation. Thus, deregulated E2F activity is an attractive potential therapeutic tool to specifically target cancer cells.

The turnover of kindergarten teachers has drastically increased in the past 10 years. Reducing the turnover rates among preschool workers has become an important issue worldwide. Parents have avoided enrolling children in preschools due to insufficient care, which affects their ability to work. Therefore, this study developed a diagnostic model to understand preschool workers' unwillingness to continue working. A total of 1002 full-time preschool workers were divided into 2 groups. Predictors were drawn from general questionnaires, including those for mental health. We compared 3 algorithms: the least absolute shrinkage and selection operator, eXtreme Gradient Boosting, and logistic regression. Additionally, the SHapley Additive exPlanation was used to visualize the relationship between years of work experience and intention to continue working. The logistic regression model was adopted as the diagnostic model, and the predictors were "not living with children," "human relation problems with boss," "high risk of mental distress," and "work experience." The developed risk score and the optimal cutoff value were 14 points. By using the diagnostic model to determine workers' unwillingness to continue working, supervisors can intervene with workers who are experiencing difficulties at work and can help resolve their problems., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)