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Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain.

Background: Intellectual disability and mental health disorders constitute a major health problem globally with higher economic burden in low- and middle-income countries such as Bangladesh. In 2017, the World Bank estimated that 85% of the global population lived in low-middle-income countries. Limited research has explored health practitioner knowledge and/or confidence in the diagnosis and treatment of mental health issues in persons with intellectual disabilities (IDs) in low-income countries such as Bangladesh. Method: One hundred and ninety-seven Bangladeshi-based health practitioners were grouped into 7 main professional groups according the current Bangladeshi health hierarchy (psychiatrists; traditional healers and community workers; medical doctors; nurses; psychologists; allied health: speech therapists, occupational therapists, social workers; and others: teachers physiotherapists, administration staff). A 34-item online survey was completed, which included questions measuring symptoms of common mental health disorders with reference to the Psychiatric Assessment Schedule for Adults with Developmental Disabilities, and questions measuring confidence working with persons with IDs from the Therapy Confidence Scale-Intellectual Disabilities. Results: Participants demonstrated low knowledge of symptomology but were "confident" working with people with IDs. Kruskal-Wallis H tests indicated a significant effect of professional group on both overall knowledge and confidence levels, respectively. Traditional healers and community health workers had significantly more knowledge of symptoms than all other practitioners for obsessive-compulsive disorder, depression, psychosis, and hypomania. Conclusion: Participants demonstrated confidence, but low knowledge, in treating individuals with IDs. The development of training programs to address specific deficits in knowledge of mental health symptoms, and confidence in using assessment and assessment-based communication, is recommended.

Abstract The expansion and development of urban areas require a strategic priority of social sustainability to protect their inhabitants’ quality of life and well-being. However, social sustainability in urban areas, particularly in developing regions, becomes more apparent due to the social problems caused by rapid urbanization. The main objective of this study is to propose a model of social sustainability for socially sustainable cities in developing regions. To accomplish this objective, a quantitative research strategy was used to gather responses from residents of Dhaka city via a structured questionnaire survey; Dhaka served as a representative city from a developing region. This study used a multistage sampling technique to select 564 residents of Dhaka city. The results showed that social sustainability significantly influenced socially sustainable urban development in Dhaka, determining 38 indicators under 11 social sustainability themes using exploratory and confirmatory factor analysis utilizing structural equation modeling. The implication of this model serves as a guiding framework intended to assist governmental bodies, policymakers, and urban planners in navigating the path toward achieving sustainable cities. Likewise, the proposed model provides policy implications for enacting and revising urban sector policies in developing regions, considering the fundamental themes of social sustainability. Eventually, this study contributes to implementing Sustainable Cities and Communities (SDG 11) in the 2030 Agenda for Sustainable Development, bridging the gap between urbanization and sustainable urban societies. Also, this model is a valuable tool for promoting socially sustainable urban development in developing regions.

Background: AT-rich interaction domain 1A (ARID1A) has been proposed as a new biomarker for predicting response to immune checkpoint inhibitors (ICIs). The predictive value of ARID1A for predicting ICI effectiveness has not been reported for endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts ICI effectiveness for endometrial cancer treatment. Methods: We evaluated ARID1A expression, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunostaining endometrial samples from patients with endometrial cancer. Samples in which any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were determined to be negative via immunostaining were excluded. In the ARID1A-negative group, microsatellite instability (MSI) status was confirmed via MSI analysis. Results: Of the 102 samples investigated, 25 (24.5%) were ARID1A-negative. CD8 and PD-1 expression did not differ significantly between the ARID1A-negative group and the ARID1A-positive group; however, the ARID1A-negative group showed significantly lower PD-L1 expression. Only three samples (14.2%) in the ARID1A-negative group showed high MSI. Sanger sequencing detected three cases of pathological mutation in the MSH2-binding regions. We also established an ARID1A-knockout human ovarian endometriotic epithelial cell line (HMOsisEC7 ARID1A KO), which remained microsatellite-stable after passage. Conclusion: ARID1A negativity is not suitable as a biomarker for ICI effectiveness in treating endometrial cancer.

Herein, we present the successful treatment of a 92-year-old woman who experienced recurrent EC in the vaginal stump and para-aortic lymph nodes. The patient was first treated with paclitaxel and carboplatin for recurrent EC, which was abandoned after two cycles of chemotherapy because of G4 hematologic toxicity. Later, the patient was treated with letrozole for early-stage breast cancer, which was diagnosed simultaneously with EC recurrence. After four months of hormonal therapy, a partial response was observed not only in the lesions in the breast, but also those in the vaginal stump and para-aortic lymph nodes. She had no recurrence of breast cancer or EC, even after six years of treatment with letrozole-based hormonal therapy. Subsequent whole-exome sequencing using the genomic DNA isolated from the surgical specimen in the uterine tumor identified several genetic variants, including actionable mutations, such as CTNNB1 (p.S37F), PIK3R1 (p.M582Is_10), and TP53 c.375 + 5G>T. These data suggest that the efficacy of letrozole is mediated by blocking the mammalian target of the rapamycin pathway. The findings of this study, substantiated via genetic analysis, suggest the possibility of long-term disease-free survival, even in elderly patients with recurrent EC, which was thought to be difficult to cure completely.

Tumor heterogeneity remains an ongoing challenge in the field of cancer therapy. Intratumor heterogeneity significantly complicates the diagnosis of cancer and presents challenging clinical problems due to resistance to drug therapy. This study aimed to elucidate the genetic changes histologically (mucinous cystadenoma (MCA), mucinous borderline tumor (MBT), and mucinous ovarian carcinoma (MOC)) in a portion of mucinous ovarian tumors within the same sample. Seven tumor samples obtained from different patients were used to evaluate the genetic mutations in each component. Intratumor genetic heterogeneity was observed in all patients; among them, BRAF (V600E) and p53 (T118I, P142S, T150I, and T170M) point mutations were observed in the MBT component, while KRAS (G12D and G13D) and PIK3CA (E545K) mutations were found in the MOC component. The current findings suggest that diverse genetic alterations occur in mucinous tumors, according to tumor histology. Tumor heterogeneity and genetic diversity in mucinous ovarian tumors might be the cause of treatment failure. Knowledge of intertumor heterogeneity may lead to an increased understanding of the tumor response to treatment.

Background: Since malignant struma ovarii is a very rare disease, its carcinogenic mechanism has not been elucidated. Here, we sought to identify the genetic lesions that may have led to the carcinogenesis of a rare case of malignant struma ovarii (follicular carcinoma) with peritoneal dissemination. Methods: DNA was extracted from the paraffin-embedded sections of normal uterine tissues and malignant struma ovarii for genetic analysis. Whole-exome sequencing and DNA methylation analysis were then performed. Results: Germline variants of RECQL4, CNTNAP2, and PRDM2, which are tumor-suppressor genes, were detected by whole-exome sequencing. Somatic uniparental disomy (UPD) was also observed in these three genes. Additionally, the methylation of FRMD6-AS2, SESN3, CYTL1, MIR4429, HIF3A, and ATP1B2, which are associated with tumor growth suppression, was detected by DNA methylation analysis. Conclusions: Somatic UPD and DNA methylation in tumor suppressor genes may be associated with the pathogenesis of malignant struma ovarii. To our knowledge, this is the first report of whole-exome sequencing and DNA methylation analysis in malignant struma ovarii. Genetic and DNA methylation analysis may help elucidate the mechanism of carcinogenesis in rare diseases and guide treatment decisions.

Background: This study aimed to compare the oncologic and surgical outcomes of patients treated with robot-assisted modified radical hysterectomy (RAMRH) and total laparoscopic modified radical hysterectomy (TLMRH) for endometrial cancer (EC) with those of patients treated with abdominal modified radical hysterectomy (AMRH). Methods: We performed a retrospective analysis of 133 patients with early-stage EC who underwent different surgical approaches (RAMRH, n = 14; TLMRH, n = 94; AMRH, n = 25) between 2018 and 2021 at Shimane University Hospital. The data on clinical outcomes, including estimated blood loss, duration of surgery, duration of hospital stay, and number of dissected lymph nodes were collected from the patients’ electronic medical records. Kaplan–Meier curves were used to plot survival data, and log-rank tests were used to determine the statistical significance of differences in survival rates. Results: RAMRH showed the lowest bleeding volume (RAMRH: 95 ± 123.21 mL; TLMRH: 140.74 ± 172.60 mL; AMRH: 482.6 ± 429 mL) and shortest hospital stay (RAMRH: 6.43 ± 1.09 days; TLMRH: 7.30 ± 3.39 days; AMRH: 9.88 ± 2.65 days) among the three groups. The number of dissected lymph nodes tended to be higher in the RAMRH group than that in the TLMRH or AMRH group. The different surgical approaches did not correlate with progression-free survival and overall survival. Conclusions: Both RAMRH and TLMRH are safe, feasible, innovative, and minimally invasive surgical alternatives to AMRH for patients with EC.

This research paper investigates the efficacy of various machine learning models, including deep learning and hybrid models, for text classification in the English and Bangla languages. The study focuses on sentiment analysis of comments from a popular Bengali e-commerce site, ''DARAZ,'' which comprises both Bangla and translated English reviews. The primary objective of this study is to conduct a comparative analysis of various models, evaluating their efficacy in the domain of sentiment analysis. The research methodology includes implementing seven machine learning models and deep learning models, such as Long Short-Term Memory (LSTM), Bidirectional LSTM (Bi-LSTM), Convolutional 1D (Conv1D), and a combined Conv1D-LSTM. Preprocessing techniques are applied to a modified text set to enhance model accuracy. The major conclusion of the study is that Support Vector Machine (SVM) models exhibit superior performance compared to other models, achieving an accuracy of 82.56% for English text sentiment analysis and 86.43% for Bangla text sentiment analysis using the porter stemming algorithm. Additionally, the Bi-LSTM Based Model demonstrates the best performance among the deep learning models, achieving an accuracy of 78.10% for English text and 83.72% for Bangla text using porter stemming. This study signifies significant progress in natural language processing research, particularly for Bangla, by enhancing improved text classification models and methodologies. The results of this research make a significant contribution to the field of sentiment analysis and offer valuable insights for future research and practical applications.

With cities sprawling and populations booming in developing regions, ensuring social sustainability in urban areas has become more urgent. This study investigates the challenges of implementing social sustainability initiatives for cities in developing countries, focusing on Dhaka as a representative city. A mixed-method approach involving structured questionnaire surveys and key informant interviews was used to collect quantitative and qualitative data. The study identified eighteen challenges to implementing social sustainability initiatives in Dhaka city, including a lack of poor urban governance, an inefficient city management system, a lack of political stability, a long delay in the planning approval process, etc. Additionally, experts identified additional challenges that require attention. The study offers empirical evidence to assist government officials, policymakers, and urban planners overcome these challenges and implement social sustainability effectively. To address the identified challenges, the study recommends revisiting the Structure Plan, Urban Area Plan, Detailed Area Plan, and Urban Sector Policy-2011. It highlights the crucial role of community social workers in mitigating specific issues in socially sustainable urban development. Eventually, the study will contribute to the implementation of SDG-11 in the 2030 Agenda for Sustainable Development by bridging the gap between urbanization and socially sustainable cities.

Introduction: Intellectual disability (ID) and co-morbid mental health problems are more common in developing countries such as Bangladesh. However, little is known about how Bangladeshi health practitioners diagnose mental health disorders in people with an ID. Studies in developed countries have explored the impact of the diagnostic overshadowing bias (DOB): the tendency for health practitioners to misattribute mental health symptomology to a client's ID, rather than a separate mental health disorder. To date, no study has investigated the presence of the DOB in Bangladesh. Method: A range of Bangladeshi health practitioners (N = 243) were randomly assigned a clinical vignette describing a client displaying symptoms of a mental health disorder. Vignette 1 described a client with an IQ of 105 who graduated from secondary school. Vignette 2 described a client with an IQ of 55 who attended special education. All other details were identical. Participants rated the likelihood of seven mental health diagnoses on a 5-point Likert scale. Results: Practitioners were more likely to diagnose schizophrenia, drug problems and being bullied in people with a typical IQ compared to those with an ID. Doctors, psychiatrists, and psychologists appeared to be more affected by the DOB than community health workers, traditional healers, and allied health practitioners. Conclusion: Findings indicate that the bias may be present in Bangladesh healthcare professionals. The development and implementation of specific training programs to meet the differing needs of practitioners, across the health fields are recommended.

Few studies have reported hormonal agent use in the treatment of low-grade serous ovarian carcinomas (LGSOCs), which are chemoresistant. Considering the need for novel effective therapies, we investigated the hormone receptor expression and hormonal inhibition efficacy in LGSOCs. Using immunohistochemistry, we assessed the estrogen receptor (ER) expression status in 33 cases of histologically confirmed serous ovarian tumors, including 10, 11, and 12 cases of LGSOCs, serous borderline tumors (SBTs), and serous cystadenomas (SCAs), respectively. The genetic background reported in our previous study was used in the current study. MPSC1 cells, which were established from LGSOCs, were used in cell proliferation assays. We observed a higher ER expression in LGSOCs and SBTs than in SCAs (70%, 81%, and 50%, respectively). Thus, LGSOCs and SBTs exhibit higher ER expression than SCAs. Moreover, the PIK3CA mutation positively correlated with ER expression in LGSOCs (p = 0.0113). MPSC1 cells showed low ER expression on Western blotting. MPSC1 cell proliferation was significantly inhibited by fulvestrant (a selective ER downregulator). The activation of ER and PI3K/AKT signaling pathways may play an important role in LGSOC carcinogenesis. ER downregulation with fulvestrant or combination therapy with PI3K inhibitors is a possible novel treatment for patients with LGSOCs.

Ovarian seromucinous tumors (SMBTs) are relatively rare, and their carcinogenesis is largely unknown. In this study, the molecular features of SMBTs in Japan are assessed. DNA was extracted from microdissected paraffin-embedded sections from 23 SMBT cases. Genetic mutations (KRAS, BRAF, PIK3CA, and ERBB2) were evaluated using Sanger sequencing. Immunohistochemistry for p53, ARID1A, and PTEN was also performed as a surrogate for the loss of functional mutations in these tumor suppressor genes. The prevalence of KRAS, BRAF, PIK3CA, and ERBB2 mutations was 4.3% (1/23), 8.6% (2/23), 8.6% (2/23), and 17.3% (4/23), respectively. Overexpression or loss of p53 expression occurred in 26% (6/23), loss of ARID1A expression in 4.3% (1/23), and none of the cases showed expression of PTEN loss. These findings suggest that KRAS/BRAF/PIK3CA and PTEN mutations are rare carcinogenic events in SMBTs. The high frequency of positive p53 staining and a low frequency of loss of ARID1A staining suggests that SMBT carcinogenesis may be related to the alteration of p53 rather than that of ARID1A. ERBB2 oncogenic mutations may play an important role in the tumorigenesis of Japanese SMBTs.