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TLR7/8 signaling activation enhances the potency of human pluripotent stem cell-derived eosinophils in cancer immunotherapy for solid tumors

Exp Hematol Oncol. 2025 Mar 1;14(1):26. doi: 10.1186/s40164-025-00613-y.

ABSTRACT

BACKGROUND: Efficient tumor T-cell infiltration is crucial for the effectiveness of T-cell-based therapies against solid tumors. Eosinophils play crucial roles in recruiting T cells in solid tumors. Our group has previously generated induced eosinophils (iEOs) from human pluripotent stem cells and exhibited synergistic efficacy with CAR-T cells in solid tumor inhibition. However, administrated eosinophils might influx into inflammatory lungs, posing a potential safety risk. Mitigating the safety concern and enhancing efficacy is a promising development direction for further application of eosinophils.

METHODS: We developed a new approach to generate eosinophils with enhanced potency from human chemically reprogrammed induced pluripotent stem cells (hCiPSCs) with the Toll-like receptor (TLR) 7/8 signaling agonist R848.

RESULTS: R848-activated iEOs (R-iEOs) showed significantly decreased influx to the inflamed lungs, indicating a lower risk of causing airway disorders. Furthermore, these R-iEOs had enhanced anti-tumor functions, preferably accumulated at tumor sites, and further increased T-cell infiltration. The combination of R-iEOs and CAR-T cells suppressed tumor growth in mice. Moreover, the chemo-trafficking signaling increased in R-iEOs, which may contribute to the decreased lung influx of R-iEOs and the increased tumor recruitment of T cells.

CONCLUSION: Our study provides a novel approach to alleviate the potential safety concerns associated with eosinophils while increasing T-cell infiltration in solid tumors. This finding offers a prospective strategy for incorporating eosinophils to improve CAR-T-cell immunotherapy for solid tumors in the future.

PMID:40025520 | DOI:10.1186/s40164-025-00613-y

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Two birds with one stone: sustainable smart spectrophotometric methods for concurrent determination of silodosin and mirabegron: application to dosage forms and greenness assessment

BMC Chem. 2025 Mar 3;19(1):56. doi: 10.1186/s13065-025-01411-7.

ABSTRACT

A new combination of silodosin and mirabegron has recently obtained approval in the Indian market for addressing the benign prostatic hyperplasia symptoms associated with overactive bladder syndrome. In this study, we present four validated UV-spectrophotometric methods that rely on straightforward mathematical calculations for the quick and simultaneous assay of MRB and SLD in commercial tablets and synthetic mixes without the need for prior separation. The suggested methods include dual-wavelength, induced dual-wavelength, ratio difference, and area under the curve. These methods were effectively used to determine SLD and MRB simultaneously in combinations with severe spectrum overlap, showing excellent recoveries free from interference from pharmaceutical excipients. The proposed approaches were assessed and validated following the guidelines set forth by the International Conference for Harmonization (ICH). The methods exhibited linear ranges of 1-20 μg mL-1 and 1-25 μg mL-1 for SLD and MRB, respectively. Their environmental friendliness was assessed using the Analytical Greenness Calculator (AGREE) and The Green Analytical Procedure Index (GAPI) tools, demonstrating their supremacy in terms of greenness compared to the reported chromatographic method. There were no appreciable variations in accuracy or precision between the reported chromatographic method and statistical comparisons based on t- and F values. Consequently, these suggested methods are deemed effective in routine analysis of SLD and MRB, serving as cost-effective alternatives in quality control laboratories lacking expensive chromatographic instruments.

PMID:40025518 | DOI:10.1186/s13065-025-01411-7

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Assessment of cortical and trabecular bone structure in the mandible of patients with Behçet’s Disease

BMC Oral Health. 2025 Mar 1;25(1):323. doi: 10.1186/s12903-025-05667-2.

ABSTRACT

OBJECTIVE: Behçet’s Disease (BD) may impair bone remodeling, increasing osteoporosis risk. This study evaluates mandibular trabecular bone fractal dimension (FD), mandibular cortical index (MCI), and temporomandibular joint (TMJ) degeneration in BD patients versus healthy controls.

MATERIALS AND METHODS: A total of 106 panoramic radiographs, comprising 53 from BD patients and 53 from healthy individuals, were examined. Fractal analysis was performed using ImageJ software, selecting 50 × 50 pixel regions of interest (ROIs) from the gonial, interdental, and condylar areas. Degenerative changes in the TMJ, including osteophytes, sclerosis, surface flattening, erosion, and subchondral cysts, were recorded. Statistical analysis was conducted with SPSS v.21 (IBM, Armonk, USA), using a significance level of p < 0.05.

RESULTS: The BD group exhibited significantly lower FD values compared to the control group (p < 0.05). Similarly, MCI scores differed significantly between the groups (p < 0.05). BD patients showed more pronounced radiological evidence of mandibular cortical resorption than controls. Additionally, degenerative changes in the TMJ were more prevalent among BD patients (p < 0.05).

CONCLUSION: Comprehensive evaluation of the mandibular cortex, trabecular bone, and TMJ is crucial in BD patients to effectively detect and monitor osteoporotic alterations.

CLINICAL SIGNIFICANCE: BD patients may face considerable oral health challenges, such as jawbone deterioration and TMJ complications. Prompt diagnosis and treatment of these issues can enhance therapeutic outcomes and improve overall quality of life.

PMID:40025517 | DOI:10.1186/s12903-025-05667-2

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Clinical and cost-effectiveness of paramedics working in general practice: a mixed-methods realist evaluation

Health Soc Care Deliv Res. 2025 Feb;13(6):1-137. doi: 10.3310/GTJJ3104.

ABSTRACT

BACKGROUND: General practice services are under pressure due increased demand. Alongside substantial national recruitment challenges, there exists a shortage of general practitioners to meet current need. Resultingly, allied healthcare professionals, including paramedics, are being utilised in general practice.

AIM: To determine the models of paramedics in general practice settings; the mechanisms that underpin effective paramedics in general practice; and the impact of paramedics in general practice on safety, costs and clinical and patient-reported outcomes and experience.

DESIGN: A mixed-methods realist evaluation comprised a rapid realist review followed by an evaluation of paramedics in general practice in general practice case study sites. Patient and public involvement and input was integral, ensuring validity from a patient and carer perspective.

SETTING: General practices in England.

PARTICIPANTS: A total of 34 general practices participated as case study sites, of which 25 were ‘paramedics in general practice’ sites. Data from qualitative realist interviews (n = 69), quantitative questionnaires (n = 489) and electronic records (n = 22,509 consultations) were collected.

INTERVENTIONS: Paramedics in general practice models were classified according to: (1) level of integration of the paramedic to the general practice team; and (2) complexity of patients seen by paramedics.

MAIN OUTCOME MEASURES: Qualitative interviews investigated initial programme theories with staff and patient participants. Patient participant questionnaires utilised validated measures: the Patient-Reported Experiences and Outcomes of Safety in Primary Care (safety); EuroQol-5 Dimensions, five-level version (health-related quality of life); Primary Care Outcomes Questionnaire; the Modular Resource Use Measure (health and care resource utilisation). Electronic health records provided data on primary care use.

REVIEW METHODS: A rapid realist review of the published and grey literature, supplemented with direct enquiry with system leaders and key stakeholders.

RESULTS: The rapid realist review highlighted significant variation in paramedics’ roles in general practice. Qualitative interviews identified domains related to access, safety, workforce reconfiguration, infrastructure, patient experience, and outcomes. Lower Patient-Reported Experiences and Outcomes of Safety in Primary Care practice activation scores were found at paramedics in general practice sites (perceived less engaged in promoting safety), in particular those with medium and low levels of paramedics in general practice integration and complexity. There was a small statistically significant difference in the Primary Care Outcomes Questionnaire ‘Confidence in Health Plan’ by paramedics in general practice complexity, such that confidence had deteriorated slightly more in the high-complexity group compared to non-paramedics in general practice. Paramedics in general practice sites had lower scores at initial visit and 30 days for the Primary Care Outcomes Questionnaire ‘Confidence in Health Provision’. We found little evidence that paramedics in general practice care led to substantial spillover effects via increased reconsultations, prescriptions, secondary care referrals or unplanned hospital admission costs.

LIMITATIONS: The study faced challenges in recruitment. Self-selected participating sites may not be representative of all general practitioners in England, and categorising paramedics in general practice models for analysis was more complex than anticipated. The comparison of costs and outcomes between paramedics in general practice and non-paramedics in general practice sites was based on an observational study design.

CONCLUSIONS: Paramedics in general practice care improves access to general practice. Safety and acceptability require resources for induction, supervision, training and education. Paramedics in general practice integration affects staff satisfaction and role longevity. Paramedics in general practice allows paramedics to develop and evolve.

FUTURE WORK: Larger studies utilising different study designs with longer follow-up are needed to fully understand the impact of paramedics in general practice on clinical outcomes and episode of care costs.

STUDY REGISTRATION: This study is registered as ISRCTN56909665 https://doi.org/10.1186/ISRCTN56909665.

FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132736) and is published in full in Health and Social Care Delivery Research; Vol. 13, No. 6. See the NIHR Funding and Awards website for further award information.

PMID:40022721 | DOI:10.3310/GTJJ3104

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Polypropylene Mesh in Nipple-Sparing Mastectomy and Immediate Implant-based Breast Reconstruction in Vietnamese Early Breast Cancer Patients: Safe and Feasible

Asian Pac J Cancer Prev. 2025 Feb 1;26(2):685-689. doi: 10.31557/APJCP.2025.26.2.685.

ABSTRACT

BACKGROUND: Breast cancer is the most common malignancy in women worldwide, and breast reconstruction following mastectomy is an integral part of patient care to improve quality of life and aesthetic outcomes. Nipple-sparing mastectomy (NSM) combined with immediate breast reconstruction (IBR) with implant is becoming increasingly preferred due to its ability to preserve breast aesthetics. Acellular dermal matrix (ADM) is commonly used in these procedures, but is often prohibitively expensive, particularly in resource-limited settings like Vietnam. Polypropylene mesh (PPM) has emerged as a more affordable alternative; however, its safety and effectiveness in NSM and IBR remain unknown, especially in low-resource healthcare environments.

METHODS: This retrospective single-arm study included early breast cancer (EBC) patients who underwent NSM followed by IBR with PPM at a single institution between January 1, 2022, and January 31, 2024. The inclusion criteria were EBC stage 0, I, or II, with no prior neoadjuvant therapy or chest wall radiotherapy. Descriptive statistics were applied, and chi-square or Fisher’s exact tests were used to assess associations between clinical variables and postoperative complications.

RESULTS: Among the 37 patients, the mean age was 40.9 years (range: 25-57). Most (70.3%) had invasive carcinoma, and 73.0% were luminal/HER2-negative. High-profile implants were used in 76.7% of cases. Two patients (5.4%) experienced mild-to-moderate complications, including infection (2.7%) and nipple-areolar necrosis (2.7%). Both were treated successfully with medical therapy. No cases of implant loss occurred, and no significant associations were found between complications and clinical variables (p > 0.05).

CONCLUSION: PPM use in IBR after NSM for EBC patients is a safe and viable option, with low complication rates. PPM may serve as a cost-effective alternative to ADM, particularly in resource-constrained settings, such as Vietnam. Larger studies are recommended to confirm these results and assess long-term outcomes.

PMID:40022718 | DOI:10.31557/APJCP.2025.26.2.685

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Knowledge, Attitude and Practice on Human Papillomavirus Vaccination among Healthcare Providers at a Tertiary Care Centre in North Delhi

Asian Pac J Cancer Prev. 2025 Feb 1;26(2):671-676. doi: 10.31557/APJCP.2025.26.2.671.

ABSTRACT

OBJECTIVE: In India, majority of cancer-related deaths are attributed to Human Papillomavirus (HPV), which is preventable through vaccines such as Gardasil and Gardasil 9. Despite their efficacy, uptake of these vaccines among healthcare providers (HCPs) remains low. This study aimed to evaluate knowledge, attitudes, and practices (KAP) regarding HPV vaccination among HCPs at a tertiary care center in India.

METHODS: A survey was conducted among 399 HCPs at a tertiary care hospital. Data were collected using an online questionnaire focusing on knowledge of HPV, attitudes towards HPV vaccination, personal vaccine uptake, and perceived barriers to vaccination. Statistical analysis was conducted using chi-squared tests, p-value of <0.05 were considered statistically significant.

RESULT: Significant knowledge gaps were identified, particularly among nurses and paramedical staff. While 95.9% of doctors were aware of HPV, only 66.7% of nurses and 73.4% of paramedical staff had similar knowledge. Awareness of HPV transmission was highest among doctors (98.5%) compared to nurses (87.1%) and paramedical staff (91.7%). Despite 89.34% of doctors expressing confidence in the vaccine’s safety, only 11.67% had received it. Fewer than 9% of nurses and paramedical staff reported being vaccinated. The primary barriers to vaccine uptake were affordability and lack of awareness.

CONCLUSION: The study highlights the need for targeted educational efforts to improve knowledge about HPV and its vaccines among HCPs, especially nurses and paramedical staff. Addressing misconceptions and integrating the HPV vaccine into national immunization programs could improve vaccine accessibility and uptake, ultimately reducing cervical cancer burden in India.

PMID:40022716 | DOI:10.31557/APJCP.2025.26.2.671

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Effectiveness of Normal Saline Irrigation in Reducing Wound Contamination during Oral Cancer Surgery: A Cytological Analysis

Asian Pac J Cancer Prev. 2025 Feb 1;26(2):657-661. doi: 10.31557/APJCP.2025.26.2.657.

ABSTRACT

BACKGROUND: Tumour manipulation during surgery can lead to the dissemination of malignant cells and potential wound contamination. Despite the widespread practice of irrigating surgical sites with normal saline, the efficacy of this measure in reducing epithelial contamination in oral cancer surgery remains unclear.

OBJECTIVES: This study aimed to assess the proportion of normal saline wash effluents contaminated by epithelial cells or debris during oral cavity cancer surgery, and to evaluate the effectiveness of saline irrigation in reducing contamination.

METHODS: A total of 132 patients with biopsy-proven, treatment-naïve squamous cell carcinoma of the oral cavity undergoing surgery were included. Wash effluents from the tumour bed and neck incisions were collected post-irrigation with normal saline and analysed using cell block cytology. Cytology smears from the tumour bed and incision edges were examined for cellular contaminants. Data were analysed using Chi-square tests and Mann-Whitney tests.

RESULTS: Epithelial or abnormal epithelial cells were detected in 24% of cell block samples, while 21% showed cellular debris. Following normal saline irrigation, the positivity rate for epithelial cells or debris in smears decreased from 55% to 7.6%, a statistically significant reduction (p < 0.001). Perineural invasion was significantly associated with the presence of exfoliated cells (p = 0.037).

CONCLUSIONS: Irrigation with normal saline significantly reduces the presence of exfoliated epithelial cells and cellular debris in wound sites during oral cancer surgery. The results support the continued use of mechanical cleansing measures during surgery to minimize the risk of tumour cell implantation.

PMID:40022714 | DOI:10.31557/APJCP.2025.26.2.657

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Comparison of Pain, Cortisol, and IL6 Levels Pre and Post SEFT in Stage III B Cervical Cancer Patients

Asian Pac J Cancer Prev. 2025 Feb 1;26(2):625-630. doi: 10.31557/APJCP.2025.26.2.625.

ABSTRACT

OBJECTIVE: The objective of the study is to assess the impact of Spiritual Emotional Freedom Technique (SEFT) intervention on pain severity, cortisol, and IL6 levels in stage III B cervical cancer patients undergoing chemoradiation.

METHODS: A quasi-experimental study with a one-group pre-test post-test design was conducted at Gatot Soebroto Hospital, Jakarta, Indonesia, focusing on stage III B cervical cancer patients who received chemoradiation. Pain severity was quantified using the Numeric Rating Scale (NRS), while cortisol and IL6 levels were determined via serum specimen collection and ELISA analysis. Statistical analysis revealed significant disparities in pain severity, cortisol levels, and IL6 levels pre- and post-intervention. A significant correlation emerged between pain severity, cortisol, and IL6 levels (p<0.001).

RESULT: The average pre-intervention pain severity was 4.5 and the average post-intervention pain severity was 1.6. The average pre-intervention cortisol level was 632.9 and the average post-intervention cortisol level was 305.3 (p-value <0.001). The average pre-intervention IL6 level was 260.1 and the average post-intervention IL6 level was 106.7.

CONCLUSION: The SEFT proves highly effective in alleviating pain among cervical cancer patients undergoing chemoradiation.

PMID:40022710 | DOI:10.31557/APJCP.2025.26.2.625

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Therapeutic Targeting of PARP Expression and Glycolysis Rate-Limiting Enzymes in Breast Cancer Patients

Asian Pac J Cancer Prev. 2025 Feb 1;26(2):611-617. doi: 10.31557/APJCP.2025.26.2.611.

ABSTRACT

BACKGROUND: Breast cancer is a heterogeneous disease characterized by diverse biochemical, histological, and clinical features. PARP1 and glycolysis rate-limiting enzymes play critical roles in cancer progression, making them promising therapeutic targets.

AIM: This study aimed to evaluate the expression levels of PARP1 and key glycolytic enzymes (HK, PFK, and PK) in breast cancer patients and assess their potential as therapeutic indicators.

MATERIALS AND METHODS: A total of 120 participants (60 breast cancer patients and 60 healthy controls) were included in the study. Blood samples were collected to measure PARP1 expression and the levels of glycolytic enzymes using ELISA. Statistical analyses were performed to compare the two groups.

RESULTS: PARP1 expression and glycolytic enzyme levels (HK, PFK, and PK) were significantly higher in breast cancer patients compared to healthy controls (p < 0.0001).

CONCLUSION: The overexpression of PARP1 and key glycolytic enzymes indicates their involvement in breast cancer progression and underscores their potential as therapeutic targets and biomarkers.

PMID:40022708 | DOI:10.31557/APJCP.2025.26.2.611

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Human Papillomavirus Vaccination for Boys: Insights into Knowledge, Acceptance, and Willingness to Pay among Parents in Yogyakarta, Indonesia

Asian Pac J Cancer Prev. 2025 Feb 1;26(2):593-602. doi: 10.31557/APJCP.2025.26.2.593.

ABSTRACT

OBJECTIVE: This study aimed to measure knowledge, acceptance, and willingness to pay (WTP) towards Human Papillomavirus (HPV) vaccination for boys among parents in Yogyakarta Province, Indonesia.

METHODS: The cross-sectional, descriptive study was conducted from September to November 2023 through electronic self-reported questionnaires survey. The parents of boys aged 11 to 15 years of age and had never had an HPV vaccination for their son before were recruited as survey respondents. The study respondents were recruited through school-based approach involving 12 elementary schools and 15 junior high schools that distributed in 3 districts of Yogyakarta Province. The survey examined demographic details, knowledge about HPV and its vaccine, understanding of HPV-related issues, willingness to receive the HPV vaccination, and readiness to pay for the vaccine.

RESULT: A total of 410 parents that coincidentally all were women participated in this study. The average knowledge score was 6.58 (43.9%), indicating that overall knowledge about HPV was moderate among the respondents. In contrast, a total of 346 parents (84.4%) expressed their willingness to vaccinate their son. The bivalent vaccine had mean of an out-of-pocket WTP of IDR 172,279 (USD 11.11) and the quadrivalent vaccine of IDR 223,144 (USD 14.39), with a median WTP of IDR 100,000 (USD 6.4) for both vaccines. These WTP values were about 20% of the market price. There was significant difference of WTP mean between group of respondents’ characteristics for variables such as marital status, education, and income. There was also significant relationship between knowledge, acceptance, and WTP toward HPV vaccine.

CONCLUSION: Despite the high acceptance towards HPV vaccination, knowledge and WTP were still considered low. Such strategies are required to increase awareness regarding impact of HPV toward men’s and women’s health. In addition, at current situation voluntary HPV vaccination for boys was not favourable program.

PMID:40022706 | DOI:10.31557/APJCP.2025.26.2.593