• Knowledge, attitudes, and practice in breast cancer early detection: evidence from a nationally stratified study of healthcare providers in Jordan.
    2 weeks ago
    Breast cancer remains the most prevalent cancer among women in Jordan. Although national early detection efforts have expanded over recent years, opportunities remain to further improve timely diagnosis and screening uptake. Healthcare providers (HCPs) play a central role in influencing screening uptake, and strengthening their knowledge, attitudes, and practices (KAP) can support program effectiveness.

    To assess KAP of HCPs related to breast cancer early detection in Jordan and identify factors influencing their translation into practice.

    A nationally stratified cross-sectional study was conducted among 544 HCPs between January and June 2025 using a structured, interviewer-administered questionnaire. Composite scores for KAP were calculated and further dichotomized for multivariable logistic regression to identify predictors of KAP domains.

    The mean knowledge score was 57.0%, with high knowledge of signs and symptoms (78.1%) but substantially lower knowledge of screening recommendations, including clinical breast examination (27.4%) and mammography guidelines (28.6%). Attitudes were generally favorable (53.5%), with strong professional orientation (82.2%) and high perceived patient-level barriers (77.3%). Mean practice score was reflecting moderate implementation (49.0%). While most providers reported encouraging screening (98.9%) and appropriate case management (91.9%), correct screening practices were limited, including initiation age (30.3%) and screening intervals (20.8%). Female providers demonstrated higher odds of adequate knowledge (OR 1.78) and optimal practice (OR 1.93), while nurses had significantly lower knowledge (OR 0.46) and practice (OR 0.17). Regional disparities were observed, with lower knowledge but higher practice in southern regions.

    The findings indicate opportunities to better align provider knowledge, attitudes, and routine practice, particularly in screening-related competencies. Strengthening role-specific training, integrating guidelines into routine care, and addressing implementation and service-delivery factors are essential to improve early detection outcomes in Jordan and similar settings.
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  • Real-world safety profile of mitotane in adrenocortical carcinoma: a retrospective cross-sectional study integrating pharmacovigilance and interpretable machine learning.
    2 weeks ago
    Mitotane remains the cornerstone of adrenocortical carcinoma. However, its real-world safety profile is poorly defined. This study systemically evaluated mitotane-associated adverse events (AEs) and characterized multivariable patterns of serious outcomes using a combined pharmacovigilance and machine learning approach.

    Mitotane-related AE reports (2004-2025) were extracted from the FDA Adverse Event Reporting System (FAERS). Disproportionality analyses were performed via four algorithms. Detected signals were categorized using a clinical priority scoring system based on signal strength, mortality, seriousness, and existing evidence. Time-to-onset was evaluated utilizing Kaplan-Meier methods. Elastic net logistic regression and Extreme Gradient Boosting (XGBoost) models characterized features associated with serious outcomes, with performance assessed by the area under the receiver operating characteristic curve (AUROC).

    Among 870 identified reports, 45.7% involved serious outcomes. We detected 75 safety signals, predominantly involving gastrointestinal, neurological, endocrine, and metabolic systems. Notably, 21 signals (28.0%) were assigned moderate clinical priority, with adrenal insufficiency as the highest-priority signal. Time-to-onset analysis showed that endocrine AEs had a significantly longer onset time than non-endocrine AEs. Both models demonstrated consistent characterization of multivariable patterns associated with serious outcomes (elastic net AUROC = 0.830, XGBoost AUROC = 0.869). Key contributors to serious outcomes included reporting country, medical event designation, organ system involvement, and medication complexity.

    This large-scale study provides a real-world safety assessment of mitotane. Integrating signal detection, clinical prioritization, and interpretable machine learning reveals multivariable patterns underlying serious AEs. These findings support a risk-stratified monitoring approach to enhance the clinical safety of mitotane therapy.
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  • HDL-C presents a suggestive negative moderating trend for the association between total cholesterol and colorectal polyps: model construction and bootstrap internal assessment of a predictive nomogram.
    2 weeks ago
    Colorectal polyps are classic precancerous lesions of colorectal cancer, closely linked to lipid metabolic disorders. Elevated total cholesterol does not consistently raise polyp risk, implying interactive effects among lipoprotein fractions. This study aimed to explore whether HDL-C exhibits a moderating trend in the TC-polyp association and construct a predictive nomogram with bootstrap internal performance evaluation.

    A retrospective single-center case-control study enrolling 411 hospitalized colonoscopy patients. Our pre-defined primary multivariate logistic regression was adjusted for age and standardized objective baseline indicators (gender, BMI category, Helicobacter pylori, GSP, CST4). Normal weight was set as BMI reference; restricted cubic splines were applied to test BMI nonlinearity. Data on smoking, alcohol intake, diet, physical activity and family history of colorectal polyps were incompletely recorded in inpatient medical records and thus excluded from regression adjustment. Sensitivity analyses substituting non-HDL-C for TC were performed to eliminate compositional coupling bias between TC and HDL-C. Subgroup analyses stratified by polyp pathological subtypes were conducted. Nomogram discrimination and calibration were evaluated via ROC curves and 500 bootstrap resampling on the full cohort without train-test splitting. Random forest was used to rank variable importance; such rankings cannot independently corroborate the TC × HDL-C interaction term.

    After adjustment for age and baseline clinical covariates, we detected a suggestive inverse TC × HDL-C interaction (OR = 0.787, 95% CI: 0.626-0.994, P = 0.040). Sensitivity analysis with non-HDL-C reproduced this consistent inverse trend (P = 0.023). Restricted cubic spline modeling indicated no nonlinear correlation between continuous BMI and polyp risk (P for non-linearity=0.348). The internally assessed nomogram achieved an AUC of 0.834 (95% CI: 0.789-0.879) with satisfactory bootstrap calibration. Consistent inverse moderating trends were observed across adenomatous and hyperplastic polyp subgroups at the descriptive level.

    We identified a suggestive inverse TC-HDL-C moderating trend after covariate adjustment, which remained robust in non-HDL-C sensitivity analysis. HDL-C exhibited no independent main effect on colorectal polyps, yet it exerted a suggestive negative moderating trend that attenuated the positive association between total cholesterol and colorectal polyps. The internally assessed nomogram provides preliminary reference for individualized colorectal polyp risk stratification. Observations are constrained by inpatient-only recruitment and incomplete lifestyle covariate adjustment; further large community-based cohorts are needed to replicate these findings.
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  • Coagulation dysfunction as an independent predictor of early pregnancy loss in women with polycystic ovary syndrome: a machine learning-based retrospective cohort study.
    2 weeks ago
    Current studies on adverse pregnancy outcomes in polycystic ovary syndrome (PCOS) have primarily focused on metabolic and endocrine abnormalities, whereas systematic investigations addressing live birth outcomes and coagulation dysfunction remain limited. In addition, there is a lack of comprehensive tools for early pregnancy risk stratification. This study aimed to explore the associations between early pregnancy indicators and early pregnancy loss (EPL) in women with PCOS, identify key risk factors, and subsequently develop a clinically interpretable predictive model to facilitate early risk identification and individualized management.

    In this single-center retrospective cohort study, 2,290 women with PCOS who achieved natural singleton pregnancies were included. Participants were randomly divided into a training set (n=1,832) and a validation set (n=458). Demographic, endocrine-metabolic, and coagulation parameters were collected. Independent predictors were identified by multivariable logistic regression. Predictive models were constructed using logistic regression, random forest, and XGBoost algorithms, with model interpretability evaluated using Shapley Additive Explanations (SHAP). Furthermore, a temporally independent external cohort was introduced for external validation to assess the generalizability of the model.

    Key predictors included D-dimer, fibrin degradation products (FDP), body mass index (BMI), anti-Müllerian hormone (AMH), and activated partial thromboplastin time (APTT). Elevated D-dimer and FDP levels were associated with increased EPL risk, suggesting enhanced coagulation activation and impaired microcirculation at the maternal-fetal interface. The XGBoost model showed the best performance, achieving an AUC of 0.926 (95% CI: 0.902-0.950). The model also maintained stable discriminative ability in temporal external validation (AUC = 0.705), although a certain degree of calibration drift was observed.

    Coagulation abnormalities during early pregnancy are closely associated with the occurrence of EPL in women with PCOS and may serve as independent risk factors. Machine learning models integrating multidimensional clinical indicators can effectively enable early identification of high-risk populations. Temporal external validation further suggested a certain degree of model generalizability, although additional optimization and validation are still required. These findings may provide valuable support for risk stratification and intervention decision-making during early pregnancy.
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  • Morphology-defined bacterial vaginosis and HPV-related cervical screening abnormalities: a two-year real-world study with histopathologic correlation.
    2 weeks ago
    Bacterial vaginosis (BV) is characterized by reduced Lactobacillus dominance and enrichment of anaerobic bacteria. Although BV has been associated with human papillomavirus (HPV) infection, its relationship with cytologic abnormalities and biopsy-confirmed cervical lesions remains incompletely defined in real-world laboratory settings.

    We conducted a retrospective real-world study integrating vaginal fluorescence microscopy, 21-genotype HPV genotyping, thin-prep cytology (TCT), and cervical histopathology records from January 2024 through December 2025 at a tertiary hospital in China. Morphology-defined BV was defined by clue cells or Gardnerella-like anaerobic bacteria on vaginal fluorescence microscopy and was not equivalent to Nugent scoring, Amsel criteria, culture-based diagnosis, or molecular microbiome profiling. HPV and TCT records were matched within a prespecified 30-day window after patient-level deduplication. Multivariable logistic regression adjusted for year, age, and vaginal microecological covariates. A 90-day sensitivity analysis was performed. The histopathology cohort was clinically selected and was analyzed as a correlation subgroup rather than as a random sample of the screening cohort.

    The main 30-day analysis included 4,492 unique patients, of whom 587 (13.07%) had morphology-defined BV. After multivariable adjustment, morphology-defined BV remained associated with overall HPV positivity (adjusted odds ratio [aOR] 1.560; 95% confidence interval [CI] 1.293-1.883), high-risk HPV positivity (aOR 1.611; 95% CI 1.327-1.957), HPV multiple infection (aOR 1.976; 95% CI 1.526-2.559), TCT abnormality (aOR 1.465; 95% CI 1.125-1.907), and concurrent high-risk HPV positivity plus TCT abnormality (aOR 1.558; 95% CI 1.174-2.066). After additional adjustment for high-risk HPV, the BV-TCT association was attenuated and non-significant. Among 825 patients with cervical histopathology records, BV was not independently associated with any histologic lesion grade, whereas high-risk HPV, HPV16/18, and TCT abnormality were the principal predictors of histopathologic disease.

    Morphology-defined BV was associated with HPV infection and HPV-related cytologic abnormalities, but not with histologic cervical lesions in the clinically selected biopsy subgroup. These findings suggest that routine morphologic evidence of BV marks an HPV-related screening-positive phenotype rather than an independent histopathologic lesion predictor.
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  • Post-transplant anti-thymocyte globulin exposure predicts graft-versus-host disease and donor chimerism outcomes in reduced intensity conditioning allogeneic stem cell transplantation.
    2 weeks ago
    Although anti-thymocyte globulin (ATG) is commonly used as prophylaxis against graft-versus-host disease (GVHD) following allogeneic haematopoietic stem cell transplantation (alloSCT), there is considerable inter-patient variability in ATG exposure. The impact of ATG exposure in outcomes following reduced intensity conditioning (RIC)-alloSCT remains unknown. We explored the impact of post-transplant ATG exposure (PT-ATG-exp) in 68 adults with haematological malignancies undertaking first RIC-alloSCT with ATG (Thymoglobulin, total dose 4.5mg/kg, day -3 to -1 alloSCT). Post-transplant ATG exposure was determined by area under the curve (AUC) through analysis of sera collected at standardised timepoints. Post-transplant ATG exposure range was highly variable [46-420 arbitrary units (AU) per day/mL]. Day 0 ATG concentration and day 0-14 ATG AUC highly correlated with PT-ATG-exp (R = 0.93 and 0.99, respectively, P < 0.001). Using a Cox proportional hazards model, patients with PT-ATG-exp between 80-135 AU per day/mL had inferior 2-year GRFS compared to the remainder of the cohort [25% (95% CI, 11%-56%) vs 54% (95% CI, 40%-73%), P = 0.02; HR 2.01 (95% CI, 1.04-3.86, P = 0.04] due to higher incidence of grade III-IV acute GVHD [33% (95% CI, 16%-51%) vs 12% (95% CI, 4%-24%), P = 0.034; HR 2.95 (95% CI, 0.99-8.83, P = 0.05)]. Recipients with the highest PT-ATG-exp (quartile 4: 185-420 AU per ml/day) had the lowest incidence of grade III-IV acute GVHD (0% at 180-days) but also lowest median CD3+ chimerism (85%) and highest incidence of mixed donor chimerism (CD3+: 93% and CD3-: 33%) at day 100. In this analysis, PT-ATG-exp influenced post-transplant outcomes including GVHD incidence and donor chimerism following in RIC-alloSCT.
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  • Feasibility of routine clinical liquid-based cytology for lung cancer compact panel testing.
    2 weeks ago
    The Lung Cancer Compact Panel (cPANEL) is a recently approved highly sensitive multiplex gene panel in Japan that supports both DNA- and RNA-based next-generation sequencing. Although cytological specimens are acceptable for cPANEL, unfixed cell pellets or dedicated preservation tubes are typically recommended. However, evidence remains limited regarding whether residual liquid-based cytology (LBC) cell suspensions prepared for routine cytological diagnosis can be used directly for cPANEL testing without dedicated molecular preservation or additional preanalytical processing. In this study, we evaluated the feasibility of applying LBC specimens that are widely used in contemporary clinical practice to cPANEL.

    We analyzed DNA and RNA quality in 69 clinical LBC specimens. Among these, 51 specimens containing non-small cell lung cancer cells with previously determined driver alteration status were subjected to cPANEL testing to evaluate assay concordance with clinical companion diagnostic results.

    DNA integrity was generally well preserved (DNA Integrity Number [DIN]: 6.2 ± 1.5). In contrast, RNA integrity showed greater variability (DV200: 16.4 ± 12.1%). ThinPrep-fixed specimens demonstrated lower DIN and DV200 values compared with CytoRich Red-fixed specimens. Although all samples successfully passed the DNA-based cPANEL assay, six cases (11.8%) failed the RNA-based assay, with RNA yield being a major contributing factor. Among the 46 evaluable specimens, concordance was 95.7% and sensitivity was 92.3%, or 88.9% including RNA module failures as cPANEL-negative.

    With appropriate fixative selection and adequate cellularity, cPANEL using clinical LBC specimens may serve as a practical diagnostic platform. We demonstrated that routine LBC specimens can be directly applied to cPANEL without special preanalytical processing.
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  • Chemotherapy and Radiotherapy Regimens for Limited-Stage Small Cell Lung Cancer Treated With Accelerated Hyperfractionated Radiotherapy Combined With Chemotherapy: A Real-World Study.
    2 weeks ago
    The standard treatment regimen for limited-stage small cell lung cancer (LS-SCLC) is 4-6 cycles of chemotherapy combined with thoracic radiotherapy. However, most patients still experience disease recurrence in a short period. Therefore, this study aims to evaluate the associations of different chemotherapy and radiotherapy strategies with survival outcomes.

    This retrospective analysis included LS-SCLC patients treated with chemotherapy and accelerated hyperfractionated radiotherapy. Progression-free survival (PFS) served as the primary endpoint, while overall survival (OS) and brain metastasis-free survival (BMFS) were evaluated as secondary endpoints.

    A total of 201 eligible patients were included. No significant survival difference was observed between patients receiving 4 cycles and those receiving 5-6 cycles of chemotherapy (HR: 0.83, 95% CI: 0.58-1.21, p = 0.332). Patients who received more than 45 Gy did not gain more survival benefit compared to those who received the standard 45 Gy dose, with median PFS of 13.1 and 13.9 months, respectively (HR: 1.43, 95% CI: 0.90-2.26, p = 0.125). This study found that radiotherapy interval > 75 days was associated with improved PFS compared with an interval ≤ 75 days (HR: 0.71, 95% CI: 0.48-0.97, p = 0.044).

    For LS-SCLC patients receiving accelerated hyperfractionated radiotherapy, higher total doses did not provide significant benefits compared to the standard dose (45 Gy/30 F). Although a radiotherapy interval > 75 days was associated with improved PFS and OS, this finding should be interpreted cautiously and requires prospective validation before being used to guide radiotherapy timing. Regarding chemotherapy, patients receiving 5-6 cycles of chemotherapy did not show significant benefits compared to those receiving 4 cycles.
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  • Upper Versus Middle-Neck Involvement in TNM-9 Stage IB Nasopharyngeal Carcinoma: Implications for De-Escalation and Intensification Strategies.
    2 weeks ago
    TNM-9 Stage IB nasopharyngeal carcinoma (NPC) encompasses markedly heterogeneous risk profiles, yet lacks reliable biomarkers to guide the choice between de-escalation and intensification strategies. This study aimed to explore the prognostic significance of upper- and middle-neck nodal involvement (UNI and MNI) in this population and how it affects treatment outcomes and prognosis.

    Patients with Stage IB NPC treated between June 2016 and December 2019 at our institution were included. Nodal levels were classified into UNI and MNI. Survival outcomes, including overall survival (OS), progression-free survival (PFS), distant control (DC), and regional control (RC), were analyzed.

    A total of 370 patients were analyzed, with 257 (69.5%) classified in the UNI group and 113 (30.5%) in the MNI group, respectively. MNI was found to be associated with significantly worse prognosis compared to UNI. Specifically, the MNI group had lower 5-year OS (91.1% vs. 98.8%, p < 0.001), PFS (78.6% vs. 95.6%, p < 0.001), DC (90.2% vs. 98.8%, p < 0.001), and RC (93.3% vs. 98.4%, p = 0.005) than the UNI group. Association analysis revealed that nodal level was significantly associated with other known adverse prognostic factors, including the maximum diameter of positive lymph nodes, matted nodes, and high EBV-DNA levels (all p < 0.001). Crucially, after multivariate adjustment, nodal level is the only independent prognostic factor.

    The nodal level was a critical factor in predicting patient outcomes in Stage IB NPC. These findings are hypothesis-generating: UNI patients may represent a candidate population for prospective de-escalation trials, whereas MNI patients may warrant evaluation of intensified or novel strategies in future studies. Prospective validation is required before any change in clinical management.
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  • Coping Styles of Adolescents With Leukemia at a Tertiary Care Cancer Centre in India: A Qualitative Study.
    2 weeks ago
    Adolescents with cancer face unique psychological, social, and developmental challenges that are distinct from those faced by children and adults. While coping strategies influence psychological outcomes, the evidence is limited to high-income countries. Minimal longitudinal data exist in low- and middle-income contexts, where sociocultural factors may shape coping strategies differently.

    We conducted a longitudinal qualitative study of adolescents newly diagnosed with Acute Lymphoblastic Leukaemia (ALL) at a tertiary cancer centre in India. Thirty participants were purposively sampled and interviewed at baseline,3- and 6-months after treatment initiation. The interviews were transcribed, translated, and analysed using thematic analysis.

    Among the 30 participants, 93% were male, with a median age of 16.5 years. Coping strategies evolved over time, initially dominated by maladaptive mechanisms such as avoidance, distancing, and blaming. At 3 months, participants employed a combination of strategies, including avoidance, humour, religious coping, and support-seeking. By 6 months, there was an increase in adaptive strategies, including acceptance, meaning-making, and post-traumatic growth. Gender differences emerged: females favoured religious coping and reported concerns about body image, while males preferred humour and fatalistic attributions.

    Coping in adolescents with ALL evolved during treatment, with an early reliance on maladaptive responses and a subsequent shift towards adaptive strategies. Gendered patterns reflect cultural and developmental contexts. These findings underscore the importance of culturally sensitive and developmentally tailored psychosocial interventions, including structured psychoeducation, fertility counselling, and identity-focused support, to enhance resilience and improve psychosocial outcomes.
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