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464 papers

Ectonucleotidases CD39 and CD73 expression levels are independent and inverse predictors of survival in muscle-invasive bladder cancer.

Ledderose S et al. · Jul 1, 2026

Bladder cancer is one of the leading causes of cancer-related mortality worldwide. Long-term survival is particularly poor in patients with muscle-invasive bladder cancer (MIBC). Modulation of purinergic signaling through the ectonucleotidases CD39 and CD73 has emerged as a promising therapeutic strategy in cancer medicine. Altered expression patterns of these molecules have been linked to prognosis in various malignancies. In this study, we assessed the value of CD39 and CD73 expression as prognostic markers and potential therapeutic targets in MIBC. CD39 and CD73 expression was determined by immunohistochemistry using tissue microarrays from 180 patients with MIBC. Associations between tumoral and stromal expression and clinicopathological variables, including overall survival (OS), tumor-specific survival (TSS) and disease-free survival (DFS), were analyzed. Tumor cells did not express CD39. High stromal CD39 expression was significantly associated with a lower T category and UICC stage as well as prolonged median OS, TSS, and DFS. High CD73 expression by tumor cells was significantly associated with poorer OS and TSS. Stromal CD73 expression was not significantly correlated with survival outcomes. Our findings indicate distinct and compartment-specific roles for CD39 and CD73 in MIBC. They suggest that high CD73 expression in tumor cells and low CD39 expression in stromal cells are negative prognostic indicators and potential therapeutic targets in MIBC.

Biochemistry, Genetics and Molecular Biology

Polygenic Risk Scores for Incident Dementia in the Multi-Ethnic Study of Atherosclerosis.

Xue D et al. · Jul 1, 2026

Over 75 Alzheimer's disease (AD) and dementia-associated variants have been identified through genome-wide association studies, but the utility of polygenic risk scores (PRS) for predicting AD and dementia in diverse and admixed populations remains unclear. We compared how PRS approaches differing in p-value thresholds, variant weights, and source ancestry perform in predicting dementia in 6338 African American, Chinese, Hispanic, and White individuals from the Multi-Ethnic Study of Atherosclerosis. We tested clumping and thresholding (C+T) methods with varying parameters against Bayesian approaches (PRS-CS, PRS-CSx). We compared the ability of each method to predict incident dementia in all participants and in groups stratified by self-reported race/ethnicity. We additionally analyzed performance across groups stratified by estimated proportion of non-Finnish European (NFE)-like ancestry. Including more variants does not improve performance. We found comparable associations between dementia and PRS when comparing a C+T method with only 15 SNPs and PRS derived from Bayesian models that include > 800,000 SNPs (HR 5e-08 = 1.18, 95% CI: 1.08-1.28; HR CSx = 1.17, 95% CI: 1.07-1.27). The p lowNFE _ 5e-08 = 1.27, 95% CI: 1.08-1.50; HR lowNFE _ CSx = 1.12, 95% CI: 0.94-1.33). More selective PRS models using genome-wide significant SNPs may be preferable for dementia prediction in diverse populations.

Biochemistry, Genetics and Molecular Biology

Initiation of High-Potency Benzodiazepine Prescriptions Among Survivors of Severe Trauma.

Oldner A et al. · Jul 1, 2026

Background Trauma is a major public health concern that often leads to long-term psychological distress and chronic pain. Benzodiazepines (BZDs) are sometimes prescribed for anxiety, insomnia, or acute stress-related symptoms, but long-term use is associated with dependence and adverse outcomes. The extent to which BZDs are initiated after trauma, and their implications for long-term health, remain poorly understood. This study aimed to assess the association between trauma exposure and initiation of high-potency BZDs, identify risk factors within the trauma cohort and examine the association between new BZD use and long-term mortality. Methods We conducted a population-based cohort study using data from a regional trauma registry linked to Swedish national health registers. New initiation of BZD prescriptions was defined as filling at least one prescription within 6 months after trauma. Multivariable logistic regression was used to assess associations between trauma exposure and BZD initiation and to identify risk factors within the trauma cohort. Cox proportional hazards regression evaluated the association between new BZD use and 6-18-month mortality. Results The study included 12,206 BZD-naive trauma patients and 66,801 matched controls. Trauma exposure was independently associated with new high-potency BZD use. Within the trauma cohort, risk factors included older age, psychiatric comorbidity, substance abuse, pre-traumatic opioid or sedative-hypnotic drug use, penetrating trauma, and higher injury severity. New BZD use was associated with markedly elevated 6-18-month mortality (adjusted HR 2.9, 95% CI 2.0-4.2, p Conclusions Trauma exposure independently predicted initiation of high-potency BZDs among previously BZD-naive patients. Psychiatric comorbidity, substance use, and greater injury severity were important risk factors. The association between new BZD use and increased long-term mortality underscores the need for cautious prescribing and structured follow-up after trauma. Editorial comment This study examines initiation of high-potency benzodiazepines among previously naive survivors of severe trauma using linked registry data. It shows that trauma exposure is strongly associated with new benzodiazepine use, particularly in older, comorbid, and vulnerable patients. Initiation is also associated with higher subsequent mortality, likely reflecting underlying clinical and psychosocial risk rather than a causal drug effect.

Psychology

Effect of Structured Training on ICU Nurses' Knowledge-Based Competence in Ventilator-Associated Pneumonia Prevention in a Resource-Limited Setting: An Explanatory Sequential Mixed-Methods Study.

Yakubu YH et al. · Jul 1, 2026

Aim To evaluate the effect of a structured training intervention on ICU nurses' knowledge-based competence in VAP prevention in a resource-limited setting and identify personal, environmental and organisational barriers to implementation. Design An explanatory sequential mixed-methods design was employed, integrating a single-group quasi-experimental pre-test-post-test quantitative strand with a qualitative interview strand. Because participant responses were not linked across assessment points, findings represent group-level improvements rather than within-individual change. Methods ICU nurses completed pre-test (n = 57) and post-test (n = 56) assessments using an adapted eight-item VAP prevention knowledge questionnaire. A structured 3-h workshop on VAP prevention bundles, infection control and airway management was delivered between tests; the post-test occurred within 2 weeks. Group differences were analysed using an independent-samples t-test and chi-square tests. Qualitative interview data (n = 8) were analysed thematically to explain and contextualise the quantitative findings. Results Mean knowledge scores increased from 3.63 (SD 1.57) to 5.29 (SD 1.57) out of 8 (t(111) = -5.61, p 2 (2) = 22.43, p Conclusions A brief, context-specific training workshop significantly improved ICU nurses' knowledge-based competence in VAP prevention. However, systemic barriers-equipment shortages, absent protocols, limited supervision and workload pressures-constrain the translation of knowledge gains into consistent bedside practice. Sustainable improvement requires embedding education within broader quality improvement efforts. No patient or public contribution No patient or public contribution.

Medicine

Health, Social and Recidivism Outcomes Among People Who Have Been Incarcerated in New South Wales, Australia: Study Protocol and Cohort Profile for the Prison Outcomes STudy (POST).

Degenhardt L et al. · Jul 1, 2026

Introduction We have been funded to examine post-incarceration health and social outcomes for all people incarcerated in New South Wales, Australia, 2000-2022; assess treatment and services for drug dependence and serious mental illness; and project the impact of expanding intervention coverage. We will use a linked cohort, the Prison Outcomes STudy (POST), which we also describe. Methods The POST cohort was established using linked administrative data for all adults (≥ 18 years) admitted to full-time custody in New South Wales, 2000-2022. Custody records were probabilistically linked to 18 health, justice and mortality datasets. We report baseline sociodemographic and custody characteristics and the frequency of key post-release events. Results 200,486 adults, 15% women (n = 30,698), were incarcerated, with 2,282,367 person-years of follow-up and 11% (257,545 person-years) of follow-up spent in custody. First Nations people comprised 27% of the cohort. Half (48%) of the cohort (n = 95,563) had at least one contact with community mental health services, and 27% (n = 54,100) had received alcohol and other drug treatment. POST will provide population-wide evidence on health and social outcomes after custody, including the effects of treatment for drug dependence and serious mental illness. We will compare across subgroups and the outcomes of post-release service engagement. Mathematical modelling will test the impact of expanding access to care in prison and post-release on outcomes in the community. Discussion and conclusions POST will inform policy and service responses across justice, health and community settings to reduce harms among people who experience incarceration.

Social Sciences

A Multi-Stage Drop-the-Loser Design With Superiority Boundaries.

Greenstreet P et al. · Jul 1, 2026

Multi-arm multi-stage (MAMS) trials have gained popularity, due to their improved efficiency in evaluating multiple treatments. A traditional MAMS trial often decreases the expected sample size of the trial compared with just running a multi-arm approach, but with the drawback of an increase in maximum sample size. For academic led trials, this poses a particular challenge, as funding is typically based on the maximum required sample size. To address this, drop-the-loser designs were introduced, where a fixed number of treatments are dropped at each interim stage, thereby reducing the maximum sample size. In this work, we propose an enhanced multi-stage drop-the-loser design that also allows for early stopping of the entire trial for superiority. This approach aims to retain the benefits of a reduced maximum sample size while also lowering the expected sample size. The proposed design is motivated by a trial in atrial fibrillation. We derive analytical expressions for the type I error rate, power, and expected sample size, and compare the proposed design's performance to alternative methods. We outline the key requirements for implementing the proposed design and discuss the contexts in which it should be considered. For the motivating example, the results show that the proposed design substantially reduces the expected sample size compared to a standard drop-the-loser design, while lowering the maximum sample size relative to running a traditional MAMS trial or multiple separate trials.

Mathematics

Validation of an automated chromogenic in situ hybridization protocol for detection of cytomegalovirus in formalin-fixed, paraffin-embedded renal graft biopsies.

Rangel JV et al. · Jul 1, 2026

Introduction Histopathological diagnosis of human cytomegalovirus (HCMV) infection in formalin-fixed, paraffin-embedded (FFPE) tissues stained with hematoxylin-eosin relies on the identification of characteristic cytopathic changes, including eosinophilic intranuclear and cytoplasmic viral inclusions. Chromogenic in situ hybridization (CISH) enables the localization of specific nucleic acid sequences in histological sections, increasing diagnostic sensitivity. Automated CISH platforms allow standardized and reproducible detection of viral RNA or DNA in FFPE tissues. This study aimed to validate an automated CISH protocol for the detection of HCMV in multiple tissue types, including renal allograft biopsies processed at the Anatomical Pathology Division of UERJ. Methods Two groups of FFPE samples were analyzed. The first group included ten samples from various tissues, including kidney, palate, esophagus, stomach, and colon; nine positive and one negative for HCMV by immunohistochemistry (IHC). The second group included twenty renal allograft biopsies; nineteen without previous diagnosis and one positive by IHC. For CISH, fluorescein-conjugated oligonucleotide probes targeting HCMV RNA expressed during the early replication phase were used, with hybridization and detection performed on an automated platform. Results In Group 1, all samples, including the case previously negative by IHC, were positive for HCMV by CISH. In Group 2, six of the twenty renal biopsies were positive, including the sample already identified as positive by IHC. Conclusions The automated CISH protocol demonstrated high sensitivity and reproducibility for HCMV detection, supporting its validation and use in the diagnosis of renal biopsies and other tissues, as well as its incorporation into the routine workflow of Anatomical Pathology laboratories.

Medicine

Dual-scan conformal cone-beam CT for targeted image-quality improvement using dynamic collimation.

Liu Y et al. · Jul 1, 2026

Background Cone-beam computed tomography (CBCT) is routinely used for image guidance in radiation therapy, but conventional full-field CBCT acquisition may expose anatomically irrelevant regions and generate substantial scatter, which degrades soft-tissue contrast and limits the accuracy of target localization and adaptive radiotherapy workflows. A clinically practical imaging strategy should improve image quality in the region of clinical interest while preserving sufficient full-field anatomical information for patient setup and dose-related assessment. Purpose To improve image quality within clinically relevant regions without increasing the total imaging dose, this study developed a dual-scan conformal cone-beam CT method using dynamic collimation. Methods A dual-scan conformal acquisition strategy using dynamic collimation was designed. Dynamic collimation was defined as angle-dependent shaping of the X-ray field around a preplanned target region; it was implemented with a multi-leaf collimator model in the digital phantom and patient-data simulations and with the movable kV collimator in the physical phantom measurement. Collimator positions were calculated from forward projections of the target region, and a target-region-based intensity-optimization model was used to allocate more photons to projection angles and detector regions contributing to the target region. The dual-scan protocol, consisting of a low-dose full-field-of-view (FOV) scan and a higher-dose conformal scan, was reconstructed using a regularized weighted least-squares algorithm with anisotropic total-variation regularization. The method was evaluated using a FORBILD head phantom, patient planning CT datasets, and an anthropomorphic head phantom measured on a Varian Edge on-board imaging system. Results The proposed method achieved the best overall image quality among the compared methods. In the FORBILD phantom, for target region 1 (VOI1), SSIM increased from 0.702 to 0.855, CNR increased from 0.514 to 1.463, and SNR1/SNR2 increased from 33.8/32.8 to 113.1/114.6 compared with conventional FDK reconstruction. In the prostate cancer case, CNR increased from 0.44 to 1.94, and SNR1/SNR2 increased from 25.6/23.3 to 74.6/82.4. In the measured anthropomorphic head phantom, CNR improved from 1.036 to 2.379, and SNR1/SNR2 improved from 42.8/50.1 to 89.8/98.0. Conclusion The proposed dual-scan conformal CBCT strategy using dynamic collimation improves local image quality in the clinically relevant target region while maintaining full-FOV information through the two-scan protocol. This method may provide a practical route toward patient-specific CBCT guidance for adaptive radiotherapy.

Physics and Astronomy

Understanding Multi-Victimization: Identifying Socioecological Supports Among Adolescents.

Smith EK et al. · Jul 1, 2026

Background Transgender and gender-diverse adolescents (TGDA) experience multiple victimization types (i.e., multi-victimization) more often than their cisgender peers. While greater socioecological supports are associated with reduced victimization, their role in protecting TGDA against multi-victimization is underexplored. Methods We conducted a cross-sectional analysis of health risk behavior survey data from students (N = 4207) across 13 high schools in a mid-sized U.S. city. We compared victimization rates and socioecological support levels (i.e., parental monitoring, perceived social support, food and housing security) and associations between socioecological support and victimization, accounting for between-school differences. We included two-way interactions between gender and socioecological supports. Results TGDA reported more frequent multi-victimization and lower socioecological support than cisgender adolescents. Across all groups, greater socioecological support was associated with experiencing fewer victimization types. Food security was more protective for cisgender girls than cisgender boys. Implications for school health policy, practice, and equity Enhancing socioecological support may reduce multi-victimization for all youth, with TGDA having the greatest need. Schools' advocacy and innovative efforts to bolster socioecological support are critical to TGDA wellbeing. Conclusions Modifiable socioecological supports may reduce adolescent multi-victimization. TGDA have lower support rates and higher multi-victimization rates, suggesting the need for tailored interventions.

Psychology

The intergenerational transmission of reflective functioning in adoptive families: A prospective study from pre-adoption to early adolescence.

Fiore S et al. · Jul 1, 2026

Parental reflective functioning is crucial for the development of children's reflective functioning, with cross-sectional evidence supporting this idea. However, there is a lack of long-term, prospective studies in this area and no previous studies have examined parental reflective functioning and child reflective functioning in the context of adoption. Using a structural equation modeling approach, this study addressed this knowledge gap by examining the associations between 96 Belgian adoptive mothers' and fathers' reflective functioning during the transition to adoptive parenthood, their levels of parental reflective functioning during their adopted child's early childhood, and the children's reflective functioning in early adolescence (M age = 12 years, SD = .58, range = 11-13; 17 boys, 11 girls). Findings showed that parents' pre-adoptive reflective functioning was positively associated with parental reflective functioning in early childhood. Parental reflective functioning in early childhood, but not pre-adoptive reflective functioning, predicted child reflective functioning in early adolescence. Maternal reflective functioning mediated the association between pre-adoptive reflective functioning and child reflective functioning. Although the small sample size precludes drawing strong conclusions from this study, this study provides new evidence for the intergenerational transmission of reflective functioning even in the context of adoption. Implications for future research are discussed.

Psychology