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176 papers

Towards optimized CT lung cancer screening scan protocols.

Iball GR et al. · Jul 1, 2026

Objectives To evaluate radiation dose and image quality for CT lung cancer screening protocols and to determine which reconstruction kernels deliver accurate nodule volumetry. Methods A variable size anthropomorphic chest phantom and a lung screening image quality phantom were scanned on 17 different scanner models. Dose metrics from the chest phantom scans were compared against international dose recommendations. Image quality phantom scans were used to assess whether the protocol yielded accurate nodule volumetry as per the Quantitative Imaging Biomarkers Alliance (QIBA) criteria, and to determine whether changes were needed to enable this. Results Doses varied by up to a factor of 7 for the largest phantom size. All protocols delivered doses below the UK standards but only 2 scanners met the European dose criteria. Many scanners failed to meet the QIBA criteria with lung reconstruction kernels, primarily due to excessive edge enhancement and insufficient 3D spatial resolution. With alternative reconstruction kernels, the QIBA criteria were met on all bar 2 scanners. Conclusions Standard lung screening CT protocols on contemporary scanners produce images of varying image quality, over a wide range of radiation doses. Scanner-specific reconstruction kernel selection is required to meet the QIBA criteria. The study findings enable the development of optimized CT scanning protocols for lung cancer screening program. Advances in knowledge Standard lung cancer screening scanning protocols demonstrate notable variations in dose. Lung reconstruction kernels often yield inaccurate measurements of nodule volume; instead, soft tissue kernels are necessary to obtain reliable results.

Medicine

Socioeconomic Factors and Their Role in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review.

Wiering L et al. · Jul 1, 2026

Metabolic dysfunction-associated steatotic liver disease (MASLD), a major public health concern, is influenced by an interplay of genetic, environmental, and lifestyle factors, with socioeconomic factors functioning as important upstream determinants whose roles remain not yet fully understood. This review synthesizes current evidence on how different indicators of socioeconomic status as well as related social determinants of health-income, poverty, food insecurity, health insurance, education, migration, and composite indices-relate to MASLD prevalence, severity, and outcomes across different world regions. Several studies associate these socioeconomic factors with an increased risk of MASLD, illustrating the disease's link with socioeconomic disadvantages. However, socioeconomic factors often lose or attenuate their independent association with MASLD once key downstream determinants-such as diet quality, physical inactivity, and metabolic comorbidities-are considered, supporting a model in which socioeconomic factors mainly shape exposure to metabolic and behavioural risk factors rather than exerting a direct causal effect. Among the factors examined, education and food insecurity demonstrate the most consistent independent associations with MASLD. Notably, the direction of socioeconomic gradients appears to differ by regional income level, with lower SES associated with higher MASLD burden in high-income countries but an inverse pattern in several middle-income settings. Evidence remains largely limited to the United States, Europe, and a small number of Asian cohorts, underscoring the need for more geographically diverse research. This review highlights the association of different socioeconomic factors with MASLD, while also revealing the need for more detailed studies which systematically disentangle individual and area-level social determinants of health, model mediating pathways and incorporate underrepresented regions and paediatric populations. A deeper understanding of how socioeconomic factors and downstream mediators jointly drive MASLD could inform targeted clinical strategies and multi-level policies aimed at mitigating the social gradient in MASLD.

Medicine

Oxidative Stress-Induced Expression Levels of PXDN and NF-κB in Type 2 Diabetic Patients With Nephropathy.

Hanin Z et al. · Jul 1, 2026

Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in patients with diabetes mellitus (DM). Early detection remains difficult, but essential for timely management. In this study, we assessed Peroxidasin (PXDN) gene expression as a biomarker for early detection of DN and for reflection of oxidative stress status. We also compared PXDN and Nuclear factor-κB (NF-κB) expression levels in DN patients, aiming to identify a reliable diagnostic biomarker. Methods This prospective cross-sectional study included 40 patients with T2DM with and without nephropathy, and 20 matched healthy controls. PXDN mRNA expression was quantified by real-time polymerase chain reaction (qRT-PCR). Biochemical analyses of malondialdehyde (MDA) and total antioxidant capacity (TAC) were also done to assess the oxidative stress status. Laboratory parameters, including glycated haemoglobin, urinary albumin-to-creatinine ratio, estimated glomerular filtration rate, and microalbuminuria, were measured and correlated with gene expression levels and the oxidative stress status. Results PXDN mRNA expression was significantly upregulated in patients with DN compared to diabetic cases without nephropathy and control subjects. MDA levels were significantly elevated in both diabetic groups relative to controls, but no significant difference was found between DN and DM without renal impairment. TAC was significantly lower in DN cases compared to DM and controls. The NF-κB gene was upregulated in both diabetic groups compared to control subjects, but no significant difference was found between DN and DM without nephropathy. Furthermore, PXDN expression did not correlate with MDA, TAC, or NF-κB levels. Receiver operating characteristic (ROC) analysis identified PXDN as a highly specific and sensitive marker for DN, outperforming conventional oxidative stress biomarkers in distinguishing DN from both diabetic and healthy individuals. Conclusion PXDN is significantly upregulated in DN and may serve as a sensitive and specific molecular marker for early detection of nephropathy compared to NF-κB.

Medicine

Adolescent Acceptability of School and Home Micronutrient Supplementation and Nutrition Curriculum in Mozambique.

Bauler S et al. · Jul 1, 2026

Iron-deficiency anemia is the most common micronutrient deficiency and a leading cause of disability-adjusted life years among adolescent girls and young women (AGYW) globally. Although multiple micronutrient supplementation (MMS) provides a broader range of micronutrients than iron-folic acid supplementation (IFAS) prior to conception, the acceptability of MMS and home-based supplementation strategies remains underexplored. We assessed the acceptability of MMS, IFAS, and a contextualized nutrition curriculum delivered via school clubs in a two-arm cluster-randomized trial across three rural secondary schools in Monapo District, Mozambique. Fourteen teachers (clusters) were randomized to deliver either weekly school-based IFAS or daily home-based MMS. A total of 492 AGYW aged 13-20 years were enrolled (240 IFAS; 252 MMS); both arms received the same nutrition curriculum. Participants in both arms reported increased energy, improved appetite, and relief from menstrual symptoms. IFAS was significantly more acceptable than MMS for smell, and some participants perceived the once-weekly IFAS regimen as less burdensome than daily MMS. Some AGYW also reported that male peers perceived MMS as birth control, or assumed the girls were pregnant, due to the image of a pregnant woman on the pill bottle. Ratings of the nutrition curriculum and teachers' facilitation were positive in both arms. Participants generally preferred the regimen they were assigned, and family support facilitated adherence. These findings suggest home-based supplementation may be a feasible and acceptable strategy for reaching in-school and out-of-school AGYW in Mozambique. Including boys in future interventions and redesigning the MMS label could help reduce misconceptions and enhance acceptability.

Medicine

Drug Use and Social Connectivity Related to Hepatitis C Infection Among Rural People Who Use Drugs.

Rains A et al. · Jul 1, 2026

People who use drugs (PWUD) have a disproportionately elevated risk of hepatitis C virus (HCV). Appropriate screening and treatment may be limited, especially in rural environments experiencing healthcare shortages. In order to develop targeted intervention strategies for rural PWUD, we investigated individual and network-level correlates of HCV positivity. Survey data were collected from PWUD from the Illinois region of the Federal Delta Regional Authority (DRA). The primary outcome of interest was HCV positivity by self-report. We explored associations between HCV positivity and individual demographic, drug use, and service utilisation characteristics as well as degree of connectedness within social networks. Three hundred and two participants were included in analyses. At the individual level, HCV positivity was associated with injection drug use, overdose history, and prior receipt of substance use treatment. Two hundred and one participants had at least one connection to a peer via referral chains, most of which contained a mix of HCV-negative and positive individuals. Of note, isolated individuals had comparable rates of HCV positivity compared to their socially connected peers. Degree of connectedness was not associated with HCV positivity. This study highlights the heterogeneity, both with respect to HCV positivity and other characteristics, among networks of rural PWUD. Given that most participants were connected to others, HCV interventions led by peer champions may facilitate improved access to critical services for risk mitigation.

Medicine

The combination of low-intensity resistance exercise and electrical muscle stimulation effectively enhances executive function in men.

Dora K et al. · Jul 1, 2026

Objectives Resistance exercise enhances executive function (EF) more effectively at moderate or higher intensities than at low intensity resistance exercise (LRE), probably with increased neural activity and lactate production to meet brain energy demands. Given that LRE remains widely applicable with less perceived exertion, and electrical muscle stimulation (EMS) increases lactate production and neural activation, we investigated whether combining LRE with EMS (LRE-EMS) effectively enhances EF, without increasing perceived exertion. Design A crossover randomized study. Methods Seventeen young men participated in a crossover randomized study to assess the cognitive effects of LRE alone, EMS alone, and LRE-EMS. The LRE protocol involved knee extensions at 40% one-repetition maximum for 4 sets of 10 repetitions. During the EMS condition, the participants remained seated for 260 s to match the duration of the other conditions, with EMS applied to the lower limb muscles. Subjective perceptions of exertion and fatigue during exercise were recorded. Results IC and lactate were measured at baseline, immediately postexercise, and 15 min postexercise. The LRE condition did not significantly increase IC (p = 0.100), whereas LRE-EMS resulted in significant IC improvements immediately and 15 min postexercise (both p  Conclusions Perceived exertion and fatigue were greater with LRE-EMS compared with LRE and EMS. These findings suggest that LRE combined with EMS and EMS alone are effective strategies for cognitive improvement, but increased perceived exertion still exists.

Medicine

Hypertrophic Osteopathy Associated With Primary Pulmonary Histiocytic Sarcoma in a Dog.

Rinaldi V et al. · Jul 1, 2026

Hypertrophic osteopathy (HO) is a paraneoplastic or parainflammatory syndrome characterised by painful periosteal new bone formation and soft tissue swelling, most commonly associated with thoracic neoplasia. The pathogenesis of HO remains incompletely understood and may involve neurovascular mechanisms, altered pulmonary filtration of megakaryocytes and platelets and increased release of growth factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). This report describes the first documented case of HO associated with primary pulmonary histiocytic sarcoma (PHS) in a dog. A 7-year-old male Golden Retriever was referred for evaluation of diffuse pain, limb swelling and lameness. Diagnostic imaging revealed bilateral periosteal proliferation affecting the forelimbs and a pulmonary mass within the right caudal lung lobe. Histopathology and immunohistochemistry following lung lobectomy and lymphadenectomy confirmed a diagnosis of PHS with nodal metastasis. Surgical excision resulted in complete clinical resolution of pain despite persistent radiographic evidence of HO. Subsequent disease progression occurred despite multiple chemotherapy protocols, including lomustine, vinorelbine, and metronomic chemotherapy; however, the dog remained consistently pain-free throughout follow-up. Overall survival time was 450 days. This case expands the spectrum of neoplasms associated with HO and further supports the hypothesis that tumour location, rather than histotype, plays a central role in the development of this syndrome. Moreover, the sustained absence of pain despite persistent periosteal lesions and metastatic progression suggests that tumour burden and tumour microenvironment may significantly influence clinical manifestations of HO.

Medicine

Age, Age-Related Comorbidities and Survival in Palbociclib, Ribociclib and Abemaciclib Users With Advanced Breast Cancer: A Nation-Wide Retrospective Cohort Study.

Rajamaki B et al. · Jul 1, 2026

Purpose Prevalence of breast cancer (BC) increases with age, but the external validity of data obtained from pivotal trials of medicinal products remains a concern due to the underrepresentation of frail and older adults. Cyclin-dependent kinase inhibitors (CDKi), palbociclib, abemaciclib, and ribociclib are considered an essential part of the standard-of-care in the management of advanced/metastatic breast cancer. We investigated age, comorbidities, and survival in a nationwide real-world cohort of CDKi users. Methods Data from the Finnish Cancer Registry, reimbursed dispensed prescriptions, Electronic Prescription Database, Care Register for Health Care (CRHC), and Causes of Death Register were combined and analysed. Results Altogether 1921 women with BC initiated CDKi treatment in 2018-2022. The median age at initiation was 66.9 years, with 43.2% of the study cohort being Conclusions Real-world CDKi users are older than women included in the pivotal trials, and the survival differences between age groups imply challenges in the generalisability of data from pivotal trials. The real-world CDKi user population is characterised by a low prevalence of major comorbidities.

Medicine

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

Oestrogen receptor phosphorylation profiles and in silico PAM50 subtyping reflect sexual dimorphism in breast cancer.

Chatterji S et al. · Jul 1, 2026

Breast cancer (BC) is most prevalent in females but also accounts for <1% of male cancer cases and 0.2% of male cancer-related deaths. Distribution of histological subtypes, receptor status, and age of diagnosis varies based on sex, and a growing body of evidence supports sex-specific molecular differences in BC. However, this is limited by the smaller number of male cases available for study compared to the thousands of cases of female BC. We combined publicly available male BC gene expression datasets for 195 patients from 4 studies and split randomly into discovery and validation sets. Clustering and gene expression analysis were performed. Two stable clusters were identified initially, confirmed in the validation set. Cluster C1 was enriched for genes associated with MAPK signalling and arylesterase activity. Cluster C2 showed enrichment of genes associated with proliferation, invasion, and metastasis, along with enrichment of gene ontology and pathway terms related to ECM regulation, particularly collagen-containing ECM. Of note, when stratified by ERα and PR status, no enrichment was observed with the predicted PAM50 classification. ERα and MAPK signalling were enriched in both clusters, albeit through different gene sets. Since these pathways were enriched, we investigated the signalling regulation of ERα based on immunohistochemical expression of phosphorylated ERα (S104, S118, S167, S294) and their prognostic roles. This analysis also revealed distinctions from female BC, showing a lack of prognostic outcome for any of these biomarkers. We show that male BC does not align with female BC in the same way that intrinsic subtypes of female BC are not identical. As BC heterogeneity is well recognised, we propose that male BC should be considered as a potentially unique clinical subtype of BC.

Medicine