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176 papers

Previous Hamstring Injury Does Not Impact Biceps Femoris Long Head Fascicle Length and Eccentric Knee Flexion Strength Changes Following a Low-Volume Resistance Training Intervention in Elite Under-20-Year-Old Male Gaelic Footballers.

Mooney T et al. · Jul 1, 2026

This study reports biceps femoris long head (BFlh) fascicle length and eccentric knee flexion strength changes following a 9-week in-season low-volume resistance training intervention in elite under-20-year-old (U20) male Gaelic footballers with and without previous hamstring injury. We included 26 male Gaelic footballers (age = 18.5 ± 0.5 years; height = 183.1 ± 5.1 cm; body mass = 79.2 ± 7.9 kg) in this study, with 10 of these participants reporting previous hamstring injuries within the last 12 months. Participants performed two sets of four Nordic hamstring exercise (NHE) repetitions and three sets of six staggered-stance Romanian deadlift (RDL) repetitions once per week for nine weeks. Before and after the intervention, BFlh fascicle length was assessed via ultrasound and eccentric knee flexion strength was measured during the NHE. We ran separate linear mixed-effects models for BFlh fascicle length and eccentric knee flexion strength, with fixed-effects of time (baseline and follow-up), limb-type (previously injured and contralateral uninjured limbs of previously injured participants and between-limb average of uninjured participants) and the time*limb-type interaction. The linear mixed-effects model for BFlh fascicle length revealed a significant main effect of time (β = 0.31 cm; SE = 0.15 cm; p = 0.04), while the time*limb-type interaction was not statistically significant. The linear mixed-effects model for eccentric knee flexion strength revealed no significant increase in eccentric knee flexion strength (β = 9.53 N, SE = 12.97 N, p = 0.47), while the time*limb-type interaction was not statistically significant. These findings suggest changes to BFlh fascicle length and eccentric knee flexion strength from baseline to follow-up were comparable across all limb-types.

Medicine

Exploring the Social and Cultural Influences on Advance Care Planning Engagement for Patients Living With Cancer: A Hermeneutic Phenomenology Study.

Lin CP et al. · Jul 1, 2026

Guided by Leininger's Theory of Culture Care, this hermeneutic phenomenological study explored how social and cultural contexts shape engagement in advance care planning (ACP) among people living with cancer in Taiwan. Semi-structured interviews were conducted with 26 stakeholders, including 8 patients, 7 family caregivers, and 11 healthcare providers, recruited from oncology and ACP outpatient clinics, inpatient wards, and home care services at a tertiary medical center. Data were audio-recorded, transcribed verbatim, and analyzed using Naeem's six-step approach. Six interrelated influences on ACP engagement were identified: socioeconomic circumstances, prior experiences and personal background, religious beliefs and life values, relational dynamics with family and significant others, wider social norms, and political and legal requirements. These factors shaped whether ACP was seen as acceptable, when it was introduced, who was involved in decision-making, and how discussions were negotiated within families and with healthcare professionals. The findings show that ACP engagement in Taiwan is a relational, culturally embedded process. Culturally congruent, nurse-led ACP approaches that address relational, socioeconomic, and legal structural influences are needed to support family-centered cancer care.

Medicine

Deep learning models to predict mammographic density jointly on standard dose and low dose images.

Squires S et al. · Jul 1, 2026

Objectives Mammographic density is associated with increased risk of developing breast cancer. Automated estimation of density in women below normal screening age would enable earlier risk stratification. We are piloting the use of low dose mammograms at 10% of standard dose combined with models that make accurate mammographic density estimates. Methods Three models were trained on a joint set (107 619) of standard dose mammograms with associated density scores and their simulated low dose counterparts such that the models made predictions on standard and low dose mammograms. A second set of models was trained separately on the standard and simulated low dose mammograms. All models were tested on a held-out set from the training data and an independent dataset with 294 pairs of standard and real low dose mammograms. Results The root mean squared errors (RMSE) between model predictions and density scores on standard and simulated low dose images were 8.26 (8.16-8.36) and 8.27 (8.17-8.38) respectively. The RMSE between predictions on standard and simulated low dose images for the jointly trained models was 1.91 (1.88-1.96). The RMSE of the predictions on real low dose images compared to standard dose images was 3.79 (2.75-4.99). Conclusions Deep learning models make density predictions on low dose images with similar quality as on standard dose images. Automated analysis of low dose mammograms could contribute to accurate breast cancer risk estimation in younger women enabling stratification for further monitoring and preventative therapy. Advances in knowledge Mammographic density can be estimated in low dose mammograms with similar quality to standard dose mammograms.

Medicine

ICU Clinicians' View on Platelet Transfusion Thresholds for a Future Trial-Protocol for an International Survey.

Barakji JA et al. · Jul 1, 2026

Background Thrombocytopenia is frequent in adult intensive care unit (ICU) patients and may contribute to adverse outcomes, including bleeding, morbidity and mortality. To reduce the risk of bleeding, platelet transfusions are commonly used, yet transfusion thresholds vary, and the evidence base is very limited. Randomised clinical trials investigating platelet transfusion strategies in ICU patients are therefore a high research priority. With this survey, we aim to assess ICU doctors' willingness to randomise adult ICU patients to restrictive versus liberal platelet transfusion thresholds across clinically relevant scenarios in a future randomised trial. Methods We will conduct an international, web-based survey targeting ICU doctors within an established research network. The survey includes questions on respondent characteristics and willingness to enrol patients with an indication for platelet transfusion across a range of transfusion thresholds in different clinical scenarios, including non-bleeding patients, those undergoing invasive procedures, and those with bleeding. The survey has been pilot-tested and refined twice before distribution. We will summarise results using descriptive statistics and conduct stratified analyses by country and ICU type. Conclusions This international survey will assess ICU doctors' willingness to randomise adult ICU patients to restrictive versus liberal platelet transfusion strategies across multiple clinical scenarios.

Medicine

Clinicopathological and molecular characterization of HPV-associated cervical poorly cohesive carcinoma: a rare aggressive entity.

Liu W et al. · Jul 1, 2026

Primary signet-ring cell carcinoma and poorly differentiated adenocarcinoma with poorly cohesive morphology in the cervix are rare conditions, and their clinicopathological features remain poorly described. This study defines primary cervical poorly differentiated adenocarcinomas meeting the diagnostic criteria for poorly cohesive carcinoma as outlined in the 2019 WHO Classification of Digestive System Tumors as 'HPV-associated cervical poorly cohesive carcinomas' (HPV-associated CPCC) and describe their clinicopathological and molecular features. Sixteen HPV-associated CPCC cases were analyzed and classified into three histological subtypes: signet-ring cell carcinoma (n = 4), not otherwise specified (n = 6), and mixed types (n = 6). All patients were Chinese (median age: 46 years; range: 30-66). Vaginal bleeding was the primary presenting symptom (100.0%). High-risk human papillomavirus (HPV) was identified in all tumors, with HPV-18 as the predominant genotype (n = 13), HPV-16 in two cases, and a single case exhibiting concurrent infection with HPV-16, -18, and -58. Overall, 56.3% presented with advanced-stage disease (International Federation of Gynecology and Obstetrics [FIGO] IIIB-IVB), frequently involving regional lymph nodes (56.3%) and distant sites (18.8%). Histopathological examination revealed diffuse stromal infiltration (100%), lymphovascular invasion (75.0%), necrosis (75.0%), and desmoplasia. Immunohistochemically, all cases showed p16 block positivity. Variable expression of antibody-drug conjugate targets was observed, with HER2-low expression (33.3%), and positive staining for Trop-2 (85.7%), nectin-4 (42.9%), and tissue factor (92.3%). During follow-up, disease-specific mortality was 50.0%. The 3-year overall survival rate was 56.3%, which was significantly lower in advanced-stage disease (45.0%) than in early-stage disease (75.0%). Whole-exome sequencing revealed low tumor mutational burden (median 1.28 Muts/Mb), recurrent mutations in AK1, ARHGAP39, KRT24, MICAL3, SLC6A9 (27.3%), KRAS, and KMT2C (18.2%), alongside MUC2 copy gain (63.6%) and bidirectional Y_RNA alterations (gain 54.5%/loss 45.5%). Collectively, HPV-associated CPCC represents a distinct and aggressive subtype characterized by distinctive histopathological features, a predominant association with HPV18, frequent presentation at advanced stages, and marked molecular and biomarker heterogeneity.

Medicine

Agreement Between Methods Assessing Changes in Plasma Volume During Fluid Therapy-A Post Hoc Analysis of a Randomized Trial.

Grubb D et al. · Jul 1, 2026

Volume status of a patient is difficult to assess clinically. Methods to measure plasma volume as well as changes in plasma volume in connection with fluid therapy are therefore valuable for research purposes and could potentially be used bedside to guide fluid therapy in individual patients. The objective of the present study was to evaluate hematocrit as a marker of changes in plasma volume and an anthropometric formula to estimate absolute plasma volume against the reference method, plasma volume measurements using radiolabeled albumin. A total of 64 postoperative patients received 10 mL/kg of albumin. The plasma volumes were measured with the reference method (radiolabeled albumin) at baseline, after 30 and 180 min. Plasma volumes were compared with plasma volumes derived from either the baseline measurements and subsequent changes in hematocrit (calibrated method) or from an anthropometric formula and subsequent hematocrit changes (anthropometric method). Bland-Altman plots were used to test agreements between methods. The mean difference in plasma volume between the anthropometric and the reference method at baseline was -0.1 mL/kg (95% CI -2.1 to 1.8) with lower and upper LOA of -18.0 and 17.0 mL/kg. The agreement remained essentially unchanged after fluid therapy (mean difference -0.1 mL/kg (95% CI -1.8 to 1.5) with LOAs of -18.0 and 17.0 mL/kg). The mean difference between the calibrated and reference methods was -0.1 mL/kg (95% CI -0.9 to 0.7) with LOAs of -9.4 and 9.2 mL/kg. The anthropometric formula yields low precision in predicting plasma volumes in postsurgical patients. Changes in hematocrit during fluid therapy cannot replace the reference method to assess changes in plasma volume in the individual patient because of the imprecision. EDITORIAL COMMENT: Clinical appreciation of plasma volume is relevant for assessing treatment where intravenous fluid resuscitation is involved. This analysis, using a reference method for plasma volume assessment, and comparing to simpler methods to estimate the same, demonstrates that there are important limitations with some simpler and readily acceptable methods to perform this estimation.

Medicine

Linking the Pre-Assessment Information Form (PIF) to the ICF: Enhancing Standardized Functional Assessment in Parkinson's Disease.

Rogatto FBT et al. · Jul 1, 2026

Background and purpose Systematic documentation of functioning in people with Parkinson's disease (pwPD) requires a standardized language to enable comparability across services and countries. The International Classification of Functioning, Disability and Health (ICF) provides this framework; however, instruments recommended by the European Physiotherapy Guideline for Parkinson's disease have not previously been linked to its categories. This study aimed to link items from the Pre-Assessment Information Form (PIF) to ICF categories using the refined linking rules. Methods Methodological study. Two independent evaluators with extensive knowledge of the ICF taxonomic framework applied 10 refined linking rules to 26 PIF items, working independently and blindly. Disagreements were resolved by a third evaluator with prior ICF experience. Inter-rater agreement was assessed using the Kappa coefficient (95% confidence interval). Results Initial inter-rater agreement was moderate across all ICF taxonomy levels (k = 0.42-0.54; p Discussion The resulting set of 25 ICF categories provides a structured description of the mobility and body function domains represented in the instrument. The application of ICF qualifiers to grade the severity of patient-reported limitations represents a potential next step, subject to implementation and validation in applied clinical settings.

Medicine

Sense of School Belonging and School Reintegration for Students Hospitalized With Chronic or Complex Medical Diseases: Insights From a Grounded Theory Study.

Tomberli L et al. · Jul 1, 2026

Background A strong sense of school belonging (SoSB) supports students' emotional well-being, engagement, and adjustment. For students hospitalized because of chronic or complex conditions, maintaining SoSB is challenging yet essential for successful school reintegration. Methods Using a Grounded Theory approach, this study combined interviews with 16 parents, 32 mainstream teachers, 31 hospital teachers, and one association, alongside drawings from 14 hospitalized students. Data were collected pre- and post-COVID-19. Drawings were analyzed through a meaning-making approach, and all materials underwent iterative coding and constant comparison. Results Students reported strong emotional bonds with hospital teachers but felt forgotten by their mainstream schools. Peer contact was limited, and teachers felt unprepared to manage absences and reintegration. Structural gaps and weak communication between schools hindered continuity. Both formal (e.g., remote lessons) and informal (e.g., messages, drawings) exchanges, along with psychologists and associations, emerged as protective factors. Implications for school health policy, practice, and equity Findings highlight the need for integrated school-health policies, teacher training, and structured collaboration to ensure equitable relational continuity. Conclusions Promoting SoSB during hospitalization is crucial for recovery, resilience, and educational equity.

Medicine

Blinded, bias-controlled multi-rater evaluation of human-versus-AI brain metastasis segmentation using a hybrid foundation-model framework.

Han Y et al. · Jul 1, 2026

Background Accurate segmentation of brain metastases (BM) is essential for diagnosis, stereotactic radiosurgery planning, and longitudinal assessment. However, manual contouring is time-intensive, limiting clinical scalability, and exhibits substantial inter-observer variability. This variability complicates objective assessment of automated segmentation methods and challenges interpretation of model performance. Purpose To address these limitations, we developed TUM-SAM, a hybrid foundation-model framework for fully automated BM segmentation, and introduced a bias-controlled, blinded multi-rater evaluation paradigm to determine whether AI-based BM segmentation has reached expert-level performance and whether AI-generated contours are preferred by human experts under unbiased assessment. Methods TUM-SAM integrates nnU-Net-based lesion detection with a tumor-adapted Med-SAM segmentation model to enable prompt-free, fully automated segmentation. Training used 301 patients (2548 lesions), and external evaluation used an independent cohort of 105 patients (397 lesions). Segmentation accuracy was benchmarked against DeepMedic and nnU-Net using Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (HD95). Two physicians contoured all external cases, and a third physician contoured a 20-patient subset for a blinded, tumor-level, multi-rater preference study. Pairwise contour preferences were analyzed using a Bradley-Terry probabilistic model to obtain bias-adjusted estimates of relative contour quality while accounting for rater-specific tendencies and case difficulty. Results In the external cohort, TUM-SAM achieved a lesion-wise detection sensitivity of 0.94 and outperformed DeepMedic and nnU-Net across all tumor sizes, with a mean DSC of 0.84 and HD95 of 1.9 mm (nnU-Net/DeepMedic: DSC 3.3 mm). Across voxel-wise evaluation, TUM-SAM's geometric performance fell within the range of inter-observer variability among physicians and was sensitive to reference construction. In contrast, in the blinded rater study, experts preferred TUM-SAM-generated contours over individual physician contours in 81-87% of raw comparisons; Bradley-Terry analysis yielded conservative, bias-corrected win probabilities of 55-56%, indicating consistent preference after adjustment for rater and case difficulty. Conclusion Using a bias-controlled, blinded multi-rater evaluation framework, TUM-SAM demonstrates brain metastasis segmentation quality that is consistently preferred by expert physicians, highlighting the limitations of agreement-based voxel-wise metrics under inter-observer variability. These findings underscore the dependence of conventional evaluation on reference definition and support preference-based assessment as a complementary approach for evaluating AI segmentation quality in BM MRI.

Medicine

Population Pharmacokinetics and Pharmacodynamics of Paracetamol in Malaysian Patients With Plasmodium knowlesi Malaria.

Wattanakul T et al. · Jul 1, 2026

Paracetamol may improve renal function in patients with severe Plasmodium knowlesi malaria, particularly in those with acute kidney injury and hemolysis, via inhibition of cell-free hemoglobin mediated oxidative kidney damage. We developed a population pharmacokinetic/pharmacodynamic (PK/PD) model to assess effects of paracetamol on creatinine, hepatotoxicity, fever clearance, and parasite clearance among Malaysian patients with predominantly non-severe knowlesi malaria using data from the PACKNOW trial (Clinical Trials Registration: NCT03056391). A total of 372 patients were included in the PK/PD analyses (paracetamol: n = 183, control: n = 189). Paracetamol PK was described using a prior PK model published in patients with falciparum malaria. The PK/PD demonstrated that higher paracetamol exposures were associated with a faster decline in both creatinine and fever clearance time, supporting its renoprotective and antipyretic effects. Increased paracetamol exposure was not associated with hepatotoxicity or serious adverse events, despite a weak positive association with liver transaminases over time. No significant relationship was observed between paracetamol exposure and parasite clearance. Overall, these findings highlight an exposure-response relationship for paracetamol and a decline in creatinine, supporting its use as a renoprotective drug in treating Plasmodium knowlesi malaria.

Medicine