Atzori S et al. · Jul 1, 2026
Backgrounds and aims Ultrasound-based spleen stiffness measurement (SSM) is a valid non-invasive tool to assess portal hypertension (PH) in chronic liver disease. Whereas the role of the respiratory phase during liver stiffness measurements is established, no study has specifically addressed how respiration influences SSM by transient elastography. Aims To evaluate the influence of respiration on SSM assessed with FibroScan 630 (Echosens, Paris, France). Methods Eighty-three patients with chronic liver disease of different aetiologies underwent SSM using vibration-controlled transient elastography (VCTE). Results SSM acquired during a normal respiratory cycle showed better diagnostic accuracy than measurements obtained during breath-hold after deep inspiration (AUROC 0.835 [95% CI 0.743-0.928] vs. 0.798 [95% CI 0.697-0.899]). Conclusion SSM by VCTE should be performed during quiet breathing, as it showed good diagnostic accuracy for predicting the presence of oesophageal varices (OV) in patients with chronic liver disease.
Medicine
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
Nguyen HV. · Jul 1, 2026
Issue addressed Underage alcohol use has been linked to risks of physical, mental, and social harms to young people. Despite the known risks, research shows that parents may choose to supply alcohol to their children on occasions for various reasons. This has prompted several health promotional campaigns aimed at parents to discourage the practice of parental supply of alcohol, but there has been little evidence of how the messages are received by the target audiences, i.e., parents of adolescents. Methods Grounded in the existing literature on alcohol-related harms, social dimensions and communication of risks, the current paper conducted a qualitative analysis of interviews with parents of adolescents to understand their interpretation of risks in a series of Australian health promotion campaigns that addressed underage drinking. Result The study demonstrated how target audiences brought in their own lived experiences and social worldviews to interpret and internalise messaging about risks in ways that are nuanced and situational. Conclusions The findings demonstrated how parents' lived experiences and worldviews influenced their interpretation and alignment with the health promotion messages about parental supply of alcohol. While the ways the parents negotiated with the health promotion messages may not be scientifically-grounded, it was not always due to unawareness of risks but based upon strategies and assessment of risks in situational contexts. SO WHAT?: Understanding of how lived experiences inform interpretation of health promotion campaigns has implications for more effective alcohol-related risk communication aimed at behaviour change to reduce alcohol-related harms among young people.
Medicine
Felicitus S et al. · Jul 1, 2026
Poly(A)-specific ribonuclease (PARN) and telomerase are two indispensable tail-modifying enzymes that are required in two critical cellular processes: the control of the rate of RNA stability and maintenance of telomere integrity, respectively. Pathogenic variations in genes that code for PARN and telomerase complex enzymes have been implicated in several rare genetic diseases, including bone marrow failure syndromes, telomere biology-related disorders, and neoplastic ailments. This is further exemplified by defects in p53 signaling, which not only exacerbate the effects of telomere shortening but also negatively regulate PARN activity, thereby promoting cancer development and accelerated aging. This review examines the molecular interactions between PARN and telomerase, as well as their implications in disease development, with a focus on emerging therapeutic strategies that target the pathways regulated by these two enzymes.
Medicine
Sebbag L et al. · Jul 1, 2026
Antimicrobial resistance (AMR) is a growing challenge in veterinary ophthalmology, particularly in cases of bacterial keratitis, where progressive stromal infection can threaten vision and globe integrity within hours to days. This review synthesizes current evidence on pathogen distribution, antimicrobial susceptibility profiles, multidrug resistance (MDR) prevalence, and determinants of nonsusceptibility in veterinary patients, highlighting the emerging role of antibiotic-sparing alternatives. Across contemporary studies, Staphylococcus pseudintermedius, β-hemolytic streptococci, and Pseudomonas aeruginosa are consistently among the most frequently isolated pathogens. The highest MDR burdens are reported in referral populations and among methicillin-resistant staphylococci worldwide. Feline data remain comparatively limited but show regional variability in resistance patterns, while equine studies reveal temporal shifts in isolate distribution and a rising prevalence of methicillin-resistant organisms in tertiary settings. Recent topical antimicrobial exposure is the most consistently identified predictor of reduced culture positivity and elevated resistance rates in subsequent ocular isolates, highlighting the importance of early microbiologic sampling and judicious antibiotic use. Interpreting antimicrobial susceptibility testing (AST) in ophthalmology remains challenging because clinical breakpoints are generally derived from systemic dosing regimens, despite substantially higher, albeit transient, drug concentrations being achieved at the ocular surface following topical administration. Moreover, the ocular surface microenvironment, including tear proteins, inflammation, biofilm formation, and concurrent serum therapy, may substantially influence antimicrobial activity and therapeutic response. The review concludes with practical ophthalmology-specific stewardship recommendations, a One Health perspective on resistant ocular pathogens, and a forward-looking discussion of antibiotic-sparing adjuncts within a broader multimodal strategy to preserve antimicrobial effectiveness.
Medicine
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
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
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
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
Kuchar L et al. · Jul 1, 2026
Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disorder caused by deficient activity of lysosomal alpha-galactosidase A (AGAL, E.C. 3.2.1.22) due to pathogenic variants in the GLA gene (HGNC:4296, Xq22.1). Plasmatic deacylated globotriaosylceramide (lysoGb3) is elevated in FD patients as a reflection of lysosomal accumulation of Gb3. Specific (AGALopathic) GLA variants have been recently shown to accumulate within the secretory pathway and trigger endoplasmic reticulum stress and unfolded protein response rather than result in profound enzymatic deficiency. In part due to lack of integrative measures of clinical severity and biochemical/molecular parameters, specific impacts and consequences of X-chromosomal inactivation (XCI) on clinical manifestation in FD female heterozygotes still remain to be fully understood. Our study aimed at evaluation of XCI (% of inactive wt GLA allele) in untreated female FD heterozygotes with classic FD (n = 17), late-onset FD (n = 19) and individuals carrying GLA variants (p.(L394P) (n = 7), p.(A143T) (n = 4), and p.(D313Y) (n = 4)) with predominant AGALopathic effects. XCI was correlated with age of the patients, clinical phenotype, (residual) AGAL activity, and lysoGb3. AGAL activity corresponded to XCI independently of the type of the GLA mutation. The best separation of the clinical phenotypes (classic FD, late-onset FD and AGALopathy) was achieved by correlating XCI to the ratio of AGAL activity to lysoGb3. This three parametric calculated marker was then confronted with the Mainz Severity Score Index (MSSI) to generate an Integrative Clinical-Laboratory quotient (ICLq). ICLq discriminated the three female patient groups and demonstrated group-dependent differences in its average age-related increase.
Medicine