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176 papers

Humanin Mitigates Aβ-Induced Retinal Pigment Epithelium Injury via AMPK-Beclin1-Dependent Mitophagy.

Jang HY et al. · Jul 1, 2026

Amyloid beta (Aβ), a key component of drusen in age-related macular degeneration (AMD), induces oxidative stress, mitochondrial dysfunction, and degeneration in the retinal pigment epithelium (RPE), contributing to progressive vision loss in the elderly. We investigated the protective role of Humanin (HN), a mitochondria-derived peptide with known neuroprotective effects in Aβ-related neurodegenerative diseases, in retinal pathology induced by subretinal injection of FITC-labeled Aβ. HN enhanced the clearance of Aβ-accumulated mitochondria in the RPE while preserving retinal function and RPE barrier integrity. In ARPE-19 cells, HN activated AMP-activated protein kinase (AMPK), leading to phosphorylation of ULK1 and Beclin1, which promoted the interaction between Beclin1 and Parkin and their translocation to mitochondria. This process facilitated the removal of Aβ-accumulated mitochondria in the RPE. Our results demonstrate that targeting mitophagy in the RPE with HN may offer a promising therapeutic strategy for AMD.

Medicine

Comparative Evaluation of Smartphone-Based Fundus Imaging Systems in Dogs and Cats.

Michaud B. · Jul 1, 2026

Objective To compare the feasibility, image quality, acquisition time, and evaluator preference of four smartphone-based fundus imaging (SBFI) systems in dogs and cats using a handheld fundus camera as a reference device. Animals studied Twenty client-owned animals, including 10 dogs and 10 cats. Procedures Fundus images were obtained from 40 eyes (20 mydriatic and 20 non-mydriatic) using four SBFI systems (iExaminer Panoptic, NUN WFE-02S, OQVet, and VistaView) and a handheld infrared fundus camera (Aurora). Image acquisition success and acquisition time were recorded for each device. Image quality was independently graded using a 10-point Likert scale by a masked panel of 32 veterinary ophthalmologists. Evaluators also selected their preferred image among the four SBFI systems. Results Image acquisition was successful in all animals for all devices under both mydriatic and non-mydriatic conditions (100%). Image quality differed significantly between devices. Among SBFI systems, OQVet achieved the highest median score (7; interquartile range [IQR] 6-8), followed by VistaView (6; IQR 5-8), NUN (5; IQR 4-7), and iExaminer (4; IQR 3-5). OQVet received approximately 50% of evaluator preference votes. The reference camera achieved the highest image quality in 77.5% of imaging sets but was outperformed by OQVet (15%) and VistaView (7.5%) in some examinations. Pupil dilation did not significantly influence image quality or acquisition time. Conclusions Smartphone-based fundus imaging enables reliable retinal imaging in dogs and cats and represents an accessible option for retinal documentation and screening in veterinary practice.

Medicine

Probiotics and Their Functional Role in Mitigating Antinutrient Effects In Vivo-A Systematic Review and Meta-Analysis.

Olar-Pop L et al. · Jul 1, 2026

Antinutrients like phytic acid and oxalates reduce mineral bioavailability by forming insoluble complexes with iron, zinc, and calcium. Probiotic supplementation may counteract these effects through enzymatic activity (e.g., phytase, oxalate decarboxylase) and microbiota modulation. This PRISMA-based meta-analysis evaluated 27 in vivo studies (chickens, mice, rats) published between 2005 and 2025. Controlled trials assessing probiotic effects on mineral absorption under antinutrient-rich diets were analyzed using random effects models, expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Probiotic supplementation may enhance selected markers of mineral bioavailability across animal models (broiler, mouse, and rats), although the certainty of evidence was low and between-study heterogeneity was substantial. In broiler chickens, probiotics increased hepatic iron (SMD = 2.05; CI: 0.91-3.20) and liver ferritin levels (SMD = 2.85; CI: 0.90-4.80). In rat models of hyperoxaluria, probiotics reduced renal calcium oxalate deposition (SMD = 0.77; p = 0.0001), though the impact on urinary oxalate levels was not significant (SMD = 0.20). In mouse models, the interventions demonstrated improved gut microbiota diversity without significant alterations in total body weight (SMD = 0.02). Based on low-certainty evidence from heterogeneous animal studies, probiotic supplementation may improve selected mineral-bioavailability outcomes and may reduce calcium oxalate deposition under antinutrient-rich conditions. These findings should be interpreted cautiously. Further well-designed, species-specific studies using standardized interventions and outcome measures are needed before firm conclusions can be drawn.

Medicine

Validation of Risk Models for Predicting Post-SVR HCC in Real-World Surveillance Across Global Geographic Regions.

Toyoda H et al. · Jul 1, 2026

Background & aims Several clinical risk models have been proposed to stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis C virus (HCV) after sustained virologic response (SVR). However, validation efforts have focused on monocentric or country-specific cohorts, and it is unclear if clinical risk models can be broadly applied to global populations. We characterised regional variation in model performance for HCC risk stratification in post-SVR patients. Methods Four HCC clinical risk models (aMAP score, FIB-4 index, GES score, and Toronto HCC risk index [THRI]) were analysed in six real-world cohorts, which included 8796 post-SVR patients from different geographic regions globally. Model discrimination was assessed using Harrel's c-statistic index. HCC incidence rates were compared across low-, intermediate-, and high-risk groups for each model. Results Distributions of patient characteristics and HCC incidence rates varied across geographic regions. Predictive performances of models were comparable within each cohort despite the model with the highest c-statistics differing by regions. Performance was lower than those from original reports overall; c-statistics of models across most regions remained below 0.70. Conclusions There remains a continued need to improve discrimination and calibration of clinical models to stratify HCC risk in post-SVR patients. Accuracy of models may differ by geographic region, underscoring the importance of external validation to assess transportability of models and suggesting no single model can be universally applied.

Medicine

Establishing the Epidemiological Cut-Off Value (ECOFF) for Cefquinome Against Staphylococcus aureus Using Standardised MIC Data.

Ahmad I et al. · Jul 1, 2026

Staphylococcus aureus is a major pathogen responsible for a wide range of infections in both animals and humans, and the increasing emergence of antimicrobial resistance highlights the need for effective surveillance tools. Cefquinome, a fourth-generation cephalosporin, is widely used in veterinary medicine for the treatment of infections caused by Gram-positive and Gram-negative bacteria, including S. aureus. In this study, 110 S. aureus strains were isolated from cattle and subjected to minimum inhibitory concentration (MIC) determination using standardised agar dilution and microdilution methods. MIC values were obtained following 24 h incubation in 96-well plates. The MIC distribution was analysed using goodness-of-fit testing and non-linear least squares regression to establish the wild-type cut-off value (COWT). The MIC range for cefquinome against S. aureus was 0.03-2 µg/mL, and the epidemiological cut-off value (ECV) was determined to be 2 µg/mL, encompassing 99.1% of the wild-type population. An MIC value of 0.5 µg/mL covered 95% of the distribution, indicating its potential relevance for resistance monitoring. These findings provide a scientific basis for cefquinome susceptibility interpretation in cattle and support antimicrobial resistance surveillance. Further studies are warranted to develop population pharmacokinetic models for cefquinome in calves to optimise its therapeutic application.

Medicine

Effectiveness of a Transdiagnostic Emotion-Focused Treatment in Clinical Care: A Sequential Single-Case Experimental Design.

Zetterberg H et al. · Jul 1, 2026

Background Chronic pain frequently co-occurs with emotional problems, highlighting the need for integrated treatment approaches. Previously, we evaluated a hybrid emotion-focused treatment with positive results. However, there is a dire need for studies evaluating treatments in 'real world' clinical contexts. Therefore, this study evaluated the effectiveness of this treatment in regular clinical care. Methods Using a sequential single-case experimental AB design with randomized baseline lengths (4, 5 or 6 weeks), pain, emotional problems and cognitive behavioural factors were assessed weekly across a 20-week study period. Additional outcome measurements were collected at pre-, post- and 12-month follow-up. Patients from primary and secondary care (final n = 31) with chronic pain and anxiety/depression were recruited, and their psychologists delivered the treatment. Individual effects were evaluated using non-overlap of all pairs and aggregated effects via multilevel shift models. Acceptability, adherence and fidelity were summarized, and responders and non-responders compared using group-level analyses. Results Most (87%) demonstrated a treatment response on ≥ 1 outcome, and over half (55%) on ≥ 3 outcomes. One-third were classified as broad responders. Aggregated analysis showed a significant effect on pain interference. The treatment was viewed as credible and acceptable, with greater satisfaction among responders. Non-responders showed more variability in attendance and lower progression through later treatment phases involving exposure. Conclusion The findings support the feasibility and potential effectiveness of the hybrid emotion-focused treatment for patients in routine clinical care. The treatment benefits most patients to some extent and a smaller subset of patients to a clinically significant extent. Significance statement This pragmatic trial evaluates effectiveness in a clinically representative patient sample reflecting the complexity of routine care, including pain and psychiatric comorbidity, sociodemographic diversity and health care utilization. The hybrid emotion-focused treatment represents one of several emerging approaches targeting pain-emotion connections. These findings extend results from a prior RCT and highlight the importance of evaluating interventions under real-world clinical conditions.

Medicine

Within-Person Seasonal Variability of Aminotransferases and Long-Term Glycemic Control in Adults With Type 2 Diabetes (JDDM 85).

Toki R et al. · Jul 1, 2026

Background & aims Aminotransferases are widely used for metabolic dysfunction-associated steatotic liver disease (MASLD) evaluation, especially in type 2 diabetes mellitus (T2DM). Whether within-person seasonal variation affects classification near commonly used thresholds or relates to long-term metabolic outcomes remains unclear. Methods This registry-based cohort analysed monthly aspartate aminotransferase (AST) and alanine aminotransferase (ALT) measurements from 6039 adults with T2DM in the Japan Diabetes Clinical Data Management registry (2014-2020). Classification discordance across the 30 IU/L threshold was compared between winter-mean and summer-mean values. Individual seasonal amplitude was derived from seasonal-trend decomposition of multiply imputed monthly time series. Final glycated haemoglobin (HbA1c) and non-achievement of HbA1c Results Both AST and ALT showed significant seasonal variation, with the highest values in late autumn to early winter and the lowest in summer (p Conclusions AST and ALT exhibited reproducible seasonal variation peaking in late autumn to early winter, with approximately one in nine patients near the MASLD screening threshold reclassified depending on season. Greater seasonal amplitude, especially AST, was independently associated with poorer glycemic control, supporting season-aware interpretation in routine clinical practice.

Medicine

Early Phase Dose-Finding Designs for CAR-T Cell Therapies.

Chen W et al. · Jul 1, 2026

Chimeric Antigen Receptor (CAR)-T cell is an immunotherapy which revolutionised the treatment of relapsed/refractory lymphoma and leukaemia. It is shown to have a higher response rate, higher mid-to-long term overall survival, and lower toxicity than standard treatments. However, due to a lack of dose-limiting toxicity (DLT) and unclear dose-effect relationship, traditional phase I designs of clinical trials cannot lead to accurate selections of the optimal dose (OD). Beside clinical outcomes, the CAR-T cell expansion from serial blood samples is measured at various time points. We propose a novel early phase dose-finding design for CAR-T cells, using both toxicity and activity endpoints to locate the OD. The number of CAR-T cells measured in the peripheral blood is used to indicate activity, which is more sensitive than the short-term clinical responses traditionally used. A Bi-Exponential model is used for the repeated measures of the number of cells for each patient, and is estimated under a Bayesian framework. The model is motivated by biological concerns and is flexible enough to accommodate different shapes of the cell-expansion curve. Three criteria for activity are considered: (1) the number of cells at specific time points, (2) the duration before all cells are eliminated, (3) the area under the cell-expansion curve. Simulation studies show that the OD can be selected with high accuracy even under small sample sizes.

Medicine

Home-Based Combined Activity and Cognitive Intervention for Post-Intensive Care Syndrome: A Pilot Randomised Controlled Trial.

Li PWC et al. · Jul 1, 2026

Background ICU survivors frequently develop post-intensive care syndrome (PICS), a cluster of persistent physical, cognitive and psychological impairments that substantially impair recovery and quality of life. Existing rehabilitation approaches are predominantly monomodal and exercise-focused, yielding inconsistent outcomes and failing to address the multidimensional burden of PICS adequately. Aim To evaluate the feasibility and preliminary efficacy of COMBAT-ICU, a home-based Combined Activity and Cognitive Intervention for ICU survivors at risk of PICS. Study design A parallel, three-arm, assessor-blinded pilot randomised controlled trial randomised 36 ICU survivors (1:1:1) to COMBAT-ICU-an 8-week blended program of progressive physical exercise and computerised cognitive training delivered via supervised home visits and online sessions-an exercise-only group or an attention control group. The primary outcomes were feasibility (recruitment, retention and intervention adherence) and safety; secondary exploratory outcomes encompassed PICS severity, physical capacity, cognition, mental health and health-related quality of life (HRQoL). Results COMBAT-ICU was feasible and safe (36 ICU survivors randomised), with no serious adverse events recorded, retention exceeding 82% at follow-up and session adherence exceeding 90%. COMBAT-ICU produced significantly greater reductions in PICS severity versus attention control at post-intervention (p = 0.014, d = -0.50) and follow-up (p = 0.043, d = -0.45). It also yielded clinically meaningful moderate-to-large effect sizes for walking endurance, global cognition, short-term memory and HRQoL index scores compared with attention control and consistently outperformed exercise-only across cognitive and HRQoL domains. Between-group differences in anxiety and depressive symptoms were small across all active groups. Conclusions COMBAT-ICU is feasible and shows promising preliminary efficacy in mitigating PICS. Integrating cognitive and physical training within a home-based blended delivery model may confer synergistic benefits beyond exercise alone, providing domain-specific effect size estimates and a compelling rationale for definitive multicentre trials. Relevance to clinical practice Multidomain home-based rehabilitation is a viable post-discharge strategy for ICU survivors. COMBAT-ICU offers an evidence-informed, scalable framework to enhance survivorship care, pending confirmation in larger, fully powered trials. Trial registration The trial was registered at ClinicalTrials.gov (NCT06117761).

Medicine

Improving image quality in terbium-161 phantom imaging: Quantitative evaluation of DEW and TEW scatter correction methods.

Can M et al. · Jul 1, 2026

Background Terbium-161 (Tb-161) emits gamma rays and beta radiation, enabling both therapeutic and imaging applications. However, the multiple gamma emissions of 161 Tb can affect image quality by increasing the scattering rate during SPECT imaging. To improve image quality, appropriate scatter correction methods, such as Dual-Energy Window (DEW) and Triple-Energy Window (TEW) need to be optimized. Although these methods are used in clinical practice, studies investigating the efficacy of spectral analysis approaches for next-generation radionuclides with multiple gamma emissions, such as 161 Tb, are limited. Purpose This study aims to evaluate the effects of DEW and TEW scatter correction methods on image quality and quantitative accuracy in 161 Tb SPECT imaging compared to uncorrected images. Methods Three distinct reference geometries were utilized to determine the gamma camera calibration factor (CF) and to evaluate the image quality parameters. Five image protocols were used, each with different combinations of main photopeak and scatter energy windows. Image quality parameters (CF, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), spatial resolution) and activity bias (%) were compared using LifeX software in both uncorrected and corrected SPECT images. Results The CF calculated in images acquired with an energy window of 48.9 keV was found to be higher than that calculated in an energy window of 74.6 keV. The best CNR was calculated for images acquired in air with a photopeak of 48.9 keV ± 10% and a scatter window of 6%. In scattered media, it was observed in images obtained with a photopeak of 74.6 keV ± 10% and a scatter window of 6%. When scatter correction was applied, the images' SNR values decreased slightly, ranging from 1.188 to 1.724 across all media. Scatter correction techniques reduced the FWHM values for all protocols except the air medium, thereby improving spatial resolution. Activity bias results showed an overestimation in uncorrected protocols including the 48.9 keV peak. Conversely, utilizing the 74.6 keV peak with TEW correction improved quantitative accuracy to a 3.7%-4.2% absolute bias. Conclusion Our results show that both DEW and TEW correction approaches improve spatial resolution and increase CNR by reducing scattering contributions and background noise. However, as expected with the subtraction of scattered effects, these enhancements are accompanied by a slight decrease in SNR. The TEW method performed better than the DEW method in terms of quantitative accuracy under scattering conditions. In SPECT imaging using therapeutic amounts of Tb-161, high image quality can be achieved with an energy window of 74.6 keV ± 10%.

Medicine