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461 papers

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

Patients with chronic kidney disease stage 3b: do general practitioners and nephrologists follow KDIGO guidelines?

Macedo JG et al. · Jul 1, 2026

Background Appropriate referral and management of patients with chronic kidney disease (CKD) from primary care to nephrologists are essential to prevent disease progression and complications. Objectives To describe the demographic and follow-up characteristics of patients with CKD stage 3b at the time of nephrology referral, the medical care offered by general practitioners, and the initial care provided by nephrologists in the Brazilian Unified Health System (SUS). Methods This retrospective cohort study included all patients with CKD stage 3b on the waiting list for nephrology consultation between January 2018 and January 2020 in a large city in southern Brazil. Sociodemographic data, comorbidities, and adherence to follow-up recommendations based on the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines were analyzed. Laboratory test requests and results were compared between the periods of general practitioner care and the period following nephrology consultation. Results A total of 211 patients (mean age 74 ± 12 years) were included; 76.0% were hypertensive and 46.9% had diabetes. Approximately half had an adequate number of primary care appointments. Laboratory monitoring was suboptimal in both primary and specialized care. Before nephrology consultation, hemoglobin and urinalysis were available for 32.2% and 19.4% of patients, respectively. After consultation, hemoglobin and potassium results were documented in 68.3% and 58.8% of patients, respectively. Conclusion Although patients with CKD stage 3b were regularly followed, low adherence to KDIGO testing recommendations raises concerns about the adequacy of care. Strengthening communication and guideline implementation between primary care and nephrology services is crucial to improve CKD management within the SUS.

Medicine

The Staging Model in Psychosis and Preventive Interventions: An Emerging Field With Debates on Conceptual Models and Interpretation of the Evidence Base.

van der Gaag M et al. · Jul 1, 2026

Aims The staging model in psychiatry is heuristic and evolving, provoking debate and stimulating alternative views. This paper reviews major controversies in the field of staging and prevention of psychosis. Methods We review the literature on the classification model, the continuum model and the dynamic systems model applied to psychiatry. Other controversies are stigmatisation of early detection, the prevention paradox and the interpretation of data on prevention of transition to psychosis. Results DSM classifications still lack validity. The continuum model supports preclinical stages but has no discrete conversions to different stages of illness. The emerging dynamic systems model builds on the interaction of symptoms eliciting networks of symptoms, while at the same time it explains sudden catastrophic shifts (transitions) between different states of equilibrium. Stigmatisation of early psychosis can be balanced against the benefits of early interventions. The prevention paradox states that only a minority of first episode cases arises from the high-risk group. However, there are many reasons to combine indicated prevention with population-based preventive interventions. A long-lasting controversy is on the interpretation of the research data. Several meta-analyses are reviewed on methodological issues. Conclusion The staging model is adequate to conceptualise psychiatric disorders and the progress over time in more chronic stages. No one is suggesting that help-seeking patients with an ARMS should be denied access to psychosocial treatment and it is recommended and necessary to continue building age and stage specific services to treat them and continue with research into risk factors and helpful interventions.

Medicine

Herpes Simplex Virus Hepatitis: An Overlooked Cause of Acute Liver Failure Across a Broad Spectrum of Immunocompromise.

Mondelli MU et al. · Jul 1, 2026

Background and aims Herpes simplex virus (HSV) infection is common worldwide, but hepatic involvement is rare. HSV hepatitis is an uncommon yet frequently catastrophic cause of acute hepatitis and acute liver failure (ALF), accounting for Methods We describe three cases of HSV hepatitis presenting with distinct risk profiles and clinical manifestations and review the diagnostic and therapeutic challenges associated with this condition. Results Clinical presentation was nonspecific in all cases, and mucocutaneous lesions were absent or delayed, contributing to diagnostic uncertainty. All patients exhibited marked aminotransferase elevation with relatively modest hyperbilirubinemia ("anicteric hepatitis"), frequently accompanied by cytopenias and coagulopathy. Delayed recognition was associated with rapid clinical deterioration, whereas earlier initiation of intravenous acyclovir was associated with biochemical and clinical improvement. Diagnosis was established using polymerase chain reaction-based detection of HSV DNA in blood and tissue samples. Conclusions HSV hepatitis remains an under-recognized cause of ALF across a broad spectrum of immunocompromised and seemingly immunocompetent patients. Given the narrow therapeutic window and favourable safety profile of acyclovir, empiric intravenous antiviral therapy should be considered in patients with ALF of indeterminate aetiology while diagnostic testing is pending, particularly in high-risk clinical settings. Increased awareness of this overlooked diagnosis may improve outcomes and prevent avoidable mortality.

Medicine

Three-dimensional approaches to measuring primary cilia in hippocampal neurons: A comparative analysis.

Rasmusson S et al. · Jul 1, 2026

Primary cilia are non-motile sensory organelles that detect extracellular signals; disruptions in their functions are linked to neurodevelopmental disorders. Because cilia lengths can rapidly change in response to stressors, they are important for both plasticity and brain homeostasis. Accurate measurement of ciliary length is therefore essential but the absence of standardized methods and the variability introduced by different techniques can compromise measurement reliability and precision. To address this challenge, our study employed two distinct methods to estimate the length of primary cilia in hippocampal subregions in mice. We compared stereology-based 3D quantification, which is considered a methodological gold standard due to its unbiased sampling design and correction for tissue shrinkage, with 3D reconstruction to measure primary cilia length. 3D reconstruction imaging used a 100× oil-immersion objective. With neuronal cilia typically ∼2-10 µm long in hippocampus, a 1-µm z-step provided multiple optical sections per cilium thereby ensuring full structural visualization. Our findings show that both methods allow simple and equally precise measurements of neuronal primary cilia length in hippocampal subregions. Their strong agreement provides researchers with reliable tools for studying primary cilia on immunohistochemically stained sections and supports a consistent methodological framework for investigating cilia dynamics.

Biochemistry, Genetics and Molecular Biology

'Helpful', 'Objective', and 'Useful': User Perceptions of the Animal Welfare Assessment Grid (AWAG) for Dogs as a Decision-Making Tool.

Malkani R et al. · Jul 1, 2026

Objectives Ethical decision-making in veterinary practice and in animal welfare sectors can be particularly challenging. Decision-making is reported to be largely subjective with various influences biasing these decisions. To enhance the objectivity with ethical dilemmas and difficult decisions, the application of standardised tools is increasingly advocated. This study explores the utility of the Animal Welfare Assessment Grid (AWAG) as a decision-making tool in various sectors of dog welfare including veterinary medicine, shelter environments, and assistance dog organisations. Methods This was undertaken through an online mixed-methods questionnaire of clinicians using the AWAG in their workplace to assess dogs. A total of 38 respondents from a group of 99 veterinary and animal welfare professionals provided insights on the tool's functionality. Results Over 96% of respondents acknowledge the utility of the AWAG in aiding in decision-making and it is reported to facilitate discussions among colleagues and dog caregivers about welfare. While the overall sentiment towards the AWAG was predominantly positive, a minority of users expressed difficulties in using the tool, indicating areas where the tool could be further refined and improved. Clinical significance The results suggest that the AWAG serves as a valuable asset for veterinary clinicians and animal welfare professionals, aiding in the assessment of dogs' welfare and informing treatment and management decisions. By providing an instrument to aid in objective reasoning to the complex process of decision-making, this may help transform how welfare considerations are integrated into daily practice.

Biochemistry, Genetics and Molecular Biology

Dipolar Order Mapping Based on Spin-Lock Magnetic Resonance Imaging.

Gao Z et al. · Jul 1, 2026

Inhomogeneous magnetization transfer (ihMT) is sensitive to dipolar order associated with motion-restricted macromolecules and can be characterized by the dipolar relaxation time T1D$$ {T}_{1D} $$ . In this study, we propose a spin-lock MRI framework for T1D$$ {T}_{1D} $$ quantification. Specifically, we introduce a T1D$$ {T}_{1D} $$ -sensitive metric, RATIOdosl$$ RATI{O}_{dosl} $$ , derived from the distinct relaxation rate Rdosl$$ {R}_{dosl} $$ , defined as the difference between dual-frequency and single-frequency R1ρ$$ {R}_{1\rho } $$ measurements. To enable dual-frequency spin-lock acquisition, we developed a dedicated rotary-echo spin-lock sequence. Based on this framework, we further estimated T1D$$ {T}_{1D} $$ and the macromolecular proton fraction (MPF) within a unified acquisition. The proposed method was evaluated using numerical simulations, phantom experiments, and in vivo imaging in the healthy human brain. Simulations demonstrated high sensitivity of RATIOdosl$$ RATI{O}_{dosl} $$ to T1D$$ {T}_{1D} $$ and supported the robustness of the proposed approach under the investigated conditions. Phantom experiments showed measurable ihMT contrast and supported the feasibility of T1D$$ {T}_{1D} $$ estimation using RATIOdosl$$ RATI{O}_{dosl} $$ . In vivo experiments demonstrated simultaneous T1D$$ {T}_{1D} $$ and MPF mapping using only three spin-lock-prepared images. Across 10 healthy volunteers, mean white matter T1D$$ {T}_{1D} $$ values ranged from approximately 3.70 to 4.80 ms. By requiring only three contrast-prepared images, the proposed technique provides a rapid framework for simultaneous T1D$$ {T}_{1D} $$ and MPF mapping and may facilitate further investigation of dipolar-order-sensitive microstructural imaging in vivo.

Medicine

Educating Early Adolescents for a Sustainable Future With Digital Civic Learning: Moral Self-Concept as a Developmental Catalyst Linking Civic Competencies and Civic Purpose.

Kim S et al. · Jul 1, 2026

Education for sustainable development (ESD) is increasingly recognized as a developmental imperative in a world facing ecological, social, and political challenges. While many approaches to ESD emphasize knowledge and competencies, emerging research suggests that sustainable action in youth requires the integration of cognitive, emotional, and identity-based developmental processes. We propose that Digital Civic Learning (DCL) serves as a developmentally appropriate educational approach that can scaffold this process in early adolescence. Using a sample of 149 4th and 5th graders in Mid-Western United States, we examined how civic competencies, namely civic knowledge, skills, and dispositions, relate to civic purpose and further investigated the mediating role of moral self-concept. Our findings underscore the importance of nurturing moral self-concept so that enhanced civic competencies translate into a form of civic purpose. SUMMARY: Conceptual innovation: It introduces Digital Civic Learning as a design-based, developmentally aligned model that integrates civic learning with sustainable development goals, aiming for transformative impact in education. Methodological advancement: It develops and applies a novel civic competencies coding scheme tailored for a nuanced analysis of students' civic knowledge, skills, and dispositions. Theoretical contribution: It positions moral self-concept as a developmental link connecting civic learning with a sustainability-oriented civic purpose in early adolescence, a critical period for identity formation. Empirical rigor: It employs performance-based assessments to evaluate students' civic competencies demonstrated in authentic digital classroom settings, emphasizing real-world application of civic reasoning within sustainability education.

Environmental Science

Effects of Sedation, TEmperature and Pressure After Cardiac Arrest and REsuscitation on Major Adverse Kidney Events (STEPCARE-MAKE): A Protocol for a Pre-Planned Sub-Study of a Randomized Clinical Trial.

M KK et al. · Jul 1, 2026

Background Acute kidney injury (AKI) is a common and serious complication after cardiac arrest, affecting more than 30% of initially successfully resuscitated patients, with around 10% receiving Kidney Replacement Therapy (KRT). Currently, treatment options to prevent renal complications are limited. In this predefined sub-study of the Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial, we evaluate the effects of sedation depth, fever management strategies, and mean arterial pressure (MAP) targets on the risk of major adverse kidney events (MAKE) in post-cardiac arrest patients. Methods STEPCARE-MAKE is a predefined prospective sub-study of the international, randomized clinical STEPCARE trial. The main trial will enroll 3500 patients and employs a 2 × 2 × 2 factorial design, randomizing participants across three interventions: (1) deep sedation for 36 h or minimal sedation, (2) fever management with or without a feedback-controlled device, and (3) MAP target ≥ 65 mmHg or ≥ 85 mmHg. The primary outcome is the composite outcome MAKE, which includes death from any cause by day 30, initiation of KRT, or persistent renal dysfunction, defined as the final creatinine value ≥ 200% of the baseline at the time of discharge from the primary hospital or at day 30, whichever occurs first. Differences between baseline and the highest in-hospital creatinine, baseline and the last measured in-hospital creatinine, baseline and 72-h creatinine, and baseline and the highest creatinine within 72 h will be reported as secondary outcomes. Conclusion The findings of this sub-study will provide new evidence on the renal effects of the STEPCARE trial interventions and may inform the future of individualized kidney-protective treatment approaches.

Medicine

Practical Enantioselective Approach to 3-Amino-2-Hydroxy Acids and Application to the Synthesis of Natural Products.

Caporale M et al. · Jul 1, 2026

A practical approach to optically active erythro 3-amino-2-hydroxy acids has been developed and applied to the enantioselective synthesis of 3-phenylisoserine and naturally occurring 3-amino-2-hydroxy-6-methylheptanoic acid (AHMHA), a nonproteinogenic amino acid found in the marine cyclic oligopeptide perthamide C. The proposed synthetic methodology requires the enantioselective Sharpless syn-dihydroxylation of (E)-α,β-unsaturated esters followed by regioselective and stereoselective Mitsunobu azidation on the β-hydroxy group. Subsequent azide hydrogenation and ester hydrolysis provide the desired erythro 3-amino-2-hydroxy acids in high enantiopurity and overall yield. The proposed approach to AHMHA was more efficient and direct compared to the one previously reported in the literature. The absolute configuration of the diol precursor of AHMHA was assigned by ECD analysis of its biphenyl dioxolane, thereby also confirming the absolute configuration of the natural AHMHA.

Chemistry