Browse papers

461 papers

A cell atlas of the developing human outflow tract of the heart and its adult aortic valve derivatives.

Leshem R et al. · Jun 25, 2026

The outflow tract (OFT) of the heart carries blood away from the heart into the great arteries. During embryogenesis, the OFT divides to form the aorta and pulmonary trunk, creating the double circulation present in mammals. Defects in this area account for one-third of all congenital heart defect cases. Here, we present comprehensive transcriptomic data on the developing OFT at two distinct time points (embryonic and fetal) and its adult derivatives, the aortic valves, and use spatial transcriptomics to define the distribution of cell populations. We uncover that distinctive embryonic signatures persist in adult cells and can be used as labels to retrospectively attribute relationships between cells separated by a large timescale. Single-cell regulatory network inference identifies GATA6, a transcription factor linked to common arterial trunk and bicuspid aortic valve, as a key regulator of valve precursor cells. Its downstream network reveals candidate drivers of human cardiac defects and illuminates the molecular mechanisms of both normal and pathological valve development. Our findings define the cellular and molecular signatures of the human OFT and its distinct cell lineages, which is critical for understanding congenital heart defects and developing cardiac tissue for regenerative medicine.

Biochemistry, Genetics and Molecular Biology

Development and validation of an interpretable ultrasound radiomics model for benign and malignant classification of breast lesions: a multicenter large-sample study.

Zhang D et al. · Jun 25, 2026

Objectives To develop and validate a combined ultrasound-based radiomics-clinical model for differentiating benign and malignant breast lesions. Materials and methods A total of 3142 patients from eight hospitals between February 2012 and September 2024 were included in this multicenter retrospective development and validation study, with an additional single-center prospective test cohort. Lesions were manually segmented, and radiomics features were automatically extracted to construct five machine learning models. The best-performing radiomics model was combined with clinical features to build a combined model. Model performance and its impact on Breast Imaging Reporting and Data System (BI-RADS)-based biopsy decisions were evaluated. Results Logistic regression (LR) showed the best radiomics performance, with area under the curves (AUCs) of 0.83, 0.82, 0.81, and 0.82 across the training, internal test, external test, and prospective test sets. The clinical model achieved AUCs of 0.87, 0.85, 0.87, and 0.86, whereas the combined model achieved AUCs of 0.92, 0.90, 0.92, and 0.93, significantly outperforming both single-modality models (all p Conclusion The interpretable ultrasound-based radiomics model enables reliable, noninvasive breast lesion diagnosis and may reduce unnecessary biopsies. Critical relevance statement This work developed an interpretable radiomics-clinical combined model in a multicenter retrospective development and validation study, with additional testing in a single-center prospective cohort, and may support breast lesion risk stratification and biopsy decision-making after further prospective clinical utility evaluation. Key points Conventional ultrasound diagnosis of breast cancer shows limited specificity. A multicenter radiomics-clinical combined model showed improved diagnostic performance, with additional validation in a prospective test cohort.

Medicine

Gut microbiota and aging: current understanding and future perspectives.

Lan M et al. · Jun 25, 2026

Aging is a complex biological process characterized by progressive functional decline at molecular, cellular, and systemic levels, accompanied by increased susceptibility to chronic diseases. Accumulating evidence indicates that the gut microbiota plays a critical role in shaping aging trajectories and age-related health outcomes. This review systematically summarizes current research progress on the relationship between gut microbiota and aging. We first describe the characteristic alterations of the gut microbiota during aging, including reduced microbial diversity, shifts in core bacterial taxa, and profound changes in microbial metabolite profiles such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. We then discuss the mechanistic links between gut microbiota dysbiosis and age-related functional decline, focusing on immunosenescence and inflammaging, gut barrier dysfunction, metabolic disorders and oxidative stress, as well as endocrine and neuroendocrine regulation through gut-organ axes. In addition, major internal and external factors influencing gut microbiota composition in the elderly, including diet, medication use, lifestyle, host immunity, and living environment, are reviewed. Finally, we summarize current and emerging gut microbiota-targeted anti-aging intervention strategies, such as dietary modulation, probiotics, prebiotics, postbiotics, fecal microbiota transplantation, and natural product-based approaches, and discuss future research directions and clinical translation challenges. Overall, this review highlights the gut microbiota as a key modifiable factor in aging biology and underscores its potential as a promising target for promoting healthy aging.

Biochemistry, Genetics and Molecular Biology

A perioperative multi-modal fusion and deep learning-based prognostic system for upper tract urothelial carcinoma: a multi-institutional study.

Peng X et al. · Jun 25, 2026

Objectives Precise perioperative risk stratification for upper tract urothelial carcinoma (UTUC) is essential. We developed a multimodal prognostic model integrating perioperative clinical data, radiomics, and deep learning (DL) features from baseline CT urography to improve survival prediction and guide adjuvant management. Materials and methods We retrospectively enrolled 623 patients from six institutions, divided into training, internal validation, and independent external validation sets. Four single-modal models (clinical, radiomics, 2D DL, and 2.5D DL) were developed, and an integrated combined model was constructed by fusing their prognostic scores. Performance was evaluated using the C-index, area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Results The combined model consistently outperformed all single-modal models across all cohorts. C-indices reached 0.758 (95% CI: 0.712-0.804), 0.725 (95% CI: 0.651-0.798), and 0.704 (95% CI: 0.631-0.777) in the training, internal validation, and external validation sets, respectively, numerically surpassing the best single-modal models. Notably, our 2.5D DL model (C-index: 0.705) demonstrated a consistent incremental improvement over the 2D DL model (C-index: 0.681) in capturing prognostic information. In external validation, the combined model achieved a 3-year AUC of 0.766. DCA indicated the comprehensive model exhibited excellent calibration and provided the highest net benefits. Conclusion This multimodal system, featuring a robust 2.5D DL strategy, improves overall survival prediction in UTUC. It offers a valuable tool for accurate perioperative risk stratification immediately after radical nephroureterectomy, demonstrating particularly reliable value for 3-year intermediate-term clinical decision-making. Critical relevance statement This multimodal system advances clinical radiology by fusing perioperative clinical data, radiomics, and DL features from CTU images, enhancing risk stratification accuracy to guide postoperative adjuvant management for UTUC. Key points Current prognostic models for UTUC lack accuracy, creating an unmet clinical need for precise perioperative risk stratification to guide adjuvant management. A multimodal prognostic model fusing clinical, radiomic, and DL features from baseline CT urography consistently outperformed single-modality models in predicting overall survival.

Medicine

The development and evolution of the Irish Hip Fracture Database: a quality care initiative 2013-2024.

Brent L et al. · Jun 25, 2026

Clinical audits are central to quality improvement in healthcare, yet practical real-world descriptions of how they are implemented, governed and sustained are limited. This paper describes the establishment, evolution and impact of the Irish Hip Fracture Database (IHFD) within the Irish healthcare system as an exemplar. Introduction Clinical audits compare clinical practice against defined standards to identify areas for improvement and showcase excellence. International literature provides limited insight into how they are governed and sustained. Using the IHFD, a mature national audit, this paper reviews its development, evolution and sustained momentum from 2013 to 2024. Methods Longitudinal data were captured via the Hospital Inpatient Enquiry (HIPE) system, encompassing all eligible Irish acute hospitals. Included cases were patients aged ≥ 60 years with hip fractures, as defined by IHFD. Three organisational surveys (2016, 2020, 2024) were undertaken to assess hospital resources, care pathways, governance structures and audit supports. Results In total, 41,304 cases were included in the analysis. National coverage exceeded 90% from 2017. Demographic characteristics remain consistent. Improvements in data quality, adherence to Irish Hip Fracture Standards were observed, including geriatrician assessment (11% in 2013 to 86% in 2024) and bone health assessment (65% in 2013 to 90% in 2024). Service reconfigurations and resourcing to support hip fracture care occurred over this period. Engagement with the audit remained robust despite major challenges including COVID-19, a national cyberattack and ongoing health system reform. Conclusion Sustained success of a national hip fracture clinical audit requires strong leadership, effective governance, clear clinical standards, accessible data and timely reporting. Continued relevance requires agility and alignment with evolving system needs.

Medicine

Tumor response and tolerability under fractionated x-ray irradiation in a mouse xenograft model.

Choi K et al. · Jun 25, 2026

Objective. Modern self-contained x-ray irradiators offer a safer alternative to radionuclide sources for preclinical radiation research and can deliver conformal, clinically relevant dose distributions. However, concerns persist regarding their performance and biological toxicity as direct replacements in radiobiological studies. We assessed two preclinical x-ray platforms, a collimated cabinet X-Rad320 and an image-guided small animal radiation research platform (SARRP), for induced tumor response, tolerability, and dosimetric accuracy in a subcutaneous xenograft prostate tumor model under 2 Gy daily fractionated radiotherapy. Approach. Male athymic mice bearing 22Rv1 xenografts were randomized into cohorts receiving total doses of 10, 16, or 20 Gy (5, 8, or 10 2-Gy fractions) on either platform. Unirradiated controls were included. Tumor burden was quantified by the area under the tumor growth curve (AUC). Machine dose delivery accuracy was verified quarterly with alanine pellet dosimetry. Main results. Across regimens, no animals met humane body condition or weight endpoints or exhibited overt clinical toxicity. All irradiated groups had lower tumor normalized AUCs than controls, but the dose response was not clearly monotonic, and not all differences remained statistically significant after correcting for multiple comparisons. At 14 d post-treatment, SARRP at 16 Gy provided the greatest tumor suppression, with no significant additional benefit observed with 20 Gy. Histological γ -H2AX staining provided complementary evidence of a radiation-induced dose response. Significance. Focused x-ray platforms can reproducibly deliver conventional fractionated radiotherapy regimens in mice, inducing tumor response without overt clinical toxicity. However, platform-specific dose deviations highlight the need for rigorous dosimetric calibration and quality assurance to ensure they can effectively replace cesium-137 for in vivo research with comparable tumor control outcomes.

Medicine

Analysis of lipid-assisted self-assembly of hydrophobic CuInS2/ZnS quantum dots into water-stable nanoclusters that perform intra-cluster energy transfer.

Whipp JT et al. · Jun 25, 2026

Quantum dots (QDs) are nanocrystalline semiconductors that have the ability to perform efficient Förster resonance energy transfer (FRET) to biomolecules and other nanoparticles. Aqueous environments are required for applications related to biological systems, and common hydrophobic QDs will tend to cluster under these conditions. Whilst large (microscale) aggregates of QDs are undesirable, small (nanoscale) clusters could have applications as the active component in bio-imaging, bio-sensors or bio-photovoltaics. In this study, we developed a new procedure to utilize lipids to control the assembly of 'nanoclusters' of copper indium sulfide/zinc sulfide (CuInS 2 /ZnS) core/shell QDs. High-resolution electron microscopy revealed that the QDs had a particle size of ∼3.3 nm when they were in organic solvents and formed clusters of ∼40 nm when the nanoparticles were exchanged into aqueous solution in the presence of lipids. Particle sizing by nanoparticle tracking analysis suggested that the overall hydrodynamic size was 100-200 nm, which is consistent with an electron-dense core of clustered QDs surrounded by looser lipid assemblies or higher-order structures. The lipid was found to be essential for stabilizing the cluster, with fluorescence microscopy and spectroscopy confirming that the lipids and QDs were colocalized (using fluorescently-tagged lipids). Ensemble spectroscopy measurements revealed that there was a consistent red-shift of the emission peak, and a reduction in the excited state lifetime, for QD nanoclusters suspended in an aqueous buffer as compared to isolated QDs dissolved in organic solvents. The combined data provides strong evidence that downhill energy transfer occurs within one cluster from small, high-bandgap QDs to larger, low-bandgap QDs. Our findings contribute to a new understanding of how QD-QD and QD-lipid interactions influence their photophysical properties. Our work provides a new protocol based on a physical self-assembly that is modular and adaptable: alternative lipids or QDs and different buffer conditions (salt, pH) could be used. Future work could incorporate membrane proteins in the development of QD-biohybrid systems towards new applications in bio-nanotechnology.

Materials Science

Investigating Thermotolerance of Thylakoid Processes in Two Cotton Species using Rapid Induction Fluorescence.

Adegbenro CO et al. · Jun 25, 2026

High temperatures can hinder stand establishment, seedling growth, and photosynthetic processes in cotton. Yet, interpretations of thermotolerance in thylakoid processes often depend on whether measurements follow chronic or acute heat exposure, and species-level differences in these responses remain poorly characterized. This study evaluated the effects of chronic high temperatures (40°C/30°C) on key thylakoid processes in four-week-old Upland and Pima cotton seedlings and assessed their acclimation potential using rapid induction chlorophyll fluorescence across a range of incubation temperatures. As these processes were inferred from OJIP parameters rather than direct measurements of photosystem activity, they are interpreted as fluorescence-based indicators of thylakoid function. Chronic heat enhanced photosystem I (PSI)-related parameters in both species, with Upland exhibiting larger increases (44%-46%) compared to Pima (39%-40%), whereas photosystem II (PSII) photochemistry remained largely stable under chronic heat, declining by less than 2% at 40°C and by 6%-8% at 45°C under acute exposure. Acute temperature responses closely mirrored chronic patterns, and Upland showed higher thermal optima for PSI quantum yield and overall performance (40°C) than Pima (35°C), suggesting greater PSI electron-sink capacity. Collectively, these fluorescence-derived results suggest that PSI-related processes distinguish species-level thermotolerance in cotton. Upland's stronger enhancement of PSI acceptor-side capacity under both sustained and transient heat exposure points to a more robust acclimation strategy, whereas Pima shows limited PSI adjustment despite maintaining PSII efficiency. These findings clarify how thylakoid processes respond to heat across timescales and may help guide the development of heat-resilient cotton as growing-season temperatures rise.

Biochemistry, Genetics and Molecular Biology

Narrative Review of Lithium Disilicate Veneers in Esthetic Dentistry: Current Perspectives and Clinical Case Report.

Rojas-Ruedas S et al. · Jun 25, 2026

Objectives To provide a focused, evidence-based overview of lithium disilicate (LDS) veneers, with particular emphasis on indications, material properties, adhesive protocols, and clinical performance, supported by illustrative clinical cases. Methods A narrative review of the literature was conducted to summarize current evidence on the mechanical, optical, and adhesive characteristics of LDS ceramics in veneer applications. The review emphasizes enamel preservation, adhesive reliability, and reported clinical outcomes, without undertaking a systematic comparison of study designs. In addition, two clinical case reports are presented to illustrate the clinical workflow for esthetic rehabilitation using pressed LDS veneers. Results LDS veneers demonstrate high flexural strength (~360-400 MPa), favorable optical properties, and reliable adhesive performance when enamel is preserved and appropriate adhesive protocols are applied. Reported survival rates exceeding 95% at up to 10 years have been documented in selected patient populations. Clinical success is closely associated with appropriate case selection, conservative tooth preparation, precise adhesive procedures, and patient compliance. Common complications, including debonding, fracture, and marginal discoloration, are more frequently reported when enamel is limited or occlusal risk factors are not adequately managed. Conclusions When applied under appropriate clinical conditions, LDS veneers represent a predictable and esthetically effective treatment option in contemporary restorative dentistry. Their long-term success depends on meticulous technique, patient-specific risk assessment, and adherence to evidence-based adhesive and occlusal management principles.

Dentistry

Persistent Delirium in the Elderly: A Case Report and Review of Multifactorial Contributors and Management Challenges.

Salisbury T. · Jun 25, 2026

Introduction This case describes persistent delirium exceeding 18 months with prominent paranoid delusions in a 72-year-old woman with chronic hyponatremia, poststroke epilepsy, and alcohol use disorder. It highlights diagnostic and pharmacologic management challenges when standard agents carry prohibitive risks. Patient’s main concerns and important clinical findings A 72-year-old woman with a history of left hemispheric hemorrhagic stroke, poststroke epilepsy, and chronic alcohol use presented with acute confusion. Laboratory evaluation revealed severe hyponatremia (Na 122 mmol/L). Clinical findings included persecutory delusions, severe agitation with dangerous behaviors (attempting to leave moving vehicles, stabbing attempt), anxiety, insomnia, and fluctuating cognitive status with return to baseline between episodes. EEG demonstrated epileptiform discharges and generalized encephalopathy. Divalproex sodium levels at presentation were supratherapeutic (up to 127 mcg/mL). There was no evidence of prior dementia or progressive cognitive decline. Primary diagnoses interventions and outcomes The primary diagnosis was persistent delirium with multifactorial etiology. Interventions included hyponatremia correction, transition from divalproex to lacosamide, and initiation of mirtazapine, which was selected for its lower hyponatremia risk compared to other antidepressants, lower seizure risk compared to antipsychotics, and low deliriogenic potential. Sleep and anxiety improved with partial agitation reduction, though delirium persisted. Over 18 months, paranoid delusions evolved from episodic to continuous, creating treatment adherence barriers. Conclusion This case underscores the potential for exceptionally prolonged delirium in medically complex older adults, diagnostic complexity in differentiating persistent delirium from ictal-related psychosis and other conditions, and individualized pharmacotherapy considerations. Early multidisciplinary intervention, capacity assessments, and caregiver support are critical.

Medicine