Nakao M et al. · Jul 1, 2026
Background Accurate heterogeneity correction in high-precision radiotherapy relies on precise computed tomography (CT) number-to-density conversion via the Hounsfield unit look-up table (HLUT). While physical properties of tissue-equivalent materials are generally assumed consistent with manufacturer specifications, an independent audit identified clinically significant density discrepancies in commercially available lung-equivalent phantom inserts. Purpose This study evaluates the physical properties of nonconforming lung inserts through mass measurements and stoichiometric analysis, and assesses the clinical dosimetric impact of the associated density discrepancies. Methods Five lung-inhale inserts manufactured in 2010, 2015, and 2024 (10A, 10B, 15A, 15B, and 24A) were analyzed. Mass and physical dimensions were measured in triplicate using a precision balance (1 mg resolution) and vernier calipers. Stoichiometric analysis was conducted using reference materials to evaluate the tissue-equivalence of the inserts and quantify deviations from the theoretical baseline. A nonconforming table and a conforming reference table (RT) were established, derived from inserts 10A and 24A, respectively. For clinical impact assessment, volumetric modulated arc therapy (VMAT) plans for three clinical cases involving centrally located lung tumors (utilizing both inspiration breath-hold (IBH) and free-breathing) were optimized for stereotactic body radiotherapy (SBRT) and recalculated with the RT using the Acuros XB algorithm. Differences in gross tumor volume (GTV) mean dose and planning target volume (PTV) D95% were evaluated to quantify the dosimetric consequences. Results The 2010 inserts (10A and 10B) exhibited a 17.1% mass reduction and lower CT numbers compared to the reference 24A insert. Dimensional variations were negligible (≤ 0.2 mm) across all samples. Clinical recalculation revealed maximum dose reductions of 2.1% for the GTV mean dose and 3.0% for the PTV D95% in the worst-case scenario. These errors exceed the 2% clinical tolerance, propagated by HLUT interpolation across the low-density range. Conclusions Substantial inter-lot density variations in commercial calibration phantoms can lead to dosimetric errors that exceed established clinical limits, particularly for centrally located tumors treated with IBH. Medical physicists must not implicitly rely on nominal manufacturer values; independent audits and initial mass screening at acceptance are highly recommended for maintaining dose calculation accuracy.
Physics and Astronomy
Augusto AGB et al. · Jul 1, 2026
Excessive intake of saturated fats triggers inflammation in the hypothalamus, a key regulator of energy balance. In the chronic phase of this inflammatory response, bone marrow-derived and lymphoid cells are chemoattracted to this region, partially mitigating high-fat diet (HFD)-induced metabolic impairments. In rodents, the onset and magnitude of this inflammation differ between males and females, reflecting sex-specific patterns of metabolic regulation. However, how the hypothalamic chemokine profile evolves during HFD-induced inflammation, and whether it is influenced by biological sex, remains unclear. Here, male and female C57BL/6J mice were fed a HFD for 1, 3, 14, or 28 days. To isolate the role of ovarian hormones in modulating hypothalamic chemokine profile, we also analyzed ovariectomized (OVX) females with or without estrogen replacement. Quantitative polymerase chain reaction-based expression analysis revealed that most chemokines and their receptors were transiently modulated in the hypothalamus during the course of the HFD exposure, showing reduced levels in the acute phase and normalization during the chronic phase. Despite the modest sex-dependent effects observed, messenger RNA expression of the chemokine receptor C-X-C motif chemokine receptor 3 (CXCR3) was significantly higher in females than in males after 14 and 28 days of HFD, suggesting faster recruitment of CXCR3 + immune cells that may contribute to female protection against metabolic dysfunction. Females lacking ovarian hormone production displayed increased hypothalamic expression of Cxcr3 and Ccl2. Only Cxcr3 expression was partially normalized by estradiol treatment, suggesting that non-estrogenic ovarian factors may play a role in modulating specific chemokine signaling pathways. Together, our findings show that hypothalamic chemokine signaling is dynamically and transiently regulated throughout the phases of HFD-induced inflammation, with Cxcr3 modulation by HFD and ovarian hormones contributing to sex-specific resilience against metabolic inflammation.
Neuroscience
Poeta M et al. · Jul 1, 2026
Purpose Elevated transaminases have been associated with increased severity in adult influenza cases, but data in the pediatric population are limited. This study aims to evaluate the prevalence, clinical characteristics and prognostic value of elevated transaminases in children hospitalized for influenza. Methods A multicentre retrospective cohort study was conducted on 543 children hospitalized for acute viral respiratory infections. Demographic, clinical, biochemical, radiological features, and outcome were collected and analyzed, comparing children with influenza to those with other respiratory viruses. The association between elevated transaminases and clinical severity, complications, and intensive care unit (ICU) admission was assessed. Results Among 543 children, 127 (23.4%) had laboratory-confirmed influenza, with 24.4% showing elevated transaminases versus 7.2% in noninfluenza infections (p Conclusion Elevated transaminases occur in one fourth of children hospitalized for influenza and are associated with more severe disease, systemic complications, and worse outcomes. The findings suggest that transaminase elevation reflects systemic and muscular involvement rather than primary liver injury. Monitoring transaminases provides an early, easy marker to identify children at risk of severe influenza.
Medicine
Dora K et al. · Jul 1, 2026
Objectives Resistance exercise enhances executive function (EF) more effectively at moderate or higher intensities than at low intensity resistance exercise (LRE), probably with increased neural activity and lactate production to meet brain energy demands. Given that LRE remains widely applicable with less perceived exertion, and electrical muscle stimulation (EMS) increases lactate production and neural activation, we investigated whether combining LRE with EMS (LRE-EMS) effectively enhances EF, without increasing perceived exertion. Design A crossover randomized study. Methods Seventeen young men participated in a crossover randomized study to assess the cognitive effects of LRE alone, EMS alone, and LRE-EMS. The LRE protocol involved knee extensions at 40% one-repetition maximum for 4 sets of 10 repetitions. During the EMS condition, the participants remained seated for 260 s to match the duration of the other conditions, with EMS applied to the lower limb muscles. Subjective perceptions of exertion and fatigue during exercise were recorded. Results IC and lactate were measured at baseline, immediately postexercise, and 15 min postexercise. The LRE condition did not significantly increase IC (p = 0.100), whereas LRE-EMS resulted in significant IC improvements immediately and 15 min postexercise (both p Conclusions Perceived exertion and fatigue were greater with LRE-EMS compared with LRE and EMS. These findings suggest that LRE combined with EMS and EMS alone are effective strategies for cognitive improvement, but increased perceived exertion still exists.
Medicine
Meng X et al. · Jul 1, 2026
Background The lens of the eye is highly radiosensitive, yet personalized shielding during head CT remains challenging due to the lack of a rapid, pre-scan localization method. Purpose To develop and validate a deep learning solution that enables automated, patient-specific eye protection by generating a precise 3D eyeball model directly from a single-view topogram. Methods Our two-stage approach combines an advanced data simulation pipeline-which generates realistic training topograms from digitally reconstructed radiographs (DRRs) using a table-movement-aware model and CycleGAN-based stylization-with a dedicated generative network (EyeGen-Net). The model was trained on 400 synthetic and validated on 100 real clinical samples. Results EyeGen-Net achieved a Dice Similarity Coefficient of 0.79 ± 0.08, a Hausdorff Distance of 5.40 ± 1.57 mm, and an Average Surface Distance of 1.84 ± 0.65 mm against expert segmentations. Crucially, phantom validation demonstrated that the derived 3D model facilitates organ-based tube current modulation (OBTCM), yielding an approximate 30% reduction in lens dose across different scanning modes without compromising diagnostic image quality. Conclusions This work provides a practical, automated pathway for implementing personalized radioprotection in routine head CT, aligning with the ALARA (As Low As Reasonably Achievable) principle.
Medicine
Li Y. · Jul 1, 2026
Background Atrial fibrillation (AF) poses significant challenges for coronary CT angiography (CCTA) due to R-R interval variability, often necessitating high radiation dose protocols. Absolute phase gating, which uses fixed millisecond delays rather than percentage-based cardiac cycle timing, may optimize image quality while reducing radiation exposure. Purpose To evaluate whether absolute phase gating reduces radiation dose while maintaining diagnostic accuracy and image quality compared to conventional relative phase gating in patients with AF undergoing CCTA. Methods This retrospective matched cohort study included 280 consecutive patients with AF (140 per group) who underwent CCTA between January 2021 and December 2023. Patients were matched by heart rate, BMI, and calcium score. The absolute phase gating group used fixed 300-millisecond post-R-wave triggering; the relative phase gating group used conventional 75% R-R interval triggering. Primary endpoints were diagnostic accuracy (sensitivity, specificity) for ≥50% stenosis and assessable segment ratio. Secondary endpoints included radiation dose parameters and image quality scores. Invasive coronary angiography served as reference standard in 118 patients (42.14%). Results Radiation dose was 64.28% lower with absolute phase gating (median DLP: 187.50 vs. 524.80 mGy·cm, p Conclusions In patients with AF undergoing CCTA, absolute phase gating can potentially reduce radiation dose while maintaining or improving diagnostic performance relative to the conventional relative phase gating protocol used at our institution. Because the magnitude of any dose reduction depends in part on the acquisition window and dose-modulation settings of the compared protocols, the benefit should be interpreted in the context of the specific comparator. These findings are consistent with the Image Wisely initiative for responsible patient radiation dose management.
Medicine
Huang X et al. · Jul 1, 2026
Aging is a multifactorial process driven by interconnected hallmarks, including chronic inflammation, mitochondrial dysfunction, genomic and epigenetic alterations, and dysregulated intercellular communication. Extracellular vesicles (EVs), naturally derived nanoscale membrane vesicles capable of transporting diverse bioactive cargoes across tissues and biological barriers, have emerged as a highly promising platform for regenerative and anti-aging therapeutics. In this review, we systematically summarize the multifaceted anti-aging mechanisms of EVs, including suppression of the senescence-associated secretory phenotype (SASP), remodeling of the immune microenvironment, mitochondrial restoration and metabolic reprogramming, DNA damage repair, epigenetic modulation, recovery of proteostasis, activation of regenerative signaling pathways, and cross-organ communication-mediated rejuvenation. Beyond mechanistic insights, we integrate the targeting biology and cellular entry properties of EVs, encompassing natural tropism determinants, engineered targeting strategies, biodistribution profiles, receptor-ligand interactions, intracellular trafficking, and subcellular cargo release. Unlike previous reviews focusing on a single EV source or isolated pathways, we establish a comprehensive framework connecting molecular mechanisms with delivery engineering, tissue targeting, biosafety assessment, scalable manufacturing, and clinical translation. We address major technical bottlenecks limiting EV therapeutics-including EV heterogeneity, suboptimal delivery efficiency, endosomal degradation, and the lack of standardized quality-control frameworks-while highlighting emerging solutions such as bioengineered EVs, hybrid vesicle platforms, biomaterial-assisted delivery systems, and ultrasound-enhanced targeting technologies. By bridging fundamental biology, nanomedicine engineering, and clinical translation, this review provides a strategic roadmap for the development of next-generation precision anti-aging nanotherapeutics with systemic regulatory capacity, translational feasibility, and broad clinical potential.
Biochemistry, Genetics and Molecular Biology
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
Zhang X et al. · Jul 1, 2026
Metabolic dysfunction-associated steatotic liver disease (MASLD) is primarily driven by a Western-style diet and exacerbated with aging, yet underlying mechanisms remain unclear. Given the essential role of thyroid hormone (TH) in MASLD progression, we hypothesized that impaired intrahepatic TH action during aging promotes MASLD progression and severity of MASH with fibrosis. We evaluated hepatic TH metabolism in young (18-24 weeks) and old (108-120 weeks) C57BL/6J mice fed either a normal chow diet (NCD) or a Western diet with fructose (WDF) for 8 weeks. Liver histology, metabolic parameters, inflammatory and fibrotic markers, intrahepatic thyroxine (T4) and triiodothyronine (T3) concentrations, and activities of deiodinase enzymes (Dio1 and Dio3) were measured. Additionally, an in vitro hepatocyte senescence model using AML12 cells was employed to assess age-related alterations in deiodinase expression and the therapeutic efficacy of resmetirom (an FDA-approved thyromimetic). Aging and WDF synergistically exacerbated hepatic inflammation and fibrosis, accompanied by significant reductions in intrahepatic T4 and T3. Aging markedly decreased Dio1 activity, which converts T4 to active T3, whereas WDF partially restored Dio1 in old mice. Conversely, Dio3 activity, responsible for TH inactivation, increased with age but exhibited age-dependent differential responses to WDF, findings mirrored in senescent hepatocytes. Notably, resmetirom significantly reduced senescence markers, inhibited senescence-associated secretory phenotype (SASP) genes, inflammasome activation, endoplasmic reticulum (ER) stress, and activated autophagy. Collectively, our findings demonstrate that aging and stress by a Western-style diet synergistically impair hepatic TH signaling, accelerating MASLD progression. Furthermore, resmetirom improved hepatic senescence, highlighting its potential therapeutic repurposing for aging-associated hepatic pathologies, including MASLD.
Medicine
Xu H et al. · Jul 1, 2026
Arterial aging is a major risk factor for cardiovascular disease and is associated with progressive changes in vascular structure and function, including arterial stiffening, reduced elasticity, extracellular matrix remodeling, chronic low-grade inflammation, and accumulation of senescence-associated cell states. Recent advances in single-cell RNA sequencing (scRNA-seq) have provided new opportunities to resolve the cellular heterogeneity underlying these age-related alterations in the arterial wall. In this review, we summarize current single-cell studies of arterial aging by focusing first on key phenotypic programs, including cellular senescence, extracellular matrix remodeling, inflammaging, and altered intercellular communication, and then discuss how these programs are reflected in endothelial cells, smooth muscle cells, fibroblasts, and immune cells. Across studies, aging is recurrently associated with endothelial dysfunction, smooth muscle cell phenotypic modulation, fibroblast-related matrix remodeling, and immune activation, although the degree of conservation varies depending on species, vascular bed, sex, and disease context. We further discuss emerging evidence that vascular aging involves not only cell-intrinsic transcriptional changes but also alterations in communication networks across the arterial wall. Although current single-cell studies have substantially improved our understanding of arterial aging, important limitations remain, including inconsistent cell-state annotation across studies, incomplete functional validation, and limited spatial and epigenetic resolution. Future integration of cross-species analyses with spatial transcriptomics, single-cell epigenomic approaches, and functional studies will help refine the cellular framework of arterial aging and improve its translational relevance.
Biochemistry, Genetics and Molecular Biology