Search Results (1,528)

This perspective paper critically examines the emerging role of voxel-based analysis (VBA), also referred to as image-based data mining (IBDM), in dose–toxicity modeling for post-radiotherapy toxicity assessment. These techniques offer promising insights into localized organ subregions associated with toxicity, yet their current application faces substantial methodological and validation challenges. Based on prior studies and practical experience, we highlight seven key limitations: (i) lack of clinical validation for dose–toxicity models, (ii) strong dependence of results on statistical method selection (parametric vs. nonparametric), (iii) insensitivity of commonly used tests to uniform dose scaling, (iv) influence of tail selection (one- vs. two-tailed tests) on statistical power, (v) frequent misapplication of permutation testing, (vi) reliance on dose as the sole predictor while neglecting patient-, treatment-, and genomic-level covariates, and (vii) misinterpretation of voxel-wise associations as causal in the absence of appropriate causal inference frameworks. Collectively, these limitations can obscure clinically relevant dose differences, inflate false-positive or false-negative findings, obscure effect direction, introduce confounded associations, and ultimately yield inconsistent identification of high-risk subregions in organs at risk and poor reproducibility across studies. Notably, current univariable VBA/IBDM approaches should be regarded as hypothesis-generating rather than clinical decision-making tools, as unvalidated findings risk premature translation into clinical practice. Advancing personalized radiotherapy requires rigorous outcome validation, integration of multivariable and causal modeling strategies, and incorporation of clinical and genomic data. By moving beyond dose-only predictor models, VBA/IBDM can achieve greater biological relevance, reliability, and clinical utility, supporting more precise and individualized radiotherapy strategies. Full article

Nuts are nutrient-rich foods that help reduce the risk of coronary heart disease (CHD), but their potential contamination with aflatoxins (AFs) may increase the risk of liver cancer. In this study, the European Benefit–Risk Analysis for Foods (BRAFO) framework was used to evaluate both the health risks and benefits of nut consumption among Chinese adults. Based on the actual consumption patterns of nuts among the Chinese population, the current consumption level was set as the reference scenario (4.66 g/day), and three alternative scenarios were simulated with a daily nut consumption of 10, 20, and 30 g, respectively. Dose–response relationships were established using a two-stage dose–response analysis for nut consumption and CHD risk, and a one-stage dose–response analysis for aflatoxin B1 (AFB1) exposure and liver cancer risk. A Monte Carlo probabilistic model quantified the CHD prevention benefits and liver cancer risks associated with AF exposure. Disability-Adjusted Life Year (DALY) analysis indicated net health benefits in all scenarios, with nut consumptions of 10, 20, and 30 g/day reducing DALYs per 100,000 population by 104.39, 143.63, and 181.47 in men, and by 58.79, 81.29, and 102.94 in women, respectively. A nut consumption of 10 g/day was recommended for Chinese adults, considering both health benefits and the risk of AF exposure. This study presents the first application of the BRAFO framework to evaluate the net health effect of nut consumption in a Chinese population, filling a critical gap in the risk–benefit assessment of nut consumption. Full article

Alanine dosimetry based on Electron Paramagnetic Resonance (EPR) spectroscopy has been a reliable reference and transfer dosimetry method in high-dose applications, valued for its high precision, accuracy and long-term stability. Additional characteristics, such as dose-rate independence up to 10¹⁰ Gy/s under electron beam (e-beam) irradiation, electron energy independence and tissue equivalence, position alanine EPR as a promising candidate to address dosimetric challenges arising in e-beam Flash Radiotherapy (RT), where radiation energy is delivered at Ultra-High Dose-Rates (UHDR) ≥ 40 Gy/s. At such dose-rates, reliable real-time monitoring dosimeters such as ionization chambers in conventional RT, suffer from ion recombination, compromising accuracy in dose determination. Several studies are currently focused on developing real-time beam monitoring systems dedicated specifically for e-beam Flash RT. This creates a need for standardized reference dosimetry methods to validate beam parameters determined by these systems under investigation. This review provides an overview of the potential and limitations of the alanine EPR dosimetry method for control, validation and verification of e-beam Flash RT beam parameters at doses less than 10 Gy, where the method has shown low sensitivity and increased uncertainty. It further discusses strategies to optimize alanine EPR measurements to enhance sensitivity and accuracy at these dose levels. Improved measurement procedures will ensure reliable and accurate e-beam Flash RT accelerator commissioning, performance checks, patient safety and treatment efficacy across all therapeutic dose ranges. Full article

In recent years, China has experienced a notable increase in indoor radon concentrations. However, our understanding of residential radon exposure in Central China remains limited and primarily depends on the data collected from residential buildings in Wuhan before 2003. Given this context, the current radon exposure levels in Central China must be assessed immediately, and the factors influencing them be investigated. To address this gap, our study focused on five representative areas in Central China. We monitored indoor radon concentrations in residential areas using random cluster sampling while considering various building structures. The radon levels were measured through the alpha track method, and RSKS standard detectors were deployed in two separate batches to participating households. A total of 1300 detectors were distributed across 579 households, with a recovery rate of 97.15% (1263 detectors were retrieved). The annual average indoor radon concentration in Central China ranged widely from 6.25 Bq/m³ to 310.44 Bq/m³, with an arithmetic mean of 50.20 Bq/m³, which resulted in an average annual effective dose of 2.08 mSv. Referring to World Health Organization standards, the radon concentration in approximately 8.24% of the monitored rooms exceeded the recommended action level. Our analysis indicated that radon concentration is primarily influenced by factors, such as the time of measurement, geographical location, building structure, floor materials, household fuel, and ventilation practices. Multiple regression analysis revealed that these factors collectively account for 10.80% of the variation in radon concentration. Notably, geographical location, building structure, and ventilation mode emerged as important factors. Based on these findings, our study suggests several practical measures to effectively reduce indoor radon levels, including improving ventilation, switching to cleaner fuels, and using environmentally friendly building and decoration materials. Full article

Heavy metal(loid) (HM) contamination in water arises from various anthropogenic activities and natural processes, posing risks to human health through ingestion and dermal absorption. Although numerous studies have assessed health risks associated with HMs in water, inconsistencies in the selection of exposure and toxicity factors limit comparability and reliability across studies. To address this gap, the aim of this review was to provide a comprehensive synthesis of exposure and toxicity factors used in health risk assessment (HRA) of HMs in water. The objectives were to evaluate the variability in ingestion, body weight, exposure duration and frequency, and dermal contact parameters, as well as in reference doses and cancer slope factors and to propose standardized values and statistical distributions for more consistent risk estimation. A systematic search of the Scopus database retrieved 806 studies, from which highly cited articles (≥100 citations) and recent publications (2023–2025) were prioritized for analysis. The findings revealed substantial variability in factors and showed that probabilistic approaches, particularly Monte Carlo simulation, were increasingly applied and provided more reliable estimates than traditional deterministic methods. The highest agreement was observed for exposure frequency for ingestion (365 days/year) and skin surface area (18,000 cm²), each applied in 75.5% of cases. By identifying inconsistencies in current practices and proposing standardized exposure and toxicity values and distributions for water, this review is expected to offer practical recommendations to improve the robustness, reliability, and comparability of HRAs, ultimately informing more effective policy-making and water management practices. Full article

Experimental measurement of dose distributions is a pivotal step in the quality assurance of radiotherapy treatments, especially for those relying on high delivery accuracy such as hadron therapy. This study investigated the response of a polymer gel dosimeter to determine its suitability in performing geometric beam characterizations for hadron therapy under high-quenching conditions. Different extraction energies of proton and carbon ion beams were considered. Gel dose–response linearity and long-term stability were confirmed through optical measurements. Gel phantoms were irradiated with pencil beams and analyzed via magnetic resonance imaging. A multi-echo T₂-weighted sequence was used to reconstruct depth–dose profiles and transversal distributions acquired by the gels, which were benchmarked against reference data. As expected, a response-quenching effect in the Bragg peak region was noted. Nonetheless, the studied gel formulation proved reliable in acquiring the geometric characteristics of the beams, even without correcting for the quenching effect. Indeed, depth–dose distributions acquired by the gels showed an excellent agreement with measured particle range with respect to reference values, with mean discrepancies of 0.5 ± 0.2 mm. Single-spot transverse FWHM values at increasing depths also presented an average agreement within 1 mm with values determined with radiochromic films, thus supporting the excellent spatial resolving capabilities of the dosimetric gel. Full article

Flexible laryngoscopy (FL) is the standard diagnostic tool for vocal cord paralysis (VCP), but it involves patient discomfort, and its interpretation is subjective and operator-dependent. Dynamic digital radiography (DDR) is a novel imaging technique that acquires high-resolution sequential radiographs at a low radiation dose. While DDR has been widely applied in chest and diaphragmatic imaging, its use for laryngeal motion analysis has been poorly investigated. We present the case of a 50-year-old male referred for Computed Tomography (CT) of the neck and chest for suspected vocal cord paralysis. The referring physician did not specify the side of the suspected paralysis. Due to a language barrier and the absence of prior documentation, a detailed history could not be obtained. To assess vocal cord motion, we performed, for the first time in our Institution, a DDR study of the neck. During phonation maneuvers, DDR demonstrated fixation of the left vocal cord in an adducted paramedian position. CT confirmed this finding and did not highlight any further anomaly. This case demonstrates the feasibility of DDR as a low-cost, low-dose, non-invasive technique for functional evaluation of the larynx and may represent a valuable complementary imaging tool in laryngeal functional assessment. Full article

Background: In recent years, breakthrough varicella cases among individuals who have received a single dose of varicella vaccine (VarV) have increased notably, suggesting that the long-term protection following a one-dose VarV regimen requires further investigation. This study aims to evaluate the immune persistence following a single dose of Sinovac VarV at 5 and 8 years post-vaccination. Methods: In this Phase 4, open-label, observational follow-up study, participants aged 1 to 12 years (referring to the age of vaccination) who had received a single dose of either Sinovac VarV or placebo in the previous phase 3 trial were enrolled in a 1:1 ratio. Blood samples were collected 5 years and 8 years post-vaccination to measure antibody levels against varicella using the fluorescent antibody to membrane antigen (FAMA) method. A total of 487 and 422 participants were included in the 5-year and 8-year immune persistence analyses, respectively. The endpoints comprised the seropositive rates (≥1:4 and ≥1:8) and the geometric mean titers (GMTs) of varicella antibodies at both 5 and 8 years following vaccination. Results: Varicella antibody levels declined from 30 days post vaccination but remained stable from 5 to 8 years. Five years after vaccination, the seropositive rates (≥1:4) of varicella antibody were 100% in the VarV group and 80.83% in the placebo group; for ≥1:8, the rates were 89.07% and 64.17%, respectively. The corresponding GMTs were 1:13.67 and 1:7.71, respectively. Eight years after vaccination, the seropositive rates (≥1:4) were 99.54% in the VarV group and 90.69% in the placebo group; for ≥1:8, they were 88.53% and 74.51%, with GMTs of 1:13.52 and 1:9.91, respectively. Eight years post-vaccination, the seropositive rates and antibody levels in the VarV group remained nearly the same as by 5 years. Conclusions: Sinovac VarV can confer good immune persistence for up to 8 years following a single dose of vaccination in children aged 1 to 12 years. However, given the declining trend in antibody levels over time, revaccination may be needed to maintain protective immunity. Full article

To assess the influence of dietary bile acid (BA) on the phenotype associated with hepatic lipid metabolism and its regulation of lipid homeostasis in gibel carp (Carassius auratus gibelio) under high-fat diet (HFD) conditions, five HFDs were designed using soybean oil (SO) as the single lipid source and supplemented with 0, 200, 400, 600, and 800 mg/kg BA (designated as BA0, BA200, BA400, BA600, and BA800, respectively). Juvenile fish (32.37 ± 0.13 g) were fed five BA-added HFDs (12% SO) for 8 weeks. Considerably lower levels of aspartate transaminase, alanine aminotransferase, low-density lipoprotein, triglyceride, and total cholesterol in the serum were observed in gibel carp fed with HFDs with 400–600 mg/kg BA (p < 0.05). The hepatocytes of the BA400 and BA600 groups were intact without abnormal architecture or histopathological changes, compared to other groups. The presence of most genes related to fatty acid biosynthesis decreased significantly with the addition of 400–600 mg/kg BA (p < 0.05), while the gene expressions of hormone-sensitive lipase, adiponectin receptor 2, and peroxisome proliferator-activated receptor α were variably up-regulated, along with the elevation of dietary BA (p < 0.05). Critical genes involved in bile acid and cholesterol synthesis were obviously down-regulated in gibel carp receiving 600–800 mg/kg dietary BA (p < 0.05), despite the sterol 27-hydroxylase (cyp27a1) gene in the BA800 group (p < 0.05). Moreover, hepatopancreas from the BA0 and BA600 groups were isolated for transcriptome sequencing, identifying 7040 differentially expressed genes (DEGs). The enriched KEGG pathways of DEGs mainly included steroid biosynthesis, protein digestion and absorption, etc. Seven randomly selected DEGs were validated using qRT-PCR and were in agreement with the RNA-seq results. Consequently, the appropriate supplementation of dietary BA for juvenile gibel carp is recommended at doses of 400–600 mg/kg in SO-based HFDs, which could contribute to the amelioration of HFD-induced excessive fat deposition in the hepatopancreas of gibel carp by both inhibiting fatty acid intake, biosynthesis, and steroid production and enhancing lipid decomposition. The findings may elucidate the physiological role of exogenous BA in fish and its underlying mechanism, providing references for the reasonable application of BA in aquafeeds and the prevention of HFD-induced metabolic dysfunction in fish. Full article

Alcohol metabolism in the body is a key theme in medical research on alcohol. It is primarily regulated by the alcohol dehydrogenase (ADH) and mitochondrial NADH reoxidation in the liver. Class I ADH1 is a well-known ADH isozyme and a key enzyme in alcohol metabolism, with the lowest Kms for ethanol and the highest sensitivity to pyrazole (Pz) among the ADH isozymes. However, a Pz-insensitive metabolic pathway also plays a role in systemic alcohol metabolism, with increasing metabolic contributions at higher blood alcohol concentrations (BACs) and under chronic alcohol consumption (CAC). The Pz-insensitive pathway is referred to as the non-ADH pathway—specifically, it is a non-ADH1 pathway—and is assumed to involve the microsomal ethanol oxidizing system (MEOS) or catalase, as both enzymes are insensitive to Pz and exhibit higher Kms than ADH1. The MEOS is a favored candidate for this pathway, as its activity markedly increases with the rate of alcohol metabolism under CAC. However, the role of the MEOS in alcohol metabolism has not been proven in vivo (even under CAC conditions), nor has that of catalase. Here, we report Class III ADH3 as a new candidate in the non-ADH1 pathway, as it also has a lower sensitivity to Pz and a higher Km. It is markedly activated by lowering Km following the addition of amphiphilic substances, which increases the solution’s hydrophobicity in the reaction medium; additionally, Nile red staining demonstrates a higher solution hydrophobicity in the cytoplasm of mouse liver cells. The rate of alcohol metabolism in ADH1 knockout (Adh1^−/−) mice—which depends solely on the non-ADH1 pathway—increased by more than twice under CAC and was significantly correlated with the amount of liver ADH3 protein, but not with CYP2E1 protein (a main component of the MEOS). The rate of alcohol metabolism in Adh3^−/− mice lacking ADH3 decreased in a dose-dependent manner compared with wild mice. The liver ADH3 protein in wild-type mice increased in line with the ADH1 protein under CAC. These data suggest that ADH3 contributes to alcohol metabolism in vivo as a non-ADH1 pathway and to the enhancement of alcohol metabolism under CAC through activation of the ADH1/ADH3/NADH reoxidation system. In alcoholic liver diseases, ADH1 activity decreased with the progression of liver disease, while ADH3 activity increased or was maintained even in alcoholic liver cirrhosis. Therefore, the role of ADH3 in alcohol metabolism may be increased in the context of alcoholic liver diseases, complementing the reduced role of ADH1. It has also been suggested that Class II ADH2, Class IV ADH4, and aldehyde dehydrogenase (ALDH) 2 play roles in alcohol metabolism in vivo under certain limited conditions. However, ADH2 and 4 may not contribute to the enhancement of alcohol metabolism through CAC. Full article

Minocycline (MINO), a classic antibiotic, may have psychotropic activity related to the modulation of the tryptophan-kynurenine pathway. In this study, we investigated the effects of MINO on (1) memory and anxiety behaviors, (2) the modulation of brain levels of amyloid precursor protein (APP) and 2,3-indoleamine dioxygenase (IDO1) levels, and (3) peripheral inflammatory markers in a streptozotocin (STZ)-induced rat model of sporadic Alzheimer’s disease (sAD). After repeated treatment with a dose of 35 mg/kg MINO for seven consecutive days, male Wistar rats with sAD showed (1) improvements in early (29 days after injection, probe test) reference memory (decreased latency to reach the platform, increased time in the critical quadrant of the Morris water maze) and anxiety disorders (increased time in the open arms of the elevated plus maze; increased exploration and entrances in the center of the white–light illuminated open field) 45–46 and 90–91 days after STZ injection; (2) reduced APP and IDO1 levels in the hippocampus and prefrontal cortex; and (3) induction of anti-inflammatory response in blood (increased TCD4⁺ lymphocyte number and interleukin-10 production). This suggests that MINO, due to its anti-inflammatory action, improves memory and anxiety behavior related to sAD, indicating its neuroprotective and psychotropic properties. Full article

Background/Objectives: Hybrid Angio-CT suites have emerged in response to the growing demands for innovation and procedural complexity in minimally invasive therapies. It is hypothesized that enhanced image guidance capabilities enabled by multimodality imaging can improve procedural safety, accuracy, and efficacy. However, due to the current lack of sufficient data to support a systematic review, the objective of this article is to present a comprehensive synthesis of the existing literature through a narrative review. Methods: This narrative review is based on purposefully identified research reports, their critical evaluation, and synthesis by a group of experienced users. The analysis covers three key areas: (1) current state of available technologies and functionalities, (2) novel perspectives through ‘Direct Intravascular Contrast media Injection CT’ (DICI-CT), and (3) the role of Angio-CT in established and emerging image-guided procedures. Results: The review presents typical configurations and room layouts for Angio-CT systems and discusses further technological improvement potential. Selected literature is complemented by expert experience to report on the current state of the art and demonstrate its use and efficiency. Based on our expert experience, it is demonstrated how DICI-CT can be used to reduce contrast dose and improve lesion visualization, targeting, and endpoint determination. Furthermore, in this review the advantages, including survival benefit (i.e., in trans-arterial chemoembolization and in blunt trauma) and cost-effectiveness (i.e., in emergency care), are reviewed with reference to oncologic and non-oncologic applications in both elective and emergency medicine. Conclusions: Hybrid Angio-CT suites can provide significant additional imaging information with the potential to improve image-guided procedures. This perspective is increasingly supported by retrospective data in interventional oncology and beyond. Provided that further technological advancements are achieved and prospective clinical data substantiates the anticipated clinical and economical benefits, hybrid Angio-CT suites are anticipated to play a key role in the multimodality interventional suite of the future. Full article

Background: Hexavalent chromium (Cr(VI)) can migrate into soil and water, posing risks to animal health. However, it remains unclear whether Cr(VI) perturbs essential trace elements and antioxidant gene expression, triggers apoptosis, or disrupts hepatic lipid metabolism in New Zealand rabbits. Methods: To address this knowledge gap, twenty-four 30-day-old New Zealand rabbits were randomly allocated to one control and three Cr(VI)-treated groups (differing in Cr(VI) concentration) and maintained for 28 days. Livers were then harvested for analysis. Total Cr and essential trace elements were quantified by ICP-OES. Hematoxylin–eosin staining and transmission electron microscopy were employed to assess histopathological and ultrastructural alterations, respectively. Hepatic lipid accumulation was visualized with Oil Red O staining. QRT-PCR was used to determine the expression of antioxidant and lipid-metabolism-related genes. Results: Cr(VI) was detectable in liver tissue at all exposure levels and was accompanied by significant decreases in four essential trace elements (Fe, Mn, Zn, and Se); Cu displayed a biphasic response, rising at lower Cr(VI) doses before declining at higher doses. Histopathological and ultrastructural analyses revealed overt hepatic injury. Notably, all Cr(VI) treatments elevated antioxidant gene expression, indicating activation of hepatic defense pathways. Lipid metabolism was also disrupted, evidenced by increased lipid deposition and up-regulation of genes governing hepatic fat metabolism. Conclusions: Collectively, these findings demonstrate that Cr(VI) elicits dose-dependent activation of hepatic antioxidant defenses, promotes apoptosis, and induces lipid-metabolic disorders in New Zealand rabbit hepatocytes. This study provides novel mechanistic insights into Cr(VI)-induced hepatotoxicity and offers a valuable reference for evaluating the hepatic risks of environmental Cr(VI) exposure in this species. Full article

Background/Objectives: Fixed-dose combination (FDC) antihypertensive medications containing olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide are widely used for the treatment of essential hypertension. Although effective, the use of racemic amlodipine, which contains both active S(−)-amlodipine and inactive R(+)-amlodipine, has been associated with dose-dependent adverse effects, such as peripheral edema. S-amlodipine, a pharmacologically active enantiomer, provides comparable antihypertensive efficacy at half the dose with a lower incidence of side effects. Methods: In this study, a modified FDC formulation was developed by replacing racemic amlodipine with S-amlodipine to enhance tolerability while maintaining therapeutic efficacy. Results: A bilayer tablet design was employed to minimize the formation of impurities and ensure formulation stability, which was confirmed under stress and accelerated conditions. In vitro dissolution testing demonstrated pharmaceutical equivalence with the marketed reference FDC, and an in vivo pharmacokinetic study confirmed bioequivalence. Conclusions: These results suggest that the newly developed S-amlodipine besylate-containing FDC tablet is a viable alternative to existing olmesartan/amlodipine/hydrochlorothiazide combinations, offering comparable efficacy and pharmacokinetic properties with the potential for improved safety and patient adherence in the management of hypertension. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is the most common form of pulmonary fibrosis (PF) and serves as a key reference for disease severity. Progressive pulmonary fibrosis (PPF), a distinct yet heterogeneous entity arising from various interstitial lung diseases (ILDs), shares similar pathogenetic mechanisms and clinical courses driven by self-perpetuating fibrosis. Antifibrotic therapy, notably nintedanib, can slow disease progression. However, real-world data on antifibrotic therapy’s impact on survival, especially in PPF, are limited. This study aims to compare IPF and PPF regarding phenotype, radiological patterns, comorbidities, prognostic factors, and response to nintedanib, focusing on identifying the patient subsets most likely to benefit. Outcomes assessed include safety, survival, and disease progression over one year, considering various prognostic factors. Methods: This retrospective observational study evaluated patients with fibrosing ILD, affected by either IPF or PPF, and treated with nintedanib. Data collected encompassed clinical, radiological, functional, and treatment-related information. Assessments included chest CT, pulmonary function tests, comorbidities, and survival analysis, utilizing standardized methods and statistical tools to interpret outcomes and tolerability. Results: The study population was composed of 97 patients: 64 were diagnosed with IPF and 33 with PPF. The analysis showed that in PPF patients, ongoing antifibrotic treatment resulted in higher survival (71.1 months vs. 27.4 months, p < 0.001), while no statistically significant differences were found in the IPF group (67.4 months vs. 52.5 months, p = 0.216). Nintedanib was generally well tolerated. Gastrointestinal side effects, predominantly diarrhea, were reported in 61% of patients with IPF and 50% of those with PPF. Dose reduction occurred in 43.75% of IPF patients and 36% of PPF patients, while treatment discontinuation was required in 21.87% of IPF and 21% of PPF patients. Conclusions: This study highlights that in PPF patients, antifibrotic therapy with nintedanib can improve survival. This statement underlines that the primary outcome of antifibrotic treatment should focus on improving patients’ survival. Full article