Thyroid carcinoma is the most prevalent endocrine malignancy, with a worldwide increasing incidence. Capsular invasion and neural invasion (NI) are pivotal prognostic factors for recurrence and survival; however, their preoperative noninvasive assessment remains challenging. We aimed to identify computed tomography (CT) radiomic biomarkers associated with capsular invasion in thyroid carcinoma, construct machine learning models integrating radiomic and clinical data, and evaluate their utility for NI risk stratification. In this retrospective cohort, 111 patients with thyroid carcinoma were divided into capsular invasion-positive (n=63) and capsular invasion-negative (n=48) groups, with 37 (33.3%) cases presenting concurrent NI. Radiomic features were extracted from arterial and venous phase CT images at original resolution, including 111 gray-level co-occurrence matrix features. Nine key radiomic features (A1-A9) were selected via least absolute shrinkage and selection operator regression (λ=0.017). To preserve the physical meaning of texture features (eg, spatial correlation and contrast reflecting tumor microstructural heterogeneity), no resampling or scaling was performed on the regions of interest during radiomic feature extraction. Nomogram models and random forest (RF) models were constructed based on clinical indicators (galectin-3, etc) and radiomic features, respectively. Additionally, a neural network (NN) model integrating multimodal data was developed. Model stability was verified using 5-fold cross-validation and 1000-time bootstrap resampling, while performance was evaluated via receiver operating characteristic curves, calibration curves, and decision curve analysis. Model performance analysis revealed that among the nomogram models, the clinical indicator-based nomogram achieved an internally estimated area under the curve (AUC) of 0.9418 (95% CI 0.892-0.976) in the capsular invasion prediction task. The radiomic-based nomogram had an internally estimated AUC of 0.9334 (95% CI 0.881-0.968) in the capsular invasion prediction task and 0.8001 (95% CI 0.663-0.898) in the cross-label association analysis task. In RF models, clinical indicator-based and radiomic-based RFs exhibited an AUC of 0.7646 (95% CI 0.651-0.857) and 0.8102 (95% CI 0.703-0.892) in the cross-label association analysis task, respectively. The NN model performed promisingly, with an AUC of 0.775 (95% CI 0.621-0.903) in the cross-label association analysis task and a mean absolute error of <0.05 on the calibration curve. Capsular invasion is a strong predictor of NI risk in thyroid carcinoma. Radiomic models based solely on preoperative CT images show potential for preoperative NI risk stratification. Models incorporating clinical parameters (obtained from postoperative tissue), including the integrated multimodal model, are more accurately characterized as postoperative risk stratification tools. The NN model, which integrated raw CT images with clinical data, achieved an AUC of 0.775 (95% CI 0.621-0.903), underscoring the potential of such multimodal analysis to capture complex relationships between imaging phenotypes and tissue-level biomarkers for enhanced postoperative assessment. This framework's radiomic component points toward purely image-based, preoperative evaluation tools' development.

Aim. To evaluate the clinical efficacy of radiofrequency ablation in high-risk patients with localized renal cell carcinoma and to assess the limitations of glomerular filtration rate in post-ablation renal function assessment. Materials and methods. This single-center retrospective cohort included 24 patients with localized renal tumors treated with radiofrequency ablation between 2008 and 2019 at the Zaporizhzhia Regional Antitumor Center. Indications comprised solitary kidney (n = 5), bilateral tumors (n = 3), and local treatment in the setting of recurrent or metastatic disease (n = 18); categories were not mutually exclusive. A percutaneous approach was used in 21 (87.5 %) patients, laparoscopic in 1 (4.2 %), and open in 2 (8.3 %). Core-needle tissue samples from macroscopically intact parenchyma adjacent to the ablation zone were obtained intraoperatively and 72 hours after ablation. Immunohistochemical analysis of CD34 and HIF-1α expression was performed and correlated with estimated glomerular filtration rate. The Wilcoxon signed-rank test was used for statistical evaluation. Results. Complete tumor necrosis was observed in 75–100 % of cases. Most complications were minor (Clavien–Dindo I–II: 29.2 %), while serious adverse events (IIIa–IV) occurred in three patients (12.5 %). The mean hospital stay was 3.0 ± 0.8 days. Clear cell carcinoma was the predominant histology – (83.3 %), with papillary carcinoma in 16.7 %. Tumor size ranged from 2.1 cm to 4.0 cm (mean 3.2 ± 0.5 cm); 37.5 % of patients had lesions &gt;3 cm. Postoperative immunohistochemistry showed a significant decrease in CD34 expression (100 ± 15 vs. 58 ± 12; p = 0.014) and an increase in HIF-1α levels (25 ± 8 vs. 78 ± 14; p = 0.008) despite a stable estimated glomerular filtration rate (62.4 ± 7.8 mL/min/1.73 m2 vs. 61.9 ± 8.1 mL/min/1.73 m2, p = 0.74). Conclusions. Radiofrequency ablation is an effective nephron-sparing option for high-risk patients with localized renal cell carcinoma. However, stable estimated glomerular filtration rate values may mask subclinical parenchymal injury; tissue-level biomarkers capture structural and microvascular alterations. These findings support prospective validation.

Active mussel biomonitoring for the health status assessment of the Western Mediterranean Sea

The Advances in Targeted Therapies meets annually, convening experts in the field of rheumatology to both provide scientific updates and identify existing scientific gaps within the field. To review the...

Introduction: Changes in substrate utilization may be a biomarker of, or a contributor to, heart failure with reduced ejection fraction (HFrEF). Previous work has described circulating metabolites, proteins and transcripts that reflect myocardial bioenergetics, but direct assessment in relevant tissues is lacking. Here, we leverage integrative omics to identify tissue-level biomarkers and pathways of HFrEF that may play a role in pathogenesis. Methods: Myocardial tissue was obtained from 27 HFrEF donors and 21 non-failing hearts (noHF) from Duke University and the University of Colorado Medical Centers. Targeted (n=139 metabolites) and nontargeted (Metabolon, n=817) metabolic profiling was performed; in addition, 496 proteins were assayed (Olink) and ~31,000 transcripts were quantified via RNA sequencing. Individual metabolites were tested for association with HFrEF in models adjusted for age, sex and diabetes. Metabolomics, proteomics and RNA-seq data were integrated using block sparse partial least squares discriminant analysis (sPLS-DA) to identify correlated biomarkers that discriminate HFrEF from noHF hearts. Results: The targeted metabolomics platform primarily assayed metabolic fuel substrate pathways; 71 analytes (51%) were associated with HFrEF after controlling the false discovery rate (FDR) at 5%. Medium- and long-chain acylcarnitines (C10s-C18s) were significantly lower in tissue from failing hearts, while branched-chain amino acids (BCAA) and ketoacids were higher. In the nontargeted set, 293 metabolites (36%) differed between HFrEF and noHF. BCAA and acylcarnitine associations were recapitulated along with a decrease in malonylcarnitine. The sPLS-DA model selected 25 targeted and 50 nontargeted metabolites, 35 proteins and 35 transcripts, and successfully discriminated HFrEF from no HF (balanced error rate = 3.2%). 39/186 tested KEGG pathways were overrepresented in these analytes, including fatty acid metabolism (FDR q=0.002). Conclusions: Analysis of tissue-level metabolites suggests both decreased use of fatty acids as a fuel and disrupted enzymatic breakdown of BCAAs in the failing heart, while integrative omics pathway analysis also supports the association of disrupted fatty acid metabolism with HF.

Integrated assessment of biological responses to pollution in wild mussels (Mytilus edulis) from subarctic and arctic areas in the Norwegian sea

Background: Carbon monoxide (CO) is gaining increased attention in air pollution-induced arrhythmias. The severe cardiotoxic consequences of CO urgently require effective pharmacotherapy to treat it. However, existing evidence demonstrates that CO can induce arrhythmias by directly affecting multiple ion channels, which is a pathway distinct from heart ischemia and has received less concern in clinical treatment.Objective: To evaluate the efficacy of some common clinical antiarrhythmic drugs for CO-induced arrhythmias, and to propose a potential pharmacotherapy for CO-induced arrhythmias through the virtual pathological cell and tissue models.Methods: Two pathological models describing CO effects on healthy and failing hearts were constructed as control baseline models. After this, we first assessed the efficacy of some common antiarrhythmic drugs like ranolazine, amiodarone, nifedipine, etc., by incorporating their ion channel-level effects into the cell model. Cellular biomarkers like action potential duration and tissue-level biomarkers such as the QT interval from pseudo-ECGs were obtained to assess the drug efficacy. In addition, we also evaluated multiple specific IKr activators in a similar way to multi-channel blocking drugs, as the IKr activator showed great potency in dealing with CO-induced pathological changes.Results: Simulation results showed that the tested seven antiarrhythmic drugs failed to rescue the heart from CO-induced arrhythmias in terms of the action potential and the ECG manifestation. Some of them even worsened the condition of arrhythmogenesis. In contrast, IKr activators like HW-0168 effectively alleviated the proarrhythmic effects of CO.Conclusion: Current antiarrhythmic drugs including the ranolazine suggested in previous studies did not achieve therapeutic effects for the cardiotoxicity of CO, and we showed that the specific IKr activator is a promising pharmacotherapy for the treatment of CO-induced arrhythmias.

Abstract BACKGROUND OS2966 is a first-in-class, humanized, and deimmunized anti-CD29 (β1integrin) monoclonal antibody. CD29 is a mechanosignaling receptor prominently upregulated in glioblastoma. Preclinical studies in mice and non-human primates have demonstrated safety and encouraging efficacy. A phase I clinical trial was therefore initiated to evaluate the safety and feasibility of delivering OS2966 directly to the site of disease via convection-enhanced delivery (CED) in recurrent high-grade glioma patients. METHODS This study employs a 2-part design: In part 1, patients undergo stereotactic tumor biopsy followed by placement of a CED catheter(s) for delivery of OS2966 to the bulk contrast-enhancing tumor. Subsequently, in part 2, patients undergo a clinically-indicated tumor resection followed by placement of CED catheter(s) and delivery of OS2966 to the surrounding tumor-infiltrated brain. Co-convection of gadolinium enables real-time monitoring of therapeutic delivery. A concentration-based accelerated titration design is utilized for dose escalation. Given availability of pre and post-infusion samples, pharmacodynamic data will be analyzed to explore mechanism of action of OS2966. RESULTS Four patients have completed treatment in both study parts. No dose-limiting toxicity or adverse events related to treatment with OS2966 or CED catheter placement have been reported at the first 3 dose levels (ie, doses up to 0.6 mg/mL). For the four patients treated an average of 4.2 mL and 3.2 mL were infused in study parts 1 and 2 respectively. The Vd/Vi ratio ranged from 0.6 to 1.6 in part 1, and from 2.0 to 4.3 in Study Part 2. Analysis of tissue samples collected during the trial has demonstrated decreased VEGF expression post-treatment, with preinfusion samples showing &amp;gt; 50% VEGF expression and post-infusion samples showing 10% expression. Additional pharmacodynamic analysis via tissue-level biomarkers is ongoing and will be presented. CONCLUSION Initial data demonstrate the safety and feasibility of direct intracranial delivery of OS2966.

Abstract BACKGROUND OS2966 is a first-in-class, humanized and deimmunized monoclonal antibody which antagonizes CD29/β1integrin, a mechanosignaling receptor prominently upregulated in glioblastoma. Preclinical studies in mice and non-human primates have demonstrated safety and encouraging efficacy. A two-part, ascending concentration, phase I clinical trial was therefore initiated to evaluate the safety and feasibility of delivering OS2966 directly to the site of disease via convection-enhanced delivery (CED) in recurrent high-grade glioma patients. METHODS This study has a 2-part design: In part 1, patients undergo stereotactic tumor biopsy followed by placement of a multiport CED catheter for delivery of OS2966 to the bulk contrast enhancing tumor. Subsequently, patients undergo a clinically-indicated tumor resection followed by placement of two CED catheters and delivery of OS2966 to the surrounding tumor-infiltrated brain. A unique concentration-based accelerated titration design is utilized for dose escalation. Given availability of pre and post infusion samples, pharmacodynamic data will be analyzed to explore mechanism of action of OS2966. RESULTS Two subjects have been treated at two corresponding dose levels (0.2mg/mL and 0.4 mg/mL). No dose-limiting toxicity or unexpected safety issues have been identified. To date, reported adverse events were mild (i.e., grade 1) and consistent with underlying disease and surgical procedures. No adverse events were attributed to OS2966 or CED catheter placement. Further, no clinically significant changes from baseline neurological exam have been noted for either patient through initial follow-up. Maximal tumor coverage and concomitant gross total resection were achieved for both patients. Tumor volume measured 1.63 cm3 and 16 cm3 for Patient 1 and 2 respectively with an intratumoral Vd/Vi ratio of 1.3. and 0.94. Pharmacodynamic analysis via tissue-level biomarkers is ongoing and will be presented. CONCLUSION Initial data demonstrates the safety and feasibility of direct intracranial delivery of OS2966.

An integrated biomarker approach to assess the welfare status of Ompok bimaculatus (Pabda) in biofloc system with altered C/N ratio and subjected to acute ammonia stress

To assess the influence of food type on biomarkers, mussels (Mytilus galloprovincialis) were maintained under laboratory conditions and fed using 4 different microalgae diets ad libitum for 1 week: (a) Isochrysis galbana; (b) Tetraselmis chuii; (c) a mixture of I. galbana and T. chuii; and (d) a commercial food (Microalgae Composed Diet, Acuinuga). Different microalgae were shown to present different distribution and fate in the midgut. I. galbana (≈4 μm Ø) readily reached digestive cells to be intracellularly digested. T. chuii (≈10 μm Ø and hardly digestible) was retained in stomach and digestive ducts for long times and extracellularly digested. Based on these findings, it appeared likely that the presence of large amounts of microalgal enzymes and metabolites might interfere with biochemical determinations of mussel’s biomarkers and/or that the diet-induced alterations of mussels’ digestion could modulate lysosomal and tissue-level biomarkers. To test these hypotheses, a battery of common biochemical, cytological and tissue-level biomarkers were determined in the gills (including activities of pyruvate kinase, phosphoenolpyruvate carboxykinase and cytochrome c oxidase) and the digestive gland of the mussels (including protein, lipid, free glucose and glycogen total content, lysosomal structural changes and membrane stability, intracellular accumulation of neutral lipids and lipofuscins, changes in cell type composition and epithelial thinning, as well as altered tissue integrity). The type of food was concluded to be a major factor influencing biomarkers in short-term experiments though not all the microalgae affected biomarkers and their responsiveness in the same way. T. chuii seemed to alter the nutritional status, oxidative stress and digestion processes, thus interfering with a variety of biomarkers. On the other hand, the massive presence of I. galbana within digestive cells hampered the measurement of cytochemical biomarkers and rendered less reliable the results of biochemical biomarkers (as these could be attributed to both the mussel and the microalgae). Research to optimize dietary food type, composition, regime and rations for toxicological experimentation is urgently needed. Meanwhile, a detailed description of the food type and feeding conditions should be always provided when reporting aquatic toxicological experiments with mussels, as a necessary prerequisite to compare and interpret the biological responses elicited by pollutants.

Influence of season-depending ecological variables on biomarker baseline levels in mussels (Mytilus trossulus) from two Baltic Sea subregions

Collection and transport of sentinel mussels in biomarker-based coastal pollution monitoring: Current flaws and reliable practices

Effects of dietary Pb and Cd and their combination on lysosomal and tissue-level biomarkers and histopathology in digestive gland of the land snail, Cantareus apertus (Born, 1778)

Assessment of ecosystem health disturbance in mangrove-lined Caribbean coastal systems using the oyster Crassostrea rhizophorae as sentinel species

Imaging is paramount to the diagnosis and management of ischemic stroke, offering a battery of structural and functional probes of cerebrovascular physiology. The technical underpinnings of stroke imaging continue to evolve, bringing the neuroscience community increasingly closer to high-resolution, tissue-level biomarkers of brain perfusion, metabolism, and viability. The rapid expansion of neuroimaging in this domain has met with controversies, and in many respects, a lack of generalizable conclusions regarding optimized use in cerebrovascular disease. This review aims to provide the reader with the depth and scope of both established and emerging techniques, and an overview of prevailing viewpoints regarding neuroimaging in acute ischemic stroke.

Imaging is paramount to the diagnosis and management of ischemic stroke, offering a battery of structural and functional probes of cerebrovascular physiology. The technical underpinnings of stroke imaging continue to evolve, bringing the neuroscience community increasingly closer to high-resolution, tissue-level biomarkers of brain perfusion, metabolism, and viability. The rapid expansion of neuroimaging in this domain has met with controversies, and in many respects, a lack of generalizable conclusions regarding optimized use in cerebrovascular disease. This review aims to provide the reader with the depth and scope of both established and emerging techniques, and an overview of prevailing viewpoints regarding neuroimaging in acute ischemic stroke.

Assessment of the effects of Cu and Ag in oysters Crassostrea gigas (Thunberg, 1793) using a battery of cell and tissue level biomarkers

Histopathological assessment and inflammatory response in the digestive gland of marine mussel Mytilus galloprovincialis exposed to cadmium-based quantum dots

As a consequence of the growing global demand of energy supplies, intense oil and gas exploration and exploitation programs have been carried out worldwide especially within the marine environments. The release of oil-derived compounds in the sea from anthropogenic sources both as effluents or accidental spill is perceived as a major environmental concern. An approach based on a combination of biomarkers and the distribution of some classes of environmentally relevant pollutants was used to investigate the occurrence of a stress syndrome in mussels (Mytilus galloprovincialis) collected at three gas platforms placed in two distinct oceanographic districts within the Adriatic Sea. Biological responses were integrated by a ranking algorithm which demonstrated both a range of biological effects reflecting exposure gradients and a temporal related trend in the investigated responses. The overall results demonstrate a moderate to absent pollution from studied gas platforms with low but remarkable biological disturbance in sentinel organisms.