Search Results (352)

Objectives: Endocrine neoplasms, as a general rule, show systemic, neuro-inflammatory and metabolic consequences, known as paraneoplastic syndrome. The comorbidity of thyroid tumors with neurological and autoimmune diseases prompt looking for common neuro-immuno-endocrine mechanisms of these disorders. While most TCs are well described, there is a gap in the literature after the isolation of oncocytic/Hürthle cell carcinoma (HCC), as a unique type due to immunoendocrine and metabolic features (low TSH-receptor expression and radioiodine avidity). The aim of this study was to collect clearly defined reports of HCC (as a separate entity) and to attempt determining common clinical symptoms and the usefulness of various diagnostic techniques (comprehensive critical review). This may be an introduction to modern treatment (patient-centered care) since the main cause of mortality is not local progression or metastases. Results: Until now, due to misnomenclature and data misinterpretation, HCC has been treated according to general standards (with overuse of TSH-ST and RIA). High thyroglobulin level, decreased total thyroxin (with normal FT3 and spontaneous decrease in TSH), hypercalcemia, as well as the “reverse flip-flop” phenomenon, as common symptoms, indicate the neuroendocrine origin of HCC. Sparse, well-documented lymph node metastases are another feature, although from few studies. Most studies omit the N stage. Whole-body ¹³¹iodine and ¹⁸F-fluorodeoxyglucose scintigraphy may be useful before FNAB. Fine-needle aspiration biopsy (FNAB), as a “gold standard” in early diagnosis of thyroid nodules, delays HCC diagnosis because of the inability to determine a benign/malignant nature. Conclusions: Final HCC outcome may be affected by various overlapping immunoendocrine factors (paraneoplastic effects). Due to very few thyroid function tests performed in HCC, we have proposed a set of basic laboratory analyses, core biopsy in HCC differentiation, and diagnostic chain for standardization. According to the review, adaptation and treatment of HCC based on existing standards for other thyroid cancers seem to be insufficient, and the risks outweigh the benefits. The key recommendations resulting from the 5th edition of the WHO Classification of Endocrine Neoplasms are only the beginning of refuting many myths and biases. Full article

As thoracic surgeons more frequently address smaller lung lesions and perform lung-sparing resections, their objective is to resect an adequate specimen and margin without removing excess healthy lung tissue. Although perioperative lung nodule localization has been in practice for decades, the existing and emerging techniques used for the identification of targeted and occult lesions are more widely utilized today than they were in the past. In this review, we detail the logic behind this increase in use, classify the techniques into preoperative and intraoperative categories, and define the specific modalities available. Where applicable, we review the published data comparing techniques, detailing efficacy and safety. In the preoperative space, we describe standard computed tomography (CT)-guided localization, virtual-assisted lung mapping, electromagnetic navigation bronchoscopy, robotic-assisted bronchoscopy, and novel fiducial markers. In the intraoperative space, we describe classical localization techniques, novel applications of intraoperative cone-beam CT, and fluorescence-guided surgery and intraoperative molecular imaging (IMI). Lastly, we review emerging approaches for intraoperative molecular imaging including a report on agents in early-stage clinical trials and a brief survey of promising preclinical models. With each approach mentioned, we analyze the potential benefits and hazards, and appraise the evidence for (or against) the use of any specific modality. Full article

Legume–rhizobium symbiosis represents a crucial biological nitrogen fixation system. The AP2/ERF transcription factor ERN1 plays a vital role in nodulation of model legumes; however, its function in peanut (Arachis hypogaea), a typical crack-entry infection legume, remains unclear. To explore this, we performed transcriptome sequencing of peanut roots at 3 days post-inoculation (dpi) with rhizobium. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that differentially expressed genes (DEGs) were mainly enriched in DNA-binding transcription factor activity, plant–pathogen interaction, and plant hormone signal transduction pathways. The most strongly up-regulated gene was AhERN1, which was highly expressed in peanut roots and nodules. Subcellular localization indicated that AhERN1 was a nuclear-localized protein, and yeast transcriptional activation assays confirmed that AhERN1 functions as a transcriptional activator relying on its C-terminal domain. Furthermore, hairy root overexpression of AhERN1 significantly increased the number of peanut nodules. Collectively, these results reveal that AhERN1 acts as a positive regulator to promote rhizobium-induced nodule development in peanut, providing new insights into the regulatory mechanism of nodulation in dalbergoid legumes. Full article

Tumor localization during pulmonary surgery has become increasingly challenging with the earlier detection of smaller and smaller lung nodules. Concomitantly, minimally invasive surgical (MIS) techniques have been increasingly adopted within the field of thoracic surgical oncology. Surgeons face growing challenges not only with locating these small tumors, but also with immediate margin assessment, reduced tactile feedback, and nodal assessment. Intraoperative molecular imaging (IMI) has emerged as a promising adjunct to address these challenges by enabling real-time visualization of malignant tissue during pulmonary resection. In its current form, IMI integrates systemically administered, tumor-targeting near-infrared fluorophores with fluorescence-capable imaging platforms to enhance intraoperative decision-making. Early clinical experiences in thoracic surgery suggest particular utility in the localization of small or nonpalpable pulmonary nodules and for improved margin assessment during MIS. Despite encouraging preliminary data, widespread adoption of IMI remains limited by biologic variability in target expression, optical depth constraints, false-positive fluorescence in inflammatory tissue, and challenges in workflow integration. Applications for nodal evaluation, staging, and longer-term oncologic outcome improvement remain investigational. Addressing these multifaceted barriers will be essential for the translation of IMI from a promising, experimental adjunct to a more broadly implementable surgical technology. This work summarizes the current state of IMI in thoracic surgical oncology, highlighting key translational studies, established and emerging clinical applications, and critical limitations within the current landscape. The authors also outline future directions for the field, including quantitative fluorescence interpretation, standardized reporting, and outcomes-driven clinical trials evaluating margin adequacy, recurrence, staging impact, and cost-effectiveness to support widespread evidence-based implementation. Full article

To characterize the transport of the mining-induced sediment plume in the Clarion–Clipperton Zone (CCZ) nodule area, this study introduces a particle relative dispersion (RD) to assess material dispersion in 2D and 3D. In 2D, forward and backward RD results show clear sub-regional differences in particle aggregation and diffusion. Forward RD reaches a maximum ridge value of 40 km in regions of strong shear and strain. Backward RD effectively identifies upstream source regions and convergence pathways. High RD values align closely with strong strain-rate gradients, indicating that particle separation and mixing are primarily driven by transition regions between flow structures rather than uniform high- or low-strain areas. In the 3D, the vertical domain was limited to the 4500–4600 m depth range above the seabed. The overall RD patterns remain broadly consistent with the 2D results, while the maximum RD increases to approximately 80 km due to the inclusion of vertical displacement and local vertical shear effects. Within the 4500–4600 m depth range, horizontal transport remains dominant, whereas vertical variations are comparatively weak, and particle trajectories exhibit only minor local differences. Compared with the 2D case, the deep-layer 3D RD distribution exhibits lower skewness values, suggesting a more spatially balanced particle separation pattern with reduced directional asymmetry. Multi scale quasi-3D RD analysis provides essential insights into material dispersion and convergence patterns, offering valuable information for evaluating transport pathways, potential pollutant spread, and ecological risks associated with deep-sea mining. Full article

A 51-year-old woman was admitted with a malodorous ulceration covering the whole area of both breasts, without visible breast contour or remnants of breast tissue. After excision of a skin nodule an invasive ductal carcinoma was diagnosed; grade-2, hormone receptor (HR)-positive, HER2-negative, Ki-67 at 25%. Computed tomography of the thorax and abdomen showed pulmonary and osseous metastases. Six cycles of systemic chemotherapy with epirubicin and cyclophosphamide at three-week intervals were administered, followed by endocrine therapy with letrozole. Almost four years later, palbociclib became available and it was added to the patient’s treatment. Loco-regional and distant disease control was achieved attaining maximum response at 11 months after initial diagnosis and since then the patient remains progression-free with good quality of life for more than eight years. This is to the best of our knowledge an extreme case of primary metastatic ulcerative breast cancer with complete local tissue destruction and markedly prolonged progression-free survival. As this is a single-case clinical observation, any conclusions have limited generalizability. Given the rarity of primary metastatic ulcerative breast cancer there are no specific evidence-based treatment guidelines available and published studies have high heterogeneity and low level of evidence, necessitating multidisciplinary approach on a case-by-case basis. Full article

Thin-slice high-resolution computed tomography (CT) has improved the detection of small pulmonary nodules, increasing the demand for minimally invasive diagnostic and therapeutic resection. While lobectomy with lymph node dissection remains the standard surgical approach for many patients with resectable non-small cell lung cancer, accumulating evidence supports sublobar resection for selected small, peripheral, and ground-glass-dominant lesions when sufficient margins are achievable. In thoracoscopic and robotic surgery, localization of nodules ≤10 mm or lesions located >5 mm from the pleural surface can be challenging, and failure to identify the target may lead to conversion, larger resection than intended, or prolonged operative time. Several localization strategies have been developed, including CT-guided percutaneous wire/coil/dye marking, bronchoscopic dye mapping, and virtual-assisted lung mapping (VAL-MAP), robotic-assisted bronchoscopic dye or fiducial localization, radiofrequency identification microtag systems (Surgical Real-Time FInger Navigation and Detection) that provide real-time depth information, and single-stage intraoperative CT-guided marking and resection in hybrid operating rooms. This review synthesizes representative evidence and published outcome ranges, and compares workflows, marker-to-lesion precision metrics, complication profiles, operational burden, and cost structures. We emphasize the practical contrast between two-stage and single-stage workflows, the access-route differences between transthoracic and transbronchial techniques, and the need to report localization-to-incision “time at risk”. We also present an expert-consensus decision algorithm aimed at facilitating tailored selection of localization strategies for modern minimally invasive thoracic surgery. Full article

Background: Image-guided thermal ablation has been used for the treatment of primary lung carcinoma but its use in the treatment of multiple lung carcinoma and effects on survival have not been well established. Objective: This study compares the long-term survival metrics for stage 1 single primary lung cancer and multiple primary lung cancer (MPLC) in patients treated with image-guided thermal ablation (IGTA). Methods: A retrospective institutional review included 37 NSCLC patients (mean age 71.6 ± 8.8 years) with ≥5 years follow-up. In total, 119 IGTA procedures were performed. Among patients with a single tumor (n = 14, 37.8%), each underwent a single ablation session. In contrast, patients with MPLC (n = 23, 62.2%) underwent 88 ablation sessions to treat 105 tumors. Data included demographics, tumor features, procedural details, safety, adverse events, and outcomes. Primary endpoints were 5-year overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS). Results: All ablations were completed successfully. Severe AEs occurred in 5.8% (7/119) of the ablations and were limited to pneumothorax requiring chest tube placement with hospitalization. At the time of ablation, individual nodules were staged at T1A = 46 (38.7%), T1B = 54 (45.4%), T1C = 16 (13.5%) and T2A = 3 (2.5%). Local recurrence was observed in 4/119 (3.3%) ablated tumors, all at stage T1B, and all were retreated with ablation. The 5-year OS was better for patients with MPLC at 85.6% compared to patients with a single tumor at 35.7% (HR = 0.14, p = 0.003, 95% CI: 0.037, 0.51). The 5-year OS for tumors based on T classification for T1A, T1B, TIC and T2A was 71.4%, 66.8%,66.7% and 0%. The 5-year PFS was 77.4% for patients with MPLC compared to 35.7% for patients with single primary lung cancer (HR = 0.25, p = 0.014, 95% CI: 0.084, 0.76). The 5-year CSS was 95.2% for patients with MPLC compared to 83.1% for patients with single primary lung cancer (HR = 0.21, p = 0.16, 95% CI: 0.018, 2.33). Conclusions: IGTA is an effective and safe treatment for patients with stage 1 single primary lung cancer and MPLC with limited local recurrence. Tumor size up to 3 cm did not have significant impact on survival. Overall survival was improved in patients with MPLC compared to those with single NSCLC. Clinical Impact: IGTA can be safely performed in patients with single primary lung cancer and MPLC, with limited local recurrence rate. Highlights: Key Findings: IGTA effectively treats patients with stage 1 single primary lung cancer and MPLC, with 3.3% recurrence, which can be retreated with ablation. The five-year OS was higher in patients with MPLC (85.6%) versus those with single lung cancer (35.7%, p = 0.003). OS by T classification: 71.4% for T1A, 66.8% for T1B, 66.7% for TIC, and 0% for T2A. Importance: IGTA effectively treats patients with single primary lung cancer and MPLC with low recurrence. Tumor size < 3 cm showed no impact on overall survival. Full article

Although Dupuytren’s disease (DD) and relapsed Clubfoot (RC) are clinically distinct conditions, both exhibit fibrotic tissue remodeling and contracture. This exploratory study investigated whether DD and RC share molecular features associated with fibroproliferative contracture. Pathological tissues from DD nodules and contracted tissues from RC together with their respective control tissues (n = 6/group), were analyzed using label-free quantitative proteomics. The analysis identified 12 significantly upregulated proteins shared between both pathological conditions relative to their controls (|log₂FC| ≥ 1, p ≤ 0.05). These proteins included structural, signaling and tensile stress ECM proteins. Functional enrichment and network analyses revealed partially overlapping dysregulation of pathways associated with ECM organization and degradation, ECM–receptor interaction, matricellular signaling and mechanobiological processes. In DD samples (n = 10), immunohistochemistry confirmed increased expression of fibrosis-associated proteins (α-SMA, TGF-β1, TGFBI, COL III, COL VI, and COL XII) (at least p < 0.01). Despite these similarities, differences in individual protein abundance and collagen crosslinking were observed between tissues. The findings suggest that DD and RC may share aspects of fibrotic ECM-remodeling despite differences in age, localization, and disease origin. These findings provide initial insights into shared ECM-remodeling processes, although their interpretation should consider the relatively small sample size and biological heterogeneity of the analyzed tissues. Full article

Background/Objectives: Lung cancer survival depends on early detection; however, in the Philippines, high radiologist workloads and the anatomical complexity of chest X-rays (CXRs) contribute to missed pulmonary nodules and false-negative diagnoses. This study aims to develop an enhanced deep learning model to improve nodule classification and localization sensitivity. Methods: We propose RNNet-MST, an extension of ResNet-50 that incorporates Multi-Scale Transformer blocks for global context modeling and a custom spatial attention mechanism for attention-based weak localization of disease-relevant regions. The model was trained and evaluated on the NODE21 chest X-ray dataset and compared with a baseline ResNet-50 using classification metrics, with attention maps used for weak localization analysis. Results: RNNet-MST demonstrated consistent improvements over the baseline ResNet-50 across evaluated metrics. Mean Nodule Recall improved from 88.02 ± 1.92% to 91.55 ± 1.41%, reducing false negatives. Mean Test Precision reached 90.46 ± 0.99%, and mean Nodule F1-Score improved to 90.99 ± 0.39%. On the isolated small-nodule subset, RNNet-MST achieved a 12.3% improvement in sensitivity over the baseline. Conclusions: The integration of multi-scale transformer features improved classification sensitivity, while the attention mechanism provided weak localization cues that aligned more closely with annotated nodule regions than the baseline. RNNet-MST shows potential as a diagnostic support tool, warranting further validation on larger and more diverse clinical datasets to reduce perceptual errors and facilitate early lung cancer detection in resource-constrained settings. Full article

Lung cancer rates are the highest among cancers, making it the leading cause of death worldwide. With advances in new technologies and diverse diagnostic methods, Computer-Aided Diagnosis Systems (CADx) have improved pulmonary nodule classification with notable accuracy and speed. However, limited data availability and privacy concerns remain significant challenges, in addition to the reported rates of false negatives and false positives. This work aims to develop an approach based on collaborative feature extraction between multiple centers, thus achieving data efficiency and diversity while ensuring privacy and reducing false positives and false negatives. This work proposes a new explainable feature-based split learning approach using diverse Computed Tomography (CT) scan datasets to evaluate data diversity and privacy. It adopts a split ResNet-50 architecture on the client side for feature extraction. On the server side, a hybrid 2D-CNN combined with an attention mechanism is used for final classification and decision-making. The architecture was evaluated using two ablation studies based on ConvNeXt-Tiny and EfficientNetB0. In addition, the model was tested on two external datasets to assess its robustness and generalizability, and with Local Interpretable Model-agnostic Explanations (LIMEs) and Grad-CAM to assess trustworthiness. This proposed approach showed an accuracy and F1-score of 99.38%, with a 1.23% false negative rate and zero false positives. Moreover, when tested on totally unseen datasets, the approach achieved an accuracy and an F1-score of 99.28% on the first dataset, with 1.24% false negatives and 0% false positives. In addition, when tested on the second dataset, the results indicate an ability to generalize, with 95.74% accuracy, with false negative and false positive rates of 7.07% and 1.41%, respectively. Full article

Salivary adenoid cystic carcinoma (SACC) is a malignant salivary gland neoplasm characterized by aggressive local invasion and a marked propensity for metastasis. However, the role of MEOX1 in SACC progression remains poorly defined. In this study, we examined the effects of MEOX1 overexpression on the malignant behavior of SACC cells in vitro and in vivo. Human SACC-83 and SACC-LM cells were transduced with lentiviral vectors encoding MEOX1 or an empty vector control, and cell proliferation, migration, invasion, and cell cycle distribution were assessed using CCK-8, wound healing, Transwell, and flow cytometric assays, respectively. RNA sequencing was performed to characterize transcriptional changes associated with MEOX1 overexpression. In vivo, tumor growth was evaluated in BALB/c nude mice bearing subcutaneous xenografts, and pulmonary metastatic colonization was assessed using a tail vein injection model. MEOX1 overexpression reduced the proliferation, migration, and invasion of SACC cells in vitro and increased the G2/M phase fraction. In xenograft models, MEOX1-overexpressing cells formed smaller tumors and showed lower Ki67 staining than control cells. In the experimental lung metastasis model, mice injected with MEOX1-overexpressing cells developed fewer pulmonary metastatic nodules. RNA-seq identified 588 differentially expressed genes associated with MEOX1 overexpression, with enrichment in pathways including cytokine–cytokine receptor interaction, Toll-like receptor signaling, and G protein-coupled receptor signaling. Together, these findings indicate that enforced MEOX1 expression is associated with reduced malignant phenotypes in SACC models and with transcriptomic alterations in pathways related to immune response, G protein-coupled receptor signaling, and DNA damage response. Full article

Cytokinin (CK) is a central regulator of plant development, yet its roles cannot be understood fully without considering how CK signaling was assembled during evolution and redeployed in different physiological contexts. In this review, we examine how prokaryotic two-component modules were elaborated into the land–plant CK system and how this system now integrates biosynthesis, transport, receptor selectivity, and feedback control to shape developmental and symbiotic outcomes. We argue that three recurring interpretive dimensions are especially useful for organizing current evidence: compartmentalized CK pools, context-dependent decoding of local CK availability, and the coupling of local CK responses to whole-plant nutrient status. These dimensions help organize current observations on why CK effects in arbuscular mycorrhiza (AM) are often conditional and readout-dependent, whereas evidence from legume–rhizobium symbiosis supports a more direct role for CK in cortical competence, nodule organogenesis, and autoregulation of nodulation. Rather than treating CK as a generic positive regulator of symbiosis, we propose that it functions as a spatially partitioned and nutritionally gated integrator whose outputs depend on cell type, developmental stage, transport route, and resource context. We conclude by highlighting key mechanistic gaps—particularly in transporter-resolved CK partitioning and systemic integration—and by outlining experimentally testable priorities for translating CK biology into crop improvement. Full article

This narrative review evaluates the current role of interventional radiology in the diagnosis and treatment of parathyroid disorders. In patients with biochemically confirmed hyperparathyroidism but inconclusive or discordant preoperative localization imaging, image-guided interventions can help establish a diagnosis that can alter management. This review outlines the current diagnostic and therapeutic modalities for the study of parathyroid pathology from the interventional radiologist’s perspective, highlighting novel techniques and their growing clinical adoption. The combination of ultrasound-guided fine-needle aspiration biopsy and measurement of parathyroid hormone (PTH) in the needle washout fluid can improve diagnostic specificity by providing biochemical evidence of parathyroid tissue. This is particularly useful for lesions that are difficult to differentiate from thyroid nodules or cervical lymph nodes based solely on imaging characteristics. Despite this, no widely accepted cut-off washout PTH level has yet been established. Due to the differences in assay techniques and laboratory procedures, results should be interpreted in conjunction with clinical findings and concomitant biochemical parameters. Ultrasound-guided thermal ablation techniques, especially radiofrequency and microwave ablation, have recently been reported as minimally invasive alternatives or adjuvants to surgery in appropriately selected patients. Evidence supporting parathyroid embolization is limited, but it may be considered a potential salvage option for persistent or recurrent disease. Given that most of the current evidence is derived from retrospective case series, multicenter prospective studies for technical standardization and long-term outcomes evaluation are clearly needed. Full article

With increasing environmental pollution and a high incidence of respiratory infections, pulmonary nodules (PN) are being detected more frequently. Although most are benign, they are often accompanied by chronic inflammation and localized fibrosis, which may predispose patients to progression toward idiopathic pulmonary fibrosis (IPF). However, the biological relationship between benign pulmonary nodules (BPNs) and IPF remains poorly understood. Therefore, this study aims to investigate the shared molecular mechanisms and identify potential biomarkers linking BPN and IPF, with the goal of elucidating the pathogenic transition from BPN to IPF. In this study, microarray data from GEO datasets were systematically analyzed to explore shared molecular mechanisms, immune infiltration characteristics, and potential early intervention strategies linking BPN and IPF. Differential expression analysis, protein–protein interaction (PPI) networks, weighted gene co-expression network analysis (WGCNA), and integrative machine learning approaches identified MME and ANKRD23 as key hub genes associated with the transition from BPN to IPF. Both genes demonstrated strong diagnostic performance, with Area Under the Curve (AUC) values exceeding 0.7, and were significantly correlated with immune cell infiltration, particularly effector memory CD8⁺ T cells. Functional enrichment and gene set enrichment analyses indicated that these genes were mainly involved in immune-related processes in BPN, while in IPF, ANKRD23 was linked to cytoskeletal organization and genomic stability, and MME was enriched in profibrotic pathways such as TGF-β signaling. The diagnostic value of these biomarkers was further validated in a bleomycin-induced IPF mouse model using quantitative polymerase chain reaction (qPCR). In addition, drug–gene interaction prediction and molecular docking analyses highlighted several naturally derived compounds with favorable binding affinity and anti-inflammatory properties, among which folic acid, curcumin, and arbutin emerged as promising candidates for safe early intervention. Collectively, these findings identify MME and ANKRD23 as potential biomarkers for early identification of BPN patients at risk of developing IPF and provide a theoretical basis for early diagnosis and targeted preventive strategies. Full article