Search Results (8,959)

Immune checkpoint inhibitors (ICIs) are now being introduced into perioperative treatment for several solid tumors. This strategy is usually explained by tumor reduction before surgery or by the elimination of minimal residual disease (MRD) after surgery. However, these explanations may not be sufficient to understand why the timing of ICI treatment, especially before lymph node (LN) removal, is important. In this review, we discuss tumor-draining lymph nodes (tdLNs) from two different aspects. tdLNs are anatomical routes for regional and distant metastasis, but they are also sites where tumor antigens are presented and tumor-specific T cell responses are generated. In particular, preclinical and translational studies suggest that tdLNs may maintain stem-like or progenitor-exhausted T cells (TPEX) that can respond to PD-1 blockade and supply more differentiated exhausted T cells to tumor sites. However, current clinical trials of perioperative ICIs demonstrate therapeutic benefit in specific diseases and regimens, but do not directly establish tdLN preservation or tdLN-resident TPEX maintenance as the decisive mechanism of efficacy. We therefore present the tdLN-reservoir model as a hypothesis-generating framework rather than as a clinically validated basis for modifying lymph node management. We also discuss the possible roles of neoadjuvant and adjuvant ICI in relation to antigen flow, minimal residual disease, metastatic-site draining LNs, postoperative lymphatic dysfunction, and future immune-guided clinical trials. Importantly, current evidence does not support altering standard lymph node surgery or radiotherapy solely to preserve putative tdLN immune-reservoir function. Full article

Systematic field data on adjuvant-amended microbial-derived pesticides against L. pratensis in arid, high-ultraviolet cotton regions remain scarce. This study systematically evaluated the laboratory toxicity and field efficacy of four kinds of microbial-derived pesticides (abamectin, emamectin benzoate, B. bassiana, and M. anisopliae) and their combinations with adjuvants against L. pratensis in Xinjiang cotton fields. As a comprehensive regional study, this work elucidates the differential enhancement patterns of d-limonene and mineral oil on antibiotic insecticides and entomopathogenic fungi, providing targeted field data for pesticide reduction strategies. The laboratory toxicity of seven microbial-derived pesticides was determined using the leaf-tube residual film method. Four effective agents were selected and combined with d-limonene or mineral oil for field efficacy trials. Abamectin and emamectin benzoate exhibited rapid and high insecticidal activity, with 48 h LC₅₀ values of 1.198 mg/L and 3.424 mg/L, respectively. The two entomopathogenic fungi exhibited slower insecticidal activity than the chemical insecticides but maintained relatively stable control effects throughout the observation period. In field trials, when abamectin or emamectin benzoate was applied at a 30% reduced rate in combination with mineral oil or d-limonene, the control efficacy was equivalent to or higher than that of the full-rate application of the pesticide alone. The treatment of abamectin (4.20 g a.i./hm²) plus mineral oil achieved the highest control efficacy (89.24%) at 3 days post-treatment. For B. bassiana and M. anisopliae, reduced-rate adjuvant-amended treatments showed numerically higher initial and residual efficacy than the full-rate single-agent fungal treatments. The treatment of M. anisopliae (7.35 × 10¹² spores/hm²) plus d-limonene reached 70.50% efficacy at 7 days post-treatment, which was significantly higher than that of the full-rate fungal treatment alone. No phytotoxicity symptoms were observed on cotton plants. Under the tested conditions, the rational combination of microbial-derived pesticides with appropriate adjuvants demonstrates the potential for a 30% reduction in pesticide dosage while maintaining or improving field efficacy, providing region-specific reference for the sustainable management of L. pratensis in Xinjiang cotton fields. Full article

Glioblastoma recurrence remains nearly inevitable despite maximal resection and adjuvant therapy, with most relapses occurring within or adjacent to the original tumor site. Conventional MRI underestimates tumor infiltration beyond contrast-enhancing margins, limiting preoperative identification of peritumoral regions at higher risk of recurrence. We developed a radiomics-based machine-learning framework to generate preoperative spatial recurrence risk maps from routine MRI. Preoperative T1-weighted contrast-enhanced and FLAIR images from 79 patients with glioblastoma were analyzed. The cohort was divided at the patient level into a training set (n = 63) and an independent test set (n = 16). Using a balanced spatial ROI sampling strategy, local radiomic features were extracted from tumor and peritumoral regions and linked to recurrence sites identified on follow-up MRI acquired after at least 12 months after surgery. A CatBoost classifier achieved an AUC of 0.743 and a recall of 0.856 on an independent test set. The framework also generated preoperative probability maps that showed qualitative spatial correspondence with observed recurrence locations. These findings indicate that radiomic patterns from standard preoperative MRI may contain spatially localized information associated with future relapse. The proposed approach supports the feasibility of preoperative spatial risk stratification and may provide useful information for surgical planning and subsequent treatment strategies. Full article

Introduction: Uterine leiomyosarcoma (uLMS) is a rare, highly aggressive malignancy arising from the smooth muscle tissue of the uterine wall. It typically presents with abnormal vaginal bleeding, pelvic pain, or a pelvic mass. In rare instances, symptoms may result from local invasion or metastasis. We report a case of uLMS initially diagnosed following colonic perforation due to direct tumor invasion, accompanied by a comprehensive narrative review of the literature on the incidental identification of uterine sarcomas during emergency general surgery to further emphasize the diagnostic challenges, treatment approaches, and need for individualized care in these complex cases. Case Presentation: A 45-year-old woman presented to the Emergency Department with acute abdominal pain of several hours’ duration, in the absence of other associated symptoms. An emergency exploratory laparotomy was performed, revealing feculent peritonitis secondary to sigmoid colon rupture, resulting from local invasion by a large uterine mass. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was undertaken, followed by en bloc resection of the sigmoid colon, appendectomy and construction of a terminal colostomy. Her postoperative course was uneventful, and she was discharged on postoperative day eight. Histopathological examination of the specimen revealed a high-grade uterine leiomyosarcoma. Following evaluation by a multidisciplinary oncology board, the patient received adjuvant chemotherapy. Methods and Results: A narrative review of the literature was performed to identify cases of uterine sarcomas incidentally diagnosed during emergency surgery performed by general surgeons. Including the present case, six cases were identified. Most patients presented with acute abdomen mimicking gastrointestinal pathology, with diagnosis established intraoperatively or postoperatively. Definitive surgical management was achieved during the initial emergency procedure in all cases. Conclusion: Although exceptionally rare, uterine sarcoma should be considered in the differential diagnosis of acute abdomen in female patients undergoing emergency surgery. Awareness of this atypical presentation, the appropriate diagnostic approach, real-time intraoperative adaptability, and individualized multidisciplinary management are essential for ensuring appropriate surgical management and optimizing patient care. Full article

Peripheral facial palsy is often attributed to idiopathic Bell’s palsy, but secondary structural causes should be considered when local red flags are present. A 61-year-old man with a 40-pack-year smoking history and former betel quid chewing presented with a verrucous-appearing mass involving the left oral commissure and buccal mucosa, intermittent purulent discharge from the lesion, progressive left facial swelling, and ipsilateral lower-motor-neuron facial palsy with lagophthalmos. Magnetic resonance imaging demonstrated a left buccal/oral-cavity lesion with ipsilateral parotid duct obstruction. He underwent tracheostomy, wide excision, left supraomohyoid neck dissection, and radial forearm free-flap reconstruction. Pathology confirmed squamous cell carcinoma, pT2N0, cM0 (stage II), with perineural invasion; surgical margins were negative, and lymphovascular invasion was not identified. At follow-up, wound healing was satisfactory and purulent discharge had resolved, but lower-motor-neuron facial palsy persisted; adjuvant radiotherapy was recommended. This case emphasizes that lower-motor-neuron facial palsy with an oral mass, purulent discharge, facial swelling, or salivary-duct obstruction should prompt careful oral examination and head-and-neck imaging. Full article

Alzheimer’s disease (AD) is a severe neurodegenerative disorder whose pathological progression is closely associated with the reduced binding affinity of apolipoprotein E ε4 (ApoE4) for amyloid-β (Aβ), which impairs Aβ clearance. Existing computational molecular design approaches are largely limited to single-target optimization and therefore lack the capacity for synergistic dual-target modulation. Herein, we proposed EvoPlay-MuZero, a hybrid computational framework incorporating a dual-peptide bridging (DPB) strategy. The framework adopted latent-state planning in MuZero reinforcement learning to enhance exploration and sequence-generation efficiency in high-dimensional sequence spaces. For the first time, it enabled the automated design of bispecific peptides targeting ApoE4 and Aβ, thereby forming a synergistic molecular bridge via a flexible linker. A full-process pipeline for structural and energetic evaluation was established by integrating AlphaFold3 and PDBePISA. Benchmark experiments on the 1SSC, 2CNZ, and 3R7G datasets demonstrated that EvoPlay-MuZero substantially outperformed the vanilla EvoPlay in convergence speed and the yield of valid generated sequences. Specifically, the optimal DPB molecule (15 × 25-3A) achieved a calculated interfacial solvation energy score (${\Delta }^{i}G$) of −29.5 kcal/mol, demonstrating substantially enhanced interface-stabilization properties compared to the native baseline control. This study provides a novel molecular intervention strategy for adjuvant therapy in AD and highlights the considerable potential of reinforcement learning in multi-target drug design. Full article

Breast implant illness (BII) describes a constellation of systemic symptoms reported by some patients after breast implantation, including fatigue, cognitive dysfunction, arthralgia, myalgia, sicca symptoms, skin manifestations, and mood disturbance. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) provides a broader conceptual framework in which silicone and other biomaterials may contribute to immune dysregulation in susceptible individuals, although causality remains controversial and no validated diagnostic biomarker exists. This narrative review summarizes current evidence on BII and implant-related ASIA, focusing on epidemiology, clinical presentation, biological plausibility, diagnostic evaluation, explantation outcomes, and implant-associated complications. Proposed mechanisms include chronic foreign-body inflammation, silicone gel bleed and particulate migration, macrophage activation, inflammasome signaling, cytokine dysregulation, bacterial biofilms and biofilm-derived metabolites, adaptive immune activation, autoantibody formation, and host genetic susceptibility. The review also distinguishes BII/ASIA-like presentations from breast implant-associated anaplastic large cell lymphoma and other rare implant-associated malignancies. A practical multidisciplinary diagnostic and management algorithm is proposed to support structured assessment, red-flag triage, exclusion of alternative diagnoses, patient-centered counseling, and individualized decision-making regarding medical management and explantation. Full article

Oral squamous cell carcinoma (OSCC) accounts for most head-and-neck cancers, and effective biological adjuvants remain limited. Gingival mesenchymal stem cells (GMSCs) exhibit anti-tumour paracrine activity, but the underlying molecular mechanisms and their relevance in patient cohorts remain incompletely understood. Consensus apoptosis–reactive oxygen species (ROS) effectors were identified through integrated transcriptomic analyses of TCGA-HNSC and three GEO cohorts. Candidate genes were evaluated in primary OSCC cells exposed to GMSC-conditioned medium or indirect Transwell co-culture. Findings were further examined using patient-cohort validation, single-cell ligand–receptor analysis, pathway and transcription-factor activity inference, and drug-repurposing approaches. Computational analyses identified an apoptosis–ROS network centred on BAX, BCL2, CASP3, CASP9, NOX1, and GPX1. Indirect GMSC co-culture reduced intracellular ROS, increased early apoptosis, and induced G2/M accumulation, whereas conditioned medium produced inconsistent effects, suggesting a requirement for live bidirectional paracrine signalling. BAX was the only consistently up-regulated effector. The axis demonstrated concordant differential expression across independent HPV-negative OSCC cohorts but was not independently prognostic under leakage-free cross-validation or external validation. Pathway analyses supported ROS suppression, apoptosis activation, and altered stromal–tumour communication. Drug-repurposing analyses identified HSP90 inhibitors and the FDA-approved TOP2 inhibitor mitoxantrone as candidate therapeutic agents. GMSC paracrine activity targets a biologically interpretable apoptosis–ROS axis in OSCC that is reproducibly expressed across patient cohorts but does not constitute an independent prognostic biomarker. The identified therapeutic candidates warrant further experimental investigation. Full article

The 27th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Calgary, Alberta, on 26–27 September 2025. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with colorectal cancer. Specialists from the fields of medical and radiation oncology, pathology, surgery, and a family physician in oncology participated in presentations and discussions for the purpose of developing the recommendations presented here. This consensus statement addresses recent advances in the management of colorectal cancer in a Western Canadian context, with respect to adjuvant exercise, as per the CHALLENGE trial, adjuvant Aspirin and PI3K testing, as per the ALASCCA trial, adjuvant immunotherapy, as per the ATOMIC trial, the use of encorafenib and an EGFR inhibitor with chemotherapy, as per the BREAKWATER trial, the use of combination immunotherapy as per the CHECKMATE 8HW trial and optimal strategies for omitting radiation and non-operative management of non-metastatic rectal cancer. Full article

Boar taint is a persistent challenge in pork production, caused primarily by the accumulation of androstenone and skatole in adipose tissue. It affects 5–40% of uncastrated male pigs and is perceived negatively by a substantial proportion of consumers, with skatole detectable by almost all individuals. Traditional surgical castration effectively prevents boar taint but is increasingly criticized on animal welfare grounds. Immunocastration using gonadotropin-releasing hormone (GnRH) vaccines has emerged as a promising alternative, providing reversible suppression of reproductive function while maintaining growth efficiency. This review integrates current knowledge on the biochemical basis of boar taint, evaluates the performance of commercial vaccines such as Improvac^® and GonaCon^®, and examines economic, regulatory, and consumer factors influencing adoption. Immunocastration presents limitations due to variability in immune responses, the need for multiple doses, and challenges related to public perception. To address these challenges, intensive research is underway on single-dose formulations, precision adjuvants, and advanced delivery technologies, all of which are expected to drive the next generation of immunocastration vaccines. Full article

Global elimination of hepatitis C virus (HCV) infection requires not only direct-acting antivirals (DAAs) but also the development of a highly effective prophylactic and/or therapeutic vaccine. Background/Objectives: Our aim was to optimize the composition of the candidate vaccine against HCV by combining recombinant non-structural proteins and a DNA construct with a complex adjuvant. Methods: C57BL/6 and DBA/2J mice were immunized three times at 2-week intervals using different schemes. The viral antigens consisted of a mixture of NS3, NS5A, and NS5B proteins and/or recombinant DNA expressing NS3-NS5B polyprotein. As adjuvants, a complex adjuvant, a mixture of Polymuramil^® and Pyrogenalum^® (NOD1/NOD2 and TLR-4 agonists), or a CpG ODN adjuvant (TLR-9 agonist) were used. Results: The most efficient regimen was three subcutaneous administrations of the combined DNA, recombinant protein components, and a new complex adjuvant. This scheme elicited a robust immune response, characterized by high antibody titers, enhanced antigen-specific lymphocyte proliferation, and significant interferon-gamma (IFN-γ) secretion in both mouse lines. Furthermore, the complex adjuvant outperformed CpG ODN in stimulating both humoral and cellular immunity against the HCV antigens. The vaccine composition stimulated the formation of CD4⁺ memory T cells and decreased the relative frequences of suppressive Treg and MDSCs. Conclusions: The presented candidate vaccine induces a strong immune response to HCV proteins. The next step would be to validate the protective effect in cell culture and animal models. This would one the path to preclinical studies of this vaccine composition. Full article

Dengue fever, a rapidly spreading mosquito-borne viral disease, poses a major global health issue, particularly in tropical and subtropical regions. The absence of a universally effective vaccine against all four dengue virus serotypes necessitates continued exploration of novel vaccine strategies. This study evaluated a PrM-derived multiple antigenic peptide (MAP) vaccine candidate in BALB/c mice. Molecular docking analyses predicted favourable interactions of the selected PrM-derived B-cell epitope with both human (human BCR Fab region PDB ID: 5IFH) and mouse (mouse BCR PDB ID: 8EMA) B-cell receptors, supporting its antigenic potential. ChemSketch was used to develop the PrM–MAP vaccine construct, which was then commercially synthesized. Mice received single, double, and triple booster doses of the vaccine, while control groups received either PBS or adjuvant alone. Humoral immune responses were measured by ELISA, and safety was evaluated through in vitro cytotoxicity assays on HEK293 cells and the in vivo histopathological examination of major organs. Mice immunized with a single booster dose produced significant levels of PrM-specific antibodies compared to subsequent booster doses, suggesting variability in the humoral response elicited. Optimal coating concentrations in ELISA demonstrated the importance of antigen concentrations in the sensitivity of the assay. The safety evaluation indicated high cell viability, up to 150 µg/mL of PrM–MAP, in HEK293 cells, and an absence of significant histopathological damage in treated animals. The PrM–MAP vaccine construct elicited a detectable humoral immune response while demonstrating a high safety profile in vitro and in vivo. These findings indicate the potential of MAP-based vaccine platforms as promising candidates for further development against the dengue virus. Full article

Background: Liver transplantation is the standard treatment for children with advanced hepato-blastoma when complete resection is not feasible. However, transplantation may be contraindicated because of persistent metastatic disease, severe comorbidities, poor clinical condition, or donor-related limitations. Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has emerged as a potential rescue strategy in highly selected patients. This study evaluated the feasibility, safety, and oncological outcomes of ALPPS in pediatric hepatoblastoma. Methods: A retrospective analysis was performed of four consecutive children with advanced hepatoblastoma who underwent classical ALPPS between 2013 and 2025 in two specialized centers. Patient characteristics, indications, future liver remnant (FLR) volumetry, perioperative outcomes, complications, and oncological follow-up were reviewed. Results: The median age at surgery was 22 months. In all patients, the FLR was considered insufficient for one-stage hepatectomy, leading to ALPPS. Rapid hypertrophy of the FLR was achieved in every case, allowing completion of the second stage after a median of 8.5 days (range, 7–11 days). FLR volume increased by 50–89% following the first stage. Despite successful liver hypertrophy, outcomes remained poor in three patients. One patient died intraoperatively from venous air embolism during the second stage, two died from disease recurrence despite aggressive multimodal treatment, and one remains in complete clinical and radiological remission following ALPPS and adjuvant chemotherapy. Conclusions: ALPPS reliably induces rapid FLR hypertrophy and may provide a potentially curative option for carefully selected children when liver transplantation is not feasible. However, its substantial perioperative risk and generally unfavorable oncological outcomes support its role only as a rescue procedure in experienced pediatric hepatobiliary centers. Further multicenter studies are needed to better define indications and patient selection. Full article

Background: Left ventricular (LV) dysfunction is a clinically important complication of anthracycline- and trastuzumab-based treatment in breast cancer. Inflammatory pathways may contribute to cancer therapy-related cardiac dysfunction, and the CD40/CD40 ligand (CD40L) axis has been implicated in vascular inflammation and myocardial injury. This study assessed longitudinal changes in CD40 and CD40L during adjuvant treatment and their association with LV dysfunction. Methods: Twenty-eight women with operable breast cancer receiving adjuvant anthracycline-based chemotherapy with or without trastuzumab were prospectively evaluated. Blood samples were collected at baseline, 6 months, and treatment completion at 15 months to measure CD40 and CD40L. Cardiac function was assessed by transthoracic echocardiography, including left ventricular ejection fraction and global longitudinal strain, at baseline and every 3 months. Repeated-measures analysis of variance examined temporal biomarker changes and interactions with LV dysfunction. Results: Participants had a mean age of 52.6 ± 10.7 years and a mean BMI of 25.8 ± 4.8 kg/m²; 64% were postmenopausal, 76% had HER2-positive disease, and 79.3% received radiotherapy and trastuzumab. During follow-up, 15 patients (53.6%) developed LV dysfunction. CD40 levels remained stable overall (p = 0.31), whereas CD40L increased significantly over time (p < 0.001). Baseline CD40 did not differ by LV dysfunction status (p = 0.79). However, CD40 showed a significant time-by-LV dysfunction interaction (p = 0.022), increasing late in patients with LV dysfunction and declining in those without it. CD40L showed no such interaction (p = 0.85). Conclusions: In this small exploratory cohort, CD40 demonstrated differential longitudinal patterns according to subsequent LV dysfunction, whereas CD40L increased over time without a clear association with LV dysfunction. These findings should be interpreted as hypothesis-generating and require validation in larger prospective cohorts. Full article

The ubiquitin ligase protein tripartite-motif containing 56 (TRIM56) positively regulates Toll-like receptor-3 (TLR3) signaling by forming a complex with Toll-Interleukin-1 receptor domain-containing adapter protein inducing interferon (IFN)-beta (TRIF), independent of its E3 ligase activity. Whether TRIM56 modulates other TLR pathways in innate antiviral immunity, however, is unclear. Herein, we show ectopic expression of TRIM56 augments activation of IFN regulatory factor-3 (IRF3)-dependent promoters following stimulation by lipopolysaccharide (LPS) in HEK293-TLR4-MD2-CD14 cells while leaving activation of NF-κB-dependent promoter unaffected, suggesting TRIM56 specifically promotes immune signaling through the TLR4-TRIF axis but not the MYD88 arm downstream of this TLR. Confirming its impact on endogenous antiviral responses in immune sentinel cells naturally harboring the TLR4 pathway, we demonstrated enforced expression of TRIM56 enhanced LPS-induced expression of IFN-beta and IFN-stimulated genes (ISGs) and establishment of an antiviral state in bone marrow-derived macrophages. Importantly, depletion of endogenous TRIM56 impaired LPS-induced antiviral gene expression and cellular antiviral defense. Altogether, these data add to understanding of the role of TRIM56 in TLR-mediated innate immune responses. Given that TRIM56 is an ISG and that many immune adjuvants and some viral proteins activate TLR4, the findings of this study could have implications for designing immunotherapies, especially those against viral infections. Full article