Search Results (11,150)

Introduction: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers, with a subset progressing to locally advanced (laSCC) or metastatic (mSCC) stages. The introduction of anti-PD1 immunotherapy has transformed treatment, but real-world data remain limited, particularly in immunosuppressed patients. Methods: This single-centre, retrospective study included 189 patients with advanced cSCC treated between 2012 and 2022. Demographic, clinical, and treatment data were analyzed to assess clinical management and outcomes before and after the introduction of anti-PD1. Results: Among the 189 patients, 72.5% were male, with a median age of 79 years. Overall, 86 patients presented with laSCC and 103 with mSCC. In 100 patients, a preceding primary cSCC was documented, and its complete resection (R0) was associated with significantly better overall survival (OS) after diagnosis of advanced disease (p < 0.001). Immunosuppressed patients, including organ transplant recipients and those with chronic lymphocytic leukemia (CLL), had significantly reduced OS (p = 0.017 and p = 0.0059, respectively). First-line treatment prior to 2018 predominantly involved surgery and radiotherapy. Following the introduction of anti-PD1 therapy, its use increased rapidly in both first- and second-line settings. From 2018 onward, the number of advanced cSCC cases discussed at the multidisciplinary tumorboard increased approximately threefold. Median OS was significantly longer for mSCC patients treated in the post-2018 era (p = 0.025), while the survival disadvantage of CLL patients compared to non-CLL patients widened, suggesting limited benefit from advances in systemic therapy in this subgroup. Best overall response to first-line anti-PD1 correlated significantly with OS, with complete responders achieving a 1-year progression-free survival of 83.3%. Conclusions: The introduction of anti-PD1 has demonstrated improved survival outcomes in advanced cSCC, though significant challenges remain for immunosuppressed patients, particularly those with CLL and solid organ transplant recipients. Future research should focus on optimizing treatment for these high-risk groups, therapeutic sequencing, and the role of perioperative (neoadjuvant and adjuvant) immunotherapy strategies. Full article

Background: Although the tumor coagulome interacts with the tumor immune microenvironment (TME) in solid tumors, its role in osteosarcoma (OS) remains uncharacterized. This study aimed to delineate this transcriptomic interplay and identify potential prognostic targets. Methods: This study was performed with bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and clinical phenotype data. Bioinformatic approaches were employed at the transcriptomic level to investigate the impact of the tumor coagulome on the TME and prognosis in OS. We validated the above findings using immunohistochemistry and immunofluorescence. Results: The activity of a coagulation-related transcriptional signature was found to correlate with the degree of malignancy in OS. Its activity score demonstrated predictive value for OS prognosis, with a maximum area under the curve (AUC) of 0.802. scRNA-seq analysis indicated that inflammatory cancer-associated fibroblasts (iCAFs) and APOE⁺ macrophages were predominantly enriched in the high coagulation score subgroup. Our data further suggest that iCAFs may facilitate the M2 polarization of APOE⁺ macrophages via the C3–C3AR1 axis, potentially contributing to poorer clinical outcomes in patients with OS. Conclusions: These findings imply that within a high coagulation-related transcriptional score group, the interaction between iCAFs and APOE⁺ macrophages, likely mediated by the C3–C3AR1 axis, could facilitate OS progression. Consequently, the C3–C3AR1 signaling pathway might represent a promising target for future therapeutic strategies and coagulome monitoring in OS. Full article

The Kalasayi tungsten deposit is a medium-sized quartz-vein scheelite tungsten deposit in the Western Tianshan, Central Asia Orogenic Belt. The Kalatawu pluton yielded Late Carboniferous zircon U–Pb ages (313.99–310.32 Ma), and molybdenite Re–Os dating gives an isochron age of 302.3 ± 1.8 Ma for W mineralization, indicating an ~8–12 Myr magmatic-hydrothermal system. Whole-rock geochemistry classifies the pluton as aluminous A₂-type granite formed in a post-collisional extensional setting. Zircon Hf isotopes (εHf(t) = +2.8 to +8.3) suggest a mixed juvenile lower crust source with mantle input. In situ LA-ICP-MS scheelite trace element analysis and REE geochemistry distinguish two populations: proximal Group I (high Mo, low Sr, low ΣREE, right-inclined REE patterns) is precipitated from oxidizing magmatic fluid, and distal Group II (low Mo, high Sr, high ΣREE, flat REE patterns, strong positive Eu anomalies) records reduced, mixed fluid with intense fluid–rock interaction. Fluid inclusion data show decreasing temperature and salinity proximally to distally, confirming that mixing of magmatic and meteoric water led to cooling and pH increase that caused W precipitation. A four-stage metallogenic model is proposed for a post-collisional extensional setting, providing robust evidence for A-type granite-related, multi-stage W mineralization and establishing exploration indicators for the southwestern Central Asia Orogenic Belt. Full article

Background/Objectives: Gastrointestinal (GI) bleeding in patients with malignancy is frequently refractory to endoscopic and conservative management. Transarterial embolization (TAE) is an established treatment option, but whether the presence of contrast extravasation on preprocedural computed tomography (CT) influences outcomes remains unclear. This study aimed to evaluate the efficacy and safety of TAE for malignancy-related GI bleeding in patients with and without CT-detected contrast extravasation. Methods: From January 2012 to December 2023, 40 consecutive patients who underwent TAE for malignancy-related GI bleeding were retrospectively analyzed and categorized into CT extravasation (n = 25) and CT no-extravasation (n = 15) groups based on preprocedural CT findings. Technical success, clinical success, 30-day mortality, overall survival (OS), and procedure-related complications were compared between groups, and factors associated with OS were evaluated using Cox regression. Results: The technical and clinical success rates were 100% (40/40) and 82.5% (33/40), respectively. Clinical success did not differ between the CT extravasation and no-extravasation groups (84.0% [21/25] vs. 80.0% [12/15]; p = 0.747). Two of 40 patients (5.0%) died within 30 days, one in each group (p = 0.708). OS did not differ significantly (log-rank p = 0.707; median, 147 vs. 187 days). A shock index > 1 was independently associated with worse OS (hazard ratio, 2.308; 95% confidence interval, 1.071–4.972; p = 0.033). No major procedure-related complications occurred. Conclusions: TAE achieved high technical success and comparable short-term clinical outcomes in patients with and without CT extravasation. Hemodynamic instability, rather than CT extravasation, was independently associated with OS. Full article

Background: Glioblastoma (GBM) shows marked heterogeneity in overall survival (OS), yet robust radiological prognostic markers remain limited. The prognostic value of peritumoral edema and tumor location remains uncertain. Objective: To evaluate whether peritumoral edema, tumor burden, and spatial tumor distribution predict OS using automated MRI analysis and Brain-Grid-based topographical mapping. Methods: In this retrospective study, preoperative T1-contrast-enhanced and T2-FLAIR MRI sequences from 271 patients with IDH-wildtype GBM were analyzed using automated segmentation (Raidionics). Tumor and edema volumes, edema-to-tumor ratio (ETR), and voxel-wise infiltration patterns were extracted. Location was mapped using the Brain-Grid system. Survival was assessed using Kaplan–Meier and multivariable Cox regression adjusted for age and tumor volume, with correction for multiple testing. Results: In multivariable analysis, only age remained a conventional independent predictor of OS (HR 1.03, p < 0.001). Tumor volume, edema volume, and ETR were not associated with survival. In contrast, Brain-Grid analysis identified two centrally located subcortical voxel regions that remained significantly associated with shorter OS after full adjustment and multiple testing correction. Total number of infiltrated voxels showed no prognostic value. Conclusions: Spatially defined subcortical infiltration patterns, rather than global tumor or edema burden, independently stratify survival in GBM. These findings highlight the prognostic relevance of voxel-level tumor topography and support further validation of Brain-Grid-based imaging biomarkers. Full article

Background: Cetuximab-based therapies continue to play an important role in the management of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) despite the increasing use of immunotherapy. However, data regarding treatment outcomes and prognostic factors remain limited. This study aimed to evaluate treatment outcomes and prognostic factors associated with survival in patients with R/M HNSCC treated with cetuximab-based regimens. Methods: This retrospective single-center cohort study included patients with recurrent/metastatic HNSCC who received cetuximab-based systemic therapy at the Department of Medical Oncology, Manisa Celal Bayar University Faculty of Medicine, between May 2012 and September 2025. Demographic, clinical, laboratory, and PET/CT data were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with survival were evaluated using univariable and multivariable Cox proportional hazards regression analyses. Results: A total of 57 patients were included in the study. The median age was 65 years, and 91.2% of patients were male. Most patients had ECOG performance status 0–1 (94.7%) and stage IV disease (71.9%). The larynx was the most common primary tumor site (50.9%), while distant lymph node metastasis (63.2%) and lung metastasis (61.4%) were the predominant metastatic sites. Median PFS and OS were 4.6 months and 13.8 months, respectively. Kaplan–Meier analysis demonstrated that patients with a body mass index (BMI) > 25 had longer OS, whereas chronic kidney disease (CKD), primary tumor localization, and best response to first-line treatment were significantly associated with survival. In multivariable Cox regression analysis, chronic kidney disease (CKD) (HR: 5.15, p = 0.004), oral cavity primary tumor localization (HR: 2.55, p = 0.013), progressive disease as the best response to first-line treatment (HR: 4.44, p < 0.001) and the absence of grade 1–2 cetuximab-related dermatologic toxicity (HR: 3.20, p = 0.027) remained independent adverse prognostic factors. BMI was not independently associated with survival in multivariable analysis. Conclusions: Cetuximab-based therapy demonstrated clinically meaningful activity in patients with R/M HNSCC. Comorbidities, primary tumor localization, the absence of grade 1–2 cetuximab-related dermatologic toxicity and treatment response appear to substantially influence survival outcomes. Larger prospective studies are warranted to validate these findings. Full article

Cr(VI) pollution severely damages plant cell wall structure and membrane integrity. Proline-rich proteins (PRPs), key cell wall structural components, rely on proline as their biosynthetic precursor. Pro accumulation has been shown to positively correlate with PRP abundance, suggesting a direct biochemical link between exogenous Pro [Pro_(exo)] application and PRP-mediated cell wall function. However, how Pro_(exo) regulates PRP expression to maintain cell wall structural integrity and membrane stability in rice seedlings under Cr(VI) stress remains unclear. In this study, the subcellular distribution of Cr, electrolyte leakage (EL), cell wall thickness, and the expression of PRP genes in rice seedlings were evaluated. The results revealed that Cr(VI) stress induced significant increases in EL and changes in cell wall thickness in rice seedling cells (p < 0.05). The application of Pro_(exo) significantly mitigated EL and increased cell wall thickness (p < 0.05). Furthermore, Pro_(exo) markedly increased the sequestration of Cr within the seedling root cell walls while reducing its distribution in the cytoplasm and organelles of seedling shoot cells (p < 0.05). Phylogenetic analysis of 48 OsPRP genes, on the basis of their homology with seven functionally characterized PRPs from other species, revealed 12 candidate genes in rice potentially involved in the regulation of cell membrane stability, cell wall assembly, thickening, and integrity. Subsequent qRT-PCR analysis and gene expression variation factor calculation revealed that Pro_(exo) significantly promoted the expression of OsPRP1.1, OsPRP3, OsRePRP2.1, OsHyPRP18, and OsHyPRP27 in roots and that of OsHyPRP27 in the shoots of rice seedlings under Cr(VI) stress. These findings indicate that Pro_(exo) enhances Cr compartmentalization within the root cell wall and improves membrane stability, thereby contributing to Cr(VI) tolerance in plants through the modulation of these key PRP genes. Our findings provide novel insights into the mechanism by which Pro_(exo) regulates PRP expression to affect plant cellular structural stability and heavy metal tolerance. Full article

Quality inspection of imported saw-ginned cotton mainly involves the determination of color grade and impurity grade. Traditional manual grading and High Volume Instrument (HVI) testing are limited by subjectivity, insufficient accuracy, single-indicator measurement, and long inspection cycles. To address these limitations, this study developed a machine vision-based intelligent identification system for saw-ginned cotton quality grading. The system integrates a portable image acquisition box, a cloud-based intelligent recognition service, and a HarmonyOS-based mobile application. A total of 6363 saw-ginned cotton images were collected using the self-developed image acquisition device for model training and testing. Based on U-Net background segmentation, a dual-branch parallel recognition framework was established for cotton color grading and impurity grading. The CA-ResNet50 model, integrating ResNet50, the Efficient Channel Attention (ECA) mechanism, and the AdamW optimization strategy, was constructed for cotton color grade recognition. The AD-UNet model, incorporating Atrous Spatial Pyramid Pooling (ASPP)-based multi-scale contextual modeling and the DySample adaptive upsampling mechanism, was developed for impurity segmentation. In addition, the HarmonyOS-based mobile application supports information query, image acquisition, intelligent recognition, and data traceability. Experimental results showed that the CA-ResNet50 color grading model achieved an F₁-Score of 94.8%. Based on the AD-UNet impurity segmentation results and the calculated impurity area ratio, the accuracy of impurity grade determination reached 97.3%. The average cloud-based inference time for a single image was approximately 0.8 s, and the complete workflow, including sample flattening, image acquisition, and recognition, required approximately 10 min. The proposed system improves the accuracy, efficiency, objectivity, and traceability of saw-ginned cotton quality identification, providing technical support for rapid inspection and quality supervision of imported cotton. Full article

Background/Objectives: Neurological impairment after glioma resection is a common postoperative event, but many deficits improve during recovery. The present study investigated whether transient and persistent postoperative neurological deficits differ in their association with overall survival (OS) and progression-free survival (PFS). Methods: We retrospectively reviewed data from patients who underwent initial surgical treatment for glioma in our institution. Neurological function was evaluated using documented clinical examinations performed before surgery, in the immediate postoperative period, and during routine follow-up 3–6 months after the procedure. Results: The study cohort comprised 496 patients, of whom 44.4% were women. The mean age at surgery was 60 years (95% CI, 58–61), and the average follow-up period was 21 months (95% CI, 19–23). According to the 2021 WHO classification, 80.0% of tumors were grade 4, 11.1% were grade 3, and 7.3% were grade 2. IDH mutations were absent in 81% of cases. Median survival for the entire cohort was 34 months (95% CI, 30–38). Preoperative neurological deficits, including hemiparesis, were not significantly associated with OS. Postoperative deficits that were resolved by the follow-up assessment showed no relationship with either OS or PFS, irrespective of IDH mutation status. In contrast, neurological deficits that persisted at follow-up were independently associated with shorter OS and PFS among patients with IDH-wild-type gliomas (p < 0.001), whereas no significant association was observed in the IDH-mutant subgroup. Similarly, when new neurological deficits were present at follow-up, poorer OS and PFS were predicted only in patients with IDH-wild-type tumors (p < 0.001). Conclusions: Temporary neurological deterioration following glioma surgery does not appear to adversely influence overall or progression-free survival, regardless of IDH status. However, persistent postoperative deficits, as well as newly acquired deficits that remain evident during follow-up, are strong indicators of an unfavorable prognosis in patients with IDH-wild-type gliomas. Full article

Effective evaluation of building fabric is essential to understanding building performance. Traditional methods, such as ISO 9869-1, provide point U-values but do not always capture the complete picture, and new measurement-led approaches are needed to support building retrofit. Heat3D is a novel iOS application that performs rapid U-value measurements of building elements by mapping thermographic images from a mobile infrared camera onto an augmented reality (AR) model of a room, from which heat flux across the element is calculated. A field trial of 22 UK properties during the 2019–2020 winter heating season assessed Heat3D’s heat flux measurements against traditional heat flux plates, with 90% of 295 Heat3D surveys falling within the combined uncertainty of the reference method. A second field trial, conducted over the 2020–2021 winter heating period, evaluated a new timelapse iteration of the method capable of measuring wall U-value within approximately 60 min; 90% of 42 Heat3D surveys fell within the combined confidence interval of the ISO 9869-1-measured U-value. These results indicate that Heat3D offers a viable, rapid alternative to traditional methods for both heat flux and U-value measurement. Full article

Drought research on quinoa has focused almost exclusively on the shoots, leaving the roots, the organ that first senses soil drying, largely unexamined, and its recovery dynamics are still poorly characterized. Here, we show that in the Chilean coastal quinoa ecotype AZ1, recovery from drought is governed belowground, and the root regains hydraulic and metabolomic competence well before the stomata reopen. After 72 h of soil drying, stomatal conductance (g_s) decreased by 98%, whole-plant transpiration declined biphasically (~92% of the loss within the first two hours), and water potential decreased steeply at the soil–root interface (with soil and root water potential declining approximately 10- and 20-fold relative to well-watered plants), while the stem remained near-stable, pinpointing the root as the dominant hydraulic bottleneck. Twenty-four hours after rewatering, root system and whole-plant water potential, osmotic root hydraulic conductance (Lp_rOS), root anatomy, and the polar metabolome were largely restored, yet g_s remained statistically indistinguishable from droughted plants. Strikingly, hydraulic recovery proceeded without rebuilding the osmotic sugar pool; instead, normalization of TCA-cycle intermediates points to an energy-powered and possible aquaporin-mediated transport route that bypasses still-suberized apoplastic barriers. Root system metabolomics, led by GABA and L-alanine, which overshot the control, tracked root rehydration but correlated negatively with g_s, suggesting that nitrogen-rich solutes may act as candidate belowground cues restraining stomatal reopening. These findings suggest that the quinoa root system acts as a pacemaker for drought recovery. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with limited effective therapies. In this study, a series of 2-(arylamino)thiazol-4(5H)-one derivatives was synthesized using an efficient microwave-assisted protocol, and evaluated for neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced oxidative stress (OS) in SH-SY5Y neuronal cells and an Aβ42-expressing Drosophila melanogaster model of AD. Among the synthesized compounds, 3n, 3i, and 3b exhibited low cytotoxicity and significant neuroprotection, as evidenced by increased cell viability, reduced reactive oxygen species (ROS) production, and preserved mitochondrial membrane potential. Notably, compound 3n demonstrated the highest activity and effectively ameliorated Aβ42-induced behavioral deficits in vivo. Molecular docking studies predicted favorable binding affinity within the acetylcholinesterase (AChE) active site, with the thiazol scaffold and aryl substituents stabilizing ligand binding through π–π stacking and hydrophobic interactions; compound 3n also formed additional hydrogen bonds enhancing its affinity. Consistent with the docking predictions, in vitro AChE inhibition studies demonstrated that compounds 3n, 3i, and 3b inhibited AChE in a concentration-dependent manner. Network pharmacology predicted seven potential core targets implicated in AD pathogenesis and related pathways, including OS, neuroinflammation, and synaptic dysfunction. Furthermore, in silico pharmacokinetic analysis indicated compliance with Lipinski’s and Veber’s rules, supporting favorable drug-like properties. While further experimental validation is essential, these findings highlight 2-(arylamino)thiazol-4(5H)-one derivatives, particularly compound 3n, as promising multifunctional candidates for further preclinical development against AD. Full article

Background: Germline and somatic variants in DNA Damage Repair (DDR) genes are found in approximately one-fourth of patients with metastatic prostate cancer (PC). However, their precise prognostic role and predictive impact on standard therapies remain controversial. Methods: This retrospective, single-center study evaluated the prevalence of germline/somatic DDR aberrations in 287 eligible patients with metastatic prostate cancer (mPC), treated between 2017 and 2022. Clinical characteristics and treatment outcomes (PFS and OS) for chemotherapy (taxanes) or next-generation hormonal therapies (NHT) were compared between DDR-mutated (DDRmut) and wild-type (DDRwt) cohorts. Results: Sixty-three patients (21.9%) were DDRmut, with BRCA2 (12.5%), ATM (3.1%), and BRCA1 (1.39%) being the most common alterations. A family history of breast, ovarian, or prostate cancer strongly predicted DDRmut status (47.0% vs. 14.0%, p = 0.0001). Tissue samples remained evaluable for sequencing up to 180 months from collection. Overall baseline characteristics were similar between cohorts, and BRCA1/2- and ATM-mutated patients treated with first-line taxanes for mCRPC presented with non significantly highermedian OS compared to DDRwt patients (70 vs. 36 months; p = 0.30). On the contrary, the DDRmut subgroup showed a trend toward shorter PFS (12 vs. 18 months; p = 0.04) when treated with first-line NHT. No significant differences were observed with third-line Cabazitaxel. Conclusions: Formalin-fixed paraffin-embedded (FFPE) prostate tissue is highly reliable for DDR, possibly integrating novel liquid biopsy approaches for DDR evaluation. In a real-world setting, BRCA1/2 and ATM variants identify a distinct molecular subgroup that derives preferential survival benefit from first-line taxanes over standard hormonal intensification. Full article

Background and Objectives: This study aimed to evaluate the effects of 24 h versus 46 h continuous 5-fluorouracil (5-FU) infusion durations on pathological response, progression-free survival (PFS), and overall survival (OS) in patients with gastric and gastroesophageal junction adenocarcinoma receiving a perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen. Materials and Methods: A total of 300 patients who received a perioperative FLOT regimen were retrospectively analyzed. The patients were divided into two groups as those receiving 24 h and 46 h continuous 5-FU infusion. Clinicopathological characteristics were compared. Survival analyses were evaluated using the Kaplan–Meier method. Factors affecting pathological response were analyzed by logistic regression, and factors affecting survival were examined by Cox regression analysis. Results: Pathological response rates were found to be significantly higher in patients receiving 46 h 5-FU infusion (multivariate analysis: OR = 2.884; 95% CI: 1.619–5.138; p < 0.001). The probability of pathological response was found to be significantly lower in patients with baseline cT4 and advanced nodal stage. Median OS times were 41.23 months and 33.73 months in the 24 h and 46 h groups, respectively, with no significant difference detected between the groups (p = 0.371). In contrast, median PFS time was significantly longer in the 24 h group (38.47 months vs. 18.00 months; p < 0.001). However, in multivariate analysis, 5-FU infusion duration could not be demonstrated as an independent prognostic factor for PFS. Moderately and poorly differentiated tumors and an increased number of positive lymph nodes were found to be independent risk factors for progression. Conclusions: Although 46 h 5-FU infusion in the perioperative FLOT regimen was associated with a higher pathological response rate, this advantage was not reflected in survival outcomes. It is considered that the observed difference in PFS may stem from the clinicopathological heterogeneity between the groups. Prospective randomized studies are needed to determine the optimal 5-FU infusion duration. Full article

Objectives: To estimate the added value of dostarlimab compared to durvalumab and pembrolizumab as first-line treatment for adult patients with primary advanced or recurrent endometrial cancer (EC) in Spain using a Multi-Criteria Decision Analysis (MCDA) framework. Methods: Following the Evidence and Value: Impact on Decision Making (EVIDEM) framework and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommendations, 25 Spanish experts (12 medical oncologists and 13 hospital pharmacists) weighted and scored 11 quantitative and 5 qualitative criteria based on an evidence matrix from a literature review. Results: Efficacy and safety were weighted as the most important criteria. Dostarlimab showed positive added value in both comparisons with scores of 0.58 versus durvalumab/durvalumab + olaparib and 0.50 versus pembrolizumab. Dostarlimab and pembrolizumab are the only therapies reimbursed in the Spanish public health system; therefore, their comparative assessment is of clinical and strategic relevance. While pembrolizumab may show longer progression-free survival (PFS) and response duration in specific subgroups, the evidence for dostarlimab—including a statistically significant improvement in overall survival (OS) in the overall population as a primary endpoint, more robust data, and favorable long-term quality-of-life outcomes—was considered by the expert panel to support a more favorable assessment. Conclusions: Within the MCDA framework, experts consider dostarlimab an option with a higher value contribution for adult patients with primary advanced or recurrent EC. Its clinical benefits, improved quality-of-life outcomes, and alignment with healthcare priorities promote treatment continuity and adherence in clinical practice. MCDA provided a transparent approach for multidimensional evaluation of these therapies. Full article