Search Results (1,860)

Background/Objectives: Standard treatment of multiply relapsed Ewing sarcoma remains to be established. Recent studies evaluating tyrosine kinase inhibitors (TKIs) with anti-angiogenic properties have shown encouraging results. Therefore, we conducted a systematic review and meta-analysis to explore the efficacy and safety of TKIs in patients with Ewing sarcoma. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases for clinical trials (CTs) and cohort studies assessing TKIs in the treatment of advanced Ewing sarcoma patients who received at least one prior line of therapy. The main outcome was objective response rate (ORR). All analyses were conducted using R software (v.4.2.2), employing random effects models with 95% confidence intervals (CIs). Results: We included 14 studies (seven phase II CT and seven retrospective cohorts), comprising 257 patients. The following TKIs were evaluated: cabozantinib, regorafenib, apatinib, anlotinib, sorafenib, lenvatinib, sunitinib, fruquintinib, and imatinib. In a pooled analysis of all Ewing sarcoma patients treated with TKIs, the ORR was 23% (95% CI, 11.2–37.1%) and the DCR was 61.1% (95% CI, 47.3–74.2%). Responses were numerically higher but statistically nonsignificant between clinical trials and real-world studies. The analysis including only single-agent TKIs showed better responses for anlotinib and apatinib, yet these drugs are not available in Western countries. Among the FDA-approved TKIs, superior outcomes were noted with single-agent cabozantinib. (ORR: 21.6%) and regorafenib (ORR: 11.3%). Several studies did not report toxicity data exclusively for Ewing sarcoma patients; thus, conclusions about toxicity are mostly based on the general population of studies and may not be fully representative of Ewing sarcoma patients. Conclusions: Anti-angiogenic TKIs have shown important anti-tumoral activity in patients with Ewing sarcoma. Efficacy was consistently seen in both clinical trials and real-world studies. Nonetheless, there are important differences in study design and population that may limit our interpretation of efficacy and toxicity findings. Full article

Background/Objectives: The oncoprotein EWS::FLI1 is a chimeric transcription factor that aberrantly brings transcriptional deregulation relevant to Ewing sarcoma. It is also regarded as a therapeutic target for suppressing oncogenic progression, but the inhibition and clearance of the EWS::FLI1 oncoprotein remain a challenge. Methods: We apply a polyglutamine (polyQ) fusion strategy to directly target EWS::FLI1 in suppression of its transcriptional malfunction in A673 cells derived from Ewing sarcoma. Based on the template of the N-terminal fragment of polyQ-expanded ataxin-7 (Atx7_93Q-N172) and the homologous peptides of EWS::FLI1, we have designed and constructed three polyQ fusion proteins, namely Atx7_93Q-N172-SYGQ1, Atx7_93Q-N172-SYGQ2, and Atx7_93Q-N172-LCD. Results: Supernatant/pellet fractionation and immunofluorescence imaging reveal that the polyQ fusion proteins co-precipitate and co-localize with EWS::FLI1 in A673 cells, indicating that the polyQ fusions we have designed can sequester endogenous EWS::FLI1 into insoluble aggregates and reduce its cellular availability. Moreover, these polyQ fusions, especially Atx7_93Q-N172-LCD, alter the expression of EWS::FLI1 downstream genes, with an increase in P21 (CDKN1A) and a decrease in c-Myc. Conclusions: These results demonstrate that the engineered polyQ fusions entrap endogenous EWS::FLI1 protein into aggregates and reduce its soluble fraction in Ewing sarcoma cells. This study provides an alternative potential for treating Ewing sarcoma and other tumors by directly targeting the oncogenic proteins in the future. Full article

Colostrum is crucial for the survival, development, and the future productivity of newborns. In this study, we evaluated the immunological and microbiological quality of colostrum in 28 Rasa Aragonesa ewes and its relationship with offspring growth during the first 48 h postpartum. Colostrum samples were collected by hand milking immediately after parturition. Immunoglobulin concentration was assessed using Brix refractometry and the samples were categorised according to their immunoglobulin content: high (>24 Brix value), medium (19–23 Brix value), and low (< 19 Brix value). Bacterial counts of aerobes and coliforms were determined with the 3M Petrifilm™ system and the weight of the lambs was recorded using a digital suspension scale. The mean aerobic count (AC) was 3.63 ± 0.69 log₁₀ CFU/mL after 24 h of incubation and the mean coliform count (CC) was 1.59 ± 0.82 log₁₀ CFU/mL after 24 h of incubation. Colostrum with a high immunoglobulin concentration had lower aerobic count after 48 h of incubation than that with poor immunological quality. In relation to coliform counts, similar values were found in all groups. No significant differences were observed in terms of lamb weight gain according to colostrum quality. In conclusion, the immunological quality of colostrum affected the AC determined, but it did not affect CC or early postnatal lamb weight. These findings offer preliminary insights into the usefulness of the Petrifilm™ system in microbiological quality determination of colostrum and its relationship with immunological quality determined in vitro. Full article

Background/Objectives: Cutaneous metastases from primary bone sarcomas are exceedingly rare and poorly characterized, often posing diagnostic challenges due to their atypical presentation. This systematic review aimed to describe the clinical patterns, temporal relationships, and prognostic implications of cutaneous metastases across major bone sarcoma histologies. Methods: A comprehensive literature search was conducted to identify all reported cases of cutaneous metastases from osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. Data on patient demographics, primary tumor site, cutaneous lesion characteristics, latency periods, synchronous metastases, morphology, and clinical outcome were extracted and analyzed descriptively. Results: 102 cases were identified, with chordoma representing the most frequent histology. Cutaneous metastases showed histology-specific patterns: osteosarcoma and Ewing sarcoma typically presented with multiple lesions in the context of widespread systemic disease and poor prognosis, whereas chordoma more often exhibited solitary or skin-dominant metastases with longer latency and occasional favorable outcomes, including complete responses after local treatment. Conclusions: Cutaneous metastases in bone sarcomas display heterogeneous behavior, with chordoma demonstrating a more indolent and potentially manageable pattern compared to other histologies. Increased clinical awareness is essential to avoid diagnostic delays and optimize management. Full article

Milk fatty acid (FA) composition derives from de novo synthesis in the mammary gland and from the uptake of preformed FA derived from diet, ruminal biohydrogenation, and body tissue mobilization. Consequently, milk FA profiles have been related to nutritional stress responses and feed efficiency (FE). This study tested whether dairy sheep with divergent FE would show different milk FA responses to a nutritional challenge. After calculating two FE indices in 40 ewes, the 9 most efficient (H-FE) and 9 least efficient (L-FE) animals were selected and subjected to a 3-day challenge replacing their total mixed ration (TMR) with wheat straw, followed by TMR refeeding. Temporal patterns of milk FA variation showed only minor differences between H-FE and L-FE ewes. The L-FE group exhibited higher concentrations of iso- and anteiso-17:0 and 18:0, suggesting differences in rumen fermentation and biohydrogenation. In contrast, underfeeding induced marked changes in milk FA composition, including a strong reduction in short- and medium-chain FAs (≤C16), consistent with a shift from de novo synthesis toward increased uptake of preformed FA. Overall, limited differences suggest that milk FA composition may not be a suitable marker for FE. Nonetheless, underfeeding-induced changes highlight its value for exploring nutritional stress responses. Full article

Background: Fragile X Syndrome (FXS) is an X-linked neurodevelopmental disorder characterised by intellectual disability, developmental delays, anxiety, and social and behavioural challenges. Currently, no effective treatments exist to address the root cause of FXS. Mouse models are the most widely used for studying molecular pathogenesis and conducting preclinical treatment testing. However, therapeutic interventions that show promise in rodent models have yet to succeed in clinical trials. After evaluating the current models, we have developed an ovine model to address this clinical translation gap. We expect this model to more accurately reflect the human condition in brain size, structure, and neurodevelopmental trajectory. We aim to establish this model as a valuable preclinical platform for testing therapies for FXS. Methods: To generate the sheep model, we used CRISPR-Cas9 dual-guide editing to knock out the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene in ovine embryos. Results: Two founder animals were created, one ram (male) and one ewe (female), both of which carried FMR1 gene knockouts. The ewe carries inactivating mutations on both alleles, with the edits in both animals resulting in no detectable Fragile X Messenger Ribonucleoprotein (FMRP) as expected. Both founders have undergone molecular characterisation and basic health checks, with the female founder showing increased joint flexibility, a characteristic of FXS. The ram has been used for breeding, with the successful transmission of the edited allele to his offspring. Importantly, specific lamb cohorts for postnatal treatment testing can be produced efficiently utilising accelerated breeding methods and preimplantation selection. Full article

Ecosystem vulnerability assessment is paramount for local environmental stability and lasting economic progress. This study selects Hubei Province as the research area, applying multi-source spatiotemporal datasets spanning the period 2000–2023. A pressure–state–response (PSR) framework, incorporating 14 distinct indicators, was developed. The selection criteria for these indicators adhered to principles of scientific rigor, all-encompassing scope, statistical representativeness, and practical applicability. The chosen indicators effectively encompass natural, anthropogenic, and socio-economic drivers, aligning with the specific ecological attributes and key vulnerability factors pertinent to Hubei Province. The analytic network process (ANP) method and entropy weighting (EW) method were integrated to ascertain comprehensive weights, thereby computing the ecological vulnerability index (EVI). In the meantime, we analyzed temporal and spatial EVI shifts. Spatial autocorrelation analysis, the geodetic detector, the Theil–Sen median, the Mann–Kendall trend test, and the Grey–Markov model were employed to elucidate spatial distribution, driving factors, and future trends. Results indicate that Hubei Province exhibited mild ecological vulnerability from 2000 to 2023, but with a notable deteriorating trend: extreme vulnerability areas expanded from 0.34% to 0.94%, while moderate and severe vulnerability zones also increased. Eastern regions demonstrate elevated vulnerability, but they were lower in the west, correlating with human activity intensity. The global Moran’s I index ranged from 0.8579 to 0.8725, signifying a significant positive spatial correlation of ecological vulnerability, with the highly vulnerable areas concentrated in regions with intense human activities, while the less vulnerable areas are located in ecologically intact areas. Habitat quality index and carbon sinks emerged as key drivers, possibly stemming from the forest–wetland composite ecosystem’s high dependence on water conservation, biodiversity maintenance, and carbon storage functions. Future projections based on Grey–Markov models indicate that ecological fragility in Hubei Province will exhibit an upward trend, with ecological conservation pressures continuing to intensify. This research offers a preliminary reference basis of grounds for ecological zoning, as well as sustainable regional development in Hubei Province, while also providing a theoretical and practical framework for constructing an ecological security pattern within the Yangtze River Economic Belt (YREB) and facilitating ecological governance in analogous river basins globally, thereby contributing to regional sustainable development goals. Full article

Background: Achieving adequate margins in pelvic bone tumor resection remains difficult, as conventional navigation provides no direct three-dimensional margin feedback. We proposed an innovative dangerous region generation method based on 3D image resampling and anisotropic distance transform, integrated with computer-assisted navigation, to enhance surgical margin accuracy. This study aimed to evaluate its oncological safety, functional outcomes, and perioperative efficacy in pelvic tumor surgery. Methods: The study was conducted on 19 patients (8 males, 11 females) with primary pelvic bone tumors between May 2018 and June 2024. The age range was 19 to 66 years (mean age: 62.67 years). Histological diagnoses included chondrosarcoma (n = 6), giant cell tumor (n = 4), osteosarcoma (n = 1), chordoma (n = 2), Ewing sarcoma (n = 3), spindle cell sarcoma (n = 1), chondromyxoid fibroma (n = 1), and peripheral nerve sheath tumor (n = 1). The feasibility of the dangerous region generation method for computer-assisted pelvic tumor resection surgery was assessed by general results, oncological and functional results. Results: All patients successfully underwent surgery with a mean operative time of 252 min and average intraoperative blood loss of 1358 mL. The mean hospital stay was 22 days, and all patients completed follow-up (mean, 37 months). Two patients developed postoperative wound complications, which resolved after debridement. Adequate surgical margins were achieved in all cases. The 5-year overall survival rate was 75.6%, increasing to 80.0% among patients with wide-margin resections. At the final follow-up, the mean MSTS score among 16 limb-salvage patients was 26.6, corresponding to an average functional recovery of 88.5%. Most patients exhibited a normal gait and were able to ambulate without assistive devices. Conclusions: This dangerous region generation method, when combined with computer-assisted techniques for pelvic bone tumor resection, is feasible and can achieve favorable clinical outcomes. Full article

This study investigated chemical variations in softwood juvenile wood, focusing on intra-ring variation between earlywood (EW) and latewood (LW) components along the radii. While no radial trends in lignin content and hydroxyphenyl/guaiacyl (H/G) ratio were found, the variation between EW and LW within a single growth ring was highly significant. Analytical pyrolysis demonstrated that earlywood contained, on average, 2.4% more lignin than latewood. Surprisingly, EW exhibited a lower H/G ratio (0.036) compared to LW (0.041), challenging the typical correlation between high lignin content and high H/G ratios. Principal component analysis (PCA) of the pyrolysis products confirmed distinct structural differences in lignin between EW and LW, reflecting their disparate functional roles—transport and mechanical support, respectively. Overall, analytical pyrolysis was highly effective for assessing the significant intra-ring variation in both lignin content and structural composition. Full article

This study utilizes Digital Elevation Models (DEMs) with different spatial resolutions (SRTM 90 m, ASTER DEM 30 m, and ALOS PALSAR 12.5 m), Landsat-8 satellite imagery, and the Bouguer WGM-12 gravity model to analyze morphotectonic features in the Upper Guajira region of Colombia, a desert area in northern South America, area that is composed by low-relief serranías of Cabo de la Vela, Carpintero, Cosinas, Simarua, Jarara, and Macuira. Three DEMs were used to extract and map morphotectonic lineaments, drainage networks, and morphological features. Lineaments were characterised by azimuth frequency, length, density, lithological distributions, and geological timeframes, with support from a digitized geological map from the Colombian Geological Service (SGC). The analysis of the east–west (E-W) Cuisa fault, using the Riedel shear model, suggests a transtensional/transpressional tectonic regime influenced by the Caribbean and South American plates, characterised by NE-SW and E-W fault orientations. Lineaments were grouped into five geochronological categories based on the geological map, revealing a shift from NE-SW to E-W orientations from the Cretaceous period onward, reflecting the ongoing movement of the Caribbean plate. Folds and faults from this tectonic activity were enhanced using Landsat-8 band combinations. The WGM-12 model was separated into regional and residual signals, with the latter highlighting the serranías subregions. Residual gravity analysis revealed significant negative anomalies, suggesting lower-density lithologies surrounded by higher-density blocks. This pattern aligns with the regional geological framework and may reflect a crustal root or terrain dragging linked to the tectonic processes that shaped the serranías. Derivative residual gravity data also revealed lineaments oriented NE–SW, whose distribution extends beyond the morphometric boundaries of the subregions. The study found a strong correlation between structural and drainage patterns, demonstrating structural control over geomorphology. This study establishes a solid morphotectonic and geophysical framework for the Upper Guajira region, demonstrating how multi-resolution DEM analysis combined with gravity data can resolve regional deformation patterns, crustal architecture, and tectonic development along the Caribbean–South American plate boundary. Full article

The valorization of cull sheep and the incorporation of agro-industrial by-products into animal feeding represent effective approaches to enhancing the sustainability of small ruminant production systems. This study investigated the effects of dietary inclusion of 17% partially destoned olive cake (OC) in the concentrate fed to Valle del Belice ewes on carcass characteristics, as well as on meat and salami quality. A 14-week feeding trial was conducted on 124 animals allocated to a control (CTR) and an experimental (EXP) group, balanced for parity, days in milk, and daily milk yield. At the end of the trial, five animals per group were slaughtered and their meat was processed into three types of salami: 100% sheep meat (SM), 90% sheep meat with 10% beef heifer brisket (HB), and 90% sheep meat with 10% pork backfat (PB). Meat and salami were evaluated for chemical composition, fatty acid profile, polyphenol content, antioxidant capacity, lipid oxidation, microbiological status, textural properties, and sensory characteristics. Dietary OC supplementation resulted in increased carcass weight, separable fat, intramuscular fat content, and monounsaturated fatty acids—particularly oleic acid—along with higher polyphenol levels and antioxidant activity. Salami produced from OC-fed ewes exhibited reduced weight loss during ripening, lower lipid oxidation, an improved MUFA/SFA ratio, and satisfactory sensory attributes. Microbiological analyses indicated a dominance of lactic acid bacteria and coagulase-negative staphylococci, with no pathogenic microorganisms detected. Overall, the inclusion of olive cake in the diet enhanced meat and processed product quality, supporting the valorization of olive oil by-products within circular economy frameworks. Full article

Anguilla japonica is a catadromous fish, and the Yangtze River Estuary serves as a crucial passage for A. japonica migrating downstream to the sea. A large number of adult A. japonica appear on the market during the peak migration period. Due to the lack of effective discrimination basis, it is difficult to distinguish the source of samples in market supervision. Therefore, there is an urgent need to trace the origin of A. japonica from different water bodies. This study analyzed muscle elemental fingerprints of 21 elements to determine the geographical origin of A. japonica. The results showed that A. japonica from different habitats had distinct elemental compositions in their muscles. Specifically, A. japonica from estuary waters (EW) was characterized by significantly higher levels of V and Hg compared to other water bodies. Na was identified as a key discriminant element among different habitats, with its content significantly increasing in river waters (RW), EW, and offshore waters (OW), respectively. Discriminant analysis selected four discriminant elements (V, Hg, Na and Cu) from 21 elemental compositions, among which V, Hg, and Na were the three key distinguishing elements. Based on the composition of these four discriminant elements in the muscles of A. japonica from different habitats, hierarchical cluster analysis (HCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and linear discriminant analysis (LDA) were applied and validated, successfully achieving rapid and accurate origin tracing and verification for new samples, achieving 100% classification accuracy. Therefore, the application of muscle EFA can achieve the geographical traceability of A. japonica from different habitats. The analytical method and verification process for origin tracing established in this study can be successfully applied to market supervision for tracing the origin of samples with unknown sources. Full article

This paper discusses the total replacement of egg white (EW) with faba bean protein concentrate (FPC) in a marshmallow formulation. The physico-chemical and techno-functional characterizations of the ingredients revealed that FPC, with a protein content of 68%, exhibited an interesting foaming capacity (200%) compared to EW, which had comparable foaming stability. The physico-chemical properties of the final products indicated that the FPC marshmallow (FPCM) had a higher density (0.519 g/mL), lower moisture (17.337%), and a water activity within the recommended range for this type of product. The FPCM had the highest hardness and elasticity values but the lowest cohesiveness and adhesiveness. Scanning electron microscopy showed that the FPCM structure is similar to that of the EW marshmallow (EWM). In front-face fluorescence spectroscopy measurements, the FPCM exhibited higher emission intensity for tryptophan with a maximum at 382 nm and vitamin A with a maximum located around 338 nm. FTIR analysis presented higher peaks at 850, 918, and 1034 cm⁻¹ for the EWM compared to the FPCM. In a hedonic evaluation, the majority of descriptors (hardness, odor, and general acceptability) showed similar scores for both formulations. All results demonstrated the success of the total substitution of egg white by FPC in the marshmallow formulation. Full article

Gastrointestinal nematodes (GIN) represent a major constraint to sheep production, and sustainable alternatives to routine anthelmintic use are increasingly required. This study compared two parasite control strategies in Zerasca sheep: routine albendazole treatment administered twice yearly (T) and a long-term non-chemical approach based on rotational grazing (relocation to a new pasture when grass height fell below 10 cm) combined with quarterly veterinary monitoring (NT). Twenty-four adult ewes (n = 12 per group) were monitored over an eight-month period. Mean faecal egg counts (EPG) differed significantly between groups (T: 210 ± 78; NT: 529 ± 89; p = 0.0007). In group T, EPG values decreased markedly 7 days after treatment but increased again by 150 days, resulting in no persistent differences between groups over time. Despite higher parasite burdens, NT sheep showed significantly higher body condition scores compared with treated animals (3.00 ± 0.61 vs. 2.51 ± 0.53; p = 0.0014). Haematological parameters were largely comparable between groups, although mild reductions in RBC, HGB, and HCT were observed in both. Treated sheep exhibited higher AST activity (p < 0.0001) and transient increases in ALT and BUN following treatment. Hair cortisol concentrations did not differ significantly between groups. Overall, these findings suggest that a non-chemical parasite management strategy, when combined with controlled grazing and veterinary monitoring, may maintain acceptable parasite levels while supporting body condition and stable welfare indicators, potentially reducing reliance on routine anthelmintic treatments. Full article

Early weaning in intensive lamb production improves reproductive efficiency but predisposes lambs to diarrhea, oxidative stress, and intestinal barrier dysfunction, highlighting the need for non-antibiotic strategies to protect gut health. This study evaluated whether a sheep-derived mixed probiotic could alleviate early weaning–induced intestinal injury and clarified its potential molecular mechanisms. Early weaning reduced body weight, average daily gain and feed efficiency, increased diarrhea, decreased plasma and colonic catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activities, increased malondialdehyde (MDA), elevated interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), reduced interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), increased plasma and mucosal immunoglobulin A, M, and G (IgA, IgM, IgG), and increased colonic lipopolysaccharide (LPS) with reduced diamine oxidase (DAO). Intestinally, EW induced villus atrophy, deeper crypts, lower villus height-to-crypt depth ratios, goblet cell loss, higher histopathological scores, and decreased colonic mucin 2, zonula occludens-1, claudin-1, and occludin. Probiotic supplementation partially reversed these alterations, restoring antioxidant enzyme activities, improving villus architecture and barrier protein expression, and rebalancing cytokine and immunoglobulin profiles. Transcriptomic and network analyses showed that early weaning activated Cytokine–cytokine receptor, NF-κB, TNF and Th17 pathways, whereas probiotics suppressed a weaning-responsive inflammatory gene module, downregulated key hub genes, and enhanced peroxisome proliferator-activated receptor (PPAR) signaling. These results show that supplementing early-weaned lambs with a mixed probiotic generated from sheep is an efficient nutritional strategy to reduce intestinal oxidative and inflammatory damage associated with weaning and to enhance their health and performance. Full article