Search Results (40)

Background: The management of metastatic hormone-sensitive prostate cancer (mHSPC) has evolved with the integration of androgen receptor signaling inhibitors (ARSIs) and metastasis-directed therapies (MDTs). Stereotactic body radiotherapy (SBRT) offers precise local control, yet real-world data on its combination with apalutamide remain limited. Methods: We conducted a multicenter retrospective cohort study including 134 patients with mHSPC treated with apalutamide and SBRT between February 2021 and December 2024. The primary endpoints were progression-free survival (PFS), local control (LC), and treatment safety. PSA kinetics and radiologic response were evaluated, and outcomes were analyzed according to PSA thresholds and treatment timing. Results: Most patients (93.3%) had low-volume disease; 97.1% presented with ≤5 metastases. At a median follow-up of 28 months, LC was 99.3% and 95.5% of patients were progression-free. Complete radiological response was achieved in 87.5% of patients, and 68.4% attained ultralow PSA levels (≤0.02 ng/mL). Undetectable PSA and radiologic complete response were independently associated with improved PFS (p = 0.010 and p = 0.011, respectively). Treatment was well tolerated, with grade ≥3 toxicity occurring in only 2.2% of patients. Conclusions: The combination of apalutamide and SBRT in mHSPC is associated with high local and systemic disease control and minimal toxicity in a real-world setting. This approach may delay systemic treatment intensification and the onset of castration resistance. Prospective studies are warranted to confirm these findings. Full article

Vascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular dynamics of VEGF in a laser-induced choroidal neovascularization (lCNV) mouse model. Tear VEGF levels were quantified using proximity qPCR immunoassays in eAMD patients (n = 29) and healthy controls (n = 21) and correlated with optical coherence tomography (OCT) findings. Molecular analyses, including immunohistochemistry, gene expression profiling, and phosphorylation assays, were conducted on choroid–retinal pigment epithelium (RPE) and lacrimal gland (LG) tissues from lCNV mice (n = 25). Tear VEGF levels were significantly elevated in eAMD patients, correlating with disease severity. Females exhibited higher VEGF levels, a pattern not replicated in the mouse model. In lCNV mice, VEGF overexpression originated from the choroid–RPE, driven by hypoxic and inflammatory signaling, with no significant LG contribution. Increased VEGF, IL-6, and vimentin expression, along with NF-κB and STAT3 activation, were observed. These findings suggest that tear VEGF is a promising non-invasive biomarker for eAMD, warranting further validation for clinical application in disease monitoring and treatment optimization. Full article

Background: Sarcopenia has been associated with poor outcomes in pancreatic cancer (PC). However, published results are heterogeneous in terms of study design, oncological outcomes, and sarcopenia measurements. This meta-analysis aims to evaluate the impact of computed tomography (CT)-based sarcopenia on overall survival (OS) and progression-free survival (PFS) in patients with PC, considering potential confounders such as the CT-based method and thresholds used to define sarcopenia, as well as treatment intention. Methods: We systematically searched databases for observational studies reporting hazard ratios (HRs) for OS and PFS in PC patients stratified by CT-based sarcopenia status. Random-effects models were used to calculate pooled crude and adjusted HRs (cHRs and aHRs, respectively), with subgroup analyses based on sarcopenia measurement methods, cutoff values, sarcopenia prevalence, and treatment intention. Heterogeneity was assessed using the I² and τ² statistics, and publication bias was evaluated using funnel plots and Egger’s test. Results: Data from 48 studies were included. Sarcopenia was significantly associated with worse OS (pooled cHR = 1.58, 95% CI: 1.38–1.82; pooled aHR = 1.39, 95% CI: 1.16–1.66) and worse PFS (pooled cHR = 1.55, 95% CI: 1.29–1.86; pooled aHR = 1.31, 95% CI: 1.11–1.55). Subgroup analyses revealed significantly different, stronger associations in studies using stricter sarcopenia cutoffs (<50 cm²/m² for males) and in patients undergoing curative treatments. Heterogeneity was substantial across analyses (I² > 67%), but with generally low τ² values (0.01–0.25). Egger’s test indicated potential publication bias for OS (p < 0.001), but no significant bias was observed for PFS (p = 0.576). Conclusions: Sarcopenia determined by CT is an independent predictor of poor OS and PFS in PC, but this association varies depending on the cutoff used for its definition as well as on the treatment intention. Therefore, its routine assessment in clinical practice could provide valuable prognostic information, but future research should focus on standardizing sarcopenia assessment methods. Full article

Leishmania major is the etiological agent of cutaneous leishmaniasis (CL) in several countries in Asia and Northern Africa. The disease is considered a zoonotic infection where rodents are the reservoirs and phlebotomine sandflies are the vectors. Once inside the human body, the parasite multiplies inside the macrophages of infected patients, but the disease eventually cures spontaneously, leaving scars where the phlebotomine bites occurred. Given the importance of the replicative forms in the parasite’s cell cycle, here, we decided to study the enzyme telomerase, which has the critical role of replenishing the chromosomal telomeric ends during cell replication. To this aim, we first conducted partial purification using Sephacryl-300 HR gel filtration, which allowed us to determine that the telomerase activity eluted as a 600 KDa complex. Second, we characterized an immunopurified L. major telomerase, and to try to explain some of our findings, we performed modeling studies using Alfa fold 3, Pyre2, and Swiss Protein Model. Finally, considering the similarity between the catalytic site of Leishmania and Homo sapiens telomerase, we decided to test typical inhibitors of human telomerase on the purified enzyme and promastigote cell forms, confirming that MST-312 and TMPYP4 efficiently inhibited L. major activity and arrested cell growth in Leishmania promastigotes. Our findings confirm the importance of telomerase activity in L. major’s replicative forms and suggest the possibility of using drugs previously tested on human telomerase to treat CL. Full article

Gun violence is a global problem that affects communities and individuals, posing challenges to safety and well-being. The use of autonomous weapons detection systems could significantly improve security worldwide. Despite notable progress in the field of weapons detection closed-circuit television-based systems, several challenges persist, including real-time detection, improved accuracy in detecting small objects, and reducing false positives. This paper, based on our extensive experience in this field and successful private company contracts, presents a detection scheme comprising two modules that enhance the performance of a renowned detector. These modules not only augment the detector’s performance but also have a low negative impact on the inference time. Additionally, a scale-matching technique is utilised to enhance the detection of weapons with a small aspect ratio. The experimental results demonstrate that the scale-matching method enhances the detection of small objects, with an improvement of +13.23 in average precision compared to the non-use of this method. Furthermore, the proposed detection scheme effectively reduces the number of false positives (a 71% reduction in the total number of false positives) of the baseline model, while maintaining a low inference time (34 frames per second on an NVIDIA GeForce RTX-3060 card with a resolution of 720 pixels) in comparison to the baseline model (47 frames per second). Full article

Background: Cancer-therapy-related cardiac dysfunction (CTRCD) is a growing concern for public health, with a growing incidence due to improved survival rates of patients with hematological malignancies due to diagnostic and therapeutic advances. The identification of patients at risk for CTRCD is vital to developing preventive strategies. Methods: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage, and echocardiographic information were collected. Results: A total of 200 patients were included. The incidence of CTRCD was 17.4% (35/200). Patients with CTRCD were older than those without CTRCD, with a mean age of 65.17 years vs. 56.77 (p = 0.008). Dyslipidemia (DL) (31.4% vs. 13.4% p = 0.017) and previous cardiovascular disease (40% vs. 13.3%; p < 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg/L ± 101.02, and they were 251.518 kg/L ± 26.22 in those who did not (p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory’s upper reference limit. Patients were followed for a median of 51.83 months (0.76–73.49). The presence of a CTCRD event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI: 1.08–2.93); p = 0.031). Conclusions: Early identification of risk factors is crucial to manage patients at risk for CTRCD. Full article

Biostimulants are substances or microorganisms that are applied to plants, soil, or seeds, to improve the growth, development, performance, and quality of crops. Their application is mainly directed towards improving the resistance of crops against abiotic and biotic stresses. These compounds are formulated from a great variety of compounds: humic substances, complex organic materials (sewage sludge extracts, composts, and manure), chemical elements (Al, Co, Na, Se, and Si), inorganic salts including phosphite, seaweed extracts (brown, red, and green), amino acids, etc. As of today, it has been observed that corn steep liquor (CSL), which is obtained from the industrial process of corn transformation, may be a good ingredient for the formulation of biostimulant products. CSL contains a large amount of different chemical compounds with biological activity for the plants and soil. The use of CSL industrial waste, previously formulated, could have a direct or indirect effect on the physiological processes and metabolic routes of plants related to the adaptation to abiotic and biotic stresses, as their compounds are part of these metabolic pathways, act as elicitor compounds, and/or have their own biological activity in the plants. There is evidence that the application of CSL could protect plants from specific abiotic and biotic stresses, such as an excess of light or temperature, nutritional limitations, salinity, drought, or pathogens. In addition, it can improve the growth of the plant when these are grown in hydroponic systems, and can improve the health of soils. The present article is focused on describing the most relevant scientific aspects of CSL when used as an ingredient to formulate biostimulants for agriculture. It will discuss its chemical composition, the analytical techniques utilized to elucidate and quantify its compounds, its uses in agriculture, and mode of action in the plants. Full article

The use of biostimulants is becoming a useful tool for increasing crop productivity while enhancing nutritional quality. However, new studies are necessary to confirm that the joint application of different types of biostimulants, together with bioactive compounds, is effective and not harmful to plants. This study examined the impact of applying the biostimulant Green Leaves, comprising Macrocystis algae extract and containing a mixture of amino acids, corn steep liquor extract, calcium, and the bioactive compound glycine betaine. The effect of applying two different doses (3 and 5 mL L⁻¹) of this biostimulant was evaluated on lettuce plants, and growth and quality parameters were analyzed along with photosynthetic efficiency, nutritional status, and nutrient efficiency parameters. The application of Green Leaves improved plant weight (25%) and leaf area and enhanced the photosynthetic rate, the accumulation of soluble sugars and proteins, and the agronomic efficiency of all essential nutrients. The 3 mL L⁻¹ dose improved the nutritional quality of lettuce plants, improving the concentration of phenolic compounds and ascorbate and the antioxidant capacity and reducing NO₃⁻ accumulation. The 5 mL L⁻¹ dose improved the absorption of most nutrients, especially N, which reduced the need for fertilizers, thus reducing costs and environmental impact. In short, the Green Leaves product has been identified as a useful product for obtaining higher yield and better quality. Full article

Sign language serves as the primary mode of communication for the deaf community. With technological advancements, it is crucial to develop systems capable of enhancing communication between deaf and hearing individuals. This paper reviews recent state-of-the-art methods in sign language recognition, translation, and production. Additionally, we introduce a rule-based system, called ruLSE, for generating synthetic datasets in Spanish Sign Language. To check the usefulness of these datasets, we conduct experiments with two state-of-the-art models based on Transformers, MarianMT and Transformer-STMC. In general, we observe that the former achieves better results (+3.7 points in the BLEU-4 metric) although the latter is up to four times faster. Furthermore, the use of pre-trained word embeddings in Spanish enhances results. The rule-based system demonstrates superior performance and efficiency compared to Transformer models in Sign Language Production tasks. Lastly, we contribute to the state of the art by releasing the generated synthetic dataset in Spanish named synLSE. Full article

In the last few years, nivolumab has become the standard of care for advanced-stage lung cancer patients. Unfortunately, up to 60% of patients do not respond to this treatment. In our study, we identified variations in gene expression related to primary resistance to immunotherapy. Bronchoscopy biopsies were obtained from advanced non-small cell lung cancer (NSCLC) patients previously characterized as responders or non-responders after nivolumab treatment. Ten tumor biopsies (from three responders and seven non-responders) were analyzed by the differential expression of 760 genes using the NanoString nCounter platform. These genes are known to be involved in the response to anti-PD1/PD-L1 therapy. All the patients were treated with nivolumab. Examining the dysregulated expression of 24 genes made it possible to predict the response to nivolumab treatment. Supervised analysis of the gene expression profile (GEP) revealed that responder patients had significantly higher levels of expression of CXCL11, NT5E, KLRK1, CD3G, GZMA, IDO1, LCK, CXCL9, GNLY, ITGAL, HLA-DRB1, CXCR6, IFNG, CD8A, ITK, B2M, HLA-B, and HLA-A than did non-responder patients. In contrast, PNOC, CD19, TP73, ARG1, FCRL2, and PTGER1 genes had significantly lower expression levels than non-responder patients. These findings were validated as predictive biomarkers in an independent series of 201 patients treated with nivolumab (22 hepatocellular carcinomas, 14 non-squamous cell lung carcinomas, 5 head and neck squamous cell carcinomas, 1 ureter/renal pelvis carcinoma, 120 melanomas, 4 bladder carcinomas, 31 renal cell carcinomas, and 4 squamous cell lung carcinomas). ROC curve analysis showed that the expression levels of ITK, NT5E, ITGAL, and CD8A were the best predictors of response to nivolumab. Further, 13/24 genes showed an adverse impact on overall survival (OS) in an independent, large series of patients with NSCLC (2166 cases). In summary, we found a strong association between the global GEP of advanced NSCLC and the response to nivolumab. The classification of NSCLC patients based on GEP enabled us to identify those patients who genuinely benefited from treatment with immune checkpoint inhibitors (ICIs). We also demonstrated that abnormal expression of most of the markers comprising the genomic signature has an adverse influence on OS, making them significant markers for therapeutic decision-making. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these biomarkers. Full article

The aim of this work is to develop different encapsulated propolis ingredients by spray-drying and to evaluate their bioaccessibility using simulated in vitro digestion. To achieve these goals, first, microparticles of a propolis extract with inulin as the coating polymer were prepared under the optimal conditions previously determined. Then, a fraction of inulin was replaced with other encapsulating agents, namely sodium alginate, pectin, and chitosan, to obtain different ingredients with controlled release properties in the gastrointestinal tract. The analysis of the phenolic profile in the propolis extract and microparticles showed 58 compounds tentatively identified, belonging mainly to phenolic acid derivatives and flavonoids. Then, the behavior of the free extract and the formulated microparticles under gastrointestinal conditions was studied through an in vitro gastrointestinal digestion process using the INFOGEST protocol. Digestion of the free extract resulted in the degradation of most compounds, which was minimized in the encapsulated formulations. Thus, all developed microparticles could be promising strategies for improving the stability of this bioactive extract under gastrointestinal conditions, thereby enhancing its beneficial effect. Full article

Introduction: Immunotherapy represents a key pillar of cancer treatments, with high response rates and long survival. Its use is increasing, mainly at the expense of the geriatric population due to the ageing of this population. However, despite its benefit, its safety in certain areas such as cardiotoxicity is largely unknown. The aim of this study is to assess the safety of immunotherapy in elderly patients using real-world data. Methods: This is an ambispective study of patients ≥ 70 years old with solid tumours who were treated with immunotherapy at the University Hospital of Salamanca. Cardiotoxicity was assessed using the CTCAEv5.0 criteria. Results: In total, 195 patients were included (76.9% male and 23.1% female), with a mean age of 75 years [70–93]. The percentage of patients with cardiotoxicity was 1.54%; 1.35% of patients with previous heart disease were diagnosed with cardiotoxicity, and 1.65% of those without previous heart disease were diagnosed with cardiotoxicity. The median time from the initiation of treatment until the cardiac event was 45 days [14–96]. The most frequent toxicity was myocarditis in 66.7% of patients, followed by arrhythmias in 33.3% of patients. Conclusions: Immunotherapy is shown to be a safe treatment in elderly cancer patients in terms of cardiotoxicity. The event rate shows no difference between patients with or without cardiac comorbidity. Full article

In recent years, non-small cell lung cancer treatment has been revolutionized. EGFR tyrosine kinase inhibitors and our improved understanding of its alterations have driven new diagnostic strategies. Liquid biopsies have emerged as a useful tool in these contexts, showing potential utility in early diagnosis combined with low-dose CT scans, as well as potential in monitoring treatment response and predicting the development of patients. We studied the circulating tumor DNA (ctDNA) of 38 EGFR-mutated non-small cell lung cancer patients at diagnosis in different moments of their disease by liquid biopsy techniques. Our results show that mean overall survival was significantly lower when a liquid biopsy was positive for the detection of EGFR mutations compared with wild-type patients in their liquid biopsy in both univariate (29 ± 4 vs. 104 ± 19 months; p = 0.004) and multivariate analysis (p = 0.008). Taking this into consideration, liquid biopsies could be key to improving the control of this disease. Full article

Salinity, caused by irrigation with water containing high salt concentrations, excessive fertilization, or the loss of leaching capacity in some soils, is a serious problem on a global scale. Its incidence leads to osmotic and specific effects, as well as an imbalance in nutrient uptake that hinders the growth of most crops. Biostimulants can improve salt tolerance by reducing the uptake and accumulation of toxic ions. Corn steep liquor (CSL) is a byproduct of corn cleaning and maceration. This study investigates whether CSL application induces adaptive responses in pepper (Capsicum annuum L.) plants cultivated under saline conditions. Four treatments were carried out with pepper plants in a culture chamber: irrigation with Hoagland nutrient solution; irrigation with 100 mM NaCl in the Hoagland nutrient solution; irrigation with 100 mM NaCl in the Hoagland nutrient solution and the foliar application of CSL at 5 mL L⁻¹ every 7 days; and irrigation with 100 mM NaCl in the Hoagland nutrient solution and root application of CSL at 5 mL L⁻¹ every 7 days. The beneficial effect of CSL in reducing the phytotoxicity of salt stress was found to be due to an improvement in the photosynthetic efficiency and a reduction in the generation of reactive oxygen species. Thus, the increase in MDA concentration due to saline treatment is less when applying CSL, which is 3.5 times less when it is performed via the foliar route and 4.6 times if the treatment is on the root. The results show that CSL application increased the aerial biomass and leaf area under saline conditions through physiological mechanisms that varied depending on the application method. Full article