Search Results (81)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient’s quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0–8) was reduced significantly in the cohort (mean change: −2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (−3.57, p < 0.0001) and smell impairment (−4.0, p < 0.0001) visual analog scale scores (0–10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population. Full article

This paper proposes an experimental procedure based on hyperspectral imaging (HSI) combined with statistical classification for assessing archaeo-paleoanthropological stratigraphic deposits at the Gran Dolina site (TD10 unit), located in the Sierra de Atapuerca (Burgos, Spain). Representative spectral reflectance signatures were determined and analyzed using HSI measurements and statistical classification methods in natural light conditions across various capture distances. This study aims to characterize and quantify cave sediments by defining spectral models for feature classification and spectral similarity analysis, evaluating the strengths and limitations of spectral captures at this specific site. HSI technology enhances the analysis and identification of materials at an internationally recognized reference site for human evolution studies. Hyperspectral imaging assessment of archaeo-paleoanthropological stratigraphic deposits emerges as an innovative digital tool, revolutionizing the sustainable management of cultural heritage and environmental sciences by enabling advanced material identification and stratigraphic analysis. Full article

Eliciting DNA damage in tumor cells continues to be one of the most successful strategies against cancer. This is the case for classical chemotherapy drugs and radiotherapy. In the modern era of personalized medicine, this strategy tries to identify specific vulnerabilities found in each patient’s tumor, to inflict DNA damage in certain cell contexts that end up in massive cancer cell death. Cells rely on multiple DNA repair pathways to fix DNA damage, but cancer cells frequently exhibit defects in these pathways, many times being tolerant to the damage. Key vulnerabilities, such as BRCA1/BRCA2 mutations, have been exploited with PARP inhibitors, leveraging synthetic lethality to selectively kill tumor cells and improving patients’ survival. In the DNA damage response (DDR) network, kinases ATM, ATR, Chk1, and Chk2 coordinate DNA repair, cell cycle arrest, and apoptosis. Inhibiting these proteins enhances tumor sensitivity to DNA-damaging therapies, especially in DDR-deficient cancers. Several small-molecule inhibitors targeting ATM/Chk2 or ATR/Chk1 are currently being tested in preclinical and/or clinical settings, showing promise in cancer models and patients. Additionally, pharmacological blockade of ATM/Chk2 and ATR/Chk1 axes enhances the effects of immunotherapy by increasing tumor immunogenicity, promoting T-cell infiltration and activating immune responses. Combining ATM/Chk2- or ATR/Chk1-targeting drugs with conventional chemotherapy, radiotherapy or immune checkpoint inhibitors offers a compelling strategy to improve treatment efficacy, overcome resistance, and enhance patients’ survival in modern oncology. Full article

Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response. Full article

In the present work, a novel and economical pH sensor has been improved through the application of the conducting polymers poly(3,4-ethylendioxythiphene) and poly(sodium 4-styrene sulphonate). Sinusoidal voltages were applied to electrodeposit the different polymers studied for different periods (10, 15, and 20 min) on the electrode surface. The presence of polyaniline and its reversible redox structure have been corroborated by cyclic voltammetry. The working range has been increased from 3–8 to 2–12, obtaining adequate sensibility and linearity. This new sensor presented satisfactory repeatability, reproducibility (RSD < 5%), AND reversibility (pH range 2–12), and excellent selectivity towards H⁺ in the presence of diverse interferents in agrifood samples. Finally, the sensor was used to measure the pH in several real samples, whose pH values ranged from 2.23 to 11.5, obtaining excellent results. In addition, the values found were very similar to those reported by the gold technique (pH meter), with an error of less than 10% for most of the samples analyzed. In addition, a preliminary survey about measurements in a continuous flow, using a 3D homemade microfluidic cell, was performed with promising results. Full article

The aim of this study was to analyze the effects of the playing position (backs vs. pivots vs. wings) and the player role (starter vs. non-starter) on the internal match load and well-being status of female handball players after official matches. Fourteen female handball players from the Spanish 2nd Division were monitored during a half-season (13 matches, n = 102 individual observations) using the rate of perceived exertion (match RPE) and the Hooper questionnaire in MD+1 and MD+2. Differences in match RPE according to playing positions and player roles were determined by one-way ANOVA or by a paired t-test, respectively. Differences in well-being status according to playing positions or player roles and time (MD+1 and MD+2) were assessed through mixed two-way ANOVA. Furthermore, partial eta-squared (ηp²) and Cohen’s d (ES) were calculated and interpreted using Hopkins’ categorization criteria. Backs registered moderately more match RPE compared to pivots (p < 0.05, ES = 0.84). By contrast, wings experienced the highest values of fatigue and muscle soreness in MD+1 and MD+2 compared to all other playing positions (p < 0.05, ES = 0.66–0.93). Also, the wings reported moderately higher Hooper index scores in MD+1 and MD+2 than backs (p < 0.01, ES = 0.73–0.77). In relation to the player role, starters reported higher absolute values of match RPE, fatigue, muscle soreness, and the Hooper index in MD+1 compared to non-starters (p < 0.05, ES = 0.25–0.29). Additionally, regardless of the playing position and the role, all of the players reported moderately less fatigue and Hooper index scores in MD+2 compared to MD+1 (p < 0.05, ES = 0.66–1.34). Therefore, coaches and practitioners should consider the internal match load and well-being status of players to implement different training stimuli (e.g., recovery or compensatory strategies) in MD+1 according to playing positions and player roles. Full article

The assessment of clinical competencies is essential in medical training, and the Objective Structured Clinical Examination (OSCE) is an essential tool in this process. There are multiple studies exploring the usefulness of artificial intelligence (AI) in medical education. This study explored the use of the GPT-4 AI model to grade clinical reports written by students during the OSCE at the Teaching Unit of the 12 de Octubre and Infanta Cristina University Hospitals, part of the Faculty of Medicine at the Complutense University of Madrid, comparing its results with those of human graders. Ninety-six (96) students participated, and their reports were evaluated by two experts, an inexperienced grader, and the AI using a checklist designed during the OSCE planning by the teaching team. The results show a significant correlation between the AI and human graders (ICC = 0.77 for single measures and 0.91 for average measures). AI was more stringent, assigning scores on an average of 3.51 points lower (t = −15.358, p < 0.001); its correction was considerably faster, completing the analysis in only 24 min compared to the 2–4 h required by human graders. These results suggest that AI could be a promising tool to enhance efficiency and objectivity in OSCE grading. Full article

Antibody–drug conjugates (ADCs) represent a therapeutic modality that guides chemotherapies to tumoral cells by using antibodies against tumor-associated antigens (TAAs). The antibody and the chemotherapy or payload are attached by a chemical structure called the linker. The strategy for the development of this type of drug was based on several rational pillars, including the use of a very potent payload and the use of specific antibodies acting only on antigens expressed on tumoral cells. In this article, by using data from all approved ADCs that have received regulatory approval, we analyze the potential contribution of each ADC component to preclinical activity. We suggest that payload potency and the drug-to-antibody ratio (DAR) have a less relevant role in relation to efficacy than previously considered. Additionally, we have observed that some ADCs have been developed against antigens also present in non-transformed tissues, which could suggest that TAA specificity is not a mandatory requirement. Finally, we have identified that ADCs with payloads harboring more favorable physicochemical characteristics showed better potential activity. In this article, we also review other aspects that should be taken into consideration for ADC design, including linker structure, stability, conjugation type, pharmacokinetics, receptor internalization, and recycling. Based on currently available data, our study summaries different concepts that should be considered in the design of novel ADCs in the future. Full article

Collecting is a form of leisure, and even a passion, consisting of collecting, preserving and displaying objects. When we look for its origin in the literature, we are taken back to “the appearance of writing and the fixing of knowledge”, specifically with the Assyrian King Ashurbanipal (7th century BC, Mesopotamia), and his fondness for collecting books, which in his case were in the form of clay tablets. This is not, however, a true reflection, for we have evidence of much earlier collectors. The curiosity and interest in keeping stones or fossils of different colors and shapes, as manuports, is as old as we are. For decades we have had evidence of objects of no utilitarian value in Neanderthal homes. Several European sites have shown that these Neanderthal groups treasured objects that attracted their attention. On some occasions, these objects may have been modified to make a personal ornament and may even have been integrated into subsistence activities such as grinders or hammers. Normally, one or two such specimens are found but, to date, no Neanderthal cave or camp has yielded as many as the N4 level of Prado Vargas Cave. In the N4 Mousterian level of Prado Vargas, 15 specimens of Upper Cretaceous marine fossils belonging to the Gryphaeidae, Pectinidae, Cardiidae, Pholadomyidae, Pleurotomariidae, Tylostomatidae and Diplopodiidae families were found in the context of clay and autochthonous cave sediments. During MIS 3, a group of Neanderthals transported at least fifteen marine fossils, which were collected from various Cretaceous units located in the surrounding area, to the Prado Vargas cave. The fossils, with one exception, show no evidence of having been used as tools; thus, their presence in the cave could be attributed to collecting activities. These activities could have been motivated by numerous tangible and intangible causes, which suggest that collecting activities and the associated abstract thinking were present in Neanderthals before the arrival of modern humans. Full article

Background: Non-Small Cell Lung Cancer (NSCLC) remains a challenging disease to manage with effectiveness. Early detection and precise monitoring are crucial for improving patient outcomes. Circulating tumor DNA (ctDNA) offers a non-invasive cancer detection and monitoring method. Emerging biomarkers, such as ctDNA methylation, have shown promise in enhancing diagnostic accuracy and prognostic assessment in NSCLC. In this review, we examined the current evidence regarding ctDNA methylation’s role in NSCLC detection through a systematic review of the existing literature and meta-analysis. Methods: We systematically searched PubMed, Medline, Embase, and Web of Science databases up to 26 June 2024 for studies on the role of ctDNA methylation analysis in NSCLC patients. We included studies from 2010 to 2024 on NSCLC patients. We excluded case reports, non-English articles, studies on cell lines or artificial samples, those without cfDNA detection, prognostic studies, and studies with non-extractable data or mixed cancer types. Funnel plots were visually examined for potential publication bias, with a p value < 0.05 indicating bias. Meta-analysis was conducted using R packages (meta, forestplot, and mada). Combined sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), positive and negative predictive values, diagnostic odds ratio (DOR), and 95% confidence intervals (95% CI) were calculated. A summary receiver operating characteristic curve (SROC) and area under the curve (AUC) with related Standard Error (SE) were used to evaluate the overall diagnostic performance. Additionally, RASSF1A, APC, SOX17, SEPT9, and RARβ2 were analyzed, since their methylation was assessed in two or more studies. Results: From 38 candidate papers, we finally identified 12 studies, including 472 NSCLC patients. The pooled sensitivity was 0.62 (0.47–0.77) and the specificity was 0.90 (0.85–0.94). The diagnostic odds ratio was 15.6 (95% CI 9.36–26.09) and the area under the curve was 0.249 (SE = 0.138). The positive and negative predictive values were 5.38 (95% CI 3.89–7.44) and 0.34 (95% CI 0.22–0.54), respectively. For single genes, the specificity reached 0.83~0.96, except for RARβ2, but the sensitivity was relatively low for each gene. Significant heterogeneity across the included studies, the potential publication bias for specificity (p = 0.0231), and the need to validate the clinical utility of ctDNA methylation for monitoring treatment response and predicting outcomes in NSCLC patients represent the main limitations of this study. Conclusions: These results provide evidence of the significant potential of ctDNA methylation as a valuable biomarker for improving the diagnosis of NSCLC, advocating for its integration into clinical practice to enhance patient management. Full article

We propose a novel mono-temporal framework with a physical basis and ecological consistency to retrieve fire severity at very high spatial resolution. First, we sampled the Composite Burn Index (CBI) in 108 field plots that were subsequently surveyed through unmanned aerial vehicle (UAV) flights. Then, we mimicked the field methodology for CBI assessment in the remote sensing framework. CBI strata were identified through individual tree segmentation and geographic object-based image analysis (GEOBIA). In each stratum, wildfire ecological effects were estimated through the following methods: (i) the vertical structural complexity of vegetation legacies was computed from 3D-point clouds, as a proxy for biomass consumption; and (ii) the vegetation biophysical variables were retrieved from multispectral data by the inversion of the PROSAIL radiative transfer model, with a direct physical link with the vegetation legacies remaining after canopy scorch and torch. The CBI scores predicted from UAV ecologically related metrics at the strata level featured high fit with respect to the field-measured CBI scores (R² > 0.81 and RMSE < 0.26). Conversely, the conventional retrieval of fire effects using a battery of UAV structural and spectral predictors (point height distribution metrics and spectral indices) computed at the plot level provided a much worse performance (R² = 0.677 and RMSE = 0.349). Full article

The KM3NeT Collaboration is building an underwater neutrino observatory at the bottom of the Mediterranean Sea, consisting of two neutrino telescopes, both composed of a three-dimensional array of light detectors, known as digital optical modules. Each digital optical module contains a set of 31 three-inch photomultiplier tubes distributed over the surface of a 0.44 m diameter pressure-resistant glass sphere. The module also includes calibration instruments and electronics for power, readout, and data acquisition. The power board was developed to supply power to all the elements of the digital optical module. The design of the power board began in 2013, and ten prototypes were produced and tested. After an exhaustive validation process in various laboratories within the KM3NeT Collaboration, a mass production batch began, resulting in the construction of over 1200 power boards so far. These boards were integrated in the digital optical modules that have already been produced and deployed, which total 828 as of October 2023. In 2017, an upgrade of the power board, to increase reliability and efficiency, was initiated. The validation of a pre-production series has been completed, and a production batch of 800 upgraded boards is currently underway. This paper describes the design, architecture, upgrade, validation, and production of the power board, including the reliability studies and tests conducted to ensure safe operation at the bottom of the Mediterranean Sea throughout the observatory’s lifespan. Full article

Background: Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer stem cells. Materials and methods: A randomized trial involving 42 patients. All patients were diagnosed with pancreatic ductal adenocarcinoma. Group I: R0 resection. Group II. R0 resection and HIPEC with gemcitabine (120 mg/m² for 30 min). Effectiveness was measured with analysis of overall survival, disease-free survival, distant recurrence, locoregional recurrence, and measuring of pancreatic cancer stem cells (EpCAM⁺CXCR4⁺CD133⁺). Results: From 2017 to 2023, 63 patients were recruited for our clinical trial; 21 patients were included in each group, and 21 were excluded. Locoregional recurrence, p-value: 0.022, was lower in the experimental group. There were no significant differences between the two groups in hospital mortality, perioperative complications, or hospital costs. We found a significant decrease in pancreatic cancer stem cells in patients in the experimental group after treatment, p -value of 0.018. Conclusions: The use of HIPEC with gemcitabine after surgery in patients with resectable pancreatic ductal adenocarcinoma reduces locoregional recurrence and may be associated with a significant decrease in pancreatic cancer stem cells. Full article

(1) Background: The increasing life expectancy brings an increase in geriatric syndromes, specifically frailty. The literature shows that exercise is a key to preventing, or even reversing, frailty in community-dwelling populations. The main objective is to demonstrate how an intervention based on multicomponent exercise produces an improvement in frailty and pre-frailty in a community-dwelling population. (2) Methods: a prospective observational study of a multicomponent exercise program for geriatric revitalization with people aged over 65 holding Barthel Index scores equal to, or beyond, 90. The program was developed over 30 weeks, three times a week, in sessions lasting 45–50 min each. Frailty levels were registered by the Short Physical Performance Battery, FRAIL Questionnaire Screening Tool, and Timed “Up & Go” at the beginning of the program, 30 weeks later (at the end of the program), and following 13 weeks without training; (3) Results: 360 participants completed the program; a greater risk of frailty was found before the program started among older women living in urban areas, with a more elevated fat percentage, more baseline pathologies, and wider baseline medication use. Furthermore, heterogeneous results were observed both in training periods and in periods without physical activity. However, they are consistent over time and show improvement after training. They show a good correlation between TUG and SPPB; (4) Conclusions: A thirty-week multicomponent exercise program improves frailty and pre-frailty status in a community-dwelling population with no functional decline. Nevertheless, a lack of homogeneity is evident among the various tools used for measuring frailty over training periods and inactivity periods. Full article

Manganosalen complexes are a class of catalytic antioxidants with beneficial effects against different neurological disorders according to various in vitro and in vivo studies. The interest in the factors that determine their antioxidant activity is based on the fact that they are key to achieving more efficient models. In this work, we report a set of new manganosalen complexes, thoroughly characterized in the solid state and in solution by different techniques. The chelating Schiff base ligands used were prepared from condensation of different substituted hydroxybenzaldehydes with 1,2-diaminoethane and 1,3-diaminopropane. The antioxidant activity of the new models was tested through superoxide dismutase and catalase probes in conjunction with the studies about their neuroprotective effects in human SH-SY5Y neuroblastoma cells in an oxidative stress model. The ability to scavenge excess reactive oxygen species (ROS) varied depending on the manganosalen models, which also yielded different improvements in cell survival. An assessment of the different factors that affect the oxidant activity for these complexes, and others previously reported, revealed the major influence of the structural factors versus the redox properties of the manganosalen complexes. Full article