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Investigación contiene los documentos generados por los docentes e investigadores de la Universidad en su labor de investigación. Este depósito tiene como objetivos el almacenamiento, la gestión, la preservación y la difusión de estos documentos, y pretende contribuir al aumento de la visibilidad del trabajo desarrollado por los miembros de la comunidad universitaria.
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- PublicationOpen Access20 Años de la Revista Arteterapia. Papeles de arteterapia y educación artística para la inclusión social.(2026-05-27) López Martínez, María Dolores; García Sandoval, Juan; Expresión Plástica, Musical y DinámicaCoordinación e Introducción al monografico especial de 20 Años de la Revista Arteterapia. Papeles de arteterapia y educación artística para la inclusión social.
- PublicationOpen Access23S rRNA and L22 ribosomal protein are involved in the acquisition of macrolide and lincosamide resistance in Mycoplasma capricolum subsp. capricolum(Elsevier, ) Prats-van der Ham, Miranda; Tatay-Dualde, Juan; Gómez-Martín, Angel; Corrales, Juan Carlos; Contreras de Vera, Antonio; Sánchez López, Antonio; de la Fe, Christian; Sanidad AnimalMycoplasma capricolum subsp. capricolum (Mcc) is one of the causative agents of contagious agalactia, and antimicrobial treatment is the most commonly applied measure to treat outbreaks of this disease. Macrolides and lincosamides bind specifically to nucleotides at domains II and V of the 23S rRNA gene. Furthermore, rplD and rplV genes encode ribosomal proteins L4 and L22, which are also implicated in the macrolide binding site. The aim of this work was to study the relationship between these genes and the acquisition of macrolide and lincosamide resistance in Mcc. For this purpose, in vitro selected resistant mutants and field isolates were studied. This study demonstrates the appearance of DNA point mutations at the 23S rRNA encoding genes (A2058G, A2059G and A2062C) and rplV gene (Ala89Asp) in association to high minimum inhibitory concentration values. Hence, it proves the importance of 23S rRNA domain V and ribosomal protein L22 as molecular mechanisms responsible for the acquisition of macrolide and lincosamide resistance in both field isolates and in vitro selected mutants. Furthermore, these mutations enable us to provide an interpretative breakpoint of antimicrobial resistance for Mcc at MIC 0.8 µg/ml.
- PublicationOpen Access31st EAO Annual Scientific Meeting Milan, 24–26 October 2024(European Association for Osseointegration, 2024) Sánchez Pérez, Arturo Joaquín; Ernesto De-Larriva; Pedro Antonio Barreiro-Gabeiras; Luis Miguel Sánchez-Suárez; Emilio Sánchez-Talaverano; Ambrosio Bernabeu-Esclapez; Jose Antonio Sánchez-Nicolás Andrés; Valdés-Beltrán; Javier Amigó-Bardají; Dermatología, Estomatología, Radiología y Medicina Física
- PublicationRestricted32nd EAO Annual Scientific Meeting Monaco, 18–20 September 2025(2025) Guillem Esteve-Pardo; Lino Esteve Colomina; Pedro Barreiro Gabeiras; Ernesto De Larriva; Emilio Sánchez Talaverano; Luis Miguel Sánchez Suárez; José Antonio Sánchez Nicolás; Ambrosio Bernabeu Esclapez; Andrés Valdés Beltrán; Javier Amigó Bardají; David Esteve Colomina; Sánchez Pérez, Arturo Joaquín; Dermatología, Estomatología, Radiología y Medicina Física
- PublicationOpen Access7,8-Dihydroxiflavone maintains retinal functionality and protects various types of RGCs in adult rats with optic nerve transection(MDPI, 2021-10-30) Gallego Ortega, Alejandro; Vidal Villegas, Beatriz; Norte Muñoz, María; Salinas Navarro, Manuel Ángel; Avilés Trigueros, Marcelino; Villegas Pérez, Maria Paz; Vidal Sanz, Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de MedicinaTo analyze the neuroprotective effects of 7,8-Dihydroxyflavone (DHF) in vivo and ex vivo, adult albino Sprague-Dawley rats were given a left intraorbital optic nerve transection (IONT) and were divided in two groups: One was treated daily with intraperitoneal (ip) DHF (5 mg/kg) (n = 24) and the other (n = 18) received ip vehicle (1% DMSO in 0.9% NaCl) from one day before IONT until processing. At 5, 7, 10, 12, 14, and 21 days (d) after IONT, full field electroretinograms (ERG) were recorded from both experimental and one additional naïve-control group (n = 6). Treated rats were analyzed 7 (n = 14), 14 (n = 14) or 21 d (n = 14) after IONT, and the retinas immune stained against Brn3a, Osteopontin (OPN) and the T-box transcription factor T-brain 2 (Tbr2) to identify surviving retinal ganglion cells (RGCs) (Brn3a+), α-like (OPN+), α-OFF like (OPN+Brn3a+) or M4-like/α-ON sustained RGCs (OPN+Tbr+). Naïve and right treated retinas showed normal ERG recordings. Left vehicle-treated retinas showed decreased amplitudes of the scotopic threshold response (pSTR) (as early as 5 d), the rod b-wave, the mixed response and the cone response (as early as 10 d), which did not recover with time. In these retinas, by day 7 the total numbers of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs decreased to less than one half and OPN+Brn3a+RGCs decreased to approximately 0.5%, and Brn3a+RGCs showed a progressive loss with time, while OPN+RGCs and OPN+Tbr2+RGCs did not diminish after seven days. Compared to vehicle-treated, the left DHF-treated retinas showed significantly greater amplitudes of the pSTR, normal b-wave values and significantly greater numbers of OPN+RGCs and OPN+Tbr2+RGCs for up to 14 d and of Brn3a+RGCs for up to 21 days. DHF affords significant rescue of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs, but not OPN+Brn3a+RGCs, and preserves functional ERG responses after IONT.
- PublicationOpen AccessA 12-week wearable-based intervention in adolescents: feasibility, adherence, and preliminary outcomes from a quasi-experimental study(Asociación Española de Ciencias del Deporte, 2026-06-30) Mateo Orcajada, Adrián; Abenza-Cano, Lucía; López Miñarro, Pedro Ángel; Meroño, Lourdes; Gallardo-Guerrero, Ana María; Morales-Belando, María T.; González-Gálvez, Noelia; Espeso-García, Alejandro; Abelleira-Lamela, Tomás; Gómez-Cuesta, Nerea; Albaladejo-Saura, Mario; Santos-Villa, María José; Pérez-Templado, Miguel Gual; Ruiz-Gutiérrez, Antonio; Farnós-Visedo, Verónica; Saura-Lucas, Sonia; Martínez-Molina, Marina; Merino-Barrero, Juan Andrés; Esparza-Ros, Francisco; Vaquero Cristóbal, Raquel; Expresión Plástica, Musical y DinámicaLittle is known about the impact of wearable devices to promote physical activity (PA) on adolescents’ body composition, physical fitness, and psychological status, or whether changes in PA predict changes in these variables. Therefore, the objectives of the present study were: (a) to analyze changes in PA levels, body composition, physical fitness, and psychological status, after a 12-week step goal–based wearable intervention; (b) to examine whether changes in objective PA predicted changes in the other variables; and (c) to explore potential gender differences. A quasi-experimental one-group pre–post design intervention was conducted with 30 adolescents (mean age: 13.89±1.35 years old). The step-based intervention with wearable devices was carried out during extracurricular hours for 12 weeks. PA levels were assessed objectively using accelerometry and subjectively using the PAQ-A questionnaire; body composition following the ISAK protocol; physical fitness through valid and reliable tests performed in an indoor sports hall (cardiorespiratory fitness, upper body strength, lower body power, speed, and abdominal strength); psychological status through questionnaire (life satisfaction and basic psychological needs); and adherence to the intervention was assessed by recording which adolescents dropped out or continued to complete the intervention objectives each week. Pre–post changes were examined using repeated-measures ANOVA, testing time × gender interactions, while associations between changes in PA and study outcomes were analyzed using hierarchical linear regression models including gender × change in PA interaction terms. The results showed that adherence was low, with 26.67% dropping out after the fourth week, and no participants completing the entire program. Pre–post analyses revealed an increase in subjective PA (p=0.043), alongside decreases in light PA, moderate-to-vigorous PA (MVPA), and daily steps (p<0.001–0.008). Competence frustration decreased (p=0.049), while curl-up performance improved (p=0.002). Regression analyses showed that changes in light PA, MVPA, and daily steps predicted subjective PA (R²=0.449), and that MVPA and daily steps explained changes in competence frustration (R²=0.319). Gender-stratified analyses indicated no significant predictors for males, whereas for females, MVPA and daily steps predicted hip girth (R²=0.425), and MVPA predicted push-up performance (R²=0.500). The findings showed an increase in perceived PA, along with a decrease in objective PA, less competence frustration, and improved curl-up performance. No significant differences were found in body composition variables (p>0.070), other psychological variables (p>0.173), or other physical fitness variables (p>0.087). Changes in objective PA predicted changes in perceived PA and competence frustration for the entire sample, but when analyzed by gender, a significant predictive capacity of changes in objective PA was observed in females. However, lack of adherence to the program and the small sample size of the study are limitations to consider when interpreting the results.
- PublicationOpen AccessA Comparative Analysis of Machine Learning and Deep Learning Approaches for Multiclass Nucleus Classifcation in Histological Images(Wiley, 2026-01-30) Sánchez-Torres, Antonio Luis; García-Salmerón, Jesús ; González Férez, María Pilar; Bernabé García, Gregorio; García Carrasco, José Manuel; Ingeniería y Tecnología de Computadores; Kalapraveen Bagadi; Facultades de la UMU::Facultad de InformáticaPrecisely classifying cells in histological images is critical for early cancer diagnosis and tumor assessment. Traditional manual methods are time-consuming and labor-intensive for histopathologists, driving the development of automated approaches using machine learning (ML) and deep learning (DL). Convolutional neural networks (CNNs) and, more recently, vision transformers (ViTs) have demonstrated signifcant potential in addressing the challenges of cell classifcation by leveraging their ability to automatically extract and learn complex features from histological images. In this work, we evaluate multiple classifcation architectures applied to stained histological images to determine their efectiveness in identifying cancerous cells. We compare traditional ML models, which rely on manually extracted features such as shape and texture, against two DL-based classifers: a CNN-based model (ResNet50) and a ViT-based model. To optimize ML models, we apply principal component analysis (PCA) to refne feature selection. Meanwhile, DL models are trained on cropped cell images using two preprocessing strategies: one that includes additional surrounding cellular context and another that uses only the cell pixels. Additionally, we investigate class balancing strategies, including downsampling and oversampling through data augmentation, to mitigate the efects of dataset imbalance. Experimental results highlight the clear advantage of DL models over traditional ML approaches. ResNet50 consistently delivers robust and reliable performance across diferent preprocessing strategies, confrming its efectiveness for histopathological classifcation tasks. Meanwhile, ViTs achieve results that are comparable to those of CNNs while demonstrating a distinct advantage in classifying underrepresented nucleus classes, likely due to their ability to capture long-range dependencies. Furthermore, incorporating the surrounding cellular environment signifcantly improves classifcation accuracy, underscoring the importance of contextual information in distinguishing between diferent types of nuclei.
- PublicationOpen AccessA Data-Centric Algorithmic Pipeline for Enhancing Cardiac MRI Segmentation Using ViTUNeT and Quality-Aware Filtering(MDPI, 2026-03-06) Salvador de Haro; Jesús Cámara; González Férez, María Pilar; José Manuel García; García Carrasco, José Manuel; Bernabé García, Gregorio; Ingeniería y Tecnología de Computadores; Facultades de la UMU::Facultad de InformáticaThe performance of deep-learning-based segmentation models is strongly dependent on the quality of the input data, which is frequently heterogeneous or degraded in real-world medical imaging scenarios. This work presents a data-centric algorithmic pipeline designed to improve cardiac MRI segmentation accuracy through systematic image enhancement and automatic slice-quality filtering. The proposed method is formalized as deterministic algorithm that combines image processing and supervised learning components. The approach integrates a contrast- and structure-preserving enhancement stage, based on bilateral filtering and adaptive histogram equalization, with a quality-aware selection algorithm. Slice quality is assessed using anatomical attributes extracted via YOLOv11sbased localization and a supervised classification model trained to identify diagnostically reliable images. When applied to transformer-based segmentation architectures such as ViTUNeT, the pipeline yields consistent improvements across all evaluation metrics without increasing model complexity or training cost. These findings emphasize the importance of algorithmic data curation as an effective strategy for enhancing robustness and stability in deep-learning segmentation pipelines and demonstrate the broader applicability of the proposed approach to computer-vision tasks involving heterogeneous or low-quality image datasets.
- PublicationOpen AccessA high-density narrow-field inhibitory retinal interneuron with direct coupling to Müller glia(Society for Neuroscience, 2021-07-14) Grimes, William N. ; Aytürk, Didem Göz ; Hoon, Mrinalini ; Yoshimatsu, Takeshi ; Gamlin, Clare ; Carrera, Daniel ; Nath, Amurta ; Ahlquist, Richard M. ; Sabnis, Adit ; Berson, David M. ; Diamond, Jeffrey S. ; Wong, Rachel O. ; Cepko, Connie ; Rieke, Fred ; Nadal-Nicolás, Francisco Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de MedicinaAmacrine cells are interneurons composing the most diverse cell class in the mammalian retina. They help encode visual features, such as edges or directed motion, by mediating excitatory and inhibitory interactions between input (i.e., bipolar) and output (i.e., ganglion) neurons in the inner plexiform layer (IPL). Like other brain regions, the retina also contains glial cells that contribute to neurotransmitter uptake, metabolic regulation, and neurovascular control. Here, we report that, in mouse retina (of either sex), an abundant, though previously unstudied inhibitory amacrine cell is coupled directly to Müller glia. Electron microscopic reconstructions of this amacrine type revealed chemical synapses with known retinal cell types and extensive associations with Müller glia, the processes of which often completely ensheathe the neurites of this amacrine cell. Microinjecting small tracer molecules into the somas of these amacrine cells led to selective labeling of nearby Müller glia, leading us to suggest the name "Müller glia-coupled amacrine cell," or MAC. Our data also indicate that MACs release glycine at conventional chemical synapses, and viral retrograde transsynaptic tracing from the dorsal lateral geniculate nucleus showed selective connections between MACs and a subpopulation of retinal ganglion cell types. Visually evoked responses revealed a strong preference for light increments; these "ON" responses were primarily mediated by excitatory chemical synaptic input and direct electrical coupling with other cells. This initial characterization of the MAC provides the first evidence for neuron-glia coupling in the mammalian retina and identifies the MAC as a potential link between inhibitory processing and glial function. SIGNIFICANCE STATEMENT Gap junctions between pairs of neurons or glial cells are commonly found throughout the nervous system and play multiple roles, including electrical coupling and metabolic exchange. In contrast, gap junctions between neurons and glia cells have rarely been reported and are poorly understood. Here we report the first evidence for neuron-glia coupling in the mammalian retina, specifically between an abundant (but previously unstudied) inhibitory interneuron and Müller glia. Moreover, viral tracing, optogenetics, and serial electron microscopy provide new information about the neuron's synaptic partners and physiological responses.
- PublicationOpen AccessA mapping study of ensemble classification methods in lung cancer decision support systems(Springer Nature, 2020-07-03) Mohamed Hosni; García Mateos, Ginés; Carrillo de Gea, Juan Manuel; Ali Idri; Fernández Alemán, José Luis; Informática y Sistemas; Facultad de InformáticaAchieving a high level of classification accuracy in medical datasets is a capital need for researchers to provide effective decision systems to assist doctors in work. In many domains of artificial intelligence, ensemble classification methods are able to improve the performance of single classifiers. This paper reports the state of the art of ensemble classification methods in lung cancer detection. We have performed a systematic mapping study to identify the most interesting papers concerning this topic. A total of 65 papers published between 2000 and 2018 were selected after an automatic search in four digital libraries and a careful selection process. As a result, it was observed that diagnosis was the task most commonly studied; homogeneous ensembles and decision trees were the most frequently adopted for constructing ensembles; and the majority voting rule was the predominant combination rule. Few studies considered the parameters tuning of the techniques used. These findings open several perspectives for researchers to enhance lung cancer research by addressing the identified gaps, such as investigating different classification methods, proposing other heterogeneous ensemble methods, and using new combination rules.
- PublicationRestrictedA Maxillary Ridge-Splitting Technique Followed by Immediate Placement of Implants: A Case Report(Lippincott Williams & Wilkins, 2005) Calvo Guirado, Jose Luis; Saez Yuguero, María Rosario; Carrión del Valle, María José; Pardo Zamora, Guillermo; Dermatología, Estomatología, Radiología y Medicina Física; Facultades de la UMUMaxillary alveolar atrophy often limits the placement of dental im- plants. This article reports on a refine- ment of a technique for widening the atrophic ridge by splitting the alveolar bone longitudinally. Treatment of a patient with a severely resorbed eden- tulous maxilla is described. Six 4-mm wide by 13-mm long threaded Osseo- tite implants were placed immediately within thesplit ridge and surrounded- with amixture of autogenous tuberos- ity and bovine bone. The advantages of this technique for patients include less surgical trauma and condensed treatment time.
- PublicationOpen AccessA new class of aggregation inhibitor of amyloid-beta peptide based on green tea catechins(2014) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e InmunologíaAlzheimer's disease (AD), the major dementing disorder of the elderly which accounts for 55% of all dementia patients worldwide, is related to amyloid-beta peptide, the main component of senile plaques in Alzheimer's disease brain. Observations suggest a broad ability for green tea catechins (GTC) to disrupt early-stage and late-stage aggregation processes but the molecular mechanism has not been fully elucidated. To advance the understanding of the potential use of GTC in the prevention or treatment of AD patients, we investigated the effect of natural and synthetic compounds on APP processing. We checked the ability of gallate containing phenolic compounds, including (-)-catechin, (-)- catechin gallate, (-)-epicatechin gallate, (-)-epigallocatechin, (-)-epigallocatechin gallate, gallic acid, and trimethoxy derivatives of epicatechin-3-gallate to inhibit acetylcholinesterase (AChE) activity and AChE-promoted Aβ aggregation. Compounds were analyzed for their ability to inhibit AChE by colorimetric and radiometric assays and for determining their type of enzyme inhibition. Fluorimetric studies with thioflavin T were performed to evaluate their effect on beta amyloid aggregation. We have found that TMCG, a 3,4,5-trimethoxy derivative of catechin gallate, exhibits a non competitive inhibition of AChE, has a disaggregating effect on amyloid fibrils and decreases the secretion of both 1-40 and 1-42 amyloid peptides to the extracellular medium of SH-SY5Y APP695 cell cultures. According to stability and bioavailability, methoxy derivates of catechins are promising drug to ameliorate the Alzheimer´s pathogenesis.
- PublicationRestrictedA new method for the prevention of skin laceration during vacuum-assisted breast biopsy(2017-04-01) Guzmán Aroca, Florentina; Berna Mestre, Juan de Dios; Hernández Gómez, Dolores; Berná Serna, Juan De Dios; Dermatología, Estomatología, Radiología y Medicina Física; Facultades de la UMU::Facultad de MedicinaObjective: To describe a new technique to prevent skin laceration during ultrasound-guided vacuum-assisted breast biopsy with the insertion of a spinal needle between the mass and the skin. Methods: The study includes 118 patients with 118 breast imaging-reporting and data system Category 3 masses located very close to the skin or areola, which were excised using the mammotome systemwith a spinal needle inserted just above the site of insertion of the probe. Results: The mean distance between the most superficial portion of the mass to the under surface of the overlying skin was 1.3 6 0.4mm. The average procedure time was 13.5 6 4.2min. A complete excision was achieved in 100% of the cases, and the procedure was well tolerated by all the patients. No patient experienced serious adverse events such as a skin laceration. Conclusion: This is the first study to prevent skin laceration during vacuum assisted breast biopsy. Advances in knowledge: The method described in this study is simple, safe and well tolerated by patients.
- PublicationOpen AccessA novel in vivo model of focal light emitting diode-induced cone-photoreceptor phototoxicity: neuroprotection afforded by brimonidine, BDNF, PEDF or bFGF(Public Library of Science , 2014-12-02) Ortín Martínez, Arturo; Valiente Soriano, Francisco Javier; García Ayuso, Diego; Jiménez López, Manuel; Bernal Garro, José Manuel; Nieto López, Leticia; Nadal-Nicolás, Francisco Manuel; Villegas Pérez, Maria Paz; Wheeler, Larry A.; Vidal Sanz, Manuel; Alarcón Martínez, Luis; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de MedicinaWe have investigated the effects of light-emitting diode (LED)-induced phototoxicity (LIP) on cone-photoreceptors and their protection with brimonidine (BMD), brain-derived neurotrophic factor (BDNF), pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF) or basic fibroblast growth factor (bFGF). In anesthetized, dark adapted, adult albino rats a blue (400 nm) LED was placed perpendicular to the cornea (10 sec, 200 lux) and the effects were investigated using Spectral Domain Optical Coherence Tomography (SD-OCT) and/or analysing the retina in oriented cross-sections or wholemounts immune-labelled for L- and S-opsin and counterstained with the nuclear stain DAPI. The effects of topical BMD (1%) or, intravitreally injected BDNF (5 µg), PEDF (2 µg), CNTF (0.4 µg) or bFGF (1 µg) after LIP were examined on wholemounts at 7 days. SD-OCT showed damage in a circular region of the superotemporal retina, whose diameter varied from 1,842.4±84.5 µm (at 24 hours) to 1,407.7±52.8 µm (at 7 days). This region had a progressive thickness diminution from 183.4±5 µm (at 12 h) to 114.6±6 µm (at 7 d). Oriented cross-sections showed within the light-damaged region of the retina massive loss of rods and cone-photoreceptors. Wholemounts documented a circular region containing lower numbers of L- and S-cones. Within a circular area (1 mm or 1.3 mm radius, respectively) in the left and in its corresponding region of the contralateral-fellow-retina, total L- or S-cones were 7,118±842 or 661±125 for the LED exposed retinas (n = 7) and 14,040±1,860 or 2,255±193 for the fellow retinas (n = 7), respectively. BMD, BDNF, PEDF and bFGF but not CNTF showed significant neuroprotective effects on L- or S-cones. We conclude that LIP results in rod and cone-photoreceptor loss, and is a reliable, quantifiable model to study cone-photoreceptor degeneration. Intravitreal BDNF, PEDF or bFGF, or topical BMD afford significant cone neuroprotection in this model.
- PublicationRestrictedA Phase I Dose Escalation and Cohort Expansion Study of CB307, a Trispecific Humabody against PSMA, CD137, and Albumin in Patients with PSMA-Positive Solid Tumors(American Association for Cancer Research, 2025-08-15) de Bon, Johann S. ; Williams, Anja ; Melero, Ignacio ; Jayaram, Anuradha ; Hawley, Jessica E.; de Speville, Bernard Doger ; Moreno, Irene ; Castellano, Daniel ; Reig, Oscar; Knapen, Daan G.; Anguera, Georgia ; Martínez, Julia ; Gort, Eelke ; de Jonge, Maja ; Alonso Romero, José Luis; Boni, Valentina ; Pérez Gracia, Jose Luis ; Falcon, Alejandro ; de Groot, Derk Jan; Pierce, Andrew J.; Leishman, Andrew J.; Lloyd, Peter ; Bartlett, Phillip D.; Bland-Ward, Philip ; Chau, Albert ; Song, Minjung ; Duffy, Kevin ; Hashimoto, Kenji ; de Vries, Eisabeth ; Medicina; Facultades de la UMU::Facultad de MedicinaPurpose: CB307 is a trispecific variable heavy-chain antibody fragment against prostate-specific membrane antigen (PSMA), CD137, and human serum albumin. It is designed to mitigate hepatotoxicity by activating T cells only in PSMA-positive tumors and to increase drug half-life through albumin binding. This phase I study investigated the safety and tolerability of CB307 as monotherapy or in combination with pembrolizumab. Patients and Methods: Patients who were heavily pretreated with PSMA-positive solid tumors were enrolled in the dose-escalation phase of CB307 monotherapy. The additional safety and efficacy of CB307 were assessed in the CB307 monotherapy expansion cohort and in combination with pembrolizumab. Results: CB307 was administered to 75 patients. CB307 was given once every 7 days as monotherapy (N = 50) or in combination with pembrolizumab (N = 25). Two dose-limiting toxicities (grade 3 transient transaminitis) were observed. A total of three grade 3 transaminitis events (one in the monotherapy cohort and two in the combination cohort) were observed, and none involved bilirubin elevation. Durable RECIST responses were observed in two patients with metastatic castration-resistant prostate cancer enrolled in the 800 mg CB307 monotherapy and in one patient in the combination cohort (overall response rates: 11.1% and 7.1%, respectively). A disease control rate (DCR) of 50% was observed in patients enrolled in the 800 mg CB307 monotherapy cohort and 42.9% in the combination cohort. In a post hoc analysis, the response was numerically better in patients who had not received chemotherapy in the 6 months prior to starting CB307 (ORR = 20%, DCR = 60% vs. ORR = 0%, DCR = 37.5%). CB307 induces cytotoxic cell expansion in tumors and PD-L1 expression. Conclusions: CB307 was well tolerated as a monotherapy and in combination with pembrolizumab, and tumor responses were observed in patients with metastatic castration-resistant prostate cancer.
- PublicationOpen AccessA rare cause of intra-abdominal cysts: pancreatic cystic lymphangiomas(Sociedad Española de Patología Digestiva, 2021) Pérez Fernández, Alejandro; López Martín, Aurelio; Alcaraz Mateos, Eduardo; Oftalmología, Optometría, Otorrinolaringología y Anatomía PatológicaEchenique et al. described a lymphangioma as a rare cystic neoplasm of the pancreas. We present a similar intra-abdominal lesion diagnosed by endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) cytology.
- PublicationOpen AccessA simple MALDI–TOF-MS method for the identification of non-mycobacterial aerobic actinomycetes growing on blood agar subcultures from positive MGIT cultures(Elsevier, 2025) Muñoz-Dávila, María José; Cabezas Fernández, María Teresa; Esteban García, Ana Belén; Martínez Lorila, Miguel José; Genética y Microbiología
- PublicationOpen AccessA systematic review and meta-analysis of the serological diagnosis of Toxoplasma gondii infection highlight the lack of a One Health integrative research(Elsevier, 2023-01-10) Huertas López, Ana; Álvarez García, Gema; Sánchez Sánchez, Roberto; Cantos Barreda, Ana; Ibáñez López, Francisco José; Martínez Subiela, Silvia; Cerón Madrigal, José Joaquín; Martínez-Carrasco Pleite, Carlos; Sanidad Animal; Facultades de la UMU::Facultad de VeterinariaToxoplasma gondii is a globally distributed food-borne zoonotic parasite with numerous infection sources. The control of this zoonosis requires a One Health response that partially depends on serological monitoring in humans and animals. Herein, a systematic review and a meta-analysis were performed to analyse and compare the transdisciplinary and integrative research under the One Health approach. We searched for articles published between January 1st 2014 and September 5th 2022, focused on the development and evaluation of serological techniques for the diagnosis of T. gondii infection in humans and animals. After an exhaustive search on three scientific databases, a quality assessment was performed on 291 articles by QUADAS-2 tool, and 113 articles were finally selected. A total of 18 variables were extracted and analysed, including bibliometric characteristics, study aims and methodology. Remarkably, none of the studies included in the meta-analysis explicitly quoted the words “One Health”, and only 23.9% of them alluded to the principles underlying the One Health approach; in particular, none were conducted by physician-only teams, with the majority of these studies involving interdisciplinary research teams, followed by veterinarians and by non-physician or non-veterinarian researchers. The One Health approach followed in the serodiagnosis of T. gondii still needs further integration among scientific disciplines, which is essential to design effective control strategies.
- PublicationRestrictedA systematic review of psychological well-being interventions for child victims of school violence(Elsevier, 2024-12-31) Cascales Martínez, Andrea; Pina, David; López López, Reyes; Puente López, Esteban; López Ros, Paloma; Molero, María del Mar; Pérez Fuentes, María del Carmen; Psiquiatría y Psicología SocialSchool violence is a serious social problem that affects many children and adolescents, with serious repercussions on their psychological well-being. In response to this situation, various prevention programs have been developed and implemented regardless of the role of the minor. Among the actions of greatest clinical and community interest are those focused on victims of bullying. The aim of this study is to analyze the interventions aimed at improving the psychological well-being of victims of school violence, as well as to describe the variables on which they intervene, and the results obtained. The methodology used was a systematic review following the PRISMA guidelines and the Cochrane Collaboration recommendations, exploring all the studies published until December 2023 in the main databases. Experimental, quasi-experimental or pre-experimental studies were included, with minors between 6 and 17 years old, victims of bullying. On the other hand, studies where the population was diagnosed with developmental disorders or where the sample size in the posttest was less than 10 participants were excluded. The search yielded 40,120 articles, of which 39 were finally included in this review. Most studies reported that the intervention improved outcomes for victims, with half of them reporting effect sizes. Generally, psychoeducational interventions were described, with the cognitive-behavioral approach predominating as the most effective. The set of interventions collected provides researchers and professionals with evidence of empirically supported techniques that can be used in future interventions with children involved in school violence situations.
- PublicationRestrictedA time-resolved fluorescence immunoassay for the detection of anti-Neospora caninum antibodies in sheep(Elsevier, 2019-11-18) Huertas López, Ana; Huertas-López, Ana; Martínez-Carrasco Pleite, Carlos; Cerón Madrigal, José Joaquín; Sánchez-Sánchez, Roberto; Vázquez-Calvo, Ángela; Álvarez-García, Gema; Martínez Subiela, Silvia; Sanidad Animal; Facultad de VeterinariaNeospora caninum is a protozoan parasite (Phylum Apicomplexa) that has been recently suggested as a relevant cause of reproductive disorders in small ruminants. The aim of the present study is to develop and validate a new serological test based on time resolved fluorescency using N. caninum GRA7 recombinant antigen (GRA7-TRFIA) for the detection of N. caninum antibodies in sheep. A total of 346 serum samples (208 from experimentally infected sheep, 117 from a dairy farm with a previous history of Neospora-associated abortion, and 21 negative sera) were used. The validation of the new assay was performed by the evaluation of assay precision, analytical sensitivity (Se), accuracy and cross reactivity. In the experimentally infected sheep, antibody kinetics was compared between GRA7-TRFIA and an in house N. caninum tachyzoite soluble extract-based ELISA (NcSALUVET ELISA) by Wilcoxon matched-pairs signed rank test. The cut-off and diagnostic Se and specificity (Sp) of GRA7-TRFIA was estimated by ROC analysis with field samples. In addition, concordance and correlation between GRA7-TRFIA and a commercial ELISA and NcSALUVET ELISA were assessed by kappa value and Spearman correlation coefficient, respectively. Overall, GRA7-TRFIA showed an adequate precision, analytical Se and accuracy to detect anti-N. caninum antibodies in ovine serum, and no cross reactivity with the closely related protozoan Toxoplasma gondii. In naturally infected sheep, 100% Se and 95.35% Sp were obtained for a cut-off point of 62.68 Units of Fluorometry for N. caninum (UFN). Moreover, GRA7-TRFIA allowed earlier detection of N. caninum infection than NcSALUVET ELISA in experimentally infected sheep.