Alberto Sols Biomedical Research Institute

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    Structural-mechanistic insights and performance engineering of chitinase MpChit35 for tailored chito-oligosaccharide production

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    Chitinase-catalysed synthesis offers a promising biotechnological route for converting chitin-rich waste into value-added chito-oligosaccharides, whose biological activity depends on their degree of polymerization and acetylation, highlighting the need for precise enzymatic tools to tailor their structures. This study investigates the structural-functional determinants of the chitinase MpChit35 from Metschnikowia pulcherrima, which mainly produces di-acetyl-chitobiose ((GlcNAc)2) and to a lesser extent tri-acetyl-chitotriose ((GlcNAc)3) from chitin. Here the MpChit35 structure was solved at 2.55 Å and structural analysis combined with site-directed mutagenesis enabled the identification of key residues involved in substrate binding and catalysis. Thus, the L253R mutation significantly increased the protein catalytic efficiency and promoted near-exclusive production of (GlcNAc)2 from chitin and oligomeric substrates, underscoring the role of polar interactions in defining the enzyme specificity and processivity. In contrast, the multiple-mutation A107D/D151N/A181S/M279A favoured the release of (GlcNAc)3 and tetra-acetyl-chitotetraose. Furthermore, residue Trp73 contributed to an unusual distal substrate-binding platform and Ala107 resulted a key determinant for the product specificity. These findings provide mechanistic insights into chitinase function and support the rational design of enzymes with tailored cleavage patterns. This work contributes to the development of efficient biocatalysts for sustainable chitin valorisation and the industrial production of custom chito-oligosaccharidesThis work was supported by: (1) Project GLYCOENZ-GREEN (PID2022-136367OB-C31/C32/C33), funded by MCIN/AEI/10.130 39/501100011033and FEDER, a Way of Making Europe; (2) Project SUST_CHIT_BIOPR (TED2021-129288B-C21/22) funded by MCIN/ AEI/10.13039/501100011033and by the European Union Next Generation EU/PRTR. We thank the Synchrotron Radiation Source at ALBA (Barcelona, Spain) for assistance with the BL13-XALOC beamline and to the Foundation Ramon Areces for an institutional grant to CBM. The first author was supported by grant PRE2020-092330 from the Spanish Ministry of Science and Innovatio

    Evolution of EEG fractal dimension along a sequential finger movement task

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    This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/978-3-031-61140-7_23We used dual EEG and EMG recordings to assess the neural dynamics of motor activity during a stereotyped sequential finger movement. We analyzed the evolution of EEG complexity, assessed using Katz fractal dimension (KFD), in three brain regions involved in the task (multisensory association (MA), sensory and left and right motor areas) and its relation with response time, defined by EMG onset. The KFD was calculated for multiple time windows, defined with respect to the go cue or the EMG onset. We observed a positive correlation between the KFD and the EMG onset latency in various time windows in all the areas. This relationship reversed for trials with a late EMG onset. While all the areas manifested a similar pattern of correlations, the motor area showed the lowest, and the MA area the highest, complexity values between these four brain regions. The KFD tended to decrease as the task progressed, consistently with previous observations of reduced neural variability with task engagementThis work was supported by the Spanish MICINN, with projects PID2021-122270OB-I00 and TED2021-129381B-C2

    The Pragmatics of Rhetorical Questions in Sophocles’ Tragedies: An Analysis of Antigone and Electra

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    This paper, focused on the tragedies Antigone and Electra, analyses both the speaker’s use of rhetorical questions (RQs) and the effect of their use on the speaker’s interaction with the addressee. The data show that RQs are basically linked with contexts of disagreement in which the speaker tries to present their beliefs and opinions as irrefutable statements. RQs usually express arguments for or against a standpoint and are frequently inserted into syllogistic-like schemes. RQs can accentuate the confrontational climate between speakers, provoking the addressee to respond to them by expressing sharp disagreement or even attempt-ing to humiliate the interlocutor and reinforce their own faceThis paper was written in the framework of the research projects titled “Indirect speech acts and inter-action in Ancient Greek” (PID2021–122489NB–100) and “Irony as a rhetorical device in Athenian legal language” (SI3/PJI/2021–00208

    Optimización de la realineación raquídea y prevención de complicaciones mecánicas en cirugía de deformidad del adulto

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    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Cirugía. Fecha de Lectura: 26-06-2025Adult spinal deformity surgery (ASD) presents significant challenges due to the complexity of restoring spinopelvic alignment and the high prevalence of postoperative mechanical complications. This dissertation examines the relationship between realignment of key sagittal profile parameters, such as relative pelvic version (RPV) and relative spinopelvic alignment (RSA), with reduced complications and improved clinical outcomes as measured by PROMs (Patient-Reported Outcome Measures), such as the Oswestry Disability Index (ODI) and the SF-36 questionnaire. Through a retrospective study based on multicenter data, 1,505 patients with ASD undergoing spinal fusion surgery were analyzed. Patients were radiographically evaluated at six weeks, six months, one year and two years after surgery, with special attention to RPV realignment, RSA, relative lumbar lordosis (RLL) and lumbar distribution index (LDI). In addition, the most common mechanical complications were analyzed: proximal junctional kyphosis (PJK), proximal junctional failure (PJF), pseudarthrosis (PA) and bar rupture (RB). The results showed that 51.6% of patients failed to achieve adequate restoration of the RPV, suggesting that this parameter is the most difficult to correct surgically. However, procedures including anterior lumbar arthrodesis (ALIF) and tricolumnar osteotomies proved to be effective in improving RPV. Regarding RSA, 21.9% of patients continued with severe postoperative positive misalignment, which significantly increased the risk of mechanical complications and was associated with worse PROMs. Major mechanical complications, which affected 17.3% of patients, followed two temporal patterns: early complications (PJK and PJF), which occurred in the first 160 days, and late complications (PA and RB), which arose after 695 days. These results underscore the importance of accurate surgical planning to minimize complications and improve clinical outcomes. In conclusion, proper restoration of spinopelvic alignment, especially RSA, is critical to reduce mechanical complications and improve patients' quality of life. Future studies should focus on advanced surgical strategies that optimize spinal realignment and minimize postoperative complications in the short, medium and long ter

    Cosmogenic neutrinos as probes of new physics

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    The scattering of extremely energetic cosmic rays with both cosmic microwave background and extragalactic background light, can produce O(1018 eV) neutrinos, known as cosmogenic neutrinos. These neutrinos are the only messengers from the extreme cosmic accelerators that can reveal the origin of the most energetic cosmic rays. Consequently, much effort is being devoted to achieving their detection. In particular, the GRAND project aims to observe the ντ and ¯ντ components of the cosmogenic neutrino flux in the near future using radio antennas. In this work, we investigate how the detection of cosmogenic neutrinos by GRAND can be used to probe beyond the Standard Model physics. We identify three well-motivated scenarios which induce distinct features in the cosmogenic neutrino spectrum at Earth: neutrino self-interactions mediated by a light scalar (νSI), pseudo-Dirac neutrinos (PDν) and neutrinos scattering on ultra-light Dark Matter (νDM). We show these scenarios can be tested by GRAND, using 10 years of cosmogenic neutrino data, in a region of parameter space complementary to current experiments. For the νSI model„ we find that GRAND can constrain the coupling to ντ in the range [10−2, 10−1] for a scalar with mass in the range 0.1 to 1 GeV. For PDν, we find that GRAND is sensitive to sterile-active mass squared splitting in the range [10−15, 10−13] eV2. Finally, for the νDM model, assuming a heavy mediator, GRAND can do substantially better than the current limits from other available data. These results rely on the fact that the actual cosmogenic flux is around the corner, not far from the current IceCube limitWe thank Rafael Alves Batista, Miguel Escudero, Enrique Fernandez-Martinez and Gaetano di Marco for helpful discussions. This project has received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N◦ 860881-HIDDeN and N◦ 101086085-ASYMMETRY. L.P.S. Leal is fully financially supported by FAPESP under Contracts No. 2021/02283-6 and No. 2023/12330-7. R. Zukanovich Funchal is partially supported by FAPESP under Contract No. 2019/04837- 9, and by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). DNT acknowledges support from the HPC-Hydra cluster at IFT. The work of DNT was supported by the Spanish MIU through the National Program FPU (grant number FPU20/05333). DNT would like to warmly thank the Department of Mathematical Physics at USP for their hospitality, where this project was started. L.P.S. Leal would like to thank the IJCLab Theory Group for their hospitalit

    L2 acquisition of english definiteness by L1-chinese and L1-spanish speakers

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    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Filosofía y Letras, Departamento de Filología inglesa. Fecha de Lectura: 10-09-2025La adquisición de la categoría funcional del inglés, en particular el sistema de artículos del inglés, se considera especialmente difícil para los estudiantes tanto de primera lenguas (L1) con artículos como sin artículos. Basándose en el marco teórico generativo, el estudio pretende explorar los factores que explican la complejidad de la adquisición de artículos en inglés por aprendices de dos antecedentes tipológicamente diferentes de L1, a saber, L1 chino (idioma sin un sistema de artículos) y L1 español (idioma con un sistema de artículos). Mediante la incorporación de datos de corpus y datos experimentales, la triangulación metodológica proporciona abundante evidencia empírica y perspectivas exhaustivas sobre el patrón de uso de artículos en inglés L2, lo que hace que el estudio sea novedoso y completo. Estudios anteriores indican que la influencia de la L1, la Gramática Universal(GU) y la entrada de L2 son las dinámicas frecuentemente citadas que subyacen en el proceso de adquisición de L2, sin embargo, su interacción y contribuciones relativas siguen siendo insuficientemente comprendidas, lo que desencadena numerosas hipótesis de investigación como la Hipótesis de Fluctuación (Ionin et al., 2004), la Hipótesis de Reensamblaje de Rasgos (Lardiere, 2008) y la Hipótesis de la Interfaz (Sorace, 2011) con el objetivo de desentrañar la interacción compleja. Entre todas, la Hipótesis de Fluctuación (HF) ha atraído mucha atención en el campo de investigación de L2. El presente estudio se centra en validar la capacidad predictiva de la HF, intentando dilucidar la complejidad inherente en la adquisición de L2, ampliando el conocimiento teórico y empírico del campo y arrojando luz sobre futuras investigaciones. Los resultados del estudio indican que los aprendices de L1 español, como se esperaba, exhiben patrones altamente similares al objetivo en la elección de artículos, mientras que la elección de artículos por aprendices de L1 chino revela un rendimiento inesperadamente nativo en contextos [+definido, +específico] y [-definido, +específico] en el estudio de corpus. El estudio experimental en línea con tarea de elicitación forzada incluso mostró que los aprendices avanzados de L1 chino presentan un patrón de uso de artículos similar al objetivo en los cuatro contextos objetivo. Los resultados indican que la variabilidad no se puede explicar simplemente por la HF sola. Al examinar cuidadosamente las características semánticas del chino, se argumenta que la razón del comportamiento nativo en la elección de artículos en inglés se debe a la influencia de la L1, ya que los demostrativos chinos a menudo se usan de manera que se asemejan al uso de artículos definidos en inglés, lo que lleva a un efecto de transferencia que mejora su comprensión y aplicación del uso de artículos en contextos específicos. Los hallazgos indican que la adquisición de L2 es una interacción compleja de múltiples factores lingüísticos, incluyendo la interacción entre la influencia de la L1, la (GU) y la entrada de L2. El estudio proporciona evidencia empírica para enriquecer el cuerpo de investigación sobre la adquisición de artículos en inglés L2, y destaca la necesidad de estrategias instruccionales adaptadas que aborden estas interdependencias lingüísticas, facilitando en última instancia resultados de aprendizaje más efectivo

    Planetary health diet, other plant-based diets and risk of type 2 diabetes: a prospective study from the UK Biobank

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    Background Type 2 diabetes remains a major global health concern, and plant-based diets (PBD) offer substantial preventive value. The Planetary Health Diet Index (PHDI) captures adherence to an environmentally sustainable PBD with potential metabolic benefits. However, evidence on its association with type 2 diabetes risk remains limited, notably in comparison with other preexisting PBD. The objective of this study was to evaluate the association between adherence to the PHDI and type 2 diabetes risk in a large British adult cohort and compare it to other well-known PBDs. Methods This analysis included 112,032 participants aged 40–69 years from the UK Biobank who were free of type 2 diabetes and cardiovascular disease at baseline (2009–2012) and were followed until 2021. Dietary intake was assessed using at least two 24-h dietary recalls, and PHDI scores (range: 0–130) were computed based on adherence to 14 food groups recommendations. The other PBDs (alternate Mediterranean Diet score (aMED), healthful plant-based index (hPBD), Dietary Approach to Stop Hypertension (DASH), and Alternate Healthy Eating Index (AHEI-2010)), were estimated using established methodologies. Incident type 2 diabetes was ascertained through clinical records, hospital admissions, and self-reporting. Cox proportional-hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs), adjusting for key confounders. Results During a median 9.4-year follow-up, 2666 cases of type 2 diabetes were identified. When comparing participants in the highest versus the lowest quartile of PHDI adherence, the multivariable-adjusted HR (95% CI) for type 2 diabetes was 0.57 (0.50, 0.64), which was more pronounced than that observed for the aMED: 0.70 (0.62, 0.78) and hPDI: 0.64 (0.57, 0.72) and similar to DASH: 0.58 (0.51, 0.65); AHEI-2010: 0.59 (0.53, 0.67). Further adjustment for BMI led to a 13–19% attenuation of the association. High consumption of vegetables and fish, and limited intake of red/processed meats and added sugars were associated with reduced type 2 diabetes risk. Conclusions In this large cohort of British adults, higher adherence to the PHDI was associated with a substantially lower risk of type 2 diabetes, with effect sizes comparable to or greater than those observed for other well-known PBDs. These findings support the promotion of the PHDI and PBDs as an environmentally sustainable choice with potential to reduce type 2 diabetes riskThis work was supported by the Carlos III Health Institute, the Secretary of R + D + I; the European Regional Development Fund/European Social Fund (FIS grants 20/00896; 22/1111; 23/00079); National Agency of Research (CNS2022-135623); Ministerio de Educación, Formación Profesional y Deportes (FPU contract to MDCAR

    Hybrid CNN architecture for hot spot detection in photovoltaic panels using fast R-CNN and GoogleNet

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    Due to the continuous increase in global energy demand, photovoltaic solar energy generation and associated maintenance requirements have significantly expanded. One critical maintenance challenge in photovoltaic installations is detecting hot spots, localized overheating defects in solar cells that drastically reduce efficiency and can lead to permanent damage. Traditional methods for detecting these defects rely on manual inspections using thermal imaging, which are costly, labor-intensive, and impractical for large-scale installations. This research introduces an automated hybrid system based on two specialized convolutional neural networks deployed in a cascaded architecture. The first convolutional neural network efficiently detects and isolates individual solar panels from high-resolution aerial thermal images captured by drones. Subsequently, a second, more advanced convolutional neural network accurately classifies each isolated panel as either defective or healthy, effectively distinguishing genuine thermal anomalies from false positives caused by reflections or glare. Experimental validation on a real-world dataset comprising thousands of thermal images yielded exceptional accuracy, significantly reducing inspection time, costs, and the likelihood of false defect detections. This proposed system enhances the reliability and efficiency of photovoltaic plant inspections, thus contributing to improved operational performance and economic viabilityThis research was funded by the Spanish Ministerio de Ciencia, Innovación y Universidades, grant number RTC2019-007364-3 (FPGM), and by the Comunidad de Madrid through the direct grant with ref. SI4/PJI/2024-00233 for the promotion of research and technology transfer at the Universidad Autónoma de Madri

    Pioneering robotic surgery for complex gynecologic conditions: implementation beyond cancer care

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    Minimally invasive surgery was introduced to minimize some of the issues associated with open surgery. Its benefits include fewer complications, less pain and blood loss, shorter hospital stays, quicker recovery, and less noticeable scars. While laparoscopy has been the gold standard for minimally invasive surgery, robot-assisted surgery has emerged as the latest major breakthrough for minimally invasive procedures, allowing surgeons to expand its use to more complex surgical procedures and operating with more precision, flexibility, control, and comfort than is possible with traditional procedures. Here we present the successful implementation of a robotic-assisted surgery program in the gynecology department of the Spanish tertiary hospital La Paz. This included the complete training of six surgeons from the three units in the department: oncology, pelvic floor, and benign organic pathology. By the end of 2024, 184 procedures had been conducted in the first year, including interventions for both cancer (N = 46) and benign pathologies (N = 138). In these, 2.2% of patients developed Clavien–Dindo grade 2 complications. The complexity of the procedures increased during implementation of the program, whereas hospitalization times and associated costs remained lo

    Estudio de la calidad de vida en pacientes con apnea obstructiva del sueño (AOS) tratados de cirugía de avance maxilomandibular mediante distracción osteogénica

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    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Cirugía. Fecha de Lectura: 25-09-2025La apnea obstructiva del sueño (AOS) es un trastorno respiratorio prevalente que afecta significativamente en la calidad de vida (CdV) de los pacientes, asociándose con alteraciones cardiovasculares, neuropsiquiátricas y metabólicas. Este trabajo analiza el impacto de la cirugía de avance maxilomandibular mediante distracción osteogénica (BIRD) en la mejora de la CdV de pacientes con AOS moderada o severa, evaluando aspectos clínicos, funcionales y de percepción subjetiva del bienestar. Pacientes y método Se diseñó un estudio prospectivo con una cohorte de pacientes diagnosticados con AOS modera o severa, tratados mediante el protocolo BIRD. Se recogieron datos clínicos, cefalométricos y polisomnográficos en tres timepoints (TP): preoperatorio (timepoint 1 o TP1), inmediatamente después del avance mandibular (timepoint 2 o TP2) y 6 meses después del avance maxilar (timepoint 3 o TP3). Asimismo, se emplearon cuestionarios estandarizados específicos, incluyendo la Escala de Somnolencia de Epworth (ESS) y el Quebec Sleep Questionnaire (QSQ) para evaluar el impacto subjetivo en la CdV. Resultados El estudio incluyó a 32 pacientes (22% con AOS moderada, 78% con AOS grave). El índice de apnea-hipoapnea (IAH) disminuyó entre T1 (48.5 ± 24,1) y T2 (16,3 ± 15,1) y T3 (8,6 ± 9,6) eventos/h (p < 0,001), con una tasa de curación final del 81,2% (definida como IAH final<5 eventos/h). El índice de 7 saturación de oxígeno (ODI) y el tiempo de saturación de oxihemoglobina por debajo del 90% (T90) también mostraron reducciones significativas (p < 0,001). Los parámetros del sueño reflejaron una normalización progresiva: la latencia del sueño disminuyó de 18,3 ± 6,2 minutos a 9,1 ± 3,7 minutos (p < 0,01), y la eficiencia del sueño aumentó de 72,8 ± 8,9% a 88,4 ± 5,2% (p < 0,001). En cuanto a las fases del sueño, se registró un aumento significativo en el porcentaje de sueño NREM profundo (N3) de un 14,7 ± 4,3% a un 23,2 ± 6,1% (p < 0,01) y una mejora en el sueño REM, que pasó de 18,5 ± 3,8% a 24,1 ± 4,2% (p < 0,01). En términos de percepción subjetiva, las puntuaciones de la ESS disminuyeron significativamente entre T1 (13,4 ± 4,4) y T2 (5,8 ± 3,6) y T3 (1,9 ± 1,8) (p < 0,001). Se observaron mejoras de la CdV en todos los dominios analizados en el QSQ: somnolencia diurna T1 (3,0 ± 1,3) T2 (5,4 ±1,4) T3 (6,3 ± 1,0); síntomas diurnos T1 (2,5 ± 1,4) T2 (5,2 ±1,3) T3 (6,2 ± 1,1); síntomas nocturnos T1 (2. 5 ± 1,1) T2 (5,6 ± 1,1) T3 (6,5 ± 0,8); emociones T1 (2,6 ± 1,6) T2 (5,3 ± 1,4) T3 (6,5 ± 0,9); e interacción social T1 (2,5 ± 1,6) T2 (5,4 ± 1,6) T3 (6,3 ± 1,2) (p < 0,001). Conclusiones La cirugía de avance maxilomandibular mediante distracción osteogénica es una intervención eficaz y segura para pacientes con AOS moderada o severa. Los resultados evidencian un impacto positivo en los parámetros clínicos como en la calidad de vida percibida, destacando la relevancia de un enfoque multidisciplinario para el tratamiento integral de esta patologí

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