IBSAL. Artículos del Instituto de Investigación Biomédica de Salamanca

A robust hybrid algorithm (neural networks-AGDC) applied to non-isothermal kinetics of consecutive chemical reactions

Thu, 01 Jan 2015 00:00:00 GMT

[EN] This paper is concerned with the application of a Hybrid Algorithm (HA) to the determination of the Thermodynamic Activation Parameters (ATP) of a kinetic system of first order consecutive reactions. The 8 ATP’s parameters involved in the Arrhenius and Eyring equations have been directly determined from the non-isothermal kinetic data without prior knowledge of the rate constants. AH is constituted by a combination of two algorithms based on different mathematical principles which are sequentially applied. In a first step, a “soft modeling” method of Artificial Neural Networks (ANN) is applied and the obtained values of ATP’s parameters are used as initial estimates of a new optimization algorithm (AGDC) applied in a second stage to improve the values of the final parameters. The great success of HA is the efficient resolution of the ambiguity of the results obtained by ANN. In addition, comparing with the classic algorithms, which present the known weak points, HA offers important advantages: (a) the lack of necessity to know a priori the initial estimates since they are calculated from ANN application, (b) the low probability of being trapped at local minima, saddle points, etc. by means of the exhaustive control and suitable correction of the movement vector during the optimization process, and (c) the simultaneous determination of a higher number of parameters endowed with very different orders of magnitude.

How Confinement Affects the Nucleation, Crystallization, and Dielectric Relaxation of Poly(butylene succinate) and Poly(butylene adipate) Infiltrated within Nanoporous Alumina Templates

Tue, 26 Nov 2019 00:00:00 GMT

[EN]This work describes the successful melt infiltration of poly(butylene succinate) (PBS) and poly(butylene adipate) (PBA) within 70 nm diameter anodic aluminum oxide (AAO) templates. The infiltrated samples were characterized by SEM, Raman, and FTIR spectroscopy. The crystallization behaviors and crystalline structures of both polymers, bulk and confined, were analyzed by differential scanning calorimetry (DSC) and grazing incidence wide angle X-ray scattering (GIWAXS). DSC revealed that a change in the nucleation process occurred from heterogeneous nucleation for bulk samples to homogeneous nucleation for infiltrated PBA and to surface-induced nucleation for infiltrated PBS. GIWAXS results indicate that PBS nanofibers crystallize in the α-phase, as well as their bulk samples. However, PBA nanofibers crystallize just in the β-phase, whereas PBA bulk samples crystallize in a mixture of α- and β-phases. The crystal orientation within the pores was determined, and differences between PBS and PBA were also found. Finally, broadband dielectric spectroscopy was applied to study the segmental dynamics for bulk and infiltrated samples. The glass temperature was found to significantly decrease in the PBS case upon infiltration, while that of PBA remained unchanged. These differences were correlated with the higher affinity of PBS to the AAO walls than PBA, in accordance with their nucleation behavior (surface-induced versus homogeneous nucleation, respectively).

Biocompatibility and bone regeneration with elastin-like recombinamer-based catalyst-free click gels

Fri, 30 Aug 2024 00:00:00 GMT

[EN]Large bone defects are a significant health problem today with various origins, including extensive trauma, tumours, or congenital musculoskeletal disorders. Tissue engineering, and in particular bone tissue engineering, aims to respond to this demand. As such, we propose a specific model based on Elastin-Like Recombinamers-based click-chemistry hydrogels given their high biocompatibility and their potent on bone regeneration effect conferred by different bioactive sequences. In this work we demonstrate, using biochemistry, histology, histomorphometry and imaging techniques, the biocompatibility of our matrix and its potent effect on bone regeneration in a model of bone parietal lesion in female New Zealand rabbits.

Designing Elastin‐Like Recombinamers for Therapeutic and Regenerative Purposes

Sat, 01 Jan 2022 00:00:00 GMT

[EN]The field of biomedicine relies on the development of advanced systems that mimic the extracellular matrix (ECM) to allow in vitro studies of cell–matrix interactions and subsequent implementation in vivo. The principalmatrices for biomedical applications are hydrogels, which are hydrophilic polymer networks that can absorb a large volume of water in resemblance to natural tissues (see Chapter 1). The materials used to obtain these biomimetic scaffolds include a large variety of synthetic polymers such as polyethylene glycol (PEG), as well as biopolymers, mostly proteins from animal tissues such as collagen (see Chapter 2). Combinations of natural and synthetic polymers have also been tested to improve the properties of hydrogels. Essential characteristics for the development of hydrogels for general biomedical applications include (i) an ability to provide a structural support to the surrounding cells, thus promoting natural and adequate cell growth that helps complete integration of the scaffold into the natural surrounding tissue and provides mechanical stability, (ii) an ability to mimic the ECM topography of tissues, (iii) an ability to mimic the natural environment so that cells can develop their normal functions and help restore damaged tissue, (iv) an ability to absorb and retain large quantities of water while maintaining their structures, thereby maintaining the hydration levels found in most tissues, (v) an ability to modulate their structures to match the shape and the size of defects, (vi) an ability to be easily manipulated, and, particularly, (vii) biocompatibility and biodegradability. Depending on the final application, hydrogels for use in regenerative medicine will need specific requirements in order to simulate the tissue to be repaired, such as cell adhesion or growth factors, which could also be included in the scaffold.

Self-assembling systems comprising intrinsically disordered protein polymers like elastin-like recombinamers

Sat, 01 Jan 2022 00:00:00 GMT

[EN]Despite lacking cooperatively folded structures under native conditions, numerous intrinsically disordered proteins (IDPs) nevertheless have great functional importance. These IDPs are hybrids containing both ordered and intrinsically disordered protein regions (IDPRs), the structure of which is highly flexible in this unfolded state. The conformational flexibility of these disordered systems favors transitions between disordered and ordered states triggered by intrinsic and extrinsic factors, folding into different dynamic molecular assemblies to enable proper protein functions. Indeed, prokaryotic enzymes present less disorder than eukaryotic enzymes, thus showing that this disorder is related to functional and structural complexity. Protein-based polymers that mimic these IDPs include the so-called elastin-like polypeptides (ELPs), which are inspired by the composition of natural elastin. Elastin-like recombinamers (ELRs) are ELPs produced using recombinant techniques and which can therefore be tailored for a specific application. One of the most widely used and studied characteristic structures in this field is the pentapeptide (VPGXG)n . The structural disorder in ELRs probably arises due to the high content of proline and glycine in the ELR backbone, because both these amino acids help to keep the polypeptide structure of elastomers disordered and hydrated. Moreover, the recombinant nature of these systems means that different sequences can be designed, including bioactive domains, to obtain specific structures for each application. Some of these structures, along with their applications as IDPs that self-assemble into functional vesicles or micelles from diblock copolymer ELRs, will be studied in the following sections. The incorporation of additional order- and disorder-promoting peptide/protein domains, such as α-helical coils or β-strands, in the ELR sequence, and their influence on self-assembly, will also be reviewed. In addition, chemically cross-linked systems with controllable order-disorder balance, and their role in biomineralization, will be discussed. Finally, we will review different multivalent IDPs-based coatings and films for different biomedical applications, such as spatially controlled cell adhesion, osseointegration, or biomaterial-associated infection (BAI).

Trends in the Development of Tailored Elastin-Like Recombinamer–Based Porous Biomaterials for Soft and Hard Tissue Applications

Fri, 01 Jan 2021 00:00:00 GMT

[EN]Porous biomaterials are of significant interest in a variety of biomedical applications as they enable the diffusion of nutrients and gases as well as the removal of metabolic waste from implants. Pores also provide 3D spaces for cell compartmentalization and the development of complex structures such as vasculature and the extracellular matrix. Given the variation in the extracellular matrix composition across and within different tissues, it is necessary to tailor the physicochemical characteristics of biomaterials and or surfaces thereof for optimal bespoke applications. In this regard, different synthetic and natural polymers have seen increased usage in the development of biomaterials and surface coatings; among them, elastin-like polypeptides and their recombinant derivatives have received increased advocacy. The modular assembly of these molecules, which can be controlled at a molecular level, presents a flexible platform for the endowment of bespoke biomaterial properties. In this review, various elastin-like recombinamer–based porous biomaterials for both soft and hard tissue applications are discussed and their current and future applications evaluated.

Effect of processing on microstructure, mechanical properties, corrosion and biocompatibility of additive manufacturing Ti-6Al-4V orthopaedic implants

Wed, 23 Apr 2025 00:00:00 GMT

[EN]This study evaluates the microstructure, porosity, mechanical properties and corrosion resistance of Ti-6Al-4V hip implant samples manufactured by Selective Laser Melting (SLM) and Electron Beam Melting (EBM), followed by different post-treatments (heat treatment and hot isostatic pressing -HIP-). Hydroxyapatite (HA) coatings were applied to enhance biocompatibility. Post-treated samples exhibited a lamellar α + β microstructure, with the EBM sample showing a coarser Widmanstätten structure, while acicular α' martensite was predominant in the as-built sample. The degree of porosity was lower than 0.2% in all samples. Microhardness was highest in the as-built sample (~ 400 HV) and lower in post-treated samples (~ 370 HV). Open Circuit Potential (OCP) tests indicated superior corrosion resistance for heat-treated samples, confirmed by Electrochemical Impedance Spectroscopy (EIS), where Sample E-HIP (HIP) showed a polarization resistance (Rpol) of 2490 kΩ/cm². In vitro tests confirmed that HA-coated samples exhibited excellent biocompatibility, slightly surpassing the Ti-6Al-4V samples. The HA-coated samples exhibited increased metabolic activity over 7 days, indicating superior biocompatibility. Finally, additive manufacturing combined with heat treatments and HA coatings effectively enhances Ti-6Al-4V for orthopaedic implants by improving the mechanical performance, corrosion resistance and biocompatibility.

Evaluating Urinary Biomarkers for Early Detection of Kidney Damage in Immune Checkpoint Inhibitors-Treated Patients

Fri, 24 Oct 2025 00:00:00 GMT

[EN]Immune checkpoint inhibitors (ICIs) have improved cancer treatment; however, their use can be limited by immune-mediated adverse events, such as kidney damage. Diagnostic limitations of nephrotoxicity may lead to worsening of the patient's prognosis. This study aimed to validate a panel of urinary biomarkers as diagnostic tools for kidney damage in patients treated with ICIs. A prospective study was conducted on patients scheduled to receive ICIs. Those who subsequently developed kidney damage were considered cases; and those who did not were considered controls. A battery of biomarkers was assessed in urine samples at PRE-1, before the first treatment cycle; PRE-3, before the third cycle; and POST-3, 1 week after the third treatment cycle. A total of 46 patients participated in the study. At PRE-1, increased urinary excretion of IGFBP7, NAG, TIMP-2 × IGFBP7, and transferrin was observed in the case group, suggesting that these markers could be useful for early risk stratification of developing kidney damage. Furthermore, increased urinary excretion of albumin and NGAL was observed at PRE-3, suggesting that these markers could be of diagnostic utility to identify patients that could develop kidney damage once treatment is initiated. All of the aforementioned biomarkers demonstrated significant discriminatory ability between cases and controls, as verified by ROC curve analysis. The proposed biomarker battery could be used as a preventive tool for decision-making in the management of oncology patients at risk for kidney damage associated with ICIs. Furthermore, its use would allow personalized adjustment of therapy that would minimize the probability of renal complications even before starting the first cycle of treatment.

Pathophysiological mechanisms underlying a rat model of triple whammy acute kidney injury

Mon, 27 Jul 2020 00:00:00 GMT

[EN]Simultaneous administration of certain antihypertensive (renin-angiotensin system inhibitors and diuretics) and nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a renal toxicity syndrome known as "triple whammy" acute kidney injury (TW-AKI), yet poorly characterized at the pathophysiological level, as no specific experimental model exists on which to conduct preclinical research. Herein, we generated and characterized a rat model of TW-AKI (0.7 mg/kg/day trandolapril +400 mg/kg/day ibuprofen +20 mg/kg/day furosemide). Double treatments involving the NSAID caused a subclinical acute kidney injury, as they reduced glomerular filtration rate to a significant but not sufficient extent to increase Crpl concentration. Only the triple treatment generated an overt AKI with increased Crpl provided that animals were under partial water ingestion restriction. Histological examination revealed no evidence of tissue renal injury, and no proteinuria or makers of renal damage were detected in the urine. These findings, along with a normal fractional excretion of sodium and glucose, indicated that these drug combinations produce a prerenal type of AKI. In fact, blood pressure and renal blood flow were also reduced (most markedly following the triple combination), although renal dysfunction was more pronounced than expected for the corresponding pressure drop, supporting a key pathological role of the interference with renal autoregulation mechanisms. In summary, prerenal TW-AKI only occurs when volemia is challenged (i.e., by furosemide in partially water-deprived animals) under the effects of renin-angiotensin system inhibitors and NSAIDs. This model will facilitate further pathophysiological knowledge for a better diagnosis and clinical handling of this syndrome.

A meta-analysis of preclinical studies using antioxidants for the prevention of cisplatin nephrotoxicity: implications for clinical application.

Tue, 10 Nov 2020 00:00:00 GMT

[EN]Cisplatin is an effective chemotherapeutic drug whose clinical use and efficacy are limited by its nephrotoxicity, which affects mainly the renal tubules and vasculature. It accumulates in proximal and distal epithelial tubule cells and causes oxidative stress-mediated cell death and malfunction. Consequently, many antioxidants have been tested for their capacity to prevent cisplatin nephrotoxicity. In this study, we made a systematic review of the literature and meta-analyzed 152 articles, which tested the nephroprotective effect of isolated compounds or mixtures of natural origin on cisplatin nephrotoxicity in preclinical models. This meta-analysis identified the most effective candidates and examined the efficacy obtained by antioxidants administered by the oral and intraperitoneal routes. By comparing with a recent, similar meta-analysis performed on clinical studies, this article identifies a disconnection between preclinical and clinical research, and contextualizes, discusses, and integrates the existing preclinical information toward the optimized selection of candidates to be further explored (clinical level). Despite proved efficacy, this article discusses the barriers limiting the clinical development of natural mixtures, such as those in extracts from Calendula officinalis flowers and Heliotropium eichwaldii roots. On the contrary, isolated compounds are more straightforward candidates, among which arjunolic acid and quercetin stand out in this meta-analysis.

Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats.

Fri, 01 Nov 2024 00:00:00 GMT

[EN]Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10 mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150 mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.

Effect of uric acid reduction on chronic kidney disease. Systematic review and meta-analysis

Tue, 26 Mar 2024 00:00:00 GMT

[EN]Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit afforded by the control of uric acid (UA) is controversial. Individual studies show discrepant results, and most existing meta-analysis, especially those including the larger number of studies, lack a placebo or control group as they aim to compare efficacy between drugs. On these grounds, we performed a me-ta-analysis restricted to studies including the action of any anti-gout therapies referenced to a control or placebo arm. This approach allows for a clearer association between UA reduction and renal effect. Of the twenty-nine papers included, most used allopurinol and febuxostat and, therefore, solid conclusions could only be obtained for these drugs. Both were very effective in reducing UA, but only allopurinol was able to significantly improve glomerular filtration rate (GFR), although not in a dose-dependent manner. These results raised doubts as to whether it is the hypouricemic effect of anti-gout drugs, or a pleiotropic effect, what provides protection of kidney function. Accordingly, in a correlation study that we next performed between UA reduction and GFR improvement, no association was found, which suggests that additional mechanisms may be involved. Of note, most trials show large inter-individual response variability, probably because they included patients with heterogeneous phenotypes and pathological characteristics, including different stages of CKD and comorbidities. This highlights the need to sub classify the effect of UA-lowering therapies according to the pathological scenario, in order to identify those CKD patients that may benefit most from them. Systematic Review Registration: CRD42022306646 https://www.crd.york.ac.uk/prospero/.

Albuminuria Pre-Emptively Identifies Cardiac Patients at Risk of Contrast-Induced Nephropathy

Tue, 26 Oct 2021 00:00:00 GMT

[EN]Contrast-induced nephropathy (CIN) is a complication associated with the administration of contrast media (CM). The CIN diagnosis is based on creatinine, a biomarker late and insensitive. The objective proposed was to evaluate the ability of novel biomarkers to detect patients susceptible to suffering CIN before CM administration. The study was carried out with patients undergoing cardiac catheterization involving CM. Patients were divided into two groups: (1) CIN, patients who developed this pathology; (2) control, patients who did not suffer CIN. Prior to the administration of CM, urine samples were collected to measure proteinuria, N-acetyl-β-d-glucosaminidase, neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, albumin, transferrin, t-gelsolin and GM2 ganglioside activator protein (GM2AP). The risk factors advanced age, low body mass index and low estimated glomerular filtration rate; and the urinary biomarkers albumin, transferrin and GM2AP showed significant predictive capacity. Of all of them, albuminuria demonstrated the highest diagnostic power. When a cutoff point was established for albuminuria at values still considered subclinical (10-30 µg/mg Cru), it was found that there was a high incidence of CIN (40-75%). Therefore, albuminuria could be applied as a new diagnostic tool to prevent and predict CIN with P4 medicine criteria, independently of risk factors and comorbidities.

Regression Modeling of the Antioxidant-to-Nephroprotective Relation Shows the Pivotal Role of Oxidative Stress in Cisplatin Nephrotoxicity.

Thu, 26 Aug 2021 00:00:00 GMT

[EN]The clinical utility of the chemotherapeutic drug cisplatin is significantly limited by its nephrotoxicity, which is characterized by electrolytic disorders, glomerular filtration rate decline, and azotemia. These alterations are consequences of a primary tubulopathy causing injury to proximal and distal epithelial cells, and thus tubular dysfunction. Oxidative stress plays a role in cisplatin nephrotoxicity and cytotoxicity, but its relative contribution to overall toxicity remains unknown. We studied the relation between the degree of oxidative reduction (provided by antioxidant treatment) and the extent of nephrotoxicity amelioration (i.e., nephroprotection) by means of a regression analysis of studies in animal models. Our results indicate that a linear relation exists between these two parameters, and that this relation very nearly crosses the value of maximal nephroprotection at maximal antioxidant effect, suggesting that oxidative stress seems to be a pivotal and mandatory mechanism of cisplatin nephrotoxicity, and, hence, an interesting, rationale-based target for clinical use. Our model also serves to identify antioxidants with enhanced effectiveness by comparing their actual nephroprotective power with that predicted by their antioxidant effect. Among those, this study identified nanoceria, erythropoietin, and maltol as highly effective candidates affording more nephroprotection than expected from their antioxidant effect for prospective clinical development.

Effect of Cognitive Training on Cancer‐Related Cognitive Impairment in Patients With Breast Cancer: A Systematic Review and Meta‐Analysis

Fri, 01 Aug 2025 00:00:00 GMT

[EN]Background: Cancer-related cognitive impairment (CRCI) associated with chemotherapy ('chemobrain') in patiens with breast cancer represents a challenging sequelae of cancer treatment. Cognitive training (CT) has shown potential to improve CRCI. Aim: This systematic review with meta-analysis aimed to evaluate the efficacy of CT in improving CRCI in patients with breast cancer. Methods: A systematic literature review was conducted in PubMed, Web of Science, Scopus, Embase, Cochrane Library, PsycInfo, CINAHL Complete, ClinicalTrials.gov and Psicodoc databases for studies published up to January 2025. Methodological quality was assessed using PRISMA, RoB 2 and the PEDro Scale. The protocol was registered in PROSPERO (CRD42025636745). Results: Of 7751 studies identified, 11 met inclusion criteria and 9 were included in the meta-analysis. Eight studies assessed the effect of CT on the FACT-Cog scale global score, showing a significant effect (SMD = 0.2; IC del 95%: -0.39 a -0.01; p = 0.04), and low heterogeneity (I2 = 0%). Seven studies analysed perceived cognitive impairments (PCI), perceived cognitive abilities (PCA), and impact on quality of life (QOL), while six included comments from others (OTH), showing a significant overall effect (SMD = 0.39; IC del 95%: -0.58 a -0.19; p < 0.001), with no significant heterogeneity. There were significant improvements in PCI and PCA. Funnel plots analysis suggested possible publication bias. Conclusions: CT could be effective in improving CRCI in patients with breast cancer. However, the existing evidence is of low quality and, therefore, higher quality studies with larger samples are still warranted.; [ES] Introducción: El deterioro cognitivo relacionado con el cáncer (DCRC) asociado a la quimioterapia (chemobrain) en pacientes con cáncer de mama representa una secuela desafiante del tratamiento oncológico. El entrenamiento cognitivo (EC) ha mostrado potencial para mejorar el DCRC.Objetivo: Esta revisión sistemática con meta-análisis tuvo como objetivo evaluar la eficacia del EC para mejorar el DCRC en pacientes con cáncer de mama.Métodos: Se realizó una revisión sistemática de la literatura en las bases de datos PubMed, Web of Science, Scopus, Embase, Cochrane Library, PsycInfo, CINAHL Complete, ClinicalTrials.gov y Psicodoc para estudios publicados hasta enero de 2025. La calidad metodológica se evaluó mediante PRISMA, RoB 2 y la Escala PEDro. El protocolo fue registrado en PROSPERO (CRD42025636745). Resultados: De los 7751 estudios identificados, 11 cumplieron los criterios de inclusión y 9 se incluyeron en el meta-análisis. Ocho estudios evaluaron el efecto del EC en la puntuación global de la escala FACT-Cog, mostrando un efecto significativo (SMD = 0,2; IC del 95%: -0,39 a -0,01; p = 0,04) y una baja heterogeneidad (I^2 = 0%). Siete estudios analizaron el deterioro cognitivo percibido (PCI), las habilidades cognitivas percibidas (PCA) y el impacto en la calidad de vida (QOL), mientras que seis incluyeron comentarios de terceros (OTH), mostrando un efecto global significativo (SMD = 0,39; IC del 95%: -0,58 a -0,19; p < 0,001), sin heterogeneidad significativa. Se observaron mejoras significativas en PCI y PCA. El análisis de los gráficos de embudo (funnel plots) sugirió un posible sesgo de publicación.Conclusiones: El entrenamiento cognitivo podría ser eficaz para mejorar el DCRC en pacientes con cáncer de mama. Sin embargo, la evidencia existente es de baja calidad y, por lo tanto, se siguen requiriendo estudios de mayor calidad con muestras más grandes.

A Cognitive Training Programme on Cancer-Related Cognitive Impairment (CRCI) in Breast Cancer Patients Undergoing Active Treatment: A RCT Study Protocol

Wed, 16 Jul 2025 00:00:00 GMT

[EN]Background: In light of increasing breast cancer survival rates, it is essential to address cancer-related cognitive impairment (CRCI), a common yet often underestimated symptom. Methods: A randomised controlled trial is proposed involving 50 newly diagnosed participants, divided into a control group (CG) and an intervention group (IG). Both groups will receive an educational leaflet, while the IG will also take part in an individualised cognitive training programme based on everyday cognition (80 sessions distributed across four periods, compiled in a training dossier). Cognitive, emotional, and functional variables will be assessed before and after the intervention: cognitive function (MoCA test), everyday cognition (PECC), anxiety (Hamilton), functionality (LB), sleep quality (PSQI), quality of life (ECOG), and subjective memory complaints (FACT-COG). Expected results: Findings may guide future interventions and tailored protocols to alleviate CRCI in breast cancer patients undergoing active treatment. Ethics and dissemination: This study was approved by the Ethics Committee of the University of Salamanca (PI 2023 12 1478-TD).