Jose L Cantero’s research while affiliated with Instituto de Salud Carlos III and other places


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Publications (197)


Spot-checking machine learning algorithms for tool wear monitoring in automatic drilling operations in CFRP/Ti6Al4V/Al stacks in the aircraft industry
  • Article

December 2024

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27 Reads

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1 Citation

Journal of Manufacturing Systems

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J.L. Cantero

Figure 4. Influence of APOE genotype and HOMA-IR on PI Performance across different subtasks. (A) Scatterplots depicting the relationship between HOMA-IR in the SlongAG (N = 53) and drop errors across different subtasks. Significant associations were observed when combining subtasks,
Figure 5. Association between network segregation and PI as influenced by HOMA-IR. (A) Scatterplots depicting the relationship between sensorimotor network segregation in the Gordon parcellation scheme and drop error among individuals of the SlongAG (N = 53) with varying HOMA-IR levels. (B) Similar analysis as in (A) but for the sensorimotor network in the Ji parcellation scheme. (C) Similar analysis as in (A) but for the associative network in the Gordon parcellation scheme. The shaded area around the regression slopes represents the 95% confidence interval. Note that in all cases, the relationship was significant for individuals with higher HOMA-IR values.
Figure 6. Association between sensorimotor network segregation and PI across the two cohorts. (A) Scatterplots illustrating the relationship between sensorimotor network segregation in the Gordon parcellation scheme and drop error in SlongAG for APOE ε4 carriers (n = 15) and non-carriers (n = 38). (B) Similar analysis as in (A) but for SshortAG (ε4 carriers = 22; non-carriers = 27). The shaded area around the regression slope represents the 95% confidence interval. Note that the relationship was significant only for ε4 carriers.
Figure 7. Impact of APOE genotype and HOMA-IR on cortical thickness. (A) Differences in cortical thickness between APOE ɛ4 carriers (ɛ4 + ) and non-carriers (ɛ4 -). Regions in red indicate cortical thinning and regions in blue cortical thickening in APOE ɛ4 carriers compared to noncarriers. (B) Association between cortical thickness and HOMA-IR. Regions in red indicate a positive association, while regions in blue indicate a negative association. Statistical results are summarized in Table 9.
Sample differences in the GM integrity.

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APOE ε4 and Insulin Resistance Influence Path-Integration-Based Navigation through Distinct Large-Scale Network Mechanisms
  • Article
  • Full-text available

November 2024

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25 Reads

Aging and Disease

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Metabolic Signature of Insulin Resistance and Risk of Alzheimer’s Disease

November 2024

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25 Reads

The Journals of Gerontology Series A Biological Sciences and Medical Sciences

Background: Substantial evidence supports the relationship between peripheral insulin resistance (IR) and the development of Alzheimer's disease (AD)-dementia. However, the mechanisms explaining these associations are only partly understood. We aimed to identify a metabolic signature of IR associated with the progression from mild cognitive impairment (MCI) to AD-dementia. Methods: This is a case-control study on 400 MCI subjects, free of type 2 diabetes, within the ACE cohort, including individuals ATN+ and ATN-. After a median of 2.1 years follow-up, 142 subjects converted to AD-dementia. IR was assessed using the HOMA-IR. A targeted multi-platform approach profiled over 600 plasma metabolites. Elastic net penalized linear regression with 10-fold cross-validation was employed to select those metabolites associated with HOMA-IR. The prediction ability of the signature was assessed using support vector machine and performance metrics. The metabolic signature was associated with AD-dementia risk using a multivariable Cox regression model. Using counterfactual-based mediation analysis we investigated the mediation role of the metabolic signature between HOMA-IR and AD-dementia. The metabolic pathways in which the metabolites were involved were identified using MetaboAnalyst. Results: The metabolic signature comprised 18 metabolites correlated with HOMA-IR. After adjustments by confounders, the signature was associated with increased AD-dementia risk (HR 1.234; 95%CI 1.019-1.494; p<0.05). The metabolic signature mediated 35% of the total effect of HOMA-IR on AD-dementia risk. Significant metabolic pathways were related to glycerophospholipid and tyrosine metabolism. Conclusions: We have identified a blood-based metabolic signature that reflects IR and may enhance our understanding of the biological mechanisms through which IR affects AD-dementia.


Fig. 2. Receiver operating characteristic (ROC) analysis of components that showed significant group differences (IC 2, 5, 8, and 12). ROC curve and the corresponding area under the curve (AUC) to differentiate between aMCI and Controls.
Fig. 3. Association between IC 6 and TMT B scores in the whole sample (pFDR < 0.05, pFWER Holm-Bonferroni = 0.26). IC, Independent Component; TMT B, Trail Making Test Part B.
Fig. 4. A) Significant positive correlations between IC 15 and diagnosis' interaction and MMSE in the aMCI group (red, pFDR = 0.036, pFWER Holm-Bonferroni = 0.02). Negative correlations in the Ct group were not significant and are displayed in blue. B) Spatial map of IC 15. Light-dark blue colored regions show decreased gray matter in Ct relative to aMCI (or vice versa, increased gray matter in aMCI relative to Ct). Red-yellow colored regions showed decreased gray matter in aMCI relative to Ct. (Z-scores, thresholded at | 3 |). x,y,z, MNI coordinates of cluster maximum intensity. The color bar indicates the color mapping for the normalized component weights (Z-scores, thresholded at | 3 |). aMCI, amnestic mild cognitive impairment; Ct, controls; IC, Independent Component; MMSE, Mini-Mental State Examination.
Alterations in Gray Matter Structural Networks in Amnestic Mild Cognitive Impairment: A Source-Based Morphometry Study

July 2024

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18 Reads

Journal of Alzheimer's Disease

Background Amnestic mild cognitive impairment (aMCI), considered as the prodromal stage of Alzheimer’s disease, is characterized by isolated memory impairment and cerebral gray matter volume (GMV) alterations. Previous structural MRI studies in aMCI have been mainly based on univariate statistics using voxel-based morphometry. Objective We investigated structural network differences between aMCI patients and cognitively normal older adults by using source-based morphometry, a multivariate approach that considers the relationship between voxels of various parts of the brain. Methods Ninety-one aMCI patients and 80 cognitively normal controls underwent structural MRI and neuropsychological assessment. Spatially independent components (ICs) that covaried between participants were estimated and a multivariate analysis of covariance was performed with ICs as dependent variables, diagnosis as independent variable, and age, sex, education level, and site as covariates. Results aMCI patients exhibited reduced GMV in the precentral, temporo-cerebellar, frontal, and temporal network, and increased GMV in the left superior parietal network compared to controls (pFWER < 0.05, Holm-Bonferroni correction). Moreover, we found that diagnosis, more specifically aMCI, moderated the positive relationship between occipital network and Mini-Mental State Examination scores (pFWER < 0.05, Holm-Bonferroni correction). Conclusions Our results showed GMV alterations in temporo-fronto-parieto-cerebellar networks in aMCI, extending previous results obtained with univariate approaches.


Association between anti-HSV IgG levels and cortical Florbetaben (FBB) binding. Significant results are projected on cortical surfaces (upper panel). Scatter plots (bottom panel) show the relationship of anti-HSV IgG levels with the peak vertex of cortical FBB binding after adjustment by age, sex, and APOE4
Association between anti-HSV IgG levels and blood markers of neurodegeneration. Scatter plots show the relationship of anti-HSV IgG levels with neurofilament light chain (NfL) (upper panel) and pTau-181 (bottom panel) after adjustment by age, sex, and APOE4
Moderating role of anti-HSV IgG levels in the relationship between regional FBB binding and rs-FC patterns. Positive and negative partial correlations adjusted by age, sex and APOE4 are displayed in warm and cool colors, respectively. (A) Abnormal pattern of rs-FC using the right anterior cingulate as FC seed (upper panel). Only participants showing the highest anti-HSV IgG levels (pink) exhibited significant positive associations between Aβ load in the right anterior cingulate and rs-FC of the right anterior cingulate with the right precuneus (bottom panel). (B) Abnormal pattern of rs-FC using the right anterior cingulate as FC seed (upper panel). Only participants showing the highest anti-HSV IgG levels (pink) exhibited significant negative associations between Aβ load in the right anterior cingulate and rs-FC of the right anterior cingulate with the left superior temporal cortex (bottom panel). (C) Abnormal pattern of rs-FC using the right inferior temporal as FC seed (upper panel). Only participants showing the highest anti-HSV IgG levels (pink) exhibited significant negative associations between Aβ load in the right inferior temporal cortex and rs-FC of the right inferior temporal cortex with the right superior temporal sulcus (bottom panel). This pattern of rs-FC appeared significantly opposite in older adults showing the lowest anti-HSV IgG levels (green). Right: right, L: left
Moderating effect of APOE4 on the relationship between anti-HSV IgG levels and cortical Florbetaben (FBB) binding. Results of the regression model is projected on the cortical surfaces (upper panel). The scatter plot (bottom panel) shows the partial correlation between anti-HSV IgG levels and Aβ load in the rostral anterior cingulate adjusted by age and sex in APOE4 carriers (pink) and noncarriers (green). Right: right
Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging

April 2024

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34 Reads

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1 Citation

Alzheimer's Research & Therapy

Background Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of AD, possibly instigating amyloid-beta (Aβ) accumulation decades before the onset of clinical symptoms. However, human in vivo evidence linking HSV-1 infection to AD pathology is lacking in normal aging, which may contribute to the elucidation of the role of HSV-1 infection as a potential AD risk factor. Methods To shed light into this question, serum anti-HSV IgG levels were correlated with ¹⁸F-Florbetaben-PET binding to Aβ deposits and blood markers of neurodegeneration (pTau181 and neurofilament light chain) in cognitively normal older adults. Additionally, we investigated whether associations between anti-HSV IgG and AD markers were more evident in APOE4 carriers. Results We showed that increased anti-HSV IgG levels are associated with higher Aβ load in fronto-temporal regions of cognitively normal older adults. Remarkably, these cortical regions exhibited abnormal patterns of resting state-functional connectivity (rs-FC) only in those individuals showing the highest levels of anti-HSV IgG. We further found that positive relationships between anti-HSV IgG levels and Aβ load, particularly in the anterior cingulate cortex, are moderated by the APOE4 genotype, the strongest genetic risk factor for AD. Importantly, anti-HSV IgG levels were unrelated to either subclinical cognitive deficits or to blood markers of neurodegeneration. Conclusions All together, these results suggest that HSV infection is selectively related to cortical Aβ deposition in normal aging, supporting the inclusion of cognitively normal older adults in prospective trials of antimicrobial therapy aimed at decreasing the AD risk in the aging population.


Principal component analysis (PCA) and heatmap plots between cerebrospinal fluid (CSF) and plasma samples of control subjects. Both PCA (A) and heatmap (A) analysis show that the expression of fatty acids is different between plasma and CSF of control subjects.
Comparison of the rate of progression predicted by the Cox hazard model (black line) with the real rate of progression in the mild cognitive impairment (MCI) population as calculated by Kaplan‒Meier analysis (blue line). The data were adjusted for age, sex, Mini‐Mental State Examination (MMSE), and apolipoprotein E (APOE) ε4.
The shift in the fatty acid composition of the circulating lipidome in Alzheimer's disease

March 2024

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23 Reads

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1 Citation

INTRODUCTION Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear. METHODS The LFA of plasma and cerebrospinal fluid (CSF) samples from 289 participants (103 AD patients, 92 MCI patients, and 94 controls) was determined by GC‐FID. The MCI subjects were followed up for 58 ± 12.5 months. RESULTS In controls, CSF has a more neuroprotective LFA than plasma. In CSF, a higher content of docosahexaenoic acid was associated with a reduced risk of MCI‐to‐AD progression. In plasma, higher oleic acid content was associated with lower risk of AD, MCI, and MCI‐to‐AD progression, whereas higher levels of vaccenic acid and docosahexaenoic acid were associated with greater risk of AD and MCI, and higher rate of MCI‐to‐AD progression, respectively. DISCUSSION The circulating LFA is involved in the pathogenesis and progression of AD. Highlights The lipidome fatty acid profile in CSF and plasma was markedly different. Higher levels of vaccenic acid and lower levels of oleic acid in plasma were associated with greater risk of Alzheimer's disease. In plasma, higher levels of oleic acid were associated with a reduced risk of MCI‐to‐AD progression. Higher levels of docosahexaenoic acid in CSF were associated with a lower risk of MCI‐to‐AD progression. Higher levels of docosahexaenoic acid in plasma were associated with a greater rate of MCI‐to‐AD progression.


Characterization of Extracellular Vesicles from Human Saliva: Effects of Age and Isolation Techniques

January 2024

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93 Reads

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10 Citations

Cells

Salivary extracellular vesicles (EVs) represent an attractive source of biomarkers due to the accessibility of saliva and its non-invasive sampling methods. However, the lack of comparative studies assessing the efficacy of different EV isolation techniques hampers the use of salivary EVs in clinical settings. Moreover, the effects of age on salivary EVs are largely unknown, hindering the identification of salivary EV-associated biomarkers across the lifespan. To address these questions, we compared salivary EV concentration, size mode, protein concentration, and purity using eight EV isolation techniques before and after magnetic bead immunocapture with antibodies against CD9, CD63, and CD81. The effects of age on salivary EVs obtained with each isolation technique were further investigated. Results showed higher expression of CD63 on isolated salivary EVs compared to the expression of CD81 and flotillin-1. Overall, magnetic bead immunocapture was more efficient in recovering salivary EVs with Norgen’s Saliva Exosome Purification Kit and ExoQuick-TC ULTRA at the cost of EV yield. Regardless of age, Invitrogen Total Exosome Isolation Solution showed the highest level of protein concentration, whereas Izon qEVOriginal-70nm columns revealed the highest purity. This study provides the first comprehensive comparison of salivary EVs in younger and older adults using different EV isolation techniques, which represents a step forward for assessing salivary EVs as a source of potential biomarkers of tissue-specific diseases throughout the life cycle.



Catastrophic Tool Failure Detection in Aeronautical Industrial Drilling Systems Based on Spindle Power Consumption Analysis

October 2023

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17 Reads

The aeronautical industry is at the forefront of the fourth industrial revolution, which implies an exponential deployment of monitorization, Data Analytics, and connectivity. In alignment with this new paradigm, this research work presents a Catastrophic Tool Failure (CTF) analysis based on spindle power consumption monitoring in an industrial aircraft fuselage drilling process. In the case under study, the airframe components are arranged in hybrid stacks of Carbon Fiber Reinforced Plastic (CFRP) and titanium (Ti6Al4V) during drilling, which adds to the highly variable industrial machining conditions. This inherent complexity can lead to CTF, a significant concern due to its associated cost and time, especially in automatic processes. Industrial CTF detection systems based on motor power consumption establish maximum and minimum power limits to detect tool breakage. However, these systems generate many false positives and false negatives due to process variability and unforeseen events. Therefore, an Exploratory Data Analysis (EDA) of the power spindle consumption signals and other machining-related features is proposed to gain insights into the breakage nature and develop more effective detection systems. This analysis is oriented to set the basis for real-time Catastrophic Tool Failure detection from power spindle consumption monitoring. As a result, advanced processing time-domain detection methods are proposed.


Data Analytics Applied to Tool Condition Monitoring during Drilling of Hybrid Stacks in Industrial Aircraft Production Systems

October 2023

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25 Reads

The aviation industry is changing significantly as market demands and customer expectations evolve. Aircraft must be designed and manufactured with a future-oriented production system that incorporates computational intelligence, connectivity, and decentralization to ensure the highest levels of quality and performance. By leveraging these technologies, real-time monitoring and continuous process improvement can be achieved through collecting and processing massive amounts of data, accompanied by more sophisticated communication protocols. Among the many operations involved in component assembly, drilling processes are particularly relevant in the aeronautical industry. When drilling airframe components, hybrid joints are generated by combining stacks of various materials, such as titanium and Carbon Fiber-Reinforced Plastic (CFRP). Due to the complexity of drilling these hybrid stacks and the need to adhere to strict quality and safety standards, the cost-per-hole can be pretty high. Consequently, scientific studies in this area are of great interest, as they offer the potential to increase productivity and reduce costs. This research aims to investigate using spindle power consumption signals obtained directly from an industrial drilling system to monitor tool wear evolution. Signal pre-processing, feature extraction, selection, and validation are used to analyze data from two sources: the spindle power consumption signals obtained from the internal instrumentation of the machine and the cutting tool. The study focuses on automatic drilling operations carried out in hybrid stacks at an aircraft manufacturing facility, and the results show a strong correlation between power consumption and tool wear. These findings suggest the potential to develop a non-intrusive tool condition monitoring system that could be applied to other machining processes in the industry.


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Citations (70)


... Its level and oxidation status are crucial for maintaining normal cell membrane integrity. Although the underlying mechanisms between OA and cognitive function have not been well elucidated, it was believed that OA was related to the onset of neurodegeneration disease [65], higher OA content was associated with lower risk of AD, MCI, and MCI-to-AD progression [66]. OA administration, converted in the gut to oleoylethanolamide and signaled to the brain via the autonomic nervous system, enhanced memory and counteracts cognitive decline by regulating neural stem and progenitor cell self-renewal and proliferation [67]. ...

Reference:

Hyperbaric Oxygen Improves Cognitive Impairment Induced by Hypoxia via Upregulating the Expression of Oleic Acid and MBOAT2 of Mice
The shift in the fatty acid composition of the circulating lipidome in Alzheimer's disease

... The detection of differentially expressed miRNAs in this final phase could be a result of the crosstalk of the periodontal ligament cells and the cells of the alveolar bones. The cellular source of EVs in the saliva is heterogenous, as various cell types can contribute [42]. Apart from the epithelial cells and immune cells of the oral cavity, a portion of the EVs found in the saliva can originate from dental-tissuederived cells, such as gingival mesenchymal stem cells and periodontal ligament stem cells [43]. ...

Characterization of Extracellular Vesicles from Human Saliva: Effects of Age and Isolation Techniques

Cells

... Oxidative stress is caused by the imbalance between the production of reactive oxygen species (ROS) and the ability of the body to neutralize or eliminate them. 17 ROS are generated by aerobic metabolism and can damage cell components by oxidizing major biomolecules such as nucleic acids and proteins. 18 OSA is also characterized as a disrupter of the pro-/antioxidant balance due to the repetition of hypoxia-reoxygenation cycles. ...

Plasma and cerebrospinal fluid nonenzymatic protein damage is sustained in Alzheimer's disease

Redox Biology

... Fernández-Pérez et al. [54] focused tool wear, hole delamination and cutting forces in the course of drilling of CFRP material. In the study, the workpiece material that they adapted the conical structure used in the aircraft tail was used. ...

Analysis of Tool Wear and Hole Delamination for Large-Diameter Drilling of CFRP Aircraft Fuselage Components: Identifying Performance Improvement Drivers and Optimization Opportunities

Journal of Manufacturing and Materials Processing

... The amyloid cascade hypothesis in Alzheimer's disease (AD) posits that the accumulation of extracellular amyloid-β (Aβ) neuritic plaques in the brain leads to tauopathy and consequent neurodegeneration (Haass & Selkoe, 2022). Hence, Aβ deposition in the brain is considered to be the first step and the principal trigger of AD pathology (Fernandez-Alvarez, Atienza, & Cantero, 2023;Haass & Selkoe, 2022). In consequence, the neurodegeneration of gray matter (GM) may be related to the deposition of Aβ plaques, resulting in cerebral atrophy and synaptic loss (Serrano-Pozo, Frosch, Masliah, & Hyman, 2011), altering many brain regions, especially subcortical areas, and functional networks. ...

Cortical amyloid-beta burden is associated with changes in intracortical myelin in cognitively normal older adults

Translational Psychiatry

... Given the evidence linking the APOE ɛ4 to cortical thinning throughout life [33] and reduced intracortical myelin in older adults [34], alongside the established impact of cortical thickness [35] and intracortical myelin content on FC [36,37], we hypothesize that variability in cortical thickness and intracortical myelin may further influence the moderating role of brain system segregation on the relationship between APOE ε4 genotype and PI. Finally, as insulin resistance has been associated with progressive atrophy in cortical regions affected by early AD in asymptomatic, late middle-aged individuals [38], the above-mentioned hypothesis can be extended to encompass the moderating role of insulin resistance. ...

Effects of non-modifiable risk factors of Alzheimer’s disease on intracortical myelin content

Alzheimer's Research & Therapy

... In recent years, many studies have been used FCD map on conditions such as diabetes, chronic migraine and Alzheimer's disease, which showed that FCD can be used to explore FC aberrations from a new perspective to reflect the mechanism and compensation for cognitive function. [18][19][20] However, the differences in the number of functional connections in the brain network and the comprehensive functional network abnormalities are currently unknown in patients with OSA, so we intend to investigate altered FCD patterns in patients with OSA using FCD map, assess their association with cognitive impairment. ...

Pre-diabetes is associated with altered functional connectivity density in cortical regions of the default-mode network

Frontiers in Aging Neuroscience

... Enhanced modeling techniques have been employed to develop advanced models capable of predicting tool wear based on machining parameters in metal cutting processes [115]. Different machining processes and tool load types result require varied measurement and analysis approaches, leading to distinct findings for milling with rotating tools focused on machining surfaces [116] and wear prediction via machine learning [117]. Prediction accuracy and machining quality have been improved through supervised learning [118]. ...

Machine learning approach in non-intrusive monitoring of tool wear evolution in massive CFRP automatic drilling processes in the aircraft industry

Journal of Manufacturing Systems

... Variations in T1w/T2w ratios in patients with risk factors (close family history, APOE4 phenotypes) were identified compared to control individuals. In addition, individuals at risk had an association with altered patterns of resting-state functional connectivity (rs-FC) [52]. These abnormalities support the idea of significant alterations in myelin developing with age and constituting signals of vulnerability [53]. ...

Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults

Frontiers in Aging Neuroscience

... These approaches aim to enhance precision and reduce energy consumption while aligning with sustainability goals (Singh, Komal, and Lila 2017;Karim et al. 2024;Kong et al. 2023). Collaborative research among material scientists, engineers, and environmentalists is essential for integrating these technological innovations with ecological considerations, fostering the development of sustainable drilling practices (Yallew, Kumar, and Singh 2016;Chai et al. 2024;Domínguez-Monferrer et al. 2022;Belaadi, Boumaaza, Alshahrani, Khan, et al. 2023). ...

CFRP drilling process control based on spindle power consumption from real production data in the aircraft industry

Procedia CIRP