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PURPOSE: To estimate the number of ocular syphilis (OS) cases diagnosed in a tertiary care centre in Portugal, correlate with increasing syphilis diagnoses and characterize the OS population. MATERIALS AND METHODS: Retrospective, observational, single-center study that included patients diagnosed with OS between 2015 and 2023 at the local health unit of Coimbra. Demographic data were collected, and a complete ophthalmological examination was performed with multimodal imaging acquisition. Data on syphilis reports from the National System of Epidemiologic Surveillance were correlated with OS data. RESULTS: Fifty-four patients with OS were observed; mean age was 54.17 ± 14.46 years, 38 (70.37%) were male and 18 (47.37%) men who have sex with men. The proportion of OS in syphilis patients per year ranged from 0% to 10.34%. One-quarter were co-infected with HIV. Forty-nine patients (91.84%) complained of decreased visual acuity on presentation. Twenty-two (40.74%) had systemic findings (mostly skin rash). Two-thirds had bilateral disease and half presented with anterior segment involvement. Eighty-five percent had posterior segment involvement, mostly placoid chorioretinitis. Forty-one percent had optic nerve involvement. All patients were admitted and underwent 2-week treatment with intravenous penicillin. Visual acuity improved from logMAR 0.70 to logMAR 0.26 (p < 0.001). CONCLUSIONS: Ocular syphilis is a heterogeneous disease with a wide range of presentations. The incidence is on the rise and therefore OS must be considered in every patient with anterior and posterior uveitis, panuveitis and optic neuritis, with or without systemic manifestations.
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An inertial measurement system, using a combination of accelerometers, gyroscopes and magnetometers, is of great interest to capture tennis movements. We have assessed the key biomechanical moments of the serve phases and events, as well as the kinematic metrics during the serve, to analyze their influence on serve speed. Eighteen male competitive tennis players, equipped with the inertial measurement units, performed a prolonged serve game consisting of 12 simulated points. Participants were divided into groups A and B in accordance with their positioning above or below the sample average serve speed. Group A (compared with their counterparts) presented with lower back hip adduction and knee flexion, and a higher leftward thoracic tilt during the impact event (-14.9 ± 6.9 vs. 13.8 ± 6.4, 2.8 ± 5.9 vs. 14.3 ± 13.0 and -28.9 ± 6.3 vs. 28.0 ± 7.3°). In addition, group A exhibited higher maximal angular velocities in the wrist and thorax, as well as a lower maximal angular velocity in the back hip than group B (427.0 ± 99.8 vs. 205.4 ± 9.7, 162.4 ± 81.7 vs. 193.5 ± 43.8, 205.4 ± 9.7 vs. 308.3 ± 111.7, 193.5 ± 43.8 vs. 81.1 ± 49.7°/s). The relevant biomechanical differences during the serve were identified, highlighting the changes in joint angles and angular velocities between the groups, providing meaningful information for coaches and players to improve their serve proficiency.
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STUDY OBJECTIVES: While various wearable EEG devices have been developed, performance evaluation of the devices and their associated automated sleep stage classification models is mostly limited to healthy subjects. A major barrier for applying automated wearable EEG sleep staging in clinical populations is the need for large-scale data for model training. We therefore investigated transfer learning as strategy to overcome limited data availability and optimize automated single-channel EEG sleep staging in people with sleep disorders. METHODS: We acquired 52 single-channel frontopolar headband EEG recordings from a heterogeneous sleep-disordered population with concurrent PSG. We compared three model training strategies: 'pre-training' (i.e., training on a larger dataset of 901 conventional PSGs), 'training-from-scratch' (i.e., training on wearable headband recordings), and 'fine-tuning' (i.e., training on conventional PSGs, followed by training on headband recordings). Performance was evaluated on all headband recordings using 10-fold cross-validation. RESULTS: Highest performance for 5-stage classification was achieved with fine-tuning (κ = .778), significantly higher than with pre-training (κ = .769) and with training-from-scratch (κ = .733). No significant differences or systematic biases were observed with clinically relevant sleep parameters derived from PSG. All sleep disorder categories showed comparable performance. CONCLUSIONS: This study emphasizes the importance of leveraging larger available datasets through deep transfer learning to optimize performance with limited data availability. Findings indicate strong similarity in data characteristics between conventional PSG and headband recordings. Altogether, results suggest the combination of the headband, classification model, and training methodology can be viable for sleep monitoring in the heterogeneous clinical population.
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Organoids are three-dimensional (3D) cultures, normally derived from stem cells, that replicate the complex structure and function of human tissues. They offer a physiologically relevant model to address important questions in cancer research. The generation of patient-derived organoids (PDOs) from various human cancers allows for deeper insights into tumor heterogeneity and spatial organization. Additionally, interrogating non-tumor stromal cells increases the relevance in studying the tumor microenvironment, thereby enhancing the relevance of PDOs in personalized medicine. PDOs mark a significant advancement in cancer research and patient care, signifying a shift toward more innovative and patient-centric approaches. This review covers aspects of PDO cultures to address the modeling of the tumor microenvironment, including extracellular matrices, air-liquid interface and microfluidic cultures, and organ-on-chip. Specifically, the role of PDOs as preclinical models in gene editing, molecular profiling, drug testing, and biomarker discovery and their potential for guiding personalized treatment in clinical practice are discussed.
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We aimed to conduct a biophysical comparison of angular (Biorower) and linear (Concept2) rowing ergometers across a wide spectrum of exercise intensities. Sixteen (eleven male) skilled rowers, aged 29.8 ± 8.6 and 23.6 ± 1.5 years, with international competitive experience, performed 7 × 3 min bouts with 30 W increments and 60 s intervals, plus 1 min of all-out rowing on both machines with 48 h in between. The ventilatory and kinematical variables were measured breath-by-breath using a telemetric portable gas analyzer and determined using a full-body markerless system, respectively. Similar values of oxygen uptake were observed between ergometers across all intensity domains (e.g., 60.36 ± 8.40 vs. 58.14 ± 7.55 mL/min/kg for the Biorower and Concept2 at severe intensity). The rowing rate was higher on the Biorower vs. Concept2 at heavy and severe intensities (27.88 ± 3.22 vs. 25.69 ± 1.99 and 30.63 ± 3.18 vs. 28.94 ± 2.29). Other differences in kinematics were observed across all intensity domains, particularly in the thorax angle at the finish (e.g., 19.44 ± 4.49 vs. 27.51 ± 7.59° for the Biorower compared to Concep2 at heavy intensity), likely due to closer alignment of the Biorower with an on-water rowing technique. The overall perceived effort was lower on the Biorower when compared to the Concept2 (14.38 ± 1.76 vs. 15.88 ± 1.88). Rowers presented similar cardiorespiratory function on both rowing ergometers, while important biomechanical differences were observed, possibly due to the Biorower's closer alignment with an on-water rowing technique.
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Ergometría , Ejercicio Físico , Consumo de Oxígeno , Deportes Acuáticos , Humanos , Masculino , Adulto , Ergometría/métodos , Ergometría/instrumentación , Deportes Acuáticos/fisiología , Ejercicio Físico/fisiología , Adulto Joven , Femenino , Consumo de Oxígeno/fisiología , Fenómenos Biomecánicos/fisiologíaRESUMEN
Overnight sleep staging is an important part of the diagnosis of various sleep disorders. Polysomnography is the gold standard for sleep staging, but less-obtrusive sensing modalities are of emerging interest. Here, we developed and validated an algorithm to perform "proxy" sleep staging using cardiac and respiratory signals derived from a chest-worn accelerometer. We collected data in two sleep centers, using a chest-worn accelerometer in combination with full PSG. A total of 323 participants were analyzed, aged 13-83 years, with BMI 18-47 kg/m2. We derived cardiac and respiratory features from the accelerometer and then applied a previously developed method for automatic cardio-respiratory sleep staging. We compared the estimated sleep stages against those derived from PSG and determined performance. Epoch-by-epoch agreement with four-class scoring (Wake, REM, N1+N2, N3) reached a Cohen's kappa coefficient of agreement of 0.68 and an accuracy of 80.8%. For Wake vs. Sleep classification, an accuracy of 93.3% was obtained, with a sensitivity of 78.7% and a specificity of 96.6%. We showed that cardiorespiratory signals obtained from a chest-worn accelerometer can be used to estimate sleep stages among a population that is diverse in age, BMI, and prevalence of sleep disorders. This opens up the path towards various clinical applications in sleep medicine.
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Acelerometría , Algoritmos , Polisomnografía , Fases del Sueño , Humanos , Persona de Mediana Edad , Adulto , Anciano , Acelerometría/instrumentación , Acelerometría/métodos , Masculino , Femenino , Adolescente , Anciano de 80 o más Años , Polisomnografía/métodos , Fases del Sueño/fisiología , Adulto Joven , TóraxRESUMEN
We investigated the acute biophysical responses of changing the mandibular position during a rowing incremental protocol. A World-class 37-year-old male rower performed two 7 × 3 min ergometer rowing trials, once with no intraoral splint (control) and the other with a mandibular forward repositioning splint (splint condition). Ventilatory, kinematics and body electromyography were evaluated and compared between trials (paired samples t-test, p ≤ 0.05). Under the splint condition, oxygen uptake was lower, particularly at higher exercise intensities (67.3 ± 2.3 vs. 70.9 ± 1.5 mL·kg-1·min-1), and ventilation increased during specific rowing protocol steps (1st-4th and 6th). Wearing the splint condition led to changes in rowing technique, including a slower rowing frequency ([18-30] vs. [19-32] cycles·min-1) and a longer propulsive movement ([1.58-1.52] vs. [1.56-1.50] m) than the control condition. The splint condition also had a faster propulsive phase and a prolonged recovery period than the control condition. The splint reduced peak and mean upper body muscle activation, contrasting with an increase in lower body muscle activity, and generated an energetic benefit by reducing exercise cost and increasing rowing economy compared to the control condition. Changing the mandibular position benefited a World-class rower, supporting the potential of wearing an intraoral splint in high-level sports, particularly in rowing.
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Beach volleyball (BV) is an intermittent sport characterised by short-duration and highly demanding activities with low intensity periods. Establishing if players' jump ability is influenced by sand granulometry is a useful information for sport scientists, coaches and players. This study aimed to assess the possible differences in the kinetics parameters of the vertical jump on different types of sand performed by BV players. Twelve elite female players performed six countermovement jumps (CMJs) in three different surface conditions (fine sand, reference, coarse sand) in a random counterbalanced order (216 jumps). A generalised mixed model approach detected differences for CMJ model in total duration (p: 0.016), eccentric phase duration (p: 0.007), concentric phase duration (p: 0.011), time to peak power (p: < 0.001), time to peak force (p: 0.014), maximum rate force development concentric phase (p: 0.004), maximum velocity (p: 0.028) and peak power eccentric (p: 0.018). Coarse sand decreases the time spent jumping compared to fine sand, without a penalty to jump height. Coaches and athletes should take this information into account to enhance their understanding of practice strategies and game conditions. One might anticipate a faster pace in games played on coarse sand and a slower pace on fine sand.
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Investigating the evolutionary trajectory of synapsid sensory and cephalic systems is pivotal for understanding the emergence and diversification of mammals. Recent studies using CT-scanning to analyze the rostral foramina and maxillary canals morphology in fossilized specimens of probainognathian cynodonts have contributed to clarifying the homology and paleobiological interpretations of these structures. In the present work, µCT-scannings of three specimens of Riograndia guaibensis, an early Norian cynodont from southern Brazil, were analyzed and revealed an incomplete separation between the lacrimal and maxillary canals, with points of contact via non-ossified areas. While the maxillary canal exhibits a consistent morphological pattern with other Prozostrodontia, featuring three main branches along the lateral region of the snout, the rostral alveolar canal in Riograndia displays variability in the number of extra branches terminating in foramina on the lateral surface of the maxilla, showing differences among individuals and within the same skull. Additionally, pneumatization is observed in the anterior region of the skull, resembling similar structures found in reptiles and mammals. Through this pneumatization, certain branches originating from the maxillary canal extend to the canine alveolus. Further investigation is warranted to elucidate the functionality of this structure and its occurrence in other cynodont groups.
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Extracellular vesicles (EVs) hold promise as a source of disease biomarkers. The diverse molecular cargo of EVs can potentially indicate the status of their tissue of origin, even against the complex background of whole plasma. The main tools currently available for assessing biomarkers of brain health include brain imaging and analysis of the cerebrospinal fluid of patients. Given the costs and difficulties associated with these methods, isolation of EVs of neuronal origin (NEVs) from the blood is an attractive approach to identify brain-specific biomarkers. This perspective describes current key challenges in EV- and NEV-based biomarker research. These include the relative low abundance of EVs, the lack of validated isolation methods, and the difficult search for an adequate target for immunocapturing NEVs. We discuss that these challenges must be addressed before NEVs can fulfill their potential for biomarker research. HIGHLIGHTS: NEVs are promising sources of biomarkers for brain disorders. Immunocapturing NEVs from complex biofluids presents several challenges. The choice of surface target for capture will determine NEV yield. Contamination by non-EV sources is relevant for biomarkers at low concentrations.
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Biomarcadores , Vesículas Extracelulares , Neuronas , Humanos , Vesículas Extracelulares/metabolismo , Biomarcadores/líquido cefalorraquídeo , Neuronas/metabolismo , Encéfalo , EncefalopatíasRESUMEN
The electrical stimulation of pedicle screws is a technique used to ensure its correct placement within the vertebrae pedicle. Several authors have studied these screws' electrical properties with the objective of understanding if they are a potential source of false negatives. As titanium screws are anodized with different thicknesses of a high electrical resistance oxide (TiO2), this study investigated, using analytical, numerical, and experimental methods, how its thickness may affect pedicle screw's resistance and conductivity. Analytical results have demonstrated that the thickness of the TiO2 layer does result in a significant radial resistance increase (44.21 mΩ/nm, for Ø 4.5 mm), and a decrease of conductivity with layers thicker than 150 nm. The numerical approach denotes that the geometry of the screw further results in a decrease in the pedicle screw conductivity, especially after 125 nm. Additionally, the experimental results demonstrate that there is indeed an effective decrease in conductivity with an increase in the TiO2 layer thickness, which is also reflected in the screw's total resistance. While the magnitude of the resistance associated with each TiO2 layer thickness may not be enough to compromise the ability to use anodized pedicle screws with a high-voltage electrical stimulator, pedicle screws should be the subject of more frequent electrical characterisation studies.
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The nasal cavity of living mammals is a unique structural complex among tetrapods, acquired along a series of major morphological transformations that occurred mainly during the Mesozoic Era, within the Synapsida clade. Particularly, non-mammaliaform cynodonts document several morphological changes in the skull, during the Triassic Period, that represent the first steps of the mammalian bauplan. We here explore the nasal cavity of five cynodont taxa, namely Thrinaxodon, Chiniquodon, Prozostrodon, Riograndia, and Brasilodon, in order to discuss the main changes within this skull region. We did not identify ossified turbinals in the nasal cavity of these taxa and if present, as non-ossified structures, they would not necessarily be associated with temperature control or the development of endothermy. We do, however, notice a complexification of the cartilage anchoring structures that divide the nasal cavity and separate it from the brain region in these forerunners of mammals.
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Fósiles , Mamíferos , Cráneo , Cornetes Nasales , Microtomografía por Rayos X , Animales , Mamíferos/anatomía & histología , Fósiles/anatomía & histología , Cráneo/anatomía & histología , Cráneo/diagnóstico por imagen , América del Sur , Cornetes Nasales/anatomía & histología , Cornetes Nasales/diagnóstico por imagen , Evolución Biológica , Cavidad Nasal/anatomía & histología , Cavidad Nasal/diagnóstico por imagen , FilogeniaRESUMEN
To explore the diversity of scenarios in nature, animals have evolved tools to interact with different environmental conditions. Chemoreceptors are an important interface component and among them, olfactory receptors (ORs) and gustatory receptors (GRs) can be used to find food and detect healthy resources. Drosophila is a model organism in many scientific fields, in part due to the diversity of species and niches they occupy. The contrast between generalists and specialists Drosophila species provides an important model for studying the evolution of chemoreception. Here, we compare the repertoire of chemoreceptors of different species of Drosophila with that of D. incompta, a highly specialized species whose ecology is restricted to Cestrum flowers, after reporting the preferences of D. incompta to the odor of Cestrum flowers in olfactory tests. We found evidence that the chemoreceptor repertoire in D. incompta is smaller than that presented by species in the Sophophora subgenus. Similar patterns were found in other non-Sophophora species, suggesting the presence of underlying phylogenetic trends. Nevertheless, we also found autapomorphic gene losses and detected some genes that appear to be under positive selection in D. incompta, suggesting that the specific lifestyle of these flies may have shaped the evolution of individual genes in each of these gene families.
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Lower limb exoskeletons have the potential to mitigate work-related musculoskeletal disorders; however, they often lack user-oriented control strategies. Human-in-the-loop (HITL) controls adapt an exoskeleton's assistance in real time, to optimize the user-exoskeleton interaction. This study presents a HITL control for a knee exoskeleton using a CMA-ES algorithm to minimize the users' physical effort, a parameter innovatively evaluated using the interaction torque with the exoskeleton (a muscular effort indicator) and metabolic cost. This work innovates by estimating the user's metabolic cost within the HITL control through a machine-learning model. The regression model estimated the metabolic cost, in real time, with a root mean squared error of 0.66 W/kg and mean absolute percentage error of 26% (n = 5), making faster (10 s) and less noisy estimations than a respirometer (K5, Cosmed). The HITL reduced the user's metabolic cost by 7.3% and 5.9% compared to the zero-torque and no-device conditions, respectively, and reduced the interaction torque by 32.3% compared to a zero-torque control (n = 1). The developed HITL control surpassed a non-exoskeleton and zero-torque condition regarding the user's physical effort, even for a task such as slow walking. Furthermore, the user-specific control had a lower metabolic cost than the non-user-specific assistance. This proof-of-concept demonstrated the potential of HITL controls in assisted walking.
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Algoritmos , Dispositivo Exoesqueleto , Torque , Humanos , Rodilla/fisiología , Aprendizaje Automático , Masculino , Músculo Esquelético/fisiología , Adulto , Fenómenos Biomecánicos/fisiología , Metabolismo Energético/fisiología , Caminata/fisiología , Articulación de la Rodilla/fisiologíaRESUMEN
Objective.Intra-esophageal pressure (Pes) measurement is the recommended gold standard to quantify respiratory effort during sleep, but used to limited extent in clinical practice due to multiple practical drawbacks. Respiratory inductance plethysmography belts (RIP) in conjunction with oronasal airflow are the accepted substitute in polysomnographic systems (PSG) thanks to a better usability, although they are partial views on tidal volume and flow rather than true respiratory effort and are often used without calibration. In their place, the pressure variations measured non-invasively at the suprasternal notch (SSP) may provide a better measure of effort. However, this type of sensor has been validated only for respiratory events in the context of obstructive sleep apnea syndrome (OSA). We aim to provide an extensive verification of the suprasternal pressure signal against RIP belts and Pes, covering both normal breathing and respiratory events.Approach.We simultaneously acquired suprasternal (207) and esophageal pressure (20) signals along with RIP belts during a clinical PSG of 207 participants. In each signal, we detected breaths with a custom algorithm, and evaluated the SSP in terms of detection quality, breathing rate estimation, and similarity of breathing patterns against RIP and Pes. Additionally, we examined how the SSP signal may diverge from RIP and Pes in presence of respiratory events scored by a sleep technician.Main results.The SSP signal proved to be a reliable substitute for both esophageal pressure (Pes) and respiratory inductance plethysmography (RIP) in terms of breath detection, with sensitivity and positive predictive value exceeding 75%, and low error in breathing rate estimation. The SSP was also consistent with Pes (correlation of 0.72, similarity 80.8%) in patterns of increasing pressure amplitude that are common in OSA.Significance.This work provides a quantitative analysis of suprasternal pressure sensors for respiratory effort measurements.
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Presión , Sueño , Humanos , Masculino , Sueño/fisiología , Femenino , Adulto , Pletismografía , Procesamiento de Señales Asistido por Computador , Respiración , Esternón/fisiología , Persona de Mediana Edad , Polisomnografía , Adulto JovenRESUMEN
BACKGROUND: Sleep-disordered breathing (SDB) affects a significant portion of the population. As such, there is a need for accessible and affordable assessment methods for diagnosis but also case-finding and long-term follow-up. Research has focused on exploiting cardiac and respiratory signals to extract proxy measures for sleep combined with SDB event detection. We introduce a novel multi-task model combining cardiac activity and respiratory effort to perform sleep-wake classification and SDB event detection in order to automatically estimate the apnea-hypopnea index (AHI) as severity indicator. METHODS: The proposed multi-task model utilized both convolutional and recurrent neural networks and was formed by a shared part for common feature extraction, a task-specific part for sleep-wake classification, and a task-specific part for SDB event detection. The model was trained with RR intervals derived from electrocardiogram and respiratory effort signals. To assess performance, overnight polysomnography (PSG) recordings from 198 patients with varying degree of SDB were included, with manually annotated sleep stages and SDB events. RESULTS: We achieved a Cohen's kappa of 0.70 in the sleep-wake classification task, corresponding to a Spearman's correlation coefficient (R) of 0.830 between the estimated total sleep time (TST) and the TST obtained from PSG-based sleep scoring. Combining the sleep-wake classification and SDB detection results of the multi-task model, we obtained an R of 0.891 between the estimated and the reference AHI. For severity classification of SBD groups based on AHI, a Cohen's kappa of 0.58 was achieved. The multi-task model performed better than a single-task model proposed in a previous study for AHI estimation, in particular for patients with a lower sleep efficiency (R of 0.861 with the multi-task model and R of 0.746 with single-task model with subjects having sleep efficiency < 60%). CONCLUSION: Assisted with automatic sleep-wake classification, our multi-task model demonstrated proficiency in estimating AHI and assessing SDB severity based on AHI in a fully automatic manner using RR intervals and respiratory effort. This shows the potential for improving SDB screening with unobtrusive sensors also for subjects with low sleep efficiency without adding additional sensors for sleep-wake detection.
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Respiración , Procesamiento de Señales Asistido por Computador , Síndromes de la Apnea del Sueño , Síndromes de la Apnea del Sueño/fisiopatología , Síndromes de la Apnea del Sueño/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Femenino , Aprendizaje Automático , Adulto , Redes Neurales de la Computación , Electrocardiografía , Anciano , Vigilia/fisiología , SueñoRESUMEN
This study aimed to systematically review and summarise the evidence about the effect of muscle fatigue on the knee proprioception of trained and non-trained individuals. A search in PubMed, Scopus, Web of Science and EBSCO databases and Google Scholar was conducted using the expression: "fatigue" AND ("proprioception" OR "position sense" OR "repositioning" OR "kinesthesia" OR "detection of passive motion" OR "force sense" OR "sense of resistance") AND "knee". Forty-two studies were included. Regarding joint-position sense, higher repositioning errors were reported after local and general protocols. Kinesthesia seems to be more affected when fatigue is induced locally, and force sense when assessed at higher target forces and after eccentric protocols. Muscle fatigue, both induced locally or generally, has a negative impact on the knee proprioception.
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Fatiga Muscular , Propiocepción , Humanos , Rodilla/fisiología , Articulación de la Rodilla/fisiología , Fatiga Muscular/fisiología , Propiocepción/fisiologíaRESUMEN
BACKGROUND: Tumor cells have the ability to invade and form small clusters that protrude into adjacent tissues, a phenomenon that is frequently observed at the periphery of a tumor as it expands into healthy tissues. The presence of these clusters is linked to poor prognosis and has proven challenging to treat using conventional therapies. We previously reported that p60AmotL2 expression is localized to invasive colon and breast cancer cells. In vitro, p60AmotL2 promotes epithelial cell invasion by negatively impacting E-cadherin/AmotL2-related mechanotransduction. METHODS: Using epithelial cells transfected with inducible p60AmotL2, we employed a phenotypic drug screening approach to find compounds that specifically target invasive cells. The phenotypic screen was performed by treating cells for 72 h with a library of compounds with known antitumor activities in a dose-dependent manner. After assessing cell viability using CellTiter-Glo, drug sensitivity scores for each compound were calculated. Candidate hit compounds with a higher drug sensitivity score for p60AmotL2-expressing cells were then validated on lung and colon cell models, both in 2D and in 3D, and on colon cancer patient-derived organoids. Nascent RNA sequencing was performed after BET inhibition to analyse BET-dependent pathways in p60AmotL2-expressing cells. RESULTS: We identified 60 compounds that selectively targeted p60AmotL2-expressing cells. Intriguingly, these compounds were classified into two major categories: Epidermal Growth Factor Receptor (EGFR) inhibitors and Bromodomain and Extra-Terminal motif (BET) inhibitors. The latter consistently demonstrated antitumor activity in human cancer cell models, as well as in organoids derived from colon cancer patients. BET inhibition led to a shift towards the upregulation of pro-apoptotic pathways specifically in p60AmotL2-expressing cells. CONCLUSIONS: BET inhibitors specifically target p60AmotL2-expressing invasive cancer cells, likely by exploiting differences in chromatin accessibility, leading to cell death. Additionally, our findings support the use of this phenotypic strategy to discover novel compounds that can exploit vulnerabilities and specifically target invasive cancer cells.
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Neoplasias del Colon , Mecanotransducción Celular , Humanos , Línea Celular Tumoral , Detección Precoz del Cáncer , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genéticaRESUMEN
Objective.Sleep staging based on full polysomnography is the gold standard in the diagnosis of many sleep disorders. It is however costly, complex, and obtrusive due to the use of multiple electrodes. Automatic sleep staging based on single-channel electro-oculography (EOG) is a promising alternative, requiring fewer electrodes which could be self-applied below the hairline. EOG sleep staging algorithms are however yet to be validated in clinical populations with sleep disorders.Approach.We utilized the SOMNIA dataset, comprising 774 recordings from subjects with various sleep disorders, including insomnia, sleep-disordered breathing, hypersomnolence, circadian rhythm disorders, parasomnias, and movement disorders. The recordings were divided into train (574), validation (100), and test (100) groups. We trained a neural network that integrated transformers within a U-Net backbone. This design facilitated learning of arbitrary-distance temporal relationships within and between the EOG and hypnogram.Main results.For 5-class sleep staging, we achieved median accuracies of 85.0% and 85.2% and Cohen's kappas of 0.781 and 0.796 for left and right EOG, respectively. The performance using the right EOG was significantly better than using the left EOG, possibly because in the recommended AASM setup, this electrode is located closer to the scalp. The proposed model is robust to the presence of a variety of sleep disorders, displaying no significant difference in performance for subjects with a certain sleep disorder compared to those without.Significance.The results show that accurate sleep staging using single-channel EOG can be done reliably for subjects with a variety of sleep disorders.
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Electrooculografía , Fases del Sueño , Trastornos del Sueño-Vigilia , Humanos , Fases del Sueño/fisiología , Electrooculografía/métodos , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/fisiopatología , Masculino , Femenino , Adulto , Estudios de Cohortes , Persona de Mediana Edad , Procesamiento de Señales Asistido por Computador , Redes Neurales de la Computación , Adulto Joven , PolisomnografíaRESUMEN
Objective. Unobtrusive long-term monitoring of cardiac parameters is important in a wide variety of clinical applications, such as the assesment of acute illness severity and unobtrusive sleep monitoring. Here we determined the accuracy and robustness of heartbeat detection by an accelerometer worn on the chest.Approach. We performed overnight recordings in 147 individuals (69 female, 78 male) referred to two sleep centers. Two methods for heartbeat detection in the acceleration signal were compared: one previously described approach, based on local periodicity, and a novel extended method incorporating maximumaposterioriestimation and a Markov decision process to approach an optimal solution.Main results. The maximumaposterioriestimation significantly improved performance, with a mean absolute error for the estimation of inter-beat intervals of only 3.5 ms, and 95% limits of agreement of -1.7 to +1.0 beats per minute for heartrate measurement. Performance held during posture changes and was only weakly affected by the presence of sleep disorders and demographic factors.Significance. The new method may enable the use of a chest-worn accelerometer in a variety of applications such as ambulatory sleep staging and in-patient monitoring.