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1.
J Clin Med ; 13(7)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38610807

RESUMEN

Background/Objective: Alzheimer's disease is a condition that can cause memory, thinking, and behaviour impairments. This type of dementia affects approximately 50 million people globally. Currently, there is no remedy for this disease, but there are different treatment approaches, both pharmacological and non-pharmacological, that try to alleviate the symptoms. The remarkable fact about Alzheimer's response to music is that musical abilities can be preserved even though language could be lost. The objective of this systematic review is to assess the benefits of music therapy on cognitive impairments in older adults with Alzheimer's disease. Methods: This is a systematic review carried out following the PRISMA guidelines. The literature searches were conducted in the following databases: PubMed, SCOPUS, Cochrane Library, and Dialnet. The inclusion criteria established were as follows: randomised controlled studies and clinical trials published in English and Spanish from 2010 to 2024, patients diagnosed with dementia of the Alzheimer's type, aged 65 years or older, who had participated in music interventions and had cognitive changes. Results: Eleven studies were included in this review. They showed that music therapy interventions mainly improved memory, language, and orientation. The results of a methodological quality analysis showed that six of the articles had good methodological quality and four had excellent methodological quality. Conclusions: The results of this review suggest that treatment with music therapy improves cognitive impairments in patients with Alzheimer's disease. In addition, we can be sure that music creates a link between the patient and the specialist.

2.
Nature ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38588697

RESUMEN

Broad-spectrum RAS inhibition holds the potential to benefit roughly a quarter of human cancer patients whose tumors are driven by RAS mutations1,2. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS, and NRAS, with affinity for both mutant and wild type (WT) variants (RAS(ON) multi-selective)3. As >90% of human pancreatic ductal adenocarcinoma (PDAC) cases are driven by activating mutations in KRAS4, we assessed the therapeutic potential of the RAS(ON) multi-selective inhibitor RMC-7977 in a comprehensive range of PDAC models. We observed broad and pronounced anti-tumor activity across models following direct RAS inhibition at exposures that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumor versus normal tissues. Treated tumors exhibited waves of apoptosis along with sustained proliferative arrest whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. In the autochthonous KPC model, RMC-7977 treatment resulted in a profound extension of survival followed by on-treatment relapse. Analysis of relapsed tumors identified Myc copy number gain as a prevalent candidate resistance mechanism, which could be overcome by combinatorial TEAD inhibition in vitro. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS-GTP inhibition in the setting of PDAC and identify a promising candidate combination therapeutic regimen to overcome monotherapy resistance.

3.
Emergencias ; 36(2): 97-103, 2024 Apr.
Artículo en Español, Inglés | MEDLINE | ID: mdl-38597616

RESUMEN

OBJECTIVES: To study differences in the emergency department treatment of acute poisoning according to biological sex of patients and to assess adherence to care quality indicators. MATERIAL AND METHODS: Retrospective observational study including all cases of acute poisoning diagnosed in patients over the age of 14 years treated in a tertiary care hospital emergency department over a period of 4 years. We analyzed demographic variables, substance type and reason for acute poisoning, degree of adherence to quality indicators, and discharge destination. RESULTS: A total of 1144 cases were included; 710 patients (62.1%) were female and 434 (37.9%) were male. The proportion of deliberate self-poisoning was higher in females (52.3% vs 41.4% in males; P .001); unintentional poisoning was less frequent in females (in 24.9% vs in 30.3% of males; P = .047). Benzodiazepine poisoning was more frequent in females (in 49.6% vs 41.2%; P = .007). Street drug and alcohol poisoning was less common in females. Adherence to quality indicators was high (> 85%) for both sexes. CONCLUSION: The epidemiologic profile of poisoning is different in females and males. General emergency department adherence to quality indicators can be considered optimal. We detected no qualitative sex-related differences in the care of patients with acute poisoning.


OBJETIVO: Estudiar las diferencias dependiendo del sexo en la atención de pacientes con intoxicaciones agudas en urgencias y en el grado de cumplimiento de los indicadores de calidad (IC). METODO: Estudio observacional y retrospectivo, que incluyó todos los casos de intoxicación aguda de pacientes mayores de 14 años atendidos en el servicio de urgencias de un hospital terciario durante 4 años. Se analizaron variables demográficas, tipo de tóxicos y causa de la intoxicación, el grado de cumplimiento de los IC y destino al alta. RESULTADOS: Se registraron 1.144 casos, un 62,1% (n = 710) eran mujeres. Las mujeres tuvieron mayor número de intoxicaciones voluntarias (52,3% vs 41,4%; p 0,001) y menos de manera accidental (24,9% vs 30,3%; p = 0,047). Los fármacos más frecuentes en mujeres fueron las benzodiacepinas (49,6% vs 41,2%; p = 0,007), y las intoxicaciones por drogas de abuso y alcohol fueron menores que en hombres. Hubo un alto grado de cumplimiento en la mayoría de los IC (> 85%) en ambos sexos. CONCLUSIONES: El perfil epidemiológico de la intoxicación aguda en mujeres es diferente al de los hombres. En general se puede considerar como óptimo el cumplimiento de los IC en urgencias. No existen diferencias cualitativas en la asistencia del paciente intoxicado con respecto a su sexo.


Asunto(s)
Servicio de Urgencia en Hospital , Indicadores de Calidad de la Atención de Salud , Adolescente , Femenino , Humanos , Masculino , Tratamiento de Urgencia , Estudios Retrospectivos
4.
Emergencias (Sant Vicenç dels Horts) ; 36(2): 1-7, Abr. 2024. tab
Artículo en Español | IBECS | ID: ibc-231794

RESUMEN

Objetivos. Estudiar las diferencias dependiendo del sexo en la atención de pacientes con intoxicaciones agudas en urgencias y en el grado de cumplimiento de los indicadores de calidad (IC). Método. Estudio observacional y retrospectivo, que incluyó todos los casos de intoxicación aguda de pacientes mayores de 14 años atendidos en el servicio de urgencias de un hospital terciario durante 4 años. Se analizaron variables demográficas, tipo de tóxicos y causa de la intoxicación, el grado de cumplimiento de los IC y destino al alta. Resultados. Se registraron 1.144 casos, un 62,1% (n = 710) eran mujeres. Las mujeres tuvieron mayor número de intoxicaciones voluntarias (52,3% vs 41,4%; p < 0,001) y menos de manera accidental (24,9% vs 30,3%; p = 0,047). Los fármacos más frecuentes en mujeres fueron las benzodiacepinas (49,6% vs 41,2%; p = 0,007), y las intoxicaciones por drogas de abuso y alcohol fueron menores que en hombres. Hubo un alto grado de cumplimiento en la mayoría de los IC (> 85%) en ambos sexos. Conclusiones. El perfil epidemiológico de la intoxicación aguda en mujeres es diferente al de los hombres. En general se puede considerar como óptimo el cumplimiento de los IC en urgencias. No existen diferencias cualitativas en la asistencia del paciente intoxicado con respecto a su sexo. (AU)


Objective. To study differences in the emergency department treatment of acute poisoning according to biological sex of patients and to assess adherence to care quality indicators. Methods. Retrospective observational study including all cases of acute poisoning diagnosed in patients over the age of 14 years treated in a tertiary care hospital emergency department over a period of 4 years. We analyzed demographic variables, substance type and reason for acute poisoning, degree of adherence to quality indicators, and discharge destination. Results. A total of 1144 cases were included; 710 patients (62.1%) were female and 434 (37.9%) were male. The proportion of deliberate self-poisoning was higher in females (52.3% vs 41.4% in males; P < .001); unintentional poisoning was less frequent in females (in 24.9% vs in 30.3% of males; P = .047). Benzodiazepine poisoning was more frequent in females (in 49.6% vs 41.2%; P = .007). Street drug and alcohol poisoning was less common in females. Adherence to quality indicators was high (> 85%) for both sexes. Conclusions. The epidemiologic profile of poisoning is different in females and males. General emergency department adherence to quality indicators can be considered optimal. We detected no qualitative sex-related differences in the care of patients with acute poisoning. (AU)


Asunto(s)
Humanos , Intoxicación , Servicio de Urgencia en Hospital , Sexo , Preparaciones Farmacéuticas , Sustancias Tóxicas , Mortalidad Prematura , Estudios Retrospectivos , España
6.
Langmuir ; 40(10): 5433-5443, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38427972

RESUMEN

An efficient and sustainable agriculture calls for the development of novel agrochemical delivery systems able to release agrochemicals in a controlled manner. This study investigated the controlled release of the insecticide methoxyfenozide (MFZ) from lignin (LN) nanoparticles (LNPs). LN-grafted poly(ε-caprolactone) (LN-g-PCL) polymers were synthesized using two grafting methods, ring-opening polymerization (ROP)(LN-g-PCLp) and acylation reaction (LN-g-PCLa), creating polymers capable of self-assembling into nanoparticles of different properties, without surfactants. The LN-g-PCLp polymers exhibited a degree of polymerization (DP) from 22 to 101, demonstrating enhanced thermal stability after LN incorporation. LNPs loaded with MFZ exhibited a spherical core-shell structure with a hydrophilic LN outer layer and hydrophobic PCL core, with sizes affected by grafting methods and DP. LNPs controlled MFZ release, displaying variation in release profiles depending on the grafting methodology used, LN-g-PCLp DP, and temperature variations (23 to 30 °C). LNPs formulated with LN-g-PCLa showed a cumulative release of MFZ of 36.78 ± 1.23% over 196 h. Comparatively, increasing the DP of the LN-g-PCLp polymers, a reduction of the LNPs release rate from 92.39 ± 1.46% to 70.59 ± 2.40% was achieved within the same time frame. These findings contribute to identifying ways to modulate the controlled release of agrochemicals by incorporating them in renewable-based LNPs.

8.
Ecol Lett ; 27(3): e14408, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38504459

RESUMEN

Although plant-soil feedback (PSF) is being recognized as an important driver of plant recruitment, our understanding of its role in species coexistence in natural communities remains limited by the scarcity of experimental studies on multispecies assemblages. Here, we experimentally estimated PSFs affecting seedling recruitment in 10 co-occurring Mediterranean woody species. We estimated weak but significant species-specific feedback. Pairwise PSFs impose similarly strong fitness differences and stabilizing-destabilizing forces, most often impeding species coexistence. Moreover, a model of community dynamics driven exclusively by PSFs suggests that few species would coexist stably, the largest assemblage with no more than six species. Thus, PSFs alone do not suffice to explain coexistence in the studied community. A topological analysis of all subcommunities in the interaction network shows that full intransitivity (with all species involved in an intransitive loop) would be rare but it would lead to species coexistence through either stable or cyclic dynamics.


Asunto(s)
Ecosistema , Suelo , Retroalimentación , Plantas , Madera
10.
J Neuroeng Rehabil ; 21(1): 4, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172975

RESUMEN

BACKGROUND: Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation. METHODS: A proof-of-concept device, consisting of implantable thin-film electrodes and a nonimplantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant. RESULTS: Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device. CONCLUSIONS: This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.


Asunto(s)
Terapia por Estimulación Eléctrica , Músculo Esquelético , Humanos , Electromiografía , Electrodos Implantados , Músculo Esquelético/fisiología , Extremidad Inferior , Tecnología Inalámbrica
11.
J Clin Med ; 13(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38276141

RESUMEN

BACKGROUND: The risk for an unexpected fall can be due to increasing age, health conditions, and loss of cognitive, sensory, or musculoskeletal functions. Falls have personal and economic consequences in many countries. Different disturbances can occur during gait, such as tripping, slipping, or other unexpected circumstances that can generate a loss of balance. The strategies used to recover balance depend on many factors, but selecting a correct response strategy influences the success of balance recovery. OBJECTIVES: (1) To collect and clarify the definitions of compensatory protective step strategies to recover balance in older adults; (2) to identify the most used methods to induce loss of balance; and (3) to identify the most used spatiotemporal variables in analyzing these actions. METHODS: The present review has followed the PRISMA guideline extension for Scoping Review (PRISMA-ScR) and the phases proposed by Askery and O'Malley. The search was conducted in three databases: PubMed, Web of Science, and Scopus. RESULTS: A total of 525 articles were identified, and 53 studies were included. Forty-five articles were quasi-experimental studies, six articles were randomized controlled trials, and two studies had an observational design. In total, 12 compensatory protective step strategies have been identified. CONCLUSIONS: There are 12 compensatory protective step strategies: lowering and elevating strategy, short- and long-step strategy, backward and forward stepping for slip, single step, multiple steps, lateral sidesteps or loaded leg sidestep unloaded leg sidestep, crossover step (behind and front), and medial sidestep. To standardize the terminology applied in future studies, we recommend collecting these strategies under the term of compensatory protective step strategies. The most used methods to induce loss of balance are the tether-release, trip, waist-pull, and slip methods. The variables analyzed by articles are the number of steps, the acceleration phase and deceleration phase, COM displacement, the step initiation or step duration, stance phase time, swing phase time and double-stance duration, stride length, step length, speed step, speed gait and the type of step.

12.
Am J Phys Med Rehabil ; 103(2): 89-98, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37205742

RESUMEN

OBJECTIVE: The aim of the study is to examine the effectiveness of extracorporeal shockwave therapy in reducing pain, improving functionality, joint range of motion, quality of life, fatigue, and health status self-perception in people with myofascial pain syndrome. METHODS: PubMed, the Cochrane Library, CINAHL, the Physiotherapy Evidence Database, and SPORTDiscus were systematically searched for only randomized clinical trials published up to June 2, 2022. The main outcome variables were pain, as reported on the visual analog scale and pressure pain threshold, and functionality. A quantitative analysis was conducted using the inverse variance method and the random effects model. RESULTS: Twenty-seven studies were included ( N = 595 participants in the extracorporeal shockwave therapy group). The effectiveness of extracorporeal shockwave therapy for relieving pain was superior for the extracorporeal shockwave therapy group compared with the control group on the visual analog scale (MD = -1.7 cm; 95% confidence interval = -2.2 to -1.1) and pressure pain threshold (mean difference = 1.1 kg/cm 2 ; 95% confidence interval = 0.4 to 1.7) and functionality (standardized mean difference = -0.8; 95% confidence interval = -1.6 to -0.04) with high heterogeneity. However, no differences were found between extracorporeal shockwave therapy and other interventions as dry needling, exercises, infiltrations, and lasers interventions. CONCLUSIONS: Extracorporeal shockwave therapy is effective in relieving pain and improving functionality in patients with myofascial pain syndrome compared with control and ultrasound therapy. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Determine the effectiveness of radial and focal extracorporeal shockwaves on pain perception, the pressure pain threshold, and functionality in people with myofascial pain syndrome; (2) Describe the intervention protocol of extracorporeal shockwave therapy to improve pain perception in people with myofascial pain syndrome; and (3) Describe the advantages and disadvantages of extracorporeal shockwave therapy versus other intervention such as dry needling. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.


Asunto(s)
Tratamiento con Ondas de Choque Extracorpóreas , Fibromialgia , Síndromes del Dolor Miofascial , Humanos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Dolor , Síndromes del Dolor Miofascial/terapia
13.
J Natl Cancer Inst ; 116(2): 239-248, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38059798

RESUMEN

INTRODUCTION: The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy. METHODS: This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data. RESULTS: A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%). CONCLUSION: Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated.


Asunto(s)
Neoplasias de la Mama , Hidrocarburos Aromáticos con Puentes , Embarazo , Recién Nacido , Femenino , Humanos , Lactante , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/inducido químicamente , Estudios de Cohortes , Taxoides/efectos adversos , Antibióticos Antineoplásicos , Antraciclinas/efectos adversos
14.
Cancer Discov ; 14(2): 348-361, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-37966260

RESUMEN

The sparse vascularity of pancreatic ductal adenocarcinoma (PDAC) presents a mystery: What prevents this aggressive malignancy from undergoing neoangiogenesis to counteract hypoxia and better support growth? An incidental finding from prior work on paracrine communication between malignant PDAC cells and fibroblasts revealed that inhibition of the Hedgehog (HH) pathway partially relieved angiosuppression, increasing tumor vascularity through unknown mechanisms. Initial efforts to study this phenotype were hindered by difficulties replicating the complex interactions of multiple cell types in vitro. Here we identify a cascade of paracrine signals between multiple cell types that act sequentially to suppress angiogenesis in PDAC. Malignant epithelial cells promote HH signaling in fibroblasts, leading to inhibition of noncanonical WNT signaling in fibroblasts and epithelial cells, thereby limiting VEGFR2-dependent activation of endothelial hypersprouting. This cascade was elucidated using human and murine PDAC explant models, which effectively retain the complex cellular interactions of native tumor tissues. SIGNIFICANCE: We present a key mechanism of tumor angiosuppression, a process that sculpts the physiologic, cellular, and metabolic environment of PDAC. We further present a computational and experimental framework for the dissection of complex signaling cascades that propagate among multiple cell types in the tissue environment. This article is featured in Selected Articles from This Issue, p. 201.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animales , Humanos , Ratones , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Proliferación Celular , Proteínas Hedgehog/genética , Neoplasias Pancreáticas/patología , Factor A de Crecimiento Endotelial Vascular
15.
Artículo en Inglés | MEDLINE | ID: mdl-37863392

RESUMEN

AIM: To determine the usefulness of neutrophil/lymphocyte (N/L) and platelet/lymphocyte (P/L) ratios as well as quantitative [18F]FDG PET/CT parameters as prognostic factors for overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) in patients with head and neck squamous cell carcinoma (HyN). MATERIAL AND METHODS: Sixty-six patients (56 men) diagnosed with HyN carcinoma were retrospectively assessed over an 8-year interval. Maximum SUV (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) parameters were determined from the PET/CT study at diagnosis. After treatment with chemoradiotherapy, patient survival was assessed. The Cox regression model and the Kaplan-Meier method were used to analyse prognostic factors and survival curves. RESULTS: Median follow-up was 50.4 months, with 39 recurrences-progressions and 39 deaths. In the univariate analysis, metabolic parameters, except SUVmax, were predictive factors for all three survivals and the two blood parameters were predictive for OS and EFS. TLG was the only predictive factor in the multivariate analysis. The three survival curves were significantly different for the metabolic parameters and the OS curve for the N/L ratio. Correlations were seen between N/L ratio, MTV and TLG. No correlations were demonstrated between P/L ratio and metabolic parameters. CONCLUSION: The use of haematological and metabolic markers would allow to identify patients with a high risk of recurrences and por survival and to individualise treatment by applying more aggressive therapies.


Asunto(s)
Neoplasias de Cabeza y Cuello , Tomografía Computarizada por Tomografía de Emisión de Positrones , Masculino , Humanos , Pronóstico , Fluorodesoxiglucosa F18/metabolismo , Estudios Retrospectivos , Radiofármacos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/terapia
16.
bioRxiv ; 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38105998

RESUMEN

Broad-spectrum RAS inhibition holds the potential to benefit roughly a quarter of human cancer patients whose tumors are driven by RAS mutations. However, the impact of inhibiting RAS functions in normal tissues is not known. RMC-7977 is a highly selective inhibitor of the active (GTP-bound) forms of KRAS, HRAS, and NRAS, with affinity for both mutant and wild type (WT) variants. As >90% of human pancreatic ductal adenocarcinoma (PDAC) cases are driven by activating mutations in KRAS, we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models, including human and murine cell lines, human patient-derived organoids, human PDAC explants, subcutaneous and orthotopic cell-line or patient derived xenografts, syngeneic allografts, and genetically engineered mouse models. We observed broad and pronounced anti-tumor activity across these models following direct RAS inhibition at doses and concentrations that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumor versus normal tissues. Treated tumors exhibited waves of apoptosis along with sustained proliferative arrest whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS inhibition in the setting of PDAC.

18.
Water Res ; 246: 120726, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37871375

RESUMEN

Monitoring the concentration of pigments like chlorophyll (Chl) in water-bodies is a key task to contribute to their conservation. However, with the existing sensor technology, measurement in real-time and with enough frequency to ensure proper risk management is not completely feasible. In this work, with the concept of data-driven soft-sensing, three hydrophysical features are used together with three meteorological ones to estimate the concentration of Chl in two tributaries of the River Thames. Data driven models, specifically neural networks, are used with three learning approaches: individual, centralized and federated. Data reduction scenarios are proposed in order to analyze the performance of each approach when less data is available. The best results in the training are usually obtained with the individual approach. However, the federated learning provides better generalization ability. It was also observed that in most of the cases the results of the federated learning approach improve those of the centralized one.


Asunto(s)
Clorofila , Aprendizaje Profundo , Clorofila/análisis , Clorofila A/análisis , Monitoreo del Ambiente/métodos , Redes Neurales de la Computación
19.
Artículo en Inglés | MEDLINE | ID: mdl-37656649

RESUMEN

Previous studies have demonstrated the potential of surface electromyography (sEMG) spectral decomposition in evaluating muscle performance, motor learning, and early diagnosis of muscle conditions. However, decomposition techniques require large data sets and are computationally demanding, making their implementation in real-life scenarios challenging. Based on the hypothesis that spectral components will present low inter-subject variability, the present paper proposes the foundational principles for developing a real-time system for their extraction by utilizing a pre-defined library of components derived from an extensive data set to match new measurements. The model library was tailored to fulfill specific requirements for real-time system application and the challenges encountered during implementation are discussed in the paper. For system validation, four distinct data sets comprising isotonic and isometric muscle activations were utilized. The extracted during validation showed low inter-subject variability, suggesting that a wide range of physiological variations can be described with them. The adoption of the proposed system for muscle analysis could provide a deeper understanding of the underlying mechanisms governing different motor conditions and neuromuscular disorders, as it allows for the measurement of these components in various daily-life scenarios.


Asunto(s)
Sistemas de Computación , Trastornos Motores , Humanos , Electromiografía
20.
Int J Gynecol Cancer ; 33(10): 1645-1648, 2023 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-37748803

RESUMEN

BACKGROUND: Advances in the treatment of gynecological cancers have led to increased survival in patients with gynecological cancers. Nevertheless, patients may still experience prevalent long term consequences, including lower limb lymphedema, depression, anxiety, sexual dysfunction, malnutrition, and sarcopenia, that negatively impact their quality of life. PRIMARY OBJECTIVE: To assess the impact on self-perceived quality of life of systematic screening and early treatment of lower limb lymphedema, anxiety and depression, sexual dysfunction, and sarcopenia and malnutrition compared with standard practice. STUDY HYPOTHESIS: Systematic screening with validated questionnaires leading to early diagnosis and treatment of side effects will have a positive impact on quality of life. TRIAL DESIGN: This prospective clinical trial will randomize candidates for surgery to either standard of care or systematic screening every 2 months for 2 years. Quality of life data will be collected every 4 months. After randomization, patients in the control group will follow standard usual care. Their screening scales will not be considered. In the experimental group, positive screenings will generate an alert to the physician, and patients will be referred to the corresponding specific area (rehabilitation unit, psycho-oncology unit, sexual health unit, or nutrition unit). MAJOR INCLUSION AND XCLUSION CRITERIA: Patients aged ≥18 years with ovarian, cervical, or endometrial cancer who are candidates for surgery will be included. PRIMARY ENDPOINT: Self-reported quality of life questionnaire score. SAMPLE SIZE: 168 patients will be randomized to detect a difference of 6 points in the questionnaires. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Study completion is estimated for January 2026 and the results will be presented in May 2026. TRIAL REGISTRATION NUMBER: NCT05918770.


Asunto(s)
Desnutrición , Neoplasias , Sarcopenia , Adolescente , Adulto , Humanos , Detección Precoz del Cáncer , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
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