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The RNA-binding protein cytoplasmic polyadenylation element binding 1 (CPEB1) plays a fundamental role in regulating mRNA translation in oocytes. However, the specifics of how and which protein kinase cascades modulate CPEB1 activity are still controversial. Using genetic and pharmacological tools, and detailed time courses, we have re-evaluated the relationship between CPEB1 phosphorylation and translation activation during mouse oocyte maturation. We show that both the CDK1/MAPK and AURKA/PLK1 pathways converge on CPEB1 phosphorylation during prometaphase of meiosis I. Only inactivation of the CDK1/MAPK pathway disrupts translation, whereas inactivation of either pathway alone leads to CPEB1 stabilization. However, CPEB1 stabilization induced by inactivation of the AURKA/PLK1 pathway does not affect translation, indicating that destabilization and/or degradation is not linked to translational activation. The accumulation of endogenous CCNB1 protein closely recapitulates the translation data that use an exogenous template. These findings support the overarching hypothesis that the activation of translation during prometaphase in mouse oocytes relies on a CDK1/MAPK-dependent CPEB1 phosphorylation, and that translational activation precedes CPEB1 destabilization.
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Meiosis , Oocitos , Biosíntesis de Proteínas , Factores de Transcripción , Factores de Escisión y Poliadenilación de ARNm , Animales , Femenino , Ratones , Aurora Quinasa A/metabolismo , Aurora Quinasa A/genética , Proteína Quinasa CDC2/metabolismo , Proteína Quinasa CDC2/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Ciclina B1/metabolismo , Ciclina B1/genética , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Factores de Escisión y Poliadenilación de ARNm/genética , Oocitos/metabolismo , Oocitos/citología , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Transducción de Señal , Factores de Transcripción/metabolismo , Factores de Transcripción/genéticaRESUMEN
Background: This study aims to investigate the impact of shoulder surgery on professional gymnasts through a case series, analyzing the mechanisms of injury and the shoulder lesion patterns, and reporting the clinical outcomes and return to sport. Methods: Twenty-nine surgically treated shoulders in twenty-seven professional gymnasts were retrospectively analyzed. Patients were stratified based on predominant symptoms and anatomical lesions in painful or unstable shoulders. Demographic and injury data, pathological findings, surgical procedure information, and data on time and level of return to sport were collected. Results: The average age of participants was 20.2 ± 3.8 years. Acute traumatic onset was reported in 51.8% of cases. Shoulders were categorized as painful in 13 cases and unstable in 16 cases. The most common pathologies were capsulolabral injuries (72%), biceps injuries (48%), and rotator cuff injuries (40%). All of the athletes returned to training within an average of 7.3 months, while the return to competition rate was 56%, achieved in an average of 10.3 months. The sport-specific subjective shoulder value was 84.8% ± 16.6%. Half of the patients who stopped competition reported reasons related to symptom persistence, while the other half reported personal reasons. No significant difference in the return to sport was reported in the cases of painful or unstable shoulder. Conclusions: Professional gymnasts requiring shoulder surgery commonly present multiple and complex lesions. Returning to training was possible in all cases; however, the possibility of persisting symptoms and other personal factors which may compromise the return to competition should be discussed with the athlete to give them insights into the possible outcomes.
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Water polo players' shoulders are exposed to repeated overhead and throwing motions as well as direct and indirect traumas. Shoulder injuries account for over half of all injuries sustained by water polo players. This is a monocentric descriptive epidemiological study on the clinical and radiological presentation of a consecutive series of water polo players from January 2002 to September 2022. All patients underwent clinical and physical examinations and an MRI arthrogram. A total of 92 water polo players were included in this study. Fifty-three patients (57.6%) reported at least one previous shoulder instability episode; 100% of patients in this group were diagnosed with a capsulolabral complex lesion, and 88.7% of these players complained of subjective symptoms of shoulder instability (RR: 4.4). A total of 39 out of 92 patients (42.4%) did not report previous shoulder dislocation episodes; the mean age at presentation in this group was significantly higher than the mean age of the patients who experienced previous instability episodes (p < 0.01), and the throwing arm was affected in 79.5% of patients (RR = 1.41).
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The ubiquitous second messenger 3',5'-cyclic adenosine monophosphate (cAMP) regulates cardiac excitation-contraction coupling (ECC) by signaling in discrete subcellular microdomains. Phosphodiesterase subfamilies 4B and 4D are critically involved in the regulation of cAMP signaling in mammalian cardiomyocytes. Alterations of PDE4 activity in human hearts has been shown to result in arrhythmias and heart failure. Here, we sought to systematically investigate specific roles of PDE4B and PDE4D in the regulation of cAMP dynamics in three distinct subcellular microdomains, one of them located at the caveolin-rich plasma membrane which harbors the L-type calcium channels (LTCCs), as well as at two sarco/endoplasmic reticulum (SR) microdomains centered around SR Ca2+-ATPase (SERCA2a) and cardiac ryanodine receptor type 2 (RyR2). Transgenic mice expressing Förster Resonance Energy Transfer (FRET)-based cAMP-specific biosensors targeted to caveolin-rich plasma membrane, SERCA2a and RyR2 microdomains were crossed to PDE4B-KO and PDE4D-KO mice. Direct analysis of the specific effects of both PDE4 subfamilies on local cAMP dynamics was performed using FRET imaging. Our data demonstrate that all three microdomains are differentially regulated by these PDE4 subfamilies. Whereas both are involved in cAMP regulation at the caveolin-rich plasma membrane, there are clearly two distinct cAMP microdomains at the SR formed around RyR2 and SERCA2a, which are preferentially controlled by PDE4B and PDE4D, respectively. This correlates with local cAMP-dependent protein kinase (PKA) substrate phosphorylation and arrhythmia susceptibility. Immunoprecipitation assays confirmed that PDE4B is associated with RyR2 along with PDE4D. Stimulated Emission Depletion (STED) microscopy of immunostained cardiomyocytes suggested possible co-localization of PDE4B with both sarcolemmal and RyR2 microdomains. In conclusion, our functional approach could show that both PDE4B and PDE4D can differentially regulate cardiac cAMP microdomains associated with calcium homeostasis. PDE4B controls cAMP dynamics in both caveolin-rich plasma membrane and RyR2 vicinity. Interestingly, PDE4B is the major regulator of the RyR2 microdomain, as opposed to SERCA2a vicinity, which is predominantly under PDE4D control, suggesting a more complex regulatory pattern than previously thought, with multiple PDEs acting at the same location.
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Calcio , Canal Liberador de Calcio Receptor de Rianodina , Ratones , Humanos , Animales , Calcio/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , AMP Cíclico/metabolismo , Miocitos Cardíacos/metabolismo , Ratones Transgénicos , Caveolinas/metabolismo , Mamíferos/metabolismoRESUMEN
The RNA-binding protein cytoplasmic polyadenylation element binding 1 (CPEB1) plays a fundamental role in the regulation of mRNA translation in oocytes. However, the nature of protein kinase cascades modulating the activity of CPEB1 is still a matter of controversy. Using genetic and pharmacological tools and detailed time courses, here we have reevaluated the relationship between CPEB1 phosphorylation and the activation of translation during mouse oocyte maturation. We show that both the CDK1/MAPK and AURKA/PLK1 pathways converge on the phosphorylation of CPEB1 during prometaphase. Only inactivation of the CDK1/MAPK pathway disrupts translation, while inactivation of either pathway leads to CPEB1 stabilization. However, stabilization of CPEB1 induced by inactivation of the AURKA/PLK1 does not affect translation, indicating that destabilization/degradation can be dissociated from translational activation. The accumulation of the endogenous CCNB1 protein closely recapitulates the translation data. These findings support the overarching hypothesis that the activation of translation in prometaphase in mouse oocytes relies on a CDK1-dependent CPEB1 phosphorylation, and this translational activation precedes CPEB1 destabilization.
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PURPOSE: SARS-CoV-2 infection may be limited to the respiratory tract or may spread to multiple organs. Besides disease severity, factors associated with virus spread within the host are elusive. Here, we tried to identify features associated with SARS-CoV-2 spread to endocrine organs. METHODS: In a retrospective autoptic cohort of 51 subjects who died because of COVID-19, we analyzed the severity and type of lung pathology, patients' features and the detection of virus in thyroid, testis, adrenal gland, pancreas, anterior pituitary, and the white adipose tissue (WAT). RESULTS: The SARS-CoV-2 genome was detected in endocrine organs of 30/51 cases. The anterior pituitary and WAT were most frequently positive for virus. While pathological features of lung were not associated with the presence of virus in endocrine organs, obesity (BMI > 30) was significantly associated to virus detection in pancreas (p = 0.01) and thyroid (p = 0.04). WAT infection was detected more frequently in males (p = 0.03). CONCLUSION: In subject with obesity dying of COVID-19, the virus frequently spreads to endocrine organs. The findings emphasize the need for optimal treatment of patients with obesity at the very onset of COVID-19. Since post-COVID conditions remain a major issue worldwide, a rigorous follow-up of endocrine function-especially of thyroid and pancreas-is advocated in subjects with obesity.
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COVID-19 , Masculino , Humanos , COVID-19/patología , SARS-CoV-2 , Estudios Retrospectivos , Pulmón , Obesidad/epidemiología , Obesidad/patología , AutopsiaRESUMEN
RATIONALE AND OBJECTIVES: Our multicentric study analysed clinical, radiologic and pathologic features in patients with atypical ductal hyperplasia (ADH) diagnosed with vacuum-assisted biopsy (VAB), to identify factors associated with the risk of upgrade, to develop a scoring system to support decision making. MATERIALS AND METHODS: Patients with ADH on VAB under stereotactic/tomosynthesis guidance (2012-2022) were eligible. Inclusion criteria were availability of surgical histopathological examination of the entire lesion or radiologic follow-up (FUP) ≥ 24 months. VAB results were compared with surgical pathological results or with imaging FUP evolution to assess upgrade. A backward stepwise linear regression was used to identify predictors of upgrade. The discriminatory power of the model was calculated through the area under the receiver operating curve (ROC-AUC); the Hosmer-Lemeshow test was used to assess model calibration. The points system was developed based on the selected risk factors, and the probability of upgrade associated with each point total was determined. RESULTS: 112 ADH lesions were included: 91 (91/112, 81.3%) underwent surgical excision with 20 diagnosis of malignancy, while 21 (21/112, 18.7%) underwent imaging FUP with one interval change (mean FUP time 48 months). Overall upgrade rate was 18.7% (21/112). Age, menopausal status, concurrent breast cancer, BIRADS classification and number of foci of ADH were identified as risk factors for upgrade. Our model showed an AUC = 0.85 (95% CI 0.76-0.94). The points system showed that the risk of upgrade is < 2% when the total score is ≤ 1. CONCLUSION: Our scoring system seemed a promising easy-to-use decision support tool for management of ADH, decreasing unnecessary surgeries, reducing patients' overtreatment and healthcare costs.
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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/cirugía , Mama/patología , Neoplasias de la Mama/patología , Biopsia con Aguja , Diagnóstico por Imagen , Estudios RetrospectivosRESUMEN
Progression through the mitotic and meiotic cell cycle is driven by fluctuations in the levels of cyclins, the regulatory subunits controlling the localization and activity of CDK1 kinases. Cyclin levels are regulated through a precise balance of synthesis and degradation. Here we demonstrate that the synthesis of Cyclin B1 during the oocyte meiotic cell cycle is defined by the selective translation of mRNA variants generated through alternative cleavage and polyadenylation (APA). Using gene editing in mice, we introduced mutations into the proximal and distal polyadenylation elements of the 3' untranslated region (UTR) of the Ccnb1 mRNA. Through in vivo loss-of-function experiments, we demonstrate that the translation of mRNA with a short 3' UTR specifies Cyclin B1 protein levels that set the timing of meiotic re-entry. In contrast, translation directed by a long 3' UTR is necessary to direct Cyclin B1 protein accumulation during the MI/MII transition. These findings establish that the progression through the cell cycle is dependent on the selective translation of multiple mRNA variants generated by APA.
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Ciclina B1 , Meiosis , Poliadenilación , Animales , Ratones , Regiones no Traducidas 3'/genética , Ciclo Celular/genética , Ciclina B1/genética , Ciclina B1/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Oocitos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Transcriptional and post-transcriptional regulations control gene expression in most cells. However, critical transitions during the development of the female gamete relies exclusively on regulation of mRNA translation in the absence of de novo mRNA synthesis. Specific temporal patterns of maternal mRNA translation are essential for the oocyte progression through meiosis, for generation of a haploid gamete ready for fertilization and for embryo development. In this review, we will discuss how mRNAs are translated during oocyte growth and maturation using mostly a genome-wide perspective. This broad view on how translation is regulated reveals multiple divergent translational control mechanisms required to coordinate protein synthesis with progression through the meiotic cell cycle and with development of a totipotent zygote.
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Oocitos , Biosíntesis de Proteínas , Oocitos/metabolismo , Oocitos/crecimiento & desarrollo , Humanos , Animales , Biosíntesis de Proteínas/genética , ARN Mensajero Almacenado/genética , ARN Mensajero Almacenado/metabolismo , Femenino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Oogénesis/genética , Genoma/genética , Regulación del Desarrollo de la Expresión Génica/genética , Meiosis/genéticaRESUMEN
Rehabilitation after rotator cuff repair is crucial for functional recovery and for minimizing the risk of retear. There are two rehabilitation protocols (early and traditional) and the debate about which is the best is open. This umbrella review aimed to compare the effect of these rehabilitation protocols in terms of reduction in pain, functional recovery, and retear risk. We selected systematic reviews and meta-analyses published between 2012 and 2022 dealing with the aim. Nineteen systematic reviews were included. No significant differences were found between early and traditional protocols in terms of pain reduction. Early rehabilitation provided better short-term results regarding Range of Motion improvement, but long-term functional outcomes were similar. Retear risk remains a significant concern for the early protocol. We found major differences between the analyzed protocols. This review suggests that both protocols are useful to recover global shoulder function, but the standard protocol has a greater safety profile for larger tears. On the other hand, the early protocol may be preferable for smaller lesions, allowing a faster recovery and having less impact on medical costs. Further research is needed to identify optimal rehabilitation strategies tailored to the individual patient's needs and characteristics.
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Background: Stroke is a main cause of disability worldwide and its neuro-rehabilitative management is not limited to the acute phase but requires continuity in the rehabilitation approach especially in the chronic phase. The aim of this scoping review was to highlight the different treatment opportunities available in neurorehabilitation, effective for patients with chronic stroke sequelae, not only in terms of maintaining motor function but also improving it. Methods: The literature search was conducted using the following databases: MEDLINE (PubMed), PEDro, Scopus, Web of Science (WOS), Cochrane from 2012 to February 2023. We selected Randomized Clinical Trials in English dealing with neurorehabilitation strategies in chronic hemiplegic patients after stroke focusing on motor function, muscular strength, gait, postural balance, spasticity, and quality of life. Results: According to the inclusion criteria, 47 articles were selected for our review. All of them were analyzed following the primary outcome and the rehabilitation technique used. Despite the different protocols used within the same technique and despite the chronicity of the disease, all studies report an improvement after the rehabilitation treatment of motor function and quality of life. Conclusion: The literature analyzed invites us to reflect respect to neurorehabilitation approach to the patient with chronic stroke sequelae often considered to have as its objective the maintenance of the present motor function and contain disability: instead, the review reports how, even in chronicity, the patient always reports margins of statistically and clinically significant improvement. The chronic stroke rehabilitation over 6 months has been proved effective in obtaining recovery in different settings.
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Nerium oleander is a plant containing cardiac glycosides, and intoxication with its leaves is a medical emergency. We report the case of a 73-year-old man who took a decoction of oleander leaves for a reckless purpose. Upon arrival in the emergency room, he presented an altered state of consciousness, drooling and vomiting. He was bradycardic with intermittent third-degree atrioventricular block and typical downsloping ST-segment depression related to glycosides toxicity. Despite initial treatment with atropine, isoprenaline and repeated bolus of digoxin-specific antibody (Fab) fragments, symptoms were persistent 12 hours after admission. Suspecting that the patient not only drank the decoction but also ingested the leaves and had slow gastric emptying, we performed gastric lavage without benefit. We subsequently performed a gastroscopy that showed an oleander phytobezoar, and its removal permitted a rapid clinical improvement. Treatment with digoxin-specific antibodies for intoxication is well described and dosage should be adapted to the plasmatic level. Such an examination is useless in oleander intoxication because it does not represent the real quantity of toxin. The dosage of antibodies is empiric and should be guided by the clinical severity. In such intoxication, the presence of a phytobezoar from oleander leaves cannot be excluded so we believe that a gastroscopy for its mechanical removal should always be considered to avoid persistent release of toxin. LEARNING POINTS: Ingestion of any part of the oleander plant can result in a severe cardioactive glycoside intoxication with potentially fatal arrhythmia and should be considered a medical emergency.Treatment consists of supportive care, correction of arrhythmias and electrolyte imbalance, and digoxin-specific antibody (Fab) fragments administration.Gastroscopy for mechanical removal of a phytobezoar responsible of persistent toxin release should be always considered.
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INTRODUCTION: The selection of surgery post-neoadjuvant chemotherapy (NACT) is difficult and based on surgeons' expertise. The aim of this study was to create a post-NEoadjuvant Score System (pNESSy) to choose surgery, optimizing oncological and aesthetical outcomes. METHODS: Patients (stage I-III) underwent surgery post-NACT (breast-conserving surgery (BCS), oncoplastic surgery (OPS), and conservative mastectomy (CMR) were included. Data selected were BRCA mutation, ptosis, breast volume, radiological response, MRI, and mammography pre- and post-NACT prediction of excised breast area. pNESSy was created using the association between these data and surgery. Area under the curve (AUC) was assessed. Patients were divided into groups according to correspondence (G1) or discrepancy (G2) between score and surgery; oncological and aesthetic outcomes were analyzed. RESULTS: A total of 255 patients were included (118 BCS, 49 OPS, 88 CMR). pNESSy between 6.896-8.724 was predictive for BCS, 8.725-9.375 for OPS, and 9.376-14.245 for CMR; AUC was, respectively, 0.835, 0.766, and 0.825. G1 presented a lower incidence of involved margins (5-14.7%; p = 0.010), a better locoregional disease-free survival (98.8-88.9%; p < 0.001) and a better overall survival (96.1-86.5%; p = 0.017), and a better satisfaction with breasts (39.8-27.5%; p = 0.017) and physical wellbeing (93.5-73.6%; p = 0.001). CONCLUSION: A score system based on clinical and radiological features was created to select the optimal surgery post-NACT and improve oncological and aesthetic outcomes.
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PURPOSE: After a total knee arthroplasty (TKA), ensuring rehabilitation is continued at home is essential for a successful recovery. The aim of this randomized clinical trial (NCT04155957) was to demonstrate the safety and efficacy of an interactive telerehabilitation system (ReHub®) to guide and provide feedback during exercise in the postoperative period of a fast-track TKA program. METHODS: Fifty-two patients who underwent TKA were randomized to intervention (N = 26) or control (N = 26). Upon discharge, they followed a 4-week plan of 5 daily exercises and up to 10 physiotherapy home visits. The intervention group performed exercises with ReHub® autonomously, control did not use any auxiliary device. Data were collected 1) on the day of discharge, 2) after 2 weeks and 3) after 4 weeks. RESULTS: Telerehabilitation patients showed higher adherence to exercise (p = 0.002) and greater quadriceps strength (p = 0.028). No significant differences between groups were found in other outcomes. Only 1 adverse event was linked to ReHub®. Patients gave the platform high System Usability Scale scores (83/100). CONCLUSION: Interactive telerehabilitation with ReHub® during a post-TKA exercise program is effective, safe, and well-received by patients. It provides real-time performance feedback and ensures communication. Quadriceps strength and adherence to the exercise plan are improved with ReHub®.IMPLICATIONS FOR REHABILITATIONTelerehabilitation platforms can be introduced into fast-track total knee arthroplasty protocols to monitor home-based exercise programmes without compromising efficacy and safety.Telerehabilitation and remote patient monitoring contribute to obtaining high levels of adherence to exercise plans, which is a current challenge faced by rehabilitation professionals.Real-time biofeedback on exercise performance facilitates correct exercise performance and motivates the patient.This technology allows professionals to monitor and adjust the patient's therapy remotely and avoid unnecessary travel.
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The knee is an essential part of our body, and identifying its injuries is crucial since it can significantly affect quality of life. To date, the preferred way of evaluating knee injuries is through magnetic resonance imaging (MRI), which is an effective imaging technique that accurately identifies injuries. The issue with this method is that the high amount of detail that comes with MRIs is challenging to interpret and time consuming for radiologists to analyze. The issue becomes even more concerning when radiologists are required to analyze a significant number of MRIs in a short period. For this purpose, automated tools may become helpful to radiologists assisting them in the evaluation of these images. Machine learning methods, in being able to extract meaningful information from data, such as images or any other type of data, are promising for modeling the complex patterns of knee MRI and relating it to its interpretation. In this study, using a real-life imaging protocol, a machine-learning model based on convolutional neural networks used for detecting medial meniscus tears, bone marrow edema, and general abnormalities on knee MRI exams is presented. Furthermore, the model's effectiveness in terms of accuracy, sensitivity, and specificity is evaluated. Based on this evaluation protocol, the explored models reach a maximum accuracy of 83.7%, a maximum sensitivity of 82.2%, and a maximum specificity of 87.99% for meniscus tears. For bone marrow edema, a maximum accuracy of 81.3%, a maximum sensitivity of 93.3%, and a maximum specificity of 78.6% is reached. Finally, for general abnormalities, the explored models reach 83.7%, 90.0% and 84.2% of maximum accuracy, sensitivity and specificity, respectively.
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Traumatismos de la Rodilla , Calidad de Vida , Humanos , Traumatismos de la Rodilla/diagnóstico por imagen , Traumatismos de la Rodilla/patología , Imagen por Resonancia Magnética/métodos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Sensibilidad y Especificidad , Aprendizaje AutomáticoRESUMEN
Angiosarcoma of the breast is a rare breast cancer, which can arise de novo (primary breast angiosarcoma, PBA) or as a secondary malignancy (secondary breast angiosarcoma, SBA) as a result of a biological insult. In the latter case, it is usually diagnosed in patients with a previous history of radiation therapy following a conserving treatment for breast cancer. Over the years, the advances in early diagnosis and treatment of breast cancer, with increasing use of breast-conserving surgery and radiation therapy (instead of radical mastectomy), brought about an increased incidence of the secondary type. PBA and SBA have different clinical presentations and often represent a diagnostic challenge due to the nonspecific imaging findings. The purpose of this paper is to review and describe the radiological features of breast angiosarcoma, both in conventional and advanced imaging to guide radiologists in the diagnosis and management of this rare tumor.
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Given the increasing prevalence of intelligent systems capable of autonomous actions or augmenting human activities, it is important to consider scenarios in which the human, autonomous system, or both can exhibit failures as a result of one of several contributing factors (e.g., perception). Failures for either humans or autonomous agents can lead to simply a reduced performance level, or a failure can lead to something as severe as injury or death. For our topic, we consider the hybrid human-AI teaming case where a managing agent is tasked with identifying when to perform a delegated assignment and whether the human or autonomous system should gain control. In this context, the manager will estimate its best action based on the likelihood of either (human, autonomous) agent's failure as a result of their sensing capabilities and possible deficiencies. We model how the environmental context can contribute to, or exacerbate, these sensing deficiencies. These contexts provide cases where the manager must learn to identify agents with capabilities that are suitable for decision-making. As such, we demonstrate how a reinforcement learning manager can correct the context-delegation association and assist the hybrid team of agents in outperforming the behavior of any agent working in isolation.
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Inteligencia , Aprendizaje , Humanos , Inteligencia ArtificialRESUMEN
(1) Background: To help to refine the accuracy of sentinel lymph node biopsy (SLNB) in breast cancer (BC) patients with biopsy-proven nodal disease prior to neoadjuvant chemotherapy (NACT), a method of marking the biopsy-proven positive LN at diagnosis to enable its removal during surgery was proposed. The aim of this study was to evaluate the accuracy of the Radio-Guided Occult Lesion Localization (ROLL) technique of biopsy-proven metastatic LN in nodal staging after NACT among node-positive BC patients. (2) Methods: Patients with invasive BC and biopsy-proven axillary metastases receiving NACT were enrolled. A clip marker was placed on the sampled LN (clipped lymph node, CLN) before NACT. Before surgery, the ROLL procedure (radioactive tracer injection into CLN under ultrasound guidance) was performed, and the CLN was surgically resected. The correspondence between the CLNs and SLNs was evaluated. The pathologic findings of the CLNs and SLN(s) were compared with remaining axillary nodes at ALND to determine false negative rates (FNRs). (3) Results: Seventy-two patients were analyzed. Surgery successfully identified the CLN in 70/72 procedures (97.2%). For 60/72 patients who underwent ALND, the FNRs dropped from 19.35% for SLNB to 3.13% for CLN biopsy. (4) Conclusions: The ROLL procedure got CLNs is accurate in axillary nodal staging after NACT in node-positive BC patients at diagnosis.
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Targeted axillary dissection (TAD) is an axillary staging technique after NACT that involves the removal of biopsy-proven metastatic lymph nodes in addition to sentinel lymph node biopsy (SLNB). This technique avoids the morbidity of traditional axillary lymph node dissection and has shown a lower false-negative rate than SLNB alone. Therefore, marking positive axillary lymph nodes before NACT is critical in order to locate and remove them in the subsequent surgery. Current localization methods include clip placement with intraoperative ultrasound, carbon-suspension liquids, localization wires, radioactive tracer-based localizers, magnetic seeds, radar reflectors, and radiofrequency identification devices. The aim of this paper is to illustrate the management of axillary lymph nodes based on current guidelines and explain the features of axillary lymph node markers, with relative advantages and disadvantages.