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Sedation is commonly used to relieve fear and anxiety during procedures. Dexmedetomidine (DEX), approved by the US Food and Drug Administration in 1999 for short-term sedation, is a selective alpha2-adrenoreceptor agonist. The use of DEX is increasing due to minimal respiratory depression and easy and quick awakening from sedation. Its sedative mechanisms are suggested to be related to changes in the interaction between brain regions. In this study, we used graph theory to investigate whether the altered network connection is associated with sedation. Electroencephalogram (EEG) recordings of 32 channels were acquired during awake and DEX-induced sedation for 20 participants. We extracted EEG epochs from the awake and the DEX sedation state. Using the graph theory, we compared the changes in the network connection parameters with the awake state. We observed that the slopes in 1/f dynamics, which indicate overall brain network characteristics, were greater during DEX-induced sedation compared to the awake state, suggesting a transition towards a random network behavior. In addition, network connections from the perspective of information processing were significantly disturbed in the alpha frequency band, unlike other frequency bands augmenting network connections. The alpha frequency band plays a prominent role in the function and interaction of cognitive activities. These results collectively indicate that changes in the brain network critical to cognition during DEX administration may also be related to the mechanism of sedation.

Advanced prostate cancer (PCa) patients with bone metastases are treated with androgen pathway directed therapy (APDT). However, this treatment invariably fails and the cancer becomes castration resistant. To elucidate resistance mechanisms and to provide a more predictive pre-clinical research platform reflecting tumor heterogeneity, we established organoids from a patient-derived xenograft (PDX) model of bone metastatic prostate cancer, PCSD1. APDT-resistant PDX-derived organoids (PDOs) emerged when cultured without androgen or with the anti-androgen, enzalutamide. Transcriptomics revealed up-regulation of neurogenic and steroidogenic genes and down-regulation of DNA repair, cell cycle, circadian pathways and the severe acute respiratory syndrome (SARS)-CoV-2 host viral entry factors, ACE2 and TMPRSS2. Time course analysis of the cell cycle in live cells revealed that enzalutamide induced a gradual transition into a reversible dormant state as shown here for the first time at the single cell level in the context of multi-cellular, 3D living organoids using the Fucci2BL fluorescent live cell cycle tracker system. We show here a new mechanism of castration resistance in which enzalutamide induced dormancy and novel basal-luminal-like cells in bone metastatic prostate cancer organoids. These PDX organoids can be used to develop therapies targeting dormant APDT-resistant cells and host factors required for SARS-CoV-2 viral entry.

The measured D-D neutron rate of neutral beam heated JET baseline and hybrid H-modes in deuterium is found to be between approximately 50% and 100% of the neutron rate expected from the TRANSP code, depending on the plasma parameters. A number of candidate explanations for the shortfall, such as fuel dilution, errors in beam penetration and effectively available beam power have been excluded. As the neutron rate in JET is dominated by beam-plasma interactions, the 'neutron deficit' may be caused by a yet unidentified form of fast particle redistribution. Modelling, which assumes fast particle transport to be responsible for the deficit, indicates that such redistribution would have to happen at time scales faster than both the slowing down time and the energy confinement time. Sawteeth and edge localised modes are found to make no significant contribution to the deficit. There is also no obvious correlation with magnetohydrodynamic activity measured using magnetic probes at the tokamak vessel walls. Modelling of fast particle orbits in the 3D fields of neoclassical tearing modes shows that realistically sized islands can only contribute a few percent to the deficit. In view of these results it appears unlikely that the neutron deficit results from a single physical process in the plasma.

Simple Summary: This study aimed to evaluate the outcomes and prognostic factors for multicentric lymphoma in 38 small breed dogs (weighing under 15 kg) treated with combination chemotherapy with vincristine, cyclophosphamide, doxorubicin, and prednisolone between January 2014 and May 2020. Significant factors for longer mean survival time in the complete remission group included being under 10 years old, no cardiovascular heart disease, and no prior hospitalization due to chemotherapy side effects. These results will help confirm the clinical characteristics and outcomes in small breed dogs with lymphoma and provide insights into the most effective treatments and prognosis for these animals. Lymphoma is one of the most common malignant tumors in dogs. Combination chemotherapy with vincristine, cyclophosphamide, doxorubicin, and prednisolone (CHOP) is the most effective treatment for multicentric lymphoma. Previous studies have evaluated the response of large dogs to CHOP treatment and identified prognostic factors; however, studies on small dogs are lacking. In this study, we investigated the outcomes and prognostic factors for small dogs with multicentric lymphoma treated with CHOP. The responses of patients to CHOP treatment were assessed, and 54.3% were evaluated as being in complete remission (CR), 31.4% in partial remission (PR), and 14.3% in no remission (NR). The overall response rate was 85.7%. The median survival times for CR, PR, and NR patients were 683 days (85–1496 days), 241 days (15–777 days), and 119 days (61–308 days), respectively. Among the CR patients, survival was longer under the following conditions: age under 10 years (p = 0.011), no cardiovascular heart disease (p = 0.046), and no history of hospitalization due to side effects from chemotherapy (p = 0.002). These results might help clinicians build treatment plans for multicentric lymphoma in small breed dogs. [ABSTRACT FROM AUTHOR]

The rapid integration of renewable energy sources and the increasing complexity of modern power systems urge the development of advanced methods for ensuring power system stability. This paper presents a novel continuation power flow (CPF) method that combines two well-known parameterization techniques: natural parameterization and arc-length parameterization. The proposed hybrid approach significantly improves computational efficiency, reducing processing time by 32.76% compared to conventional methods while maintaining high accuracy. The method enables faster and more reliable stability assessments by efficiently managing the complexities and uncertainties, particularly in grids with high penetration of renewable energy. [ABSTRACT FROM AUTHOR]

Background: Currently, there is no clearly established therapy to treat mild cognitive impairment (MCI); consequently, alternative therapies, such as acupuncture, have been attempted. In many clinical studies, the potential benefits of acupuncture for cognitive improvement have been identified in clinical outcomes; however, the mechanism remains unclear. Accordingly, this study aims to investigate the therapeutic mechanism of acupuncture therapy using functional near-infrared spectroscopy and its feasibility in treating individuals with impaired cognitive function. Methods: This study is designed to be a prospective, two-arm, parallel clinical trial involving 24 participants. The patient group will be treated with acupuncture twice per week for 12 weeks; meanwhile, the healthy control group will not undergo acupuncture treatment. Functional near-infrared spectroscopy assessment and a working memory test will be performed at baseline and every 6 weeks to investigate the therapeutic mechanism of acupuncture. The primary outcome will be measured using the Korean version of the Montreal Cognitive Assessment. The secondary outcomes will be the Alzheimer's Disease Assessment Scale-cognitive subscale score, working memory task accuracy, response rate, response time, and hemodynamic response of the prefrontal lobe. The outcomes will be evaluated at baseline, and at 6 and 12 weeks after subject allocation. Discussion: This clinical pilot trial is designed to determine the feasibility of acupuncture as an effective and safe treatment for improving cognitive function in patients with MCI. Results of this study may provide guidance for future larger-scale clinical trials. Trial registration: Clinical Research Information Service (CRIS), Republic of Korea: KCT0002451. Registered September 5, 2017. Keywords: Acupuncture, Functional near-infrared spectroscopy, Mild cognitive impairment