ALS primarily affects motor functions, but cognitive functions, including social understanding, may also be impaired. Von Economo neurons (VENs) are part of the neuronal substrate of social ...understanding and these cells are histopathologically altered in ALS. We investigated whether activity in areas including VENs is associated with an impairment of cognitive tasks that mirror social functioning.
In this observational prospective study, ALS patients (N = 26) were tested for cognitive behavioural function, encompassing different aspects of empathetic understanding (interpersonal reactivity index, IRI), social behaviour (ultimatum game), recognition of faux-pas situations, and general cognitive functioning (Edinburgh Cognitive and Behavioural ALS Screen, ECAS). For in vivo pathological staging according to Braak, DTI-MRI was performed to determine those ALS patients with expected pathological involvement of VENs (B ALS stages 3 + 4) compared to those without (B ALS stages 1 + 2). Expected hypometabolism of cerebral areas was determined with 18F-FDG PET in N = 20 ALS patients and compared to N = 20 matched healthy controls. Volume of interest analysis was performed in the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC), which contain high numbers of VENs.
Compared to those without expected pathological involvement of VENs (B/B ALS stages 1 + 2), ALS patients with anticipated pathological involvement of VENs (B/B ALS stages 3 + 4) presented with significantly reduced fantasy to understand the mindset of others (IRI) and, social behaviour was more selfish (ultimatum game) despite the fact that cognitive understanding of socially inappropriate behaviour of others (faux-pas) was unimpaired. 18F-FDG-PET showed hypometabolism in ACC and AIC in ALS patients with anticipated pathological involvement of VENs compared to those without and this was significantly correlated to cognitive-behavioral functions in certain tasks.
Here, we present evidence of altered social behaviour in ALS patients associated with regional 18FDG-PET hypometabolism in areas with a high density of VENs, thereby suggesting a possible causal association.
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Recent development in renewable energy-enabled electric vehicles (EVs) has posed challenges to the stability and efficiency of the vehicular energy network (VEN), which is a concrete implementation ...of Internet of Things (IoT) in energy and vehicular networks. In this article, we study a VEN with time-varying point-to-point traffic flow and adjustable energy storage capacity at stations. The goal is to jointly optimize the routing and dynamic storage allocation of renewable energy so as to maximize the efficiency of plant-to-station energy transferring. We first adopt a time-expanded topology graph to describe the scenario and model it as a maximum flow problem. Next, we incorporate routing in our methodology and derive a joint energy storage capacity and route planning method based on linear programming. Then, the problem is extended to a more general case, where the traffic pattern of the VEN is unknown. We apply the long short-term memory model, a deep learning method, to predict the traffic pattern and utilize the concept of reinforcement learning to iteratively improve the prediction accuracy. To evaluate the performance, we implement our method first on regular buses, then extend to EVs based on the real trace data from the PeMS system in California. The simulation results show that the joint optimization can achieve near-optimal performance and performs well even in case of high rate of missing traffic information, with the help of deep reinforcement learning.
Von Economo neurons (VENs) are specialized projection neurons with a characteristic spindle-shaped soma and thick basal and apical dendrites. VENs have been described in restricted cortical regions, ...with their most frequent appearance in layers III and V of the anterior cingulate cortex, anterior insula, and frontopolar cortex of humans, great apes, macaque monkeys, elephants, and some cetaceans. Recently, a ubiquitous distribution of VENs was reported in various cortical areas in the pygmy hippopotamus, one of the closest living relatives of cetaceans. That finding suggested that VENs might not be unique to only a few species that possess enlarged brains. In the present analysis, we assessed the phylogenetic distribution of VENs within species representative of the superordinal clade that includes cetartiodactyls and perissodactyls, as well as afrotherians. In addition, the distribution of fork cells that are often found in close proximity to VENs was also assessed. Nissl-stained sections from the frontal pole, anterior cingulate cortex, anterior insula, and occipital pole of bowhead whale, cow, sheep, deer, horse, pig, rock hyrax, and human were examined using stereologic methods to quantify VENs and fork cells within layer V of all four cortical regions. VENs and fork cells were found in each of the species examined here with species-specific differences in distributions and densities. The present results demonstrated that VENs and fork cells were not restricted to highly encephalized or socially complex species, and their repeated emergence among distantly related species seems to represent convergent evolution of specialized pyramidal neurons. The widespread phylogenetic presence of VENs and fork cells indicates that these neuron morphologies readily emerged in response to selective forces,whose variety and nature are yet to be identified.
Von Economo neurons (VENs) are rod, stick, or corkscrew cells mostly located in layer V of the frontoinsular and anterior cingulate cortices. VENs are projection neurons related to human-like social ...cognitive abilities. Post-mortem histological studies found VEN alterations in several neuropsychiatric disorders, including schizophrenia (SZ). This pilot study aimed to evaluate the role of VEN-containing areas in shaping patterns of resting-state brain activation in patients with SZ (n = 20) compared to healthy controls (HCs; n = 20). We performed a functional connectivity analysis seeded in the cortical areas with the highest density of VENs followed by fuzzy clustering. The alterations found in the SZ group were correlated with psychopathological, cognitive, and functioning variables. We found a frontotemporal network that was shared by four clusters overlapping with the salience, superior-frontal, orbitofrontal, and central executive networks. Differences between the HC and SZ groups emerged only in the salience network. The functional connectivity of the right anterior insula and ventral tegmental area within this network were negatively correlated with experiential negative symptoms and positively correlated with functioning. This study provides some evidence to show that in vivo, VEN-enriched cortical areas are associated with an altered resting-state brain activity in people with SZ.
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Provider: - Institution: National Library of the Netherlands - Koninklijke Bibliotheek - Data provided by Europeana Collections- All metadata published by Europeana are available free of restriction ...under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Venetoclax (Ven) in combination with azacitidine or decitabine (hypomethylating agent; HMA) is the standard-of-care treatment for older (≥75 years) or intensive chemotherapy ineligible adults with ...newly diagnosed acute myeloid leukemia (AML). Tumor lysis syndrome (TLS) and infectious complications are two of the most concerning associated adverse events. We studied the real-world incidence and outcomes of these adverse events with HMA/Ven in AML patients. Our retrospective analysis included 106 patients (median age 70 years). Of these, 61 (58%) received HMA/Ven in frontline setting while 45 (42%) received in salvage setting. 19 (18%) met laboratory criteria for TLS, five (5%) developed clinical TLS (acute kidney injury). The median time to develop TLS was 2 days (range −2 to 4). During cycle 1, 29 patients (27%) were diagnosed with febrile neutropenia while 26 (25%) developed new infections. Median time to development of new infection was 10 days (1−25). Pneumonia was the most common infection (8%). Febrile neutropenia and/or new infection during cycle 1 was associated with poorer median overall survival compared to those without these complications (4.9 months vs 11.6 months; p = 0.03). In conclusion, incidence of TLS and infections was high in our cohort during initiation of HMA/Ven therapy. This data emphasizes the need for closer monitoring in these patients, especially during the first 7–10 days of treatment, which is often achieved in the inpatient setting.
•18% of AML patients in our cohort developed TLS with HMA/Ven treatment.•Patients with TLS had higher baseline white blood cell count and marrow blast burden.•Febrile neutropenia occurred in 27% of patients during cycle 1 of HMA/Ven.•New infections developed in 25% of patients during cycle 1 of HMA/Ven.•Infectious complications during cycle 1 of HMA/Ven led to poorer survival outcomes.
Background: Implementation of ABC-VEN drug planning evaluation can improve the efficiency of drug stockpiles, reduce the risk of vacuum, and ensure optimal drug availability for patient care. ...Objectives: In this study, an evaluation of the 2021 drug plan was carried out at Indriati Solo Baru Hospital using ABC-VEN combination analysis to know the percentage proportions of each group as well as the characteristics of the drug. Methods: The type of research is descriptive analysis using quantitative data performed retrospectively. Primary data was used from direct interviews with the head of the pharmacy and logistics unit, as well as secondary information in terms of drug planning activities. Samples are data on drug planning, acquisition, and use in 2021. The data are then analyzed using the ABC-VEN method. Results: The results of the study show the percentage of drug items in groups A, B, and C at 13.28%, 20.68%, and 66.04%, with investment values of 69.99%, 19.99%, and 10.02%. Whereas in groups V, E, and N, there are 18.55%, 71.18%, and 10.28% with an investment value of 23.92%, 65.51%, and 10.57%. The evaluation results using the combination method ABC-VEN obtained drugs from the categories Priority (P), Main (M), and Supplementary (S), which are 148 items, 568 items, and 82 items. Conclusion: The use of ABC-VEN methods in drug stock evaluation is essential to accurately identify PMS medicines so that drug supply planning and management are more efficient and effective, as well as ensuring the availability of medicines that are optimally tailored to patient needs.
FLT3-ITD-mutated AML, which occurs in the juxta membrane domain of the FLT3 gene, is reported in 25%–30% of patients and it is associated with inferior outcomes and early relapse. Although transplant ...remains the treatment of choice, FLT3 inhibition in addition to induction chemotherapy has shown to have effect on survival outcomes. Overall induction mortality was reported to range from 7% to 40% from various centers across India. We explored the effect of low-intensity triplet therapy as an induction regimen in FLT3-ITD-mutated AML. Patients received A cumulative dosage of azacytidine 75 mg/m2 subcutaneously daily for 7 days and dosed at 100 mg daily. Venetoclax and sorafenib were also given for similar duration of azacytidine with venetoclax at the dose of 50 mg per day with azole and sorafenib at the dose of 200 mg per day. Patients were started on induction after adequate cytoreduction. Cycles were repeated at monthly intervals. We retrospectively analyzed 7 patients who have received this combination regimen from June 2022 to April 2023 and herein report the outcomes of Cycle 1 induction. Median age was 39 years (33 to 59). Out of 7 patients, 3 had diabetes and 1 had hypertension. A next-generation sequencing report was available for 4 patients. Co-mutations detected were NPM1 in 3, IDH2R140 in 2 and EZH2 in 1 patient. Median duration of venetoclax and sorafenib was 8 days. Out of 7 patients, 6 had febrile neutropenia and 2 required hospitalization. Median absolute neutrophil count recovery time was 28 days. All 7 patients had complete remission. Minimal residual disease assessment was available for 6 patients and was negative in 4 of them.
Triple therapy with azacytidine and venetoclax with sorafenib for limited duration causes adequate myelosuppression and remains a feasible induction option in FLT3-ITD-mutated AML as a bridge to transplant.
