1,487 results on '"Edison E"'
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552. The Role of the Respiratory Microbiome in the Pathogenesis of Aspiration Pneumonia: Implications for Diagnosis and Potential Therapeutic Choices.
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Vallianou NG, Skourtis A, Kounatidis D, Margellou E, Panagopoulos F, Geladari E, Evangelopoulos A, and Jahaj E
- Abstract
Although the lungs were considered to be sterile until recently, the advent of molecular biology techniques, such as polymerase chain reaction, 16 S rRNA sequencing and metagenomics has led to our expanding knowledge of the lung microbiome. These methods may be particularly useful for the identification of the causative agent(s) in cases of aspiration pneumonia, in which there is usually prior administration of antibiotics. The most common empirical treatment of aspiration pneumonia is the administration of broad-spectrum antibiotics; however, this may result in negative cultures from specimens taken from the respiratory tract. Therefore, in such cases, polymerase chain reaction or metagenomic next-generation sequencing may be life-saving. Moreover, these modern molecular methods may assist with antimicrobial stewardship. Based upon factors such as age, altered mental consciousness and recent hospitalization, there is a shift towards the predominance of aerobes, especially Gram-negative bacteria, over anaerobes in aspiration pneumonia. Thus, the therapeutic choices should be expanded to cover multi-drug resistant Gram-negative bacteria in selected cases of aspiration pneumonia.
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- 2023
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553. Sustainable Production of Molybdenum Carbide (MXene) from Fruit Wastes for Improved Solar Evaporation.
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Aizudin M, Krishna Sudha M, Goei R, Kuang Lua S, Poolamuri Pottammel R, Iing Yoong Tok A, and Huixiang Ang E
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- Water, Fruit, Solar Energy
- Abstract
Freshwater production using solar-driven interfacial evaporation is regarded as a green and sustainable strategy. The biggest barrier to practical deployment of solar desalination, however, continues to be the lack of options for renewable materials. Herein, we present a facile two-step carbonization approach that is sustainable for developing innovative two-dimensional (2D) molybdenum carbide (Mo
2 C) materials derived from carbonized fruit wastes. The resultant 2D Mo2 C photothermal layer has an efficient water evaporation rate of 1.52 kg m-2 h-1 with a photothermal conversion efficiency of 94 % under one sun irradiation, which is among the best reported values so far. The broad solar absorption band, high specific surface area (555.1 m2 g-1 ) with large micro- and meso porosity, of the Mo2 C photothermal layer are responsible for these outstanding results. The conversion of food wastes into valuable products, in this case MXene, can potentially inspire greener developments of advanced materials for solar water evaporator., (© 2022 Wiley-VCH GmbH.)- Published
- 2023
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554. Molecular Characterization of Acquired Resistance to KRASG12C-EGFR Inhibition in Colorectal Cancer.
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Yaeger R, Mezzadra R, Sinopoli J, Bian Y, Marasco M, Kaplun E, Gao Y, Zhao H, Paula ADC, Zhu Y, Perez AC, Chadalavada K, Tse E, Chowdhry S, Bowker S, Chang Q, Qeriqi B, Weigelt B, Nanjangud GJ, Berger MF, Der-Torossian H, Anderes K, Socci ND, Shia J, Riely GJ, Murciano-Goroff YR, Li BT, Christensen JG, Reis-Filho JS, Solit DB, de Stanchina E, Lowe SW, Rosen N, and Misale S
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- Animals, Humans, Signal Transduction, Disease Models, Animal, ErbB Receptors, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Mutation, Drug Resistance, Neoplasm genetics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism
- Abstract
With the combination of KRASG12C and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, and patient samples, we detected a heterogeneous pattern of putative resistance alterations expected primarily to prevent inhibition of ERK signaling by drugs at progression. Serial analysis of patient blood samples on treatment demonstrates that most of these alterations are detected at a low frequency except for KRASG12C amplification, a recurrent resistance mechanism that rises in step with clinical progression. Upon drug withdrawal, resistant cells with KRASG12C amplification undergo oncogene-induced senescence, and progressing patients experience a rapid fall in levels of this alteration in circulating DNA. In this new state, drug resumption is ineffective as mTOR signaling is elevated. However, our work exposes a potential therapeutic vulnerability, whereby therapies that target the senescence response may overcome acquired resistance., Significance: Clinical resistance to KRASG12C-EGFR inhibition primarily prevents suppression of ERK signaling. Most resistance mechanisms are subclonal, whereas KRASG12C amplification rises over time to drive a higher portion of resistance. This recurrent resistance mechanism leads to oncogene-induced senescence upon drug withdrawal and creates a potential vulnerability to senolytic approaches. This article is highlighted in the In This Issue feature, p. 1., (©2022 The Authors; Published by the American Association for Cancer Research.)
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- 2023
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555. Maternal and neonatal outcomes in pregnant women with heart disease with single evaluation vs. semi-structured evaluation by a cardio-obstetric team.
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Velásquez-Penagos J, Muñoz-Ortiz E, Toro-Lugo C, Henao-Parra DA, Correa-Vásquez M, Gándara-Ricardo JA, Zapata-Montoya AM, Holguín-Gonzalez E, Giraldo-Ardila N, Milena-Campo S, Múnera-García M, and Senior-Sánchez JM
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- Infant, Newborn, Female, Humans, Pregnancy, Pregnant Women, Heart, Retrospective Studies, Pregnancy Complications, Cardiovascular therapy, Heart Defects, Congenital complications, Heart Defects, Congenital therapy, Cardiovascular Diseases
- Abstract
Introduction: Cardiovascular diseases in pregnant women are challenging, with high maternal and perinatal morbidity and mortality, so a cardio-obstetric team is recommended for their care. Even so, little data evaluates the impact of these teams. Therefore, the present study aims to compare the obstetric, maternal, and neonatal outcomes of semi-structured follow-up (SSF) in a Cardio-obstetric clinic concerning regular or unstructured follow-up (USF) in pregnant women with heart disease., Methods: A prospective registry of pregnant women with heart disease was carried out. Patients with SSF by a cardio-obstetric team were compared with those with single evaluation or USF. The risk of events was calculated according to the modified World Health Organization (mWHO) classification and the CARPREG-II scale, and cardiac, obstetric, and neonatal outcomes were evaluated., Results: One hundred sixty-eight patients were evaluated, 37 with SSF and 131 with single evaluation (USF). The primary diagnoses were congenital heart disease, arrhythmias, and valve disease. The average CARPREG-II in USF patients was 2.48 (SD 2.3); in SSF patients, it was 3.37 (SD 2.45; p = 0.041). The average of the mWHO in patients with USF was 2.1 (SD 1.6), and with SSF, it was 2.65 (SD 0.95; p = 0.0052). There were no significant differences in primary cardiac outcomes (13.8% in USF vs. 5.4% in SSF; p = 0.134), secondary cardiac (5.3% in USF vs. 2.7% in SSF; p = 0.410), obstetric (10% in USF vs. 16.2% in SSF; p = 0.253) and neonatal (35.9% in USF and 40.5% in SSF; p = 0.486) even though patients with SSF had a higher risk than patients with USF according to the mWHO and CARPREG-II scales., Conclusions: In pregnant women with heart disease, an SSF compared with a USF by a cardio-obstetric team did not show statistically significant differences in cardiovascular, obstetric, and neonatal outcomes. However, patients with SSF had a significantly higher risk of adverse outcomes due to the mWHO and CARPREG-II scales. This result suggests that the SSF achieves at least equal outcomes despite the higher risk of adverse events that patients in this group had., (Copyright: © 2023 Permanyer.)
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- 2023
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556. When Functional Impairment Develops Early: Perspectives from Middle-Aged Adults.
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Xu E, Nicosia FM, Zamora K, Barrientos M, Spar MJ, Reyes-Farias D, Karliner LS, Potter MB, and Brown RT
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- Middle Aged, Humans, Aged, Quality of Life psychology, San Francisco, Activities of Daily Living, Disabled Persons
- Abstract
Background: Difficulty performing basic daily activities such as bathing and dressing ("functional impairment") affects more than 15% of middle-aged people, and this proportion is increasing. Little is known about the experiences and needs of individuals who develop functional impairment in middle age., Objective: To examine the experiences and needs of adults who developed functional impairment in middle age., Design: Qualitative study using semi-structured interviews., Participants: Forty patients aged 50-64 years who developed functional impairment in middle age, recruited from four primary care clinics in San Francisco., Approach: Interviews included open-ended questions about participants' daily life, ability to perform activities of daily living (ADLs), and needs related to functional impairment. We analyzed interviews using qualitative thematic analysis., Key Results: Interviews revealed several themes related to the psychosocial and physical impacts of developing functional impairment in middle age. Participants noted that losses associated with functional impairment, such as loss of independence, control, and social roles, caused conflict in their sense of identity. To cope with these losses, participants used strategies including acceptance, social comparison, adjusting standards, and engaging in valued life activities. Participants reflected on the intersection of their functional impairment with the aging process, noting that their impairments seemed premature compared to the more "natural" aging process in older adults. In terms of physical impacts, participants described how a lack of accommodations in the built environment exacerbated their impairments. While participants used behavioral strategies to overcome these challenges, unmet needs remained, resulting in downstream physical and psychological impacts including safety risks, falls, frustration, and fear., Conclusions: Unmet psychosocial and physical needs were common among middle-aged adults with functional impairment and led to negative downstream effects. Eliciting and addressing unmet needs may help mitigate downstream health consequences for this growing population, optimizing function and quality of life., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)
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- 2023
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557. Criss cross in pregnancy, a unusual crossroads.
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Herrera-Céspedes E, Flórez JP, Aguilar OE, Gándara JA, López-Gutiérrez LV, Senior JM, Velásquez-Penagos JA, and Muñoz-Ortiz E
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- Female, Humans, Pregnancy, Heart Diseases diagnosis
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- 2023
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558. Oesophageal squamous papilloma in paediatric population: a single-centre case series.
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Hernández-Almeida P, Vásconez-Muñoz F, Vásconez-Montalvo A, Montalvo-Flores N, Redrobán-Armendariz L, and Aymacaña-Albán E
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- Adult, Humans, Male, Child, Female, Adolescent, Retrospective Studies, Papillomavirus Infections diagnosis, Papillomavirus Infections epidemiology, Eosinophilic Esophagitis diagnosis, Eosinophilic Esophagitis epidemiology, Eosinophilic Esophagitis pathology, Esophageal Neoplasms diagnosis, Esophageal Neoplasms epidemiology, Papilloma, Carcinoma, Squamous Cell
- Abstract
Purpose: Oesophageal squamous papilloma (OSP) is a rare epithelial lesion with an unclear aetiology, found incidentally in upper gastrointestinal endoscopy (UGE). We evaluate the epidemiology, general features and endoscopic and histological characteristics of OSP in children in a single centre., Methods: We conducted a retrospective search of 3568 medical records of children under 18 years old who underwent UGE between 2004 and 2022, at Hospital Metropolitano de Quito, Ecuador. We described the general features of 15 patients diagnosed with OSP. Histopathology reports were analysed, including a chromogenic in situ hybridisation (CISH) for human papillomavirus (HPV) 6/11., Results: OSP was diagnosed in 15 patients between 10 and 16 years of age, with an estimated prevalence of 0.4%. The gender ratio male to female was 1:1.1. Most patients (n=14) underwent UGE due to abdominal pain. Lesions were found predominantly in the upper and lower part of the oesophagus; 12 patients had isolated lesions, and none of the lesions tested positive for HPV on CISH 6/11 analysis. Additionally, Helicobacter pylori and eosinophilic oesophagitis (EoE) were diagnosed in one patient each., Conclusion: Our study describes the clinical features of paediatric OSP in a single centre. The prevalence was similar to that in the adult population but higher than in other paediatric populations, and none of our patients had HPV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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559. Effective Approach toward Selective Near-Infrared Dyes: Rational Design, Synthesis, and Characterization of Thieno[3,4- b ]thiophene-Based Quinoidal Oligomers.
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Hei Y, Zhang X, He P, Zhao EJ, Tang E, Sharapov V, Liu X, and Yu L
- Abstract
This paper describes syntheses, photophysical properties, and electrochemical characteristics of three thieno[3,4- b ]thiophene (TT)-based quinoidal oligomers OnTTO. The rigid planar backbones of these oligomers give the molecules narrow absorption bands, and the main absorption bands were significantly red-shifted when the TT units were extended and demonstrated wide transparent windows. The compound O4TTO was found to possess strong absorption in the near-infrared (NIR) region approaching 1200 nm but remained transparent in the visible region. Electrochemical experiments have shown that the energy band gaps gradually narrow when the TT units are increased. Optical properties predicted by density functional theory calculations are in good agreement with the experimental optical results. These dye molecules could be promising candidates for future NIR photodetectors, filters, and bioimaging technologies.
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- 2022
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560. Significance of Catecholamine Biosynthetic/Metabolic Pathway in SARS-CoV-2 Infection and COVID-19 Severity.
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Mpekoulis G, Kalliampakou KI, Milona RS, Lagou D, Ioannidis A, Jahaj E, Chasapis CT, Kefallinos D, Karakasiliotis I, Kotanidou A, Chatzipanagiotou S, Vassilacopoulou D, Vassiliou AG, Angelakis E, and Vassilaki N
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- Humans, SARS-CoV-2 metabolism, Catecholamines, Dopamine, Levodopa metabolism, RNA, Viral metabolism, Biosynthetic Pathways, RNA, Messenger metabolism, COVID-19
- Abstract
The SARS-CoV-2 infection was previously associated with the expression of the dopamine biosynthetic enzyme L-Dopa decarboxylase (DDC). Specifically, a negative correlation was detected between DDC mRNA and SARS-CoV-2 RNA levels in in vitro infected epithelial cells and the nasopharyngeal tissue of COVID-19 patients with mild/no symptoms. However, DDC, among other genes related to both DDC expression and SARS-CoV-2-infection ( ACE2 , dACE2 , EPO ), was upregulated in these patients, possibly attributed to an orchestrated host antiviral response. Herein, by comparing DDC expression in the nasopharyngeal swab samples of severe/critical to mild COVID-19 cases, we showed a 20 mean-fold reduction, highlighting the importance of the expression of this gene as a potential marker of COVID-19 severity. Moreover, we identified an association of SARS-CoV-2 infection with the expression of key catecholamine biosynthesis/metabolism-related genes, in whole blood samples from hospitalized patients and in cultured cells. Specifically, viral infection downregulated the biosynthetic part of the dopamine pathway (reduction in DDC expression up to 7.5 mean-fold), while enhanced the catabolizing part (increase in monoamine oxidases A and B expression up to 15 and 10 mean-fold, respectively) in vivo, irrespectively of the presence of comorbidities. In accordance, dopamine levels in the sera of severe cases were reduced (up to 3.8 mean-fold). Additionally, a moderate positive correlation between DDC and MAOA mRNA levels (r = 0.527, p < 00001) in the blood was identified upon SARS-CoV-2-infection. These observations were consistent to the gene expression data from SARS-CoV-2-infected Vero E6 and A549 epithelial cells. Furthermore, L-Dopa or dopamine treatment of infected cells attenuated the virus-derived cytopathic effect by 55% and 59%, respectively. The SARS-CoV-2 mediated suppression of dopamine biosynthesis in cell culture was, at least in part, attributed to hypoxia-like conditions triggered by viral infection. These findings suggest that L-Dopa/dopamine intake may have a preventive or therapeutic value for COVID-19 patients.
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- 2022
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561. A new framework for host-pathogen interaction research.
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Yu H, Li L, Huffman A, Beverley J, Hur J, Merrell E, Huang HH, Wang Y, Liu Y, Ong E, Cheng L, Zeng T, Zhang J, Li P, Liu Z, Wang Z, Zhang X, Ye X, Handelman SK, Sexton J, Eaton K, Higgins G, Omenn GS, Athey B, Smith B, Chen L, and He Y
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- Humans, Host-Pathogen Interactions, COVID-19
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COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Li, Huffman, Beverley, Hur, Merrell, Huang, Wang, Liu, Ong, Cheng, Zeng, Zhang, Li, Liu, Wang, Zhang, Ye, Handelman, Sexton, Eaton, Higgins, Omenn, Athey, Smith, Chen and He.)
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- 2022
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562. Effects of mycogenic silver nanoparticles on organisms of different trophic levels.
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Assis da Silva C, Ribeiro BM, Trotta CDV, Perina FC, Martins R, Moledo de Souza Abessa D, Barbieri E, Simões MF, and Ottoni CA
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- Ammonia, Animals, Anti-Bacterial Agents pharmacology, Antifungal Agents pharmacology, Daphnia, Silver toxicity, Silver Nitrate toxicity, Zebrafish, Chlorella vulgaris, Metal Nanoparticles toxicity
- Abstract
Biogenic silver nanoparticles (AgNPs) are considered a promising alternative to their synthetic versions. However, the environmental impact of such nanomaterials is still scarcely understood. Thus, the present study aims at assessing the antimicrobial action and ecotoxicity of AgNPs biosynthesized by the fungus Aspergillus niger IBCLP20 towards three freshwater organisms: Chlorella vulgaris, Daphnia similis, and Danio rerio (zebrafish). AgNPs IBCLP20 showed antibacterial action against Klebsiella pneumoniae between 5 and 100 μg mL
-1 , and antifungal action against Trichophyton mentagrophytes in concentrations ranging from 20 to 100 μg mL-1 . The cell density of the microalgae Chlorella vulgaris decreased 40% after 96 h of exposure to AgNPs IBCLP20, at the highest concentration analysed (100 μg L-1 ). The 48 h median lethal concentration for Daphnia similis was estimated as 4.06 μg L-1 (2.29-6.42 μg L-1 ). AgNPs IBCLP20 and silver nitrate (AgNO3 ) caused no acute toxicity on adult zebrafish, although they did induce several physiological changes. Mycosynthetized AgNPs caused a significant increase (p < 0.05) in oxygen consumption at the highest concentration studied (75 μg L-1 ) and an increase in the excretion of ammonia at the lower concentrations, followed by a reduction at the higher concentrations. Such findings are comparable with AgNO3 , which increased the oxygen consumption on low exposure concentrations, followed by a decrease at the high tested concentrations, while impairing the excretion of ammonia in all tested concentrations. The present results show that AgNPs IBCLP20 have biocidal properties. Mycogenic AgNPs induce adverse effects on organisms of different trophic levels and understanding their impact is detrimental to developing countermeasures aimed at preventing any negative environmental effects of such novel materials., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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563. COMPARATIVE EVALUATION AND PROGNOSTIC UTILITY OF NEURONAL INJURY BIOMARKERS IN COVID-19 PATIENTS: A PROSPECTIVE STUDY.
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Vrettou CS, Vassiliou AG, Pratikaki M, Keskinidou C, Tsipilis S, Gallos P, Jahaj E, Orfanos SE, Kotanidou A, and Dimopoulou I
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- Humans, Biomarkers blood, Prognosis, Prospective Studies, SARS-CoV-2, Critical Illness, COVID-19 blood, COVID-19 complications, Receptors, Urokinase Plasminogen Activator blood, Nervous System Diseases blood, Nervous System Diseases diagnosis, Nervous System Diseases virology, S100 Calcium Binding Protein beta Subunit blood, Phosphopyruvate Hydratase blood
- Abstract
Abstract: Background : COVID-19 disease severity markers include mostly molecules related to not only tissue perfusion, inflammation, and thrombosis, but also biomarkers of neural injury. Clinical and basic research has demonstrated that SARS-COV-2 affects the central nervous system. The aims of the present study were to investigate the role of neural injury biomarkers and to compare them with inflammatory markers in their predictive ability of mortality. Methods : We conducted a prospective observational study in critically ill patients with COVID-19 and in a cohort of patients with moderate/severe disease. S100b, neuron-specific enolase (NSE), and inflammatory markers, including soluble urokinase plasminogen activator receptor (suPAR), were measured on intensive care unit or ward admission, respectively. Statistical comparisons between patient groups were performed for all biomarkers under investigation. Correlations between different biomarkers were tested with Spearman correlation coefficient. Receiver operating characteristic curves were plotted using mortality as the classification variable and the biomarker levels on admission as the prognostic variables. Results : A total of 70 patients with COVID-19 were included in the final analysis. Of all studied biomarkers, s100b had the best predictive ability for death in the intensive care unit, with an area under the curve of 0.73 (0.61-0.83), P = 0.0003. S100b levels correlated with NSE, interleukin (IL)-8, and IL-10 (0.27 < rs < 0.37, P < 0.05), and tended to correlate with suPAR ( rs = 0.26, P = 0.05), but not with the vasopressor dose ( P = 0.62). Conclusion : Among the investigated biomarkers, s100b demonstrated the best predictive ability for death in COVID-19 patients. The overall biomarker profile of the patients implies direct involvement of the nervous system by the novel coronavirus., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)
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- 2022
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564. Use of a Novel Clinical Decision-Making Tool in Vestibular Schwannoma Treatment.
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La Monte OA, Moshtaghi O, Tang E, Du EY, Swisher AR, Dixon PR, Nemati S, Djalilian HR, Schwartz MS, and Friedman RA
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- Humans, Middle Aged, Aged, Prospective Studies, Retrospective Studies, Pilot Projects, Clinical Decision-Making, Decision Making, Neuroma, Acoustic surgery
- Abstract
Objective: To determine the usefulness of a personalized tool and its effect on the decision-making process for those with vestibular schwannoma (VS)., Study Design: Prospective study., Setting: Single institution, academic tertiary care lateral skull base surgery program., Patients: Patients diagnosed with VS., Interventions: A comprehensive clinical decision support (CDS) tool was constructed from a previously published retrospective patient-reported data obtained from members of the Acoustic Neuroma Association from January to March 2017. Demographic, tumor, and treatment modality data, including associated side effects, were collected for 775 patients and integrated in an interactive and personalized web-based tool., Main Outcome Measures: Pre- and posttool questionnaires assessing the process of deciding treatment for VS using a decisional conflict scale (DCS) and satisfaction with decision (SWD) scale were compared., Results: A pilot study of 33 patients evaluated at a single institution tertiary care center with mean ± SD age of 63.9 ± 13.5 years and with average tumor size of 7.11 ± 4.75 mm were surveyed. CDS implementation resulted in a mean ± SD total DCS score decrease from 43.6 ± 15.5 to 37.6 ± 16.4 ( p < 0.01) and total SWD score increase from 82.8 ± 16.1 to 86.2 ± 14.4 ( p = 0.04), indicating a significant decrease in decisional conflict and increase in satisfaction., Conclusions: Implementing a decision-making tool after diagnosis of VS reduced decisional conflict and improved satisfaction with decision. Patients considered the tool to be an aid to their medical knowledge, further improving their comfort and understanding of their treatment options. These findings provide a basis for developing predictive tools that will assist patients in making informed medical decisions in the future., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)
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- 2022
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565. Singing crickets from Brazil (Orthoptera: Gryllidea), an illustrated checklist with access to the sounds produced.
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Zefa E, DE Pinho Martins L, Demari CP, Acosta RC, Centeno E, Castro-Souza RA, DE Oliveira GL, Miyoshi AR, Fianco M, Redü DR, Timm VF, Costa MKMD, and Szinwelski N
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- Animals, Brazil, Vocalization, Animal, Orthoptera, Gryllidae
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The knowledge of bioacoustics of the Neotropical crickets (Orthoptera, Gryllidea) is incipient, despite the great species diversity in the region. There are few cricket song-files deposited in the major World Sound Libraries, compared to other groups such as birds and amphibians. In order to contribute to the knowledge of the bioacoustics of Brazilian crickets, we organize, analyze and make available at Fonoteca Neotropical Jacques Vielliard (FNJV) and Orthoptera Species File (OSF) our bank of cricket songs. We deposited 876 cricket's song files in the FNJV, belonging to 31 species and 47 sonotypes. The songs were field/lab recorded, and all individuals were collected to improve species/sonotypes taxonomic determination accuracy. We present photos (in vivo) of most recorded crickets, as well as calling song spectrograms to facilitate the species/sonotype recognition. Samples of the songs can be found online on the FNJV website, using the codes available in this work, as well as on the OSF, linked to the species name. As a result, we advance the knowledge of the songs of crickets and the current perspective of the Brazilian cricket bioacoustics. We encourage researchers to share with the public their collections of their cricket file songs both in the FNJV and the OSF.
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- 2022
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566. Genome Characterization and Pathogenicity of Two New Hyptis pectinata Viruses Transmitted by Distinct Insect Vectors.
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Reyes-Proaño E, Alvarez-Quinto R, Delgado-Jiménez JA, Cornejo-Franco JF, Mollov D, Bejerman N, and Quito-Avila DF
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- Animals, Genome, Viral genetics, Virulence, Plant Diseases, Insect Vectors, Nucleotides, Phylogeny, Hyptis genetics, Begomovirus genetics, Rhabdoviridae genetics, Hemiptera
- Abstract
Two newly described viruses belonging to distinct families, Rhabdoviridae and Geminiviridae , were discovered co-infecting Hyptis pectinata from a tropical dry forest of Ecuador. The negative-sense RNA genome of the rhabdovirus, tentatively named Hyptis latent virus (HpLV), comprises 13,765 nucleotides with seven open reading frames separated by the conserved intergenic region 3'-AAUUAUUUUGAU-5'. Sequence analyses showed identities as high as 56% for the polymerase and 38% for the nucleocapsid to members of the genus Cytorhabdovirus. Efficient transmission of HpLV was mediated by the pea aphid ( Acyrthosiphon pisum ) in a persistent replicative manner. The single-stranded DNA genome of the virus tentatively named Hyptis golden mosaic virus (HpGMV) shared homology with members of the genus Begomovirus with bipartite genomes. The DNA-A component consists of 2,716 nucleotides (nt), whereas the DNA-B component contains 2,666 nt. Pairwise alignments using the complete genomic sequence of DNA-A of HpGMV and closest relatives showed identities below the cutoff (<91% shared nt) established by the ICTV as species demarcation, indicating that HpGMV should be classified in a distinct begomovirus species. Transmission experiments confirmed that the whitefly Bemisia tabaci Middle East-Asia Minor 1 (MEAM1) is a vector of HpGMV.
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- 2022
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567. Developing a Diagnostic Multivariable Prediction Model for Urinary Tract Cancer in Patients Referred with Haematuria: Results from the IDENTIFY Collaborative Study.
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Khadhouri S, Gallagher KM, MacKenzie KR, Shah TT, Gao C, Moore S, Zimmermann EF, Edison E, Jefferies M, Nambiar A, Anbarasan T, Mannas MP, Lee T, Marra G, Gómez Rivas J, Marcq G, Assmus MA, Uçar T, Claps F, Boltri M, La Montagna G, Burnhope T, Nkwam N, Austin T, Boxall NE, Downey AP, Sukhu TA, Antón-Juanilla M, Rai S, Chin YF, Moore M, Drake T, Green JSA, Goulao B, MacLennan G, Nielsen M, McGrath JS, and Kasivisvanathan V
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- Humans, Male, Urologic Neoplasms complications, Urologic Neoplasms diagnosis, Urologic Neoplasms epidemiology, Urinary Bladder Neoplasms complications, Urinary Bladder Neoplasms diagnosis, Urinary Bladder Neoplasms epidemiology, Kidney Neoplasms
- Abstract
Background: Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation., Objective: To develop a prediction model for urinary tract cancer in patients referred with haematuria., Design, Setting, and Participants: A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded., Outcome Measurements and Statistical Analysis: The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism., Results and Limitations: The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy., Conclusions: This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation., Patient Summary: We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2022
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568. xRatSLAM: An Extensible RatSLAM Computational Framework.
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de Souza Muñoz ME, Chaves Menezes M, Pignaton de Freitas E, Cheng S, de Almeida Ribeiro PR, de Almeida Neto A, and Muniz de Oliveira AC
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- Algorithms, Brain, Robotics methods
- Abstract
Simultaneous localization and mapping (SLAM) refers to techniques for autonomously constructing a map of an unknown environment while, at the same time, locating the robot in this map. RatSLAM, a prevalent method, is based on the navigation system found in rodent brains. It has served as a base algorithm for other bioinspired approaches, and its implementation has been extended to incorporate new features. This work proposes xRatSLAM: an extensible, parallel, open-source framework applicable for developing and testing new RatSLAM variations. Tests were carried out to evaluate and validate the proposed framework, allowing the comparison of xRatSLAM with OpenRatSLAM and assessing the impact of replacing framework components. The results provide evidence that the maps produced by xRatSLAM are similar to those produced by OpenRatSLAM when they are fed with the same input parameters, which is a positive result, and that implemented modules can be easily changed without impacting other parts of the framework.
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- 2022
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569. Cricotracheal Adenoid Cystic Carcinoma: Insights Into the Diagnosis and Management of an Uncommon Anatomic Variant.
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Pacheco-Ojeda L, Ríos-Deidán C Sr, Cañizares S, Pontón-Villalba P, and Moya-Paredes E
- Abstract
Adenoid cystic carcinoma (ACC) is the second most common malignant salivary gland tumor and accounts for 30% of minor salivary gland tumors. Its location in the larynx and trachea are rare. We present the case of a 45-year-old healthy male whose MRI revealed a posterior endoluminal tumor that invaded the posteroinferior perichondrium of the cricoid lamina and displaced the hypopharynx and esophagus. A left-limited cervical surgical exploration and an intraluminal incisional biopsy through the tracheostomy space were performed by another surgical team. The pathological study reported an ACC, T4aN0M0, stage IVA tumor. Then, a circular tracheal resection and an excision of the inferior part of the posterior cricoid lamina were carried out. The macroscopic study showed a lesion, 3cm long, 2.2cm wide, and 1cm thick, located at the posterior wall of the cricoid cartilage and proximal trachea. Only the upper margin was compromised. Microscopically, the tumor showed tubular, solid, cribriform, and trabecular patterns. One and a half years after surgery, the patient still has bilateral vocal cord mobility and normal speech. It is clear that a contrast-enhanced CT scan is useful to assess tumor extent and growth pattern in these rare variants. Among treatment alternatives, surgery sometimes complemented with radiotherapy is essential; constant follow-up is mandatory., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Pacheco-Ojeda et al.)
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- 2022
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570. A comprehensive update on CIDO: the community-based coronavirus infectious disease ontology.
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He Y, Yu H, Huffman A, Lin AY, Natale DA, Beverley J, Zheng L, Perl Y, Wang Z, Liu Y, Ong E, Wang Y, Huang P, Tran L, Du J, Shah Z, Shah E, Desai R, Huang HH, Tian Y, Merrell E, Duncan WD, Arabandi S, Schriml LM, Zheng J, Masci AM, Wang L, Liu H, Smaili FZ, Hoehndorf R, Pendlington ZM, Roncaglia P, Ye X, Xie J, Tang YW, Yang X, Peng S, Zhang L, Chen L, Hur J, Omenn GS, Athey B, and Smith B
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- Humans, SARS-CoV-2, Pandemics, Amino Acids, COVID-19 Drug Treatment, COVID-19, Coronavirus, Vaccines, Communicable Diseases
- Abstract
Background: The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO) in early 2020., Results: As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment., Conclusion: CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications., (© 2022. The Author(s).)
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- 2022
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571. Subdural hematoma expansion in relation to measured mean and peak systolic blood pressure: A retrospective analysis.
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Plowman K, Lindner D, Valle-Giler E, Ashkin A, Bass J, and Ruthman C
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Objective: Subdural hematomas (SDH) account for an estimated 5 to 25% of intracranial hemorrhages. Acute SDH occur secondary to rupture of the bridging veins leading to blood collecting within the dural space. Risk factors associated with SDH expansion are well documented, however, there are no established guidelines regarding blood pressure goals in the management of acute SDH. This study aims to retrospectively evaluate if uncontrolled blood pressure within the first 24 h of hospitalization in patients with acute SDH is linked to hematoma expansion as determined by serial CT imaging., Methods: A single center, retrospective study looked at 1,083 patients with acute SDH, predominantly above age 65. Of these, 469 patients met the inclusion criteria. Blood pressure was measured during the first 24 h of admission along with PT, INR, platelets, blood alcohol level, anticoagulation use and antiplatelet use. Follow-up CT performed within the first 24 h was compared to the initial CT to determine the presence of hematoma expansion. Mean systolic blood pressure (SBP), peak SBP, discharge disposition, length of stay and in hospital mortality were evaluated., Results: We found that patients with mean SBP <140 in the first 24 h of admission had a lower rate of hematoma expansion than those with SBP > 140. Patients with peak SBP > 200 had an increased frequency of hematoma expansion with the largest effect seen in patients with SBP > 220. Other risk factors did not contribute to hematoma expansion., Conclusions: These results suggest that blood pressure is an important factor to consider when treating patients with SDH with medical management. Blood pressure management should be considered in addition to serial neurological exams, repeat radiological imaging, seizure prophylaxis and reversal of anticoagulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Plowman, Lindner, Valle-Giler, Ashkin, Bass and Ruthman.)
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- 2022
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572. Past, Present, and Future of Copper Mine Tailings Governance in Chile (1905-2022): A Review in One of the Leading Mining Countries in the World.
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Cacciuttolo C and Atencio E
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- Chile, Water, Copper, Ecosystem
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How mine tailings storage facilities (TSF) are managed reflects the history, regulatory framework, and environment of a country and locale of the mine. Despite many attempts to find an environmentally friendly strategy for tailings management and governance that balances the needs of society and the ecosystem, there is no worldwide agreement regarding the best practices for tailings management and governance. This article reviews the evolution of copper tailings management and governance in Chile, current practices, and changes that could be or may need to be made to improve practices in response to local environmental conditions and local tolerance for risk. The progress to date in developing a holistic tailings management strategy is summarized. This article also describes recent proposals for the best available technologies (BATs), case histories of Chilean TSF using conventional technology, thickened tailings, paste tailings, filtered tailings, water use reduction, tailings reprocessing to obtain rare earth elements (REEs), circular economy, submarine deep-sea tailings disposal, and ways to avoid failure in a seismic region. Finally, the Chilean tailings industry's pending issues and future challenges in reducing the socioenvironmental impacts of tailings are presented, including advances made and lessons learned in developing more environmentally friendly solutions.
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- 2022
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573. Minimizing Molecular Misidentification in Imaging Low-Abundance Protein Interactions Using Spectroscopic Single-Molecule Localization Microscopy.
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Zhang Y, Wang G, Huang P, Sun E, Kweon J, Li Q, Zhe J, Ying LL, and Zhang HF
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- Fluorescent Dyes chemistry, Microscopy, Fluorescence methods, Staurosporine pharmacology, Biological Phenomena, Single Molecule Imaging methods
- Abstract
Super-resolution microscopy can capture spatiotemporal organizations of protein interactions with resolution down to 10 nm; however, the analyses of more than two proteins involving low-abundance protein are challenging because spectral crosstalk and heterogeneities of individual fluorescent labels result in molecular misidentification. Here we developed a deep learning-based imaging analysis method for spectroscopic single-molecule localization microscopy to minimize molecular misidentification in three-color super-resolution imaging. We characterized the 3-fold reduction of molecular misidentification in the new imaging method using pure samples of different photoswitchable fluorophores and visualized three distinct subcellular proteins in U2-OS cell lines. We further validated the protein counts and interactions of TOMM20, DRP1, and SUMO1 in a well-studied biological process, Staurosporine-induced apoptosis, by comparing the imaging results with Western-blot analyses of different subcellular portions.
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- 2022
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574. Synthesis of Square Planar Cu 4 Clusters.
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Osei MK, Mirzaei S, Bogetti X, Castro E, Rahman MA, Saxena S, and Hernández Sánchez R
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Template-assisted synthesis of well-defined polynuclear clusters remains a challenge for [M
4 ] square planar topologies. Herein, we present a tetraamine scaffoldR L(NH2 )4 , where L is a rigidified resorcin[4]arene, to direct the formation of C4 -symmetricR L(NH)4 Cu4 clusters with Cu-Cu distances around 2.7 Å, suggesting metal-metal direct interactions are operative since the sum of copper's van der Waals radii is 2.8 Å. DFT calculations display HOMO to HOMO-3 residing all within a 0.1 eV gap. These four orbitals display significant electron density contribution from the Cu centers suggesting a delocalized electronic structure. The one-electron oxidized [Cu4 ]+ species was probed by variable temperature X-band continuous wave-electron paramagnetic resonance (CW-EPR), which displays a multiline spectrum at room temperature. This work presents a novel synthetic strategy for [M4 ] clusters and a new platform to investigate activation of small molecules., (© 2022 Wiley-VCH GmbH.)- Published
- 2022
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575. Potential use of native fruits waste from Argentina as nonconventional sources of cosmetic ingredients.
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Orqueda ME, Zampini IC, Bravo K, Osorio E, and Isla MI
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- Humans, Plant Extracts pharmacology, Hyaluronoglucosaminidase, Argentina, Antioxidants pharmacology, Phenols pharmacology, Pancreatic Elastase, Collagenases, Fruit chemistry, Monophenol Monooxygenase
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Background: Collagenase, hyaluronidase, elastase, and tyrosinase enzymes are overexpressed and overactive in the skin aging process and hydrolyze the components of the dermal extracellular matrix (ECM) of the skin; these enzymes produce the clinical framework of aging, which includes skin dryness, hyperpigmentation, wrinkles, and inelasticity., Aims: The aim of this study was to explore the potential use of waste from two Argentine native fruits, namely Ziziphus mistol, and red and orange varieties of Solanum betaceum, as sources of bioactive compounds., Methods: Phenolic enriched extracts (PEE) from waste of Z. mistol and S. betaceum were obtained, and their total contents of phenolics and flavonoids were evaluated. The bioactive properties of the extracts were analyzed by measuring their antioxidant capacity and the inhibitory activity on collagenase, hyaluronidase, elastase, and tyrosinase enzymes., Results: The increased ability to inhibit the collagenase was demonstrated by the PEE of Z. mistol seeds and peel, while the enzyme elastase was mostly inhibited by extracts of S. betaceum skin. Z. mistol seed extract was the most active to inhibit hyaluronidase, reaching 96% inhibition at a concentration of 100 μg GAE/mL. The most active extracts to inhibit the tyrosinase enzyme were obtained from the peel of two varieties of chilto fruits, orange and red, and the mistol seed., Conclusions: The results obtained suggest that Z. mistol and S. betaceum waste may be considered as a source of bioactive phenolics. Here, Argentine native fruits waste is presented as a most promising alternative in cosmetic products, with future uses such as hydrogels, creams, or lotions., (© 2022 Wiley Periodicals LLC.)
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- 2022
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576. Institutional and infrastructure challenges for hospitals producing advanced therapies in the UK: the concept of 'point-of-care manufacturing readiness'.
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Bicudo E and Brass I
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- Cell- and Tissue-Based Therapy, Humans, United Kingdom, Hospitals, Point-of-Care Systems
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Aim: To propose the concept of point-of-care manufacturing readiness for analyzing the capacity that a country, a health system or an institution has developed to manufacture therapies in clinical settings (point-of-care manufacture). The focus is on advanced therapies (cell, gene and tissue engineering therapies) in the UK. Materials & methods: Literature review, analysis of quantitative data, and qualitative interviews with professionals and practitioners developing and administering advanced therapies. Results: Three components of point-of-care manufacturing readiness are analyzed staff and institutional procedures, infrastructure, and relations between hospitals and service providers. Conclusion: The technical and regulatory experience that has been gained through manufacturing advanced therapies at small scale in hospitals qualifies the UK for more complex and larger-scale production of therapies in the future.
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- 2022
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577. Classification of new morbillivirus and jeilongvirus sequences from bats sampled in Brazil and Malaysia.
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Wells HL, Loh E, Nava A, Solorio MR, Lee MH, Lee J, Sukor JRA, Navarrete-Macias I, Liang E, Firth C, Epstein JH, Rostal MK, Zambrana-Torrelio C, Murray K, Daszak P, Goldstein T, Mazet JAK, Lee B, Hughes T, Durigon E, and Anthony SJ
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- Animals, Brazil, Genome, Viral, Humans, Malaysia, Paramyxoviridae genetics, Phylogeny, Chiroptera, Morbillivirus genetics, Viruses
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As part of a broad One Health surveillance effort to detect novel viruses in wildlife and people, we report several paramyxovirus sequences sampled primarily from bats during 2013 and 2014 in Brazil and Malaysia, including seven from which we recovered full-length genomes. Of these, six represent the first full-length paramyxovirid genomes sequenced from the Americas, including two that are the first full-length bat morbillivirus genome sequences published to date. Our findings add to the vast number of viral sequences in public repositories, which have been increasing considerably in recent years due to the rising accessibility of metagenomics. Taxonomic classification of these sequences in the absence of phenotypic data has been a significant challenge, particularly in the subfamily Orthoparamyxovirinae, where the rate of discovery of novel sequences has been substantial. Using pairwise amino acid sequence classification (PAASC), we propose that five of these sequences belong to members of the genus Jeilongvirus and two belong to members of the genus Morbillivirus. We also highlight inconsistencies in the classification of Tupaia virus and Mòjiāng virus using the same demarcation criteria and suggest reclassification of these viruses into new genera. Importantly, this study underscores the critical importance of sequence length in PAASC analysis as well as the importance of biological characteristics such as genome organization in the taxonomic classification of viral sequences., (© 2022. The Author(s).)
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- 2022
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578. Novel Multipotent Amantadine-M30D Hybrids with Highly Selective Butyrylcholinesterase Inhibition and Neuroprotective Effects as Effective Anti-Alzheimer's Agents.
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Rada MS, Cardona-Galeano W, Quintero-Saumeth J, Sierra K, Osorio E, Gonzalez-Molina LA, Posada-Duque R, and Yepes AF
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- Acetylcholinesterase metabolism, Adenosine Triphosphate, Butyrylcholinesterase, Calcium, Cholinesterase Inhibitors therapeutic use, Glutamates, Humans, Memantine pharmacology, Memantine therapeutic use, Molecular Docking Simulation, N-Methylaspartate, Structure-Activity Relationship, Alzheimer Disease drug therapy, Neuroprotective Agents chemistry
- Abstract
As a contribution to the development of new dual/multifunctional drugs, a novel therapeutical scaffold merging key structural features from memantine and M30D was designed, synthesized, and explored for its AChE/BuChE inhibitory activity and neuroprotective effects. All synthetized hybrids were not able to inhibit AChE, but most of them exhibit inhibition with high selectivity toward butyrylcholinesterase (BuChE). Notably, among the tested compounds, amantadine/M30D hybrids with six, seven, nine, and twelve methylene groups in the spacer ( 5d , 5e , 5f , and 5g ) not only highlighted having the best potency and selective butyrylcholinesterase inhibition greater than 83% but also, particularly 5e and 5d , elicited considerable neuroprotection when evaluated in pretreatment conditions, by reducing injury effects caused by glutamate with maximum protection reached about 47.82 ± 0.81% ( 5e ) and 42 ± 2.20% ( 5d ) in comparison with memantine (37.27 ± 2.69%). Likewise, we chose 5e as the hit compound, which in a glutamate excitotoxity coculture model prevented astroglia reactivity and neuronal death, as well as a 91% restoration of calcium levels and an increasing ATP level in both pre-/post-treatments of 61.48 ± 4.60 and 45.16 ± 10.55%, respectively. Regarding docking studies, a blockade of the NMDA channel pore by 5e would explain its neuroprotective response. Finally, the hit compound 5e exhibited in vitro blood-brain barrier (BBB) permeability and human plasma stability, as well as an optimal in silico neuropharmacokinetic profile. From a therapeutic perspective, merging key pharmacophoric features from memantine and M30D provides a new medicinal scaffold with dual-/multifunctional properties and human plasma stability for the future development of potential drugs for treating AD.
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- 2022
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579. Genetic Evolution of Avian Influenza A (H9N2) Viruses Isolated from Domestic Poultry in Uganda Reveals Evidence of Mammalian Host Adaptation, Increased Virulence and Reduced Sensitivity to Baloxavir.
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Atim G, Tugume T, Ukuli QA, Erima B, Mubiru A, Kibuuka H, Mworozi E, McKenzie P, Turner JCM, Walker D, Jeevan T, Webster RG, Jones J, Webby RJ, Ducatez MF, Wabwire-Mangen F, and Byarugaba DK
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- Animals, Dibenzothiepins, Endonucleases genetics, Evolution, Molecular, Host Adaptation, Humans, Mammals, Morpholines, Nucleotides, Phylogeny, Poultry, Pyridones, Triazines, Uganda epidemiology, Virulence genetics, Influenza A Virus, H9N2 Subtype, Influenza in Birds epidemiology, Influenza, Human
- Abstract
A (H9N2) avian influenza A viruses were first detected in Uganda in 2017 and have since established themselves in live bird markets. The aim of this study was to establish the subsequent genetic evolution of H9N2 viruses in Uganda. Cloacal samples collected from live bird market stalls in Kampala from 2017 to 2019 were screened by RT-PCR for influenza A virus and H9N2 viruses were isolated in embryonated eggs. One hundred and fifty H9N2 isolates were subjected to whole genome sequencing on the Illumina MiSeq platform. The sequence data analysis and comparison with contemporary isolates revealed that the virus was first introduced into Uganda in 2014 from ancestors in the Middle East. There has since been an increase in nucleotide substitutions and reassortments among the viruses within and between live bird markets, leading to variations in phylogeny of the different segments, although overall diversity remained low. The isolates had several mutations such as HA-Q226L and NS-I106M that enable mammalian host adaptation, NP-M105V, PB1-D3V, and M1-T215A known for increased virulence/pathogenicity and replication, and PA-E199D, NS-P42S, and M2-S31N that promote drug resistance. The PA-E199D substitution in particular confers resistance to the endonuclease inhibitor Baloxavir acid, which is one of the new anti-influenza drugs. Higher EC50 was observed in isolates with a double F105L+E199D substitution that may suggest a possible synergistic effect. These H9N2 viruses have established an endemic situation in live bird markets in Uganda because of poor biosecurity practices and therefore pose a zoonotic threat. Regular surveillance is necessary to further generate the needed evidence for effective control strategies and to minimize the threats.
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- 2022
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580. Lifelong Adaptive Machine Learning for Sensor-Based Human Activity Recognition Using Prototypical Networks.
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Adaimi R and Thomaz E
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- Education, Continuing, Humans, Human Activities, Machine Learning
- Abstract
Continual learning (CL), also known as lifelong learning, is an emerging research topic that has been attracting increasing interest in the field of machine learning. With human activity recognition (HAR) playing a key role in enabling numerous real-world applications, an essential step towards the long-term deployment of such systems is to extend the activity model to dynamically adapt to changes in people's everyday behavior. Current research in CL applied to the HAR domain is still under-explored with researchers exploring existing methods developed for computer vision in HAR. Moreover, analysis has so far focused on task-incremental or class-incremental learning paradigms where task boundaries are known. This impedes the applicability of such methods for real-world systems. To push this field forward, we build on recent advances in the area of continual learning and design a lifelong adaptive learning framework using Prototypical Networks, LAPNet-HAR , that processes sensor-based data streams in a task-free data-incremental fashion and mitigates catastrophic forgetting using experience replay and continual prototype adaptation. Online learning is further facilitated using contrastive loss to enforce inter-class separation. LAPNet-HAR is evaluated on five publicly available activity datasets in terms of its ability to acquire new information while preserving previous knowledge. Our extensive empirical results demonstrate the effectiveness of LAPNet-HAR in task-free CL and uncover useful insights for future challenges.
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- 2022
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581. Natural history of postoperative neuropathies in gynecologic surgery.
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Chen E and Kowalski JT
- Subjects
- Female, Humans, Pelvis, Postoperative Period, Retrospective Studies, Gynecologic Surgical Procedures adverse effects, Peripheral Nervous System Diseases epidemiology
- Abstract
Introduction and Hypothesis: Neuropathy following pelvic surgery is an uncommon but important complication. The current literature about the natural history and treatment of these neuropathies is limited. We aim to describe the characteristics, treatments and natural history of postoperative neuropathy following benign gynecologic surgery., Methods: This retrospective case series included patients who underwent benign gynecologic surgery for ≥ 60 min in lithotomy. Patients with preexisting neurologic disease were excluded. Patient demographics, identification of postoperative neuropathy and details regarding evaluation and treatment were obtained from the medical record. Neuropathies were characterized by anatomic location and nerve/dermatome distribution. Duration of symptoms was classified as < 1 week, 1 week to 3 months or > 3 months with neuropathy symptoms grouped as resolved, persistent but improved or persistent. Data were analyzed with appropriate descriptive statistics, Pearson correlation and chi-square test., Results: The study included 2449 patients who had undergone benign gynecologic surgery, with 78 (3.2%) patients identified as having postoperative neuropathy. Most patients with neuropathies demonstrated either complete resolution [59 (75.6%)] or persistent but improved [13 (16.7%)] symptoms. Twenty-eight (35.9%) had symptoms of ≥ 3 months. Most neuropathies were sensory only [63 (80.8%)], and the most frequently documented nerve distribution was femoral [23 (29.5%)]. Evaluation and treatment of neuropathy most commonly included physical therapy consult [17 (21.8%)] and neurology consult [8 (10.3%)]., Conclusions: The incidence of postoperative neuropathy in this large, benign gynecologic surgery population was 3.2%. Most neuropathies are sensory only and self-limited. While physical therapy was the most common treatment, most patients received no specific intervention., (© 2022. The International Urogynecological Association.)
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- 2022
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582. Corrigendum to: "Metformin modulates PI3K and GLUT4 expression and Akt/PKB phosphorylation in human endometrial stromal cells after stimulation with androgen and insulin" [Eur. J. Obstet. Gynecol. Reprod. Biol. 175 (2014) 157-162].
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Ferreira GD, Germeyer A, de Barros Machado A, do Nascimento TL, Strowitzki T, Brum IS, Corleta HVE, and Capp E
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- 2022
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583. C3a and C5b-9 Differentially Predict COVID-19 Progression and Outcome.
- Author
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Detsika MG, Diamanti E, Ampelakiotou K, Jahaj E, Tsipilis S, Athanasiou N, Dimopoulou I, Orfanos SE, Tsirogianni A, and Kotanidou A
- Abstract
SARS-CoV-2 infection may result in severe pneumonia leading to mechanical ventilation and intensive care (ICU) treatment. Complement activation was verified in COVID-19 and implicated as a contributor to COVID-19 pathogenesis. This study assessed the predictive potential of complement factors C3a and C5b-9 for COVID-19 progression and outcome. We grouped 80 COVID-19 patients into severe COVID-19 patients (n = 38) and critically ill (n = 42) and subdivided into non-intubated (n = 48) and intubated (n = 32), survivors (n = 57) and non-survivors (n = 23). Results: A significant increase for C3a and C5b-9 levels was observed between: severely and critically ill patients (p < 0.001 and p < 0.0001), non-intubated vs intubated (p < 0.001 and p < 0.05), survivors vs non-survivors (p < 0.001 and p < 0.01). ROC analysis for the need for ICU treatment revealed a higher AUC for C5b-9 (0.764, p < 0.001) compared to C3a (AUC = 0.739, p < 0.01). A higher AUC was observed for C3a for the need for intubation (AUC = 0.722, p < 0.001) or mortality (AUC = 0.740, p < 0.0001) compared to C5b-9 (need for intubation AUC = 0.656, p < 0.05 and mortality AUC = 0.631, p = NS). Combining the two markers revealed a powerful prediction tool for ICU admission (AUC = 0.773, p < 0.0001), intubation (AUC = 0.756, p < 0.0001) and mortality (AUC = 0.753, p < 0.001). C3a and C5b-9 may be considered as prognostic tools separately or in combination for the progression and outcome of COVID-19.
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- 2022
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584. Squalene in oil-based adjuvant improves the immunogenicity of SARS-CoV-2 RBD and confirms safety in animal models.
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Choque-Guevara R, Poma-Acevedo A, Montesinos-Millán R, Rios-Matos D, Gutiérrez-Manchay K, Montalvan-Avalos A, Quiñones-Garcia S, Cauti-Mendoza MG, Agurto-Arteaga A, Ramirez-Ortiz I, Criollo-Orozco M, Huaccachi-Gonzales E, Romero YK, Perez-Martinez N, Isasi-Rivas G, Sernaque-Aguilar Y, Villanueva-Pérez D, Ygnacio F, Vallejos-Sánchez K, Fernández-Sánchez M, Guevara-Sarmiento LA, Fernández-Díaz M, and Zimic M
- Subjects
- Adjuvants, Immunologic, Animals, Antibodies, Neutralizing, Antibodies, Viral, Cricetinae, Emulsions, Humans, Immunogenicity, Vaccine, Mice, Mice, Inbred BALB C, Models, Animal, Pandemics prevention & control, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Squalene, Water, COVID-19 prevention & control, Viral Vaccines
- Abstract
COVID-19 pandemic has accelerated the development of vaccines against its etiologic agent, SARS-CoV-2. However, the emergence of new variants of the virus lead to the generation of new alternatives to improve the current sub-unit vaccines in development. In the present report, the immunogenicity of the Spike RBD of SARS-CoV-2 formulated with an oil-in-water emulsion and a water-in-oil emulsion with squalene was evaluated in mice and hamsters. The RBD protein was expressed in insect cells and purified by chromatography until >95% purity. The protein was shown to have the appropriate folding as determined by ELISA and flow cytometry binding assays to its receptor, as well as by its detection by hamster immune anti-S1 sera under non-reducing conditions. In immunization assays, although the cellular immune response elicited by both adjuvants were similar, the formulation based in water-in-oil emulsion and squalene generated an earlier humoral response as determined by ELISA. Similarly, this formulation was able to stimulate neutralizing antibodies in hamsters. The vaccine candidate was shown to be safe, as demonstrated by the histopathological analysis in lungs, liver and kidney. These results have shown the potential of this formulation vaccine to be evaluated in a challenge against SARS-CoV-2 and determine its ability to confer protection., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
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585. From the gas phase to the solid state: The chemical bonding in the superheavy element flerovium.
- Author
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Florez E, Smits OR, Mewes JM, Jerabek P, and Schwerdtfeger P
- Abstract
As early as 1975, Pitzer suggested that copernicium, flerovium, and oganesson are volatile substances behaving like noble gas because of their closed-shell configurations and accompanying relativistic effects. It is, however, precarious to predict the chemical bonding and physical behavior of a solid by knowledge of its atomic or molecular properties only. Copernicium and oganesson have been analyzed very recently by our group. Both are predicted to be semiconductors and volatile substances with rather low melting and boiling points, which may justify a comparison with the noble gas elements. Here, we study closed-shell flerovium in detail to predict its solid-state properties, including the melting point, by decomposing the total energy into many-body forces derived from relativistic coupled-cluster theory and from density functional theory. The convergence of such a decomposition for flerovium is critically analyzed, and the problem of using density functional theory is highlighted. We predict that flerovium in many ways does not behave like a typical noble gas element despite its closed-shell 7p
1/2 2 configuration and resulting weak interactions. Unlike the case of noble gases, the many-body expansion in terms of the interaction energy does not converge smoothly. This makes the accurate prediction of phase transitions very difficult. Nevertheless, a first prediction by Monte Carlo simulation estimates the melting point at 284 ± 50 K. Furthermore, calculations for the electronic bandgap suggests that flerovium is a semiconductor similar to copernicium.- Published
- 2022
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586. Correction to "Radially Oriented [ n ]Cyclo- meta -phenylenes".
- Author
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Castro E, Mirzaei S, and Hernández Sánchez R
- Published
- 2022
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587. Medical Residents, the Group and the Formation of Professional Identity During the COVID-19 Pandemic.
- Author
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Oliveira FA, Corleta HVE, and Capp E
- Subjects
- Female, Humans, Pandemics, Pregnancy, COVID-19, Gynecology education, Internship and Residency, Obstetrics education
- Abstract
Residency is still considered the gold standard for quality medical training, and acquiring a professional identity as a specialist is one of its central elements. Residents obtain this identity through both the educational environment and direct interaction with peers and supervisors. However, modifications in health care and educational routines during the recent coronavirus disease 2019 (COVID-19) pandemic have significantly impaired these channels. This study is part of a qualitative research project to analyze professional identity formation in a medical residency program in obstetrics and gynecology at a public hospital in southern Brazil. The authors conducted 28 semi-structured interviews with medical residents and preceptors, as well as a focus group with the residents, which was recorded, transcribed, and analyzed in an effort to construct major analytical categories. Restricted movement and physical contact have forced the use of alternative means of interpersonal interaction, such as communication through social media or instant messaging applications. This has also affected educational activities, such as morning rounds, lectures, and seminars. These changes represent a significant impact, especially in Brazil, where physical proximity is an important cultural feature, even in the work and school environments. We speculate that this new type of virtual interaction will also affect the formation of professional identity among obstetrician-gynecologists. These findings suggest that medical residency programs should be attentive to changes in resident training to ensure that the specialist profile and the expected skills, which are consolidated over many years, are not lost., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)
- Published
- 2022
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588. Lithium increases cortical and subcortical volumes in subjects with bipolar disorder.
- Author
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Jones G, Suchting R, Zanetti MV, Leung E, da Costa SC, Sousa RT, Busatto G, Soares J, Otaduy MC, Gattaz WF, and Machado-Vieira R
- Subjects
- Humans, Lithium therapeutic use, Lithium Compounds pharmacology, Lithium Compounds therapeutic use, Magnetic Resonance Imaging methods, Middle Aged, Quality of Life, Young Adult, Bipolar Disorder diagnostic imaging, Bipolar Disorder drug therapy
- Abstract
Bipolar disorder (BD) is a highly variable and burdensome disease for patients and caregivers. A BD diagnosis almost triples the likelihood of developing dementia as the disease progresses. Neurocognitive reserve appears to be one of the most important influences on lifelong functional outcomes and quality of life in BD. Though several prior studies have assessed the effects of lithium on regional gray and white matter volumes in this population, representative cohorts are typically middle-aged, have a more severe pathology, and are not as commonly assessed in the depressive phase (which represents the majority of most patients' lifespans outside of remission). Here we have shown that positive adaptations with lithium can be observed throughout the brain after only six weeks of monotherapy at low-therapeutic serum levels. Importantly, these results remove some confounders seen in prior studies (patients were treatment free at time of enrollment and mostly treatment naïve). This cohort also includes underrepresented demographics in the literature (young adult patients, mostly bipolar II, and exclusively in the depressed phase). These findings bolster the extensive body of evidence in support of long-term lithium therapy in BD, furthering the possibility of its expanded use to wider demographics., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2022
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- View/download PDF
589. Extracellular vesicles through the blood-brain barrier: a review.
- Author
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Ramos-Zaldívar HM, Polakovicova I, Salas-Huenuleo E, Corvalán AH, Kogan MJ, Yefi CP, and Andia ME
- Subjects
- Animals, Biological Transport, Mammals, Transcytosis, Zebrafish, Blood-Brain Barrier, Extracellular Vesicles metabolism
- Abstract
Extracellular vesicles (EVs) are particles naturally released from cells that are delimited by a lipid bilayer and are unable to replicate. How the EVs cross the Blood-Brain barrier (BBB) in a bidirectional manner between the bloodstream and brain parenchyma remains poorly understood. Most in vitro models that have evaluated this event have relied on monolayer transwell or microfluidic organ-on-a-chip techniques that do not account for the combined effect of all cellular layers that constitute the BBB at different sites of the Central Nervous System. There has not been direct transcytosis visualization through the BBB in mammals in vivo, and evidence comes from in vivo experiments in zebrafish. Literature is scarce on this topic, and techniques describing the mechanisms of EVs motion through the BBB are inconsistent. This review will focus on in vitro and in vivo methodologies used to evaluate EVs transcytosis, how EVs overcome this fundamental structure, and discuss potential methodological approaches for future analyses to clarify these issues. Understanding how EVs cross the BBB will be essential for their future use as vehicles in pharmacology and therapeutics., (© 2022. The Author(s).)
- Published
- 2022
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590. COVID-19 vaccine design using reverse and structural vaccinology, ontology-based literature mining and machine learning.
- Author
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Huffman A, Ong E, Hur J, D'Mello A, Tettelin H, and He Y
- Subjects
- COVID-19 Vaccines, Data Mining, Humans, Machine Learning, Vaccinology methods, COVID-19 prevention & control, Vaccines chemistry, Vaccines genetics
- Abstract
Rational vaccine design, especially vaccine antigen identification and optimization, is critical to successful and efficient vaccine development against various infectious diseases including coronavirus disease 2019 (COVID-19). In general, computational vaccine design includes three major stages: (i) identification and annotation of experimentally verified gold standard protective antigens through literature mining, (ii) rational vaccine design using reverse vaccinology (RV) and structural vaccinology (SV) and (iii) post-licensure vaccine success and adverse event surveillance and its usage for vaccine design. Protegen is a database of experimentally verified protective antigens, which can be used as gold standard data for rational vaccine design. RV predicts protective antigen targets primarily from genome sequence analysis. SV refines antigens through structural engineering. Recently, RV and SV approaches, with the support of various machine learning methods, have been applied to COVID-19 vaccine design. The analysis of post-licensure vaccine adverse event report data also provides valuable results in terms of vaccine safety and how vaccines should be used or paused. Ontology standardizes and incorporates heterogeneous data and knowledge in a human- and computer-interpretable manner, further supporting machine learning and vaccine design. Future directions on rational vaccine design are discussed., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2022
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591. Autotaxin Has a Negative Role in Systemic Inflammation.
- Author
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Nikitopoulou I, Katsifa A, Kanellopoulou P, Jahaj E, Vassiliou AG, Mastora Z, Dimopoulou I, Orfanos SE, Aidinis V, and Kotanidou A
- Subjects
- Animals, Disease Models, Animal, Inflammation, Lipopolysaccharides toxicity, Lysophospholipids metabolism, Mice, Phosphoric Diester Hydrolases metabolism, Endotoxemia, Receptors, Lysophosphatidic Acid metabolism
- Abstract
The pathogenesis of sepsis involves complex interactions and a systemic inflammatory response leading eventually to multiorgan failure. Autotaxin (ATX, ENPP2) is a secreted glycoprotein largely responsible for the extracellular production of lysophosphatidic acid (LPA), which exerts multiple effects in almost all cell types through its at least six G-protein-coupled LPA receptors (LPARs). Here, we investigated a possible role of the ATX/LPA axis in sepsis in an animal model of endotoxemia as well as in septic patients. Mice with 50% reduced serum ATX levels showed improved survival upon lipopolysaccharide (LPS) stimulation compared to their littermate controls. Similarly, mice bearing the inducible inactivation of ATX and presenting with >70% decreased ATX levels were even more protected against LPS-induced endotoxemia; however, no significant effects were observed upon the chronic and systemic transgenic overexpression of ATX. Moreover, the genetic deletion of LPA receptors 1 and 2 did not significantly affect the severity of the modelled disease, suggesting that alternative receptors may mediate LPA effects upon sepsis. In translation, ATX levels were found to be elevated in the sera of critically ill patients with sepsis in comparison with their baseline levels upon ICU admission. Therefore, the results indicate a role for ATX in LPS-induced sepsis and suggest possible therapeutic benefits of pharmacologically targeting ATX in severe, systemic inflammatory disorders.
- Published
- 2022
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592. Microbiological quality of the water in collection areas and the tissue of Mytella falcata-Cananéia (SP, Brazil).
- Author
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Rezende KFO, Garcia AV, Campos FADB, and Barbieri E
- Subjects
- Animals, Brazil, Water Microbiology, Water Pollution analysis, Mytilidae, Water
- Abstract
Changes in fauna and abiotic factors in estuaries are a consequence of their exploitation; thus, bivalve mollusks, as they filter, are widely used as environmental bioindicators. The aim of this study was to analyze the existence of seasonal variation in the concentration of total coliforms (TC) and thermotolerant coliforms (Ct), in addition to correlating the data obtained with the salinity and temperature in collection areas of Mytella falcata and the soft tissue cultivated in the Estuarine Complex of Cananéia. Two biweekly samples of water and tissue were taken, for 12 consecutive months, in nine cultivation areas of M. falcata. The analysis of the water samples showed that the Fisheries Institute, Mosquiteiro, and Itapitangui have high TC densities, with respective annual averages of 772.22, 592.67, and 563.75 most probable number (MPN).100 ml
-1 . The highest concentrations of TC and Ct occurred in the summer, in most areas. There was a decrease in both TC and Ct with increasing salinity. However, there was an increase in Ct with increasing temperature. The soft tissue showed TC densities from 9 to 26 MPN.100 ml-1 and Ct densities from 6 to 14 MPN.100 ml-1 , displaying the highest counts in the summer. Places where coliforms were found in high concentrations could indicate contamination, because Ct do not support higher salinities for a long time. PRACTITIONER POINTS: The general mean was 77.64 (total coliforms) and 39.35 (thermotolerant) MPN.100 ml-1 . Annual average (thermotolerant) exceeded the permitted Brazilian limit in five points. Higher concentrations of total and thermotolerant coliforms occurred in the summer. In mollusk's tissue, concentrations of thermotolerant were 6.30 to 26.16 MPN.100 g-1 . Coliforms' MPN varied with increasing salinity and temperature., (© 2022 Water Environment Federation.)- Published
- 2022
- Full Text
- View/download PDF
593. The role of lithium treatment on comorbid anxiety symptoms in patients with bipolar depression.
- Author
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Jones G, Rong C, Vecera CM, Gurguis CI, Chudal R, Khairova R, Leung E, Ruiz AC, Shahani L, Zanetti MV, de Sousa RT, Busatto G, Soares J, Gattaz WF, and Machado-Vieira R
- Subjects
- Anxiety complications, Anxiety drug therapy, Anxiety epidemiology, Diagnostic and Statistical Manual of Mental Disorders, Double-Blind Method, Humans, Lithium therapeutic use, Lithium Compounds therapeutic use, Treatment Outcome, Bipolar Disorder complications, Bipolar Disorder drug therapy, Bipolar Disorder epidemiology
- Abstract
Background: Comorbid anxiety is pervasive and carries an immense psychosocial burden for patients with bipolar disorder. Despite this, trials reporting anxiety-related outcomes in this population are uncommon, particularly with regards to monotherapies., Methods: Patients (n = 31) with both bipolar I or II disorder in current depressive episodes were enrolled in a six-week, open-label, single-center trial assessing the efficacy of lithium monotherapy in treating symptoms depression and comorbid anxiety. Patients were mostly medication-free and lithium-naïve at baseline., Results: Significant improvements in depression (HAMD) and anxiety (HAM-A) were observed at the six-week endpoint, with remission and response rates greater than 50%. There was a positive correlation between endpoint HAM-A scores and HAM-D scores, r = 0.80, (p < 0.01). Improvements were realized at low serum lithium concentrations (0.49 ± 0.20 mEq/L)., Limitations: Lack of placebo control and small sample size warrants validation in larger randomized studies., Conclusions: Taken in the context of prior evidence, lithium may have an important role in treating comorbid anxiety in bipolar disorder, both as adjunct and monotherapy. Lower doses of lithium may provide equivalent efficacy and enhance tolerability and compliance., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
594. A Retrospective Study of the Adjunctive Use of Gabapentin With Benzodiazepines for the Treatment of Benzodiazepine Withdrawal.
- Author
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Leung E, Ngo DH, Espinoza JA Jr, Beal LL, Chang C, Baris DA, Lackey BN, Lane SD, and Wu HE
- Subjects
- Benzodiazepines adverse effects, Gabapentin therapeutic use, Humans, Retrospective Studies, Alcoholism, Substance Withdrawal Syndrome drug therapy
- Abstract
Benzodiazepine withdrawal is a widespread problem with potentially severe and deadly consequences. Currently, the only medications available for treating benzodiazepine withdrawal are short-acting and long-acting benzodiazepines. Identifying other drugs to help in treating benzodiazepine withdrawal is necessary. Gabapentin, an anxiolytic drug that is also used off-label to treat alcohol withdrawal, is a potential candidate for modulating benzodiazepine withdrawal. Using electronic records from a large inpatient psychiatric facility, a retrospective study of 172 patients presenting with benzodiazepine withdrawal was conducted to determine if the coincidental use of gabapentin for other medical conditions was associated with better outcomes of benzodiazepine withdrawal (N=57 gabapentin, N=115 no gabapentin). The primary outcomes were hospital length of stay and total amount of benzodiazepines given (lorazepam milligram equivalent). In this retrospective analysis of electronic medical record data, the patients experiencing benzodiazepine withdrawal who received gabapentin as an adjunct to the use of benzodiazepines were administered a smaller amount of benzodiazepines and had a shorter length of hospital stay relative to the comparison group who did not receive adjunctive gabapentin. These results suggest the potential use of gabapentin as an adjunct to the use of benzodiazepines for treating benzodiazepine withdrawal. The limitations of this study included a small sample size and variability in medication management strategies across the sample., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
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595. Copper II oxide nanoparticles (CuONPs) alter metabolic markers and swimming activity in zebra-fish (Danio rerio).
- Author
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de Oliveira Eiras MI, Costa LSD, and Barbieri E
- Subjects
- Ammonia toxicity, Animals, Copper toxicity, Equidae, Oxides, Swimming, Nanoparticles toxicity, Zebrafish physiology
- Abstract
The present study aimed to compare the metabolic effects caused by using copper oxide nanoparticles with two distinct morphologies nanorods and nanosphere. The CuONPs in the form of nanorods were characterized in the order of 500 nm, on a scale of 20, 100, and 500 nm. Meanwhile, the nanosphere CuONPs were characterized in the order of 5 nm, on a 30 nm scale. The analysis of metabolic rate was performed using the closed respirometry technique, specific ammonia excretion, and swimming ability as biomarkers, the physiological effects on Danio rerio were investigated. For the experiments, 88 fish were used, exposed for 24 h at concentrations of 0, 50, 100, and 200 μg/L of copper oxide nanoparticles in the form of nanospheres and nanorods, respectively. The tests carried out with the nanorods demonstrated metabolic alterations in fish, with an increase of 294% and 321% in the metabolic rate at concentrations of 100 μg/L and 200 μg/L, respectively. Furthermore, there was a decrease in specific ammonia excretion by 34% and 83% and in swimming capacity by 34% and 55% at concentrations of 100 and 200 μg/L, respectively, when compared to the control. The tests performed with nanospheres did not show significant changes compared to the control. These experiments showed that different morphological structures of the same copper oxide nanoparticle caused different effects on fish metabolism. It is concluded that the characterization of nanoparticles is essential to understand their effects on fish, since their structural forms can cause different toxic effects on D. rerio., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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- View/download PDF
596. Male genitalia morphology and dichotomous key of the Neotropical genera of Abracrini (Orthoptera: Acrididae: Ommatolampidinae) grasshoppers.
- Author
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DA Costa MKM, Carvalho GS, and Zefa E
- Subjects
- Animal Distribution, Animals, Genitalia, Male, Male, Grasshoppers
- Abstract
The comparative analysis of the internal and external male genitalia of the Abracrini grasshoppers was conducted, including representatives of the type species of the genera, specimens compared with the same or more representative specimens of the genus, and bibliography data. We include schematic illustrations that point to the morphological differences between the genitalia, based on subgenital plate, furculae, epiproct, cerci, ectophallic sheath, aedeagal valves, expansion of gonopore and epiphallus. A dichotomous key to the 21 Abracrini genera was presented.
- Published
- 2022
- Full Text
- View/download PDF
597. Biomodifying the 'natural': from Adaptive Regulation to Adaptive Societal Governance.
- Author
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Mourby M, Bell J, Morrison M, Faulkner A, Li P, Bicudo E, Webster A, and Kaye J
- Abstract
Biomodifying technologies-such as gene editing, induced pluripotent stem cells, and bioprinting-are being developed for a wide range of applications, from pest control to lab-grown meat. In medicine, regulators have responded to the challenge of evaluating modified 'natural' material as a therapeutic 'product' by introducing more flexible assessment schemes. Attempts have also been made to engage stakeholders across the globe on the acceptable parameters for these technologies, particularly in the case of gene editing. Regulatory flexibility and stakeholder engagement are important, but a broader perspective is also needed to respond to the potential disruption of biomodification. Our case-study technologies problematize basic ideas-such as 'nature', 'product', and 'donation'-that underpin the legal categories used to regulate biotechnology. Where such foundational concepts are rendered uncertain, a socially responsive and sustainable solution would involve exploring evolutions in these concepts across different societies. We suggest that the global observatory model is a good starting point for this 'Adaptive Societal Governance' approach, in which a self-organizing network of scholars and interested parties could carry out the multi-modal (meta)analyses needed to understand societal constructions of ideas inherent to our understanding of 'life'., (© The Author(s) 2022. Published by Oxford University Press on behalf of Duke University School of Law, Harvard Law School, Oxford University Press, and Stanford Law School.)
- Published
- 2022
- Full Text
- View/download PDF
598. Increase of HO-1 Expression in Critically Ill COVID-19 Patients Is Associated with Poor Prognosis and Outcome.
- Author
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Detsika MG, Nikitopoulou I, Veroutis D, Vassiliou AG, Jahaj E, Tsipilis S, Athanassiou N, Gakiopoulou H, Gorgoulis VG, Dimopoulou I, Orfanos SE, and Kotanidou A
- Abstract
Heme-oxygenase (HO)-1 is a cytoprotective enzyme with strong antioxidant and anti-apoptotic properties and previous reports have also emphasized the antiviral properties of HO-1, either directly or via induction of interferons. To investigate the potential role of HO-1 in patients with coronavirus disease 2019 (COVID-19), the present study assessed changes in HO-1 expression in whole blood and tissue samples. Upregulation of HO-1 protein was observed in lung, liver, and skin tissue independently of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence. A significant increase of blood HO-1 mRNA levels was observed in critically ill COVID-19 patients compared to those in severe COVID-19 patients and healthy controls. This increase was accompanied by significantly elevated levels of serum ferritin and bilirubin in critically ill compared to patients with severe disease. Further grouping of patients in survivors and non-survivors revealed a significant increase of blood HO-1 mRNA levels in the later. Receiver operating characteristic (ROC) analysis for prediction of ICU admission and mortality yielded an AUC of 0.705 ( p = 0.016) and 0.789 ( p = 0.007) respectively indicating that HO-1 increase is associated with poor COVID-19 progression and outcome. The increase in HO-1 expression observed in critically ill COVID-19 patients could serve as a mechanism to counteract increased heme levels driving coagulation and thrombosis or as an induced protective mechanism.
- Published
- 2022
- Full Text
- View/download PDF
599. Intelligent Pervasive Monitoring Solution of COVID-19 Patients.
- Author
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Panagopoulos C, Menychtas A, Jahaj E, Vassiliou AG, Gallos P, Dimopoulou I, Kotanidou A, and Maglogiannis I
- Subjects
- Delivery of Health Care, Humans, Pandemics prevention & control, SARS-CoV-2, COVID-19, Telemedicine
- Abstract
The COVID-19 pandemic transforms the healthcare delivery models and accelerates the implementation and the adoption of telemedicine solutions at all levels of the healthcare system. Telehealth services ensure the continuity of care and treatment of both inpatients and outpatients during this pandemic, while reducing the spread of the virus through hospitals. The aim of this paper is to present an intelligent remote monitoring system with innovative data analytics features for COVID-19 patients. The i-COVID platform provides remote COVID-19 patients monitoring. The presented solution is addressed to patients with mild COVID-19 symptoms, as well as it can be used for post intensive-care monitoring. The platform offers advanced analytic capabilities using Proactive AI, to detect health condition deterioration, and automatically trigger personalized support workflows. Remote monitoring of COVID-19 patients using bio-sensors, seems to be an effective tool against the COVID-19 pandemic, as reduces the number of visits to patient screening centres and hospital admissions.
- Published
- 2022
- Full Text
- View/download PDF
600. New species of tree cricket Oecanthus Serville, 1831 (Orthoptera: Grylloidea) from Southern Brazilian Atlantic Forest, with bioacoustics.
- Author
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Zefa E, Acosta RC, Timm VF, and Costa MKMD
- Subjects
- Animals, Brazil, Courtship, Forests, Gryllidae
- Abstract
Tree Crickets, Oecanthus Serville, 1831 have a worldwide distribution, and are known as Tree Crickets because they are common in the treetops, even though many species occur in different strata of forest, and also in open fields. In this work we describe a new species of Oecanthus from Southern Brazil, based on the most significant diagnostic structures in the ocanthine taxonomy, such as the phallic sclerites and metanotal gland morphology, as well as calling song. The new species herein described has a distinct faint red spot between the eyes, a metanotal gland with a triangular posterior median lobe with the apex curved up and forward, the median lophi of pseudepiphallus slightly elongate with an U-shaped invagination, and the ectophallic distal arc prolongation with the posterior apex U-bifurcated. The calling song stands out among the local stridulating crickets for alternate a regular and an irregular train of chirps. Illustrations of the external morphology, information about type specimens, material examined, measurements, and spectrogram of the calling and courtship songs is provided.
- Published
- 2022
- Full Text
- View/download PDF
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