147 results on '"Shirley MA"'
Search Results
2. Encapsulation of factor IX–engineered mesenchymal stem cells in fibrinogen–alginate microcapsules enhances their viability and transgene secretion
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Bahareh Sayyar, Megan Dodd, Jianping Wen, Shirley Ma, Leah Marquez-Curtis, Anna Janowska-Wieczorek, and Gonzalo Hortelano
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Biochemistry ,QD415-436 - Abstract
Cell microencapsulation holds significant promise as a strategy for cellular therapies; however, inadequate survival and functionality of the enclosed cells limit its application in hemophilia treatment. Here, we evaluated the use of alginate-based microcapsules to enhance the viability and transgene secretion of human cord blood–derived mesenchymal stem cells in three-dimensional cultures. Given the positive effects of extracellular matrix molecules on mesenchymal stem cell growth, we tested whether fibrinogen-supplemented alginate microcapsules can improve the efficiency of encapsulated factor IX–engineered mesenchymal stem cells as a treatment of hemophilia B. We found that fibrinogen-supplemented alginate microcapsules (a) significantly enhanced the viability and proliferation of factor IX–engineered mesenchymal stem cells and (b) increased factor IX secretion by mesenchymal stem cells compared to mesenchymal stem cells in nonsupplemented microcapsules. Moreover, we observed the osteogenic, but not chondrogenic or adipogenic, differentiation capability of factor IX–engineered cord blood mesenchymal stem cells and their efficient factor IX secretion while encapsulated in fibrinogen-supplemented alginate microcapsules. Thus, the use of engineered mesenchymal stem cells encapsulated in fibrinogen-modified microcapsules may have potential application in the treatment of hemophilia or other protein deficiency diseases.
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- 2012
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3. Legends for Figures S1-S7 from Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates β-Catenin Signaling and Tumorigenesis in Multiple Cancer Types
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Austin Gurney, Timothy Hoey, John Lewicki, Ann M. Kapoun, Min Wang, Gilbert O'Young, Belinda Cancilla, Pete Yeung, Wan-Ching Yen, Michelle Stroud, Andrew Lam, May Ji, Jie Wei, Jalpa Shah, Marcus M. Fischer, Shirley Ma, Cristina Dee-Hoskins, Jennifer Cain, Chris Bond, Fumiko Axelrod, Janak Raval, and Cecile Chartier
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Supplemental figure legends also include brief methods where appropriate.
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- 2023
4. Data from Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates β-Catenin Signaling and Tumorigenesis in Multiple Cancer Types
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Austin Gurney, Timothy Hoey, John Lewicki, Ann M. Kapoun, Min Wang, Gilbert O'Young, Belinda Cancilla, Pete Yeung, Wan-Ching Yen, Michelle Stroud, Andrew Lam, May Ji, Jie Wei, Jalpa Shah, Marcus M. Fischer, Shirley Ma, Cristina Dee-Hoskins, Jennifer Cain, Chris Bond, Fumiko Axelrod, Janak Raval, and Cecile Chartier
- Abstract
Deregulation of the β-catenin signaling has long been associated with cancer. Intracellular components of this pathway, including axin, APC, and β-catenin, are frequently mutated in a range of human tumors, but the contribution of specific extracellular ligands that promote cancer development through this signaling axis remains unclear. We conducted a reporter-based screen in a panel of human tumors to identify secreted factors that stimulate β-catenin signaling. Through this screen and further molecular characterization, we found that R-spondin (RSPO) proteins collaborate with Wnt proteins to activate β-catenin. RSPO family members were expressed in several human tumors representing multiple malignancies, including ovarian, pancreatic, colon, breast, and lung cancer. We generated specific monoclonal antibody antagonists of RSPO family members and found that anti-RSPO treatment markedly inhibited tumor growth in human patient-derived tumor xenograft models, either as single agents or in combination with chemotherapy. Furthermore, blocking RSPO signaling reduced the tumorigenicity of cancer cells based on serial transplantation studies. Moreover, gene-expression analyses revealed that anti-RSPO treatment in responsive tumors strongly inhibited β-catenin target genes known to be associated with cancer and normal stem cells. Collectively, our results suggest that the RSPO family is an important stimulator of β-catenin activity in many human tumors and highlight a new effective approach for therapeutically modulating this fundamental signaling axis. Cancer Res; 76(3); 713–23. ©2015 AACR.
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- 2023
5. Tables S1-S3 from Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates β-Catenin Signaling and Tumorigenesis in Multiple Cancer Types
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Austin Gurney, Timothy Hoey, John Lewicki, Ann M. Kapoun, Min Wang, Gilbert O'Young, Belinda Cancilla, Pete Yeung, Wan-Ching Yen, Michelle Stroud, Andrew Lam, May Ji, Jie Wei, Jalpa Shah, Marcus M. Fischer, Shirley Ma, Cristina Dee-Hoskins, Jennifer Cain, Chris Bond, Fumiko Axelrod, Janak Raval, and Cecile Chartier
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Supplemental Tables include a list and brief description of xenograft models used in the study, the RSPO1-4 gene expression profile and beta-catenin activation status of all xenograft models, and the microarray analysis for 4 CRC xenograft models after treatment with anti-RSPO3 antibody.
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- 2023
6. Figures S1-S7 from Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates β-Catenin Signaling and Tumorigenesis in Multiple Cancer Types
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Austin Gurney, Timothy Hoey, John Lewicki, Ann M. Kapoun, Min Wang, Gilbert O'Young, Belinda Cancilla, Pete Yeung, Wan-Ching Yen, Michelle Stroud, Andrew Lam, May Ji, Jie Wei, Jalpa Shah, Marcus M. Fischer, Shirley Ma, Cristina Dee-Hoskins, Jennifer Cain, Chris Bond, Fumiko Axelrod, Janak Raval, and Cecile Chartier
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Supplemental figures include the RSPO gene expression analysis for CRC models, the in vitro testing of anti-RSPO antibodies on RSPO-negative tumors, the IHC analysis of anti-RSPO3+chemo-treated ovarian tumors, the LGR, ZNRF3, and RNF43 gene expression profile in therapy responsive and non-responsive PDXs, the in vivo resistance of RSPO-negative tumors to RSPO blockade, the analysis of CSC frequency in anti-RSPO3-treated NSCL and pancreatic PDXs, and the IHC detection of CD44 in anti-RSPO3-treated CRC tumors.
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- 2023
7. Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity
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Kalyan Pande, Scott A. Hollingsworth, Miranda Sam, Qinshan Gao, Sujata Singh, Anasuya Saha, Karin Vroom, Xiaohong Shirley Ma, Tres Brazell, Dan Gorman, Shi-Juan Chen, Fahimeh Raoufi, Marc Bailly, David Grandy, Karthik Sathiyamoorthy, Lan Zhang, Rob Thompson, Alan C. Cheng, Laurence Fayadat-Dilman, Bernhard H. Geierstanger, and Laura J. Kingsley
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SARS-CoV-2 ,Immunoglobulin G ,Immunology ,COVID-19 ,Humans ,Immunology and Allergy ,Immunologic Tests ,Pandemics - Abstract
The SARS-CoV-2 pandemic and particularly the emerging variants have deepened the need for widely available therapeutic options. We have demonstrated that hexamer-enhancing mutations in the Fc region of anti-SARS-CoV IgG antibodies lead to a noticeable improvement in IC50 in both pseudo and live virus neutralization assay compared to parental molecules. We also show that hexamer-enhancing mutants improve C1q binding to target surface. To our knowledge, this is the first time this format has been explored for application in viral neutralization and the studies provide proof-of-concept for the use of hexamer-enhanced IgG1 molecules as potential anti-viral therapeutics.
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- 2022
8. Floral Morphoanatomy and Pollen Viability in Miconia polystachya (naudin) r. Goldenb., (Miconieae, Melastomataceae)
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Guilherme de Almeida Caputti Araujo and Shirley Martins Silva
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apomixis ,agamospermy ,highland rocky fields ,parthenogenesis ,reproduction ,Biotechnology ,TP248.13-248.65 - Abstract
Abstract Many Melastomataceae are distributed in highland rocky fields (Campos rupestres) landscapes with their intrinsic environmental factors. These factors influence the expression of morphoanatomical characteristics and determine which adaptations are necessary for survival, including reproductive processes. The genus Miconia belongs to the Neotropical tribe Miconieae, the largest in Melastomataceae. Species of Miconieae are known to engage in apomixis, which results in much of the tribe possibly carrying out autonomous or pseudogamous reproduction. Thus, this study seeks to describe the morphoanatomy of the flowers of Miconia polystachya (Naudin) R. Goldenb. and contribute to the understanding of their reproduction. For this, flowers were collected at different stages of development in different seasons (autumn and spring) for morphoanatomical study. The flowers were fixed and cross and longitudinal sections were carried out with a rotating microtome. Pollen viability tests were also performed. The individuals of Miconia polystachya studied in highland rocky fields of the state of Paraná have a high percentage of unviable pollen, verified by the structure of pollen grains showing different degrees of degeneration. However, individuals with mature fruits were observed, corroborating the association between reproduction of this species with apomixis. The described morphological characteristics are similar to those found in previous studies for the family and genus. However, our study provides novel ecological information about the flowering and floral anatomy of M. polystachya, emphasizing the anatomy of hypanthium, fertile verticils and embryonic development of the species.
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- 2024
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9. The water extract and the lectin WSMoL from the seeds of Moringa oleifera prevent the hypertension onset by decreasing renal oxidative stress
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JEOADÃ KAROLLYNE SILVA, ALANA CAROLINA C. VERAS, SHIRLEY MARIA SOUSA, JESSICA S.S. ALBUQUERQUE, FERNANDA PRISCILA B. RIBEIRO, NATALIA KRYZIA S. LIMA, LARYSSA BEATRIZ S. NASCIMENTO, ROBSON R.V. ALVES, REGINA S. AIRES, LUANA CASSANDRA B.B. COELHO, THIAGO HENRIQUE NAPOLEÃO, PATRÍCIA MARIA G. PAIVA, ANA D. PAIXÃO, and LEUCIO D. VIEIRA
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Hypertension ,lectin ,Moringa oleifera ,reactive oxygen species ,Science - Abstract
Abstract Maternal endotoxemia disturbs the intrauterine environment, impairs nephrogenesis, and increases the risk of hypertension and kidney disease in adulthood. Here, it was investigated whether maternal treatment with the water extract of Moringa oleifera seeds (WEMoS) or the water-soluble M. oleifera seed lectin (WSMoL) prevents the oxidative stress induced by lipopolysaccharide (LPS) in pregnant rats, and the renal injury and hypertension in the adult offspring. The administration of WEMoS or WSMoL prevented the stimulatory effects of LPS on lipid peroxidation in the maternal-placenta-fetuses environment. The impact of WEMoS was linked to decreased superoxide anions production in the placenta. The effects of WSMoL were parallel to the inhibition of superoxide anion production and NADPH oxidase activity. The WSMoL also prevented increased NADPH oxidase activity in the fetal kidney. The LPS offspring presented higher systolic blood pressure (SBP) and increased lipid peroxidation, reactive oxygen species (ROS), NADPH oxidase activity, and nitrate/nitrite in the kidney; the maternal treatment with WEMoS and WSMoL prevented these changes. In conclusion, the present study demonstrates that WEMoS and WSMoL have protective effects on maternal endotoxemia, which involve antioxidant and anti-inflammatory actions that prevent the programming of hypertension.
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- 2024
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10. Orchidaceae in Iguaçu National Park, Paraná, Brazil
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Hauanna Zubek, Lizandra Boff Curtivo, Edlley Max Pessoa, Marcelo Galeazzi Caxambu, Greta Aline Dettke, Lívia Godinho Temponi, and Shirley Martins Silva
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Atlantic forest ,mixed ombrophilous forest ,orchids ,semideciduous seasonal forest. ,Biology (General) ,QH301-705.5 ,Botany ,QK1-989 - Abstract
Abstract This study presents a synopsis of the Orchidaceae species in Iguaçu National Park (ParNa Iguaçu), one of the largest Atlantic Forest remnants in the state of Paraná. Orchidaceae is represented in the area by 65 species, distributed in 41 genera, the most representative being Gomesa (7 spp.) and Acianthera (6 spp.). Representatives of three subfamilies are present: Vanilloideae (2 spp.), Orchidoideae (12 spp.) and Epidendroideae (51 spp.) which, as expected, presents the greatest richness (78% of the total). Among the species found, five are considered endemic to Brazil, 23 are endemic to the Atlantic Forest (36%) and one is endemic to Paraná. Thirty-one new records were found for the area. The areas of Mixed Ombrophilous Forest (MOF) had 29 exclusive species, the Semideciduous Seasonal Forest (SSF) had 20, while 16 species occur in both phytophysiognomies. A new occurrence was recorded for MOF. Regarding habit, exclusively epiphytic was the most representative (39 spp.), followed by exclusively terricolous (15 spp.), two vines and one mycoheterotrophic species. Among the families already inventoried in ParNa Iguaçu, Orchidaceae is among the richest and the findings of the present study reinforce the importance of floristic studies for cataloging the local flora.
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- 2024
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11. Crimean-Congo Hemorrhagic Fever Virus in Ticks Collected from Cattle, Corsica, France, 2023
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Paloma Kiwan, Shirley Masse, Geraldine Piorkowski, Nazli Ayhan, Morena Gasparine, Laurence Vial, Remi N. Charrel, Xavier de Lamballerie, and Alessandra Falchi
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Crimean-Congo hemorrhagic fever virus ,Crimean-Congo hemorrhagic fever ,viruses ,vector-borne infections ,tickborne infections ,ticks ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We report the detection of Crimean-Congo hemorrhagic fever virus (CCHFV) in Corsica, France. We identified CCHFV African genotype I in ticks collected from cattle at 2 different sites in southeastern and central-western Corsica, indicating an established CCHFV circulation. Healthcare professionals and at-risk groups should be alerted to CCHFV circulation in Corsica.
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- 2024
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12. Children and young people as research collaborators in a large-scale migration research project [version 1; peer review: 2 approved]
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Deirdre Horgan, Shirley Martin, and Reana Maier
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Refugee Children ,Migrant children ,co-creation ,collaborative participatory research ,integration ,child-centered research ,eng ,Science ,Social Sciences - Abstract
In this paper we detail and contextualise the collaborative participatory research process developed throughout the IMMERSE research project which maps the integration of migrant children in education in Europe. We begin with a brief overview of IMMERSE and thereafter discuss the research design with reference to literature on collaborative research approaches and on working with children and young people’s research advisory groups. IMMERSE involved a large-scale data collection with over 24,000 children and young people in six countries and such large-scale data collection presents a challenging context in which to include children as collaborators and influencers in the research process. We demonstrate how, drawing on existing knowledge as well as our own experiences of working with children as research partners, we developed innovative ways of ensuring children’s voices were integral to and embedded in the research at various points of the process. Throughout the duration of the project, we developed several strategies to ensure that children were involved as research partners and influencers. To ensure children and young people’s active involvement and influence on the research, a Children and Young People’s Advisory Group was established at the beginning of IMMERSE which was composed of 18 migrant and refugee children resident in Ireland. This group acted as an expert group, to reflect on the experiences of migrant children and represent their peers in this process. In addition, children across the six IMMERSE countries were involved in the design and validation of the dashboard of socio-educational integration indicators and the ensuing research instruments.
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- 2024
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13. Characterization of landfill leachate molecular composition using ultrahigh resolution mass spectrometry
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Michael Gonsior, Leanne C. Powers, Shirley Ma, Andrew Heyes, Timothy G. Townsend, Philippe Schmitt-Kopplin, Nicole M. Robey, Katherine R. Martin, and William J. Cooper
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Pollution ,chemistry.chemical_classification ,Environmental Engineering ,Chemistry ,media_common.quotation_subject ,0208 environmental biotechnology ,02 engineering and technology ,010501 environmental sciences ,Mass spectrometry ,01 natural sciences ,Fourier transform ion cyclotron resonance ,020801 environmental engineering ,chemistry.chemical_compound ,Wastewater ,Environmental chemistry ,Dissolved organic carbon ,Chlorendic acid ,Organic matter ,Leachate ,0105 earth and related environmental sciences ,Water Science and Technology ,media_common - Abstract
Landfill leachate (LL) is a complex wastewater and an important potential source of environmental contamination. LL can contain high concentrations of ammonia, metals, other inorganic species, and dissolved organic carbon; however, bulk composition of dissolved LL organic matter (LLOM) is poorly understood. A better understanding of LLOM composition will inform treatment development and improve LL pollution tracing. In this study, we addressed this need for compositional and treatment information by characterizing LL from an active bioreactor municipal solid waste (MSW) landfill as well as from a closed MSW landfill. Through non-targeted ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) we were able to assign chemical formulas to thousands of singly charged molecular ions and compare samples to natural dissolved organic matter (DOM). LLOM was differentiated by a higher presence of sulfur-, nitrogen-, and chlorine-, particularly nitrogen–sulfur-, containing formulas. The abundance of chlorine-containing molecular formulas supports the existence of a non-volatile organochlorine component in MSW LL. We performed tandem MS (MS-MS) analyses to tentatively identify the presence of the flame retardant, chlorendic acid, and likely related compounds. Additionally, we measured contaminants of emerging concern (CECs) and other chemical parameters to further characterize LLs and found evidence suggesting a significant percent of Fe may be bound in Fe–organic complexes.
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- 2021
14. Treatment of SHIV-infected, ART-suppressed rhesus macaques with bispecific HIVxCD3 DART® molecules
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Soha Moltagh, Glareh Azadi, Shirley Ma, Julie Strizki, Bonnie J. Howell, Ming-Tain Lai, Don Graham, Jeffery Nordstrom, Daria J. Hazuda, Meiqing Lu, Carolyn McHale, Romina Riener, Daniel M. Gorman, Fernando Ugarte, Yaoli Song, Marc Bailly, Wendy M. Blumenschein, SuChun Hseih, and Yanyan Zheng
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Dart ,Epidemiology ,Chemistry ,Immunology ,Public Health, Environmental and Occupational Health ,Virology ,Microbiology ,QR1-502 ,Infectious Diseases ,Public aspects of medicine ,RA1-1270 ,computer ,computer.programming_language - Published
- 2019
15. Soil acidity levels for blackberry liming recommendation and yield increase
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Enilson de Barros Silva, Ramony Cristina Lima, Jéssica Oliveira Gaurat, Ari Medeiros Braga Neto, Maria do Céu Monteiro da Cruz, Dalila Costa Aparecida Bié, Emerson Dias Gonçalves, Luiz Fernando de Oliveira Silva, Pedro Henrique Abreu Moura, and Shirley Macedo de Souza
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Rubus ,aluminum ,base saturation ,nutritional efficiency ,soil acidity ,soil pH ,Agriculture (General) ,S1-972 - Abstract
Abstract The objective of this work was to determine the acidity levels to obtain adequate soil chemical attributes for the maximum fruit yield of blackberry trees grown in acidic soils subjected to increasing limestone rates. The BRS Tupy, Brazos, Guarani, and BRS Xavante blackberry cultivars were evaluated on the Typic Hapludox (LVdf) and Rhodic Hapludox (LVd) soils, to which four rates of dolomitic limestone were applied (0, 1.5, 3.0, and 6.0 Mg ha-1). The effect of liming on soil chemical attributes, in a 2×4 factorial arrangement (soils and limestone rates), as well as leaf nutrient content and fruit yield, in a 2×4×4 factorial arrangement (soils, limestone rates, and cultivars), were evaluated. The maximum fruit yield was obtained with 3.3 Mg ha-1 dolomitic limestone. The blackberry cultivars showed a high demand for Ca, Mg, and base saturation and a low tolerance to aluminum in the soils. From 3.3 Mg ha-1 dolomitic limestone, the maximum fruit yield of blackberry trees grown in acidic soils is obtained with pH 5.6, maximum tolerated aluminum saturation of 6%, Ca and Mg concentration of 45.3 mmolc kg-1, and base saturation of 48.3%.
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- 2024
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16. Recruiting women with ductal carcinoma in situ to a randomised controlled trial: lessons from the LORIS study
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Sally Wheelwright, Lucy Matthews, Valerie Jenkins, Shirley May, Daniel Rea, Pat Fairbrother, Claire Gaunt, Jennie Young, Sarah Pirrie, Matthew G. Wallis, Lesley Fallowfield, and on behalf of the LORIS Trial Management Group
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DCIS ,LORIS ,Patient preference ,Patient interviews ,Trials ,Randomisation ,Medicine (General) ,R5-920 - Abstract
Abstract Background The LOw RISk DCIS (LORIS) study was set up to compare conventional surgical treatment with active monitoring in women with ductal carcinoma in situ (DCIS). Recruitment to trials with a surveillance arm is known to be challenging, so strategies to maximise patient recruitment, aimed at both patients and recruiting centres, were implemented. Methods Women aged ≥ 46 years with a histologically confirmed diagnosis of non-high-grade DCIS were eligible for 1:1 randomisation to either surgery or active monitoring. Prior to randomisation, all eligible women were invited to complete: (1) the Clinical Trials Questionnaire (CTQ) examining reasons for or against participation, and (2) interviews exploring in depth opinions about the study information sheets and film. Women agreeing to randomisation completed validated questionnaires assessing health status, physical and mental health, and anxiety levels. Hospital site staff were invited to communication workshops and refresher site initiation visits to support recruitment. Their perspectives on LORIS recruitment were collected via surveys and interviews. Results Eighty percent (181/227) of eligible women agreed to be randomised. Over 40% of participants had high anxiety levels at baseline. On the CTQ, the most frequent most important reasons for accepting randomisation were altruism and belief that the trial offered the best treatment, whilst worries about randomisation and the influences of others were the most frequent most important reasons for declining. Most women found the study information provided clear and useful. Communication workshops for site staff improved knowledge and confidence but only about half said they themselves would join LORIS if eligible. The most common recruitment barriers identified by staff were low numbers of eligible patients and patient preference. Conclusions Recruitment to LORIS was challenging despite strategies aimed at both patients and site staff. Ensuring that recruiting staff support the study could improve recruitment in similar future trials. Trial registration ISRCTN27544579, prospectively registered on 22 May 2014
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- 2023
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17. Factors Determining Intention to Use Contraception Among Sexually Active Women in South Africa: A Multilevel Modelling Approach
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Germinah Motshegwa, Mluleki Tsawe, Onalenna Legotlo, Marinkie Malatji, Shirley Mathabatha, Reamogetse Phateng, Kenneth Pule Tshabalala, Jaqueline Seima, Mary Berries, and Tsholofelo Seokamo
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Public aspects of medicine ,RA1-1270 - Abstract
Conclusion: The results showed that age, population group, parity, ideal number of children, desire to delay childbearing, exposure to family planning messages/advice, and province were key predictors of women’s intention to use contraception. The findings suggest the need for targeted education initiatives about contraception, particularly among older women. There is also a need to involve community leaders and the local media in sexual and reproductive health campaigns.
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- 2024
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18. Noncanonical-NF-κB activation and DDX3 inhibition reduces the HIV-1 reservoir by elimination of latently infected cells ex-vivo
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Jade Jansen, Stefanie Kroeze, Shirley Man, Matteo Andreini, Jan-Willem Bakker, Claudio Zamperini, Alessia Tarditi, Neeltje A. Kootstra, and Teunis B. H. Geijtenbeek
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HIV-1 reservoir ,human immunodeficiency virus ,DDX3 ,IAP ,latency reversal ,SMAC mimetics ,Microbiology ,QR1-502 - Abstract
ABSTRACT Latency reversal and subsequent elimination of the human immunodeficiency virus-1 (HIV-1) reservoir using a combination of compounds with different mechanisms of action are considered a promising tool for HIV-1 cure. Here, we analyzed HIV-1 reservoir reduction by targeting the two host factors; inhibitor of apoptosis proteins (IAPs) and DEAD-box polypeptide 3 (DDX3) using a SMAC mimetic (SMACm) and DDX3 inhibitor (DDX3i), respectively. We observed that SMACm efficiently reactivated HIV-1 in a latency Jurkat model, which was further enhanced by DDX3 inhibition. Strikingly, this compound combination strongly decreased the proportion of latently as well as transcriptionally active infected cells in a T cell line model with a dual-reporter virus. To determine the efficacy of compounds to eradicate the HIV-1 reservoir in people living with HIV (PWH), a novel ex vivo HIV-1 reservoir reduction assay (HIVRRA) was developed. DDX3i and SMACm alone reduced the HIV-1 reservoir in peripheral blood mononuclear cells (PBMCs) from the majority of PWH, whereas notably, the SMACm/DDX3i combination reduced the HIV-1 reservoir even further with 53%–90% in all PWH analyzed, while uninfected bystander cells were not affected. Our data highlight that IAPs as well as factors involved in HIV-1 replication like DDX3 are excellent targets for HIV-1 cure strategies. We show for the first time that the combination of SMACm and DDX3i reverses viral latency and specifically eliminates the HIV-1-infected cells in vitro and ex vivo. IMPORTANCE HIV-1 continues to be a major global health challenge. Current HIV-1 treatments are effective but need lifelong adherence. An HIV-1 cure should eliminate the latent viral reservoir that persists in people living with HIV-1. Different methods have been investigated that focus on reactivation and subsequent elimination of the HIV-1 reservoir, and it is becoming clear that a combination of compounds with different mechanisms of actions might be more effective. Here, we target two host factors, inhibitor of apoptosis proteins that control apoptosis and the DEAD-box helicase DDX3, facilitating HIV mRNA transport/translation. We show that targeting of these host factors with SMAC mimetics and DDX3 inhibitors induce reversal of viral latency and eliminate HIV-1-infected cells in vitro and ex vivo.
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- 2024
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19. Importância e desafios da vigilância em saúde em uma região de fronteira internacional: um estudo de caso
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Giane Zupellari Santos-Melo, Selma Regina de Andrade, Yone Almeida da Rocha, Keven de Oliveira Cosme, Tânia Cristine Libório Pereira, Angela Xavier Monteiro, Glaucia Maria de Araujo Ribeiro, and Shirley Maria de Araújo Passos
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Áreas de Fronteira ,Saúde na Fronteira ,Vigilância em Saúde Pública ,Gestão em Saúde ,Cooperação Internacional ,Public aspects of medicine ,RA1-1270 - Abstract
Resumo O objetivo deste artigo foi identificar os principais desafios da promoção da vigilância em saúde em uma região de tríplice fronteira da Amazônia Legal brasileira. Foi realizado um estudo de caso único, explicativo, com abordagem qualitativa, que utilizou dados documentais e entrevistas. Os resultados demonstram que a vigilância em saúde é fundamental para o controle de doenças na região. Além disso, as diferenças dos sistemas de saúde dos três países que compõem a tríplice fronteira (Brasil, Colômbia e Peru) se mostraram o principal desafio para o estabelecimento de políticas sanitárias.
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- 2023
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20. Foliar structural differences between glyphosate-resistant and glyphosate-susceptible biotypes of Digitaria insularis (L.) Fedde
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Silvio Douglas Ferreira, Jaqueline de Araújo Barbosa, Shirley Martins Silva, and Neumarcio Vilanova da Costa
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biology ,leaf ,sourgrass ,thickness of cuticles ,weed ,Agriculture (General) ,S1-972 ,Biotechnology ,TP248.13-248.65 - Abstract
ABSTRACT Digitaria insularis (L.) Fedde stands out for its resistance to glyphosate and this characteristic may have a relationship with structural alterations. In such context, this research aimed at the characterization of the foliar anatomical structure of two populations of D. insularis (glyphosate-resistant and glyphosate-susceptible biotypes) collected in agricultural areas of Paraná, a Brazilian state. The experiment was conducted at the Laboratory of Botany of the Universidade Estadual do Oeste do Paraná – Unioeste, Brazil. The resistant biotypes of D. insularis differ from the susceptible ones in several structural parameters. Among them, the Mesophyll Thickness in the interveinal region was 7.3% thicker in the resistant biotype, which was also observed in the thickness of the keel, in the percentage of 11.3%, and in the thickness of cuticles in the adaxial surface (TCad), which was 53.8% thicker in the resistant biotype. In this way, we concluded that the resistant biotypes of D. insularis differ from the susceptible ones in several anatomical foliar characteristics, therefore, they present possible mechanisms of resistance to glyphosate.
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- 2023
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21. Seroprevalence of anti-HEV IgG in children: very early exposure in young children in a hyperendemic region
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Lisandru Capai, Shirley Masse, Nathanaël Hozé, Dorine Decarreaux, Jean Canarelli, Marie-Hélène Simeoni, Xavier de Lamballerie, Alessandra Falchi, and Rémi Charrel
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hepatitis E virus ,serosurvey ,hyperendemic area ,children ,epidemiology ,Public aspects of medicine ,RA1-1270 - Abstract
Background and objectivesHepatitis E virus (HEV) can be considered an emerging zoonotic pathogen and is an important cause of acute viral hepatitis in high-income countries. Corsica has been identified as a hyperendemic region for HEV. We aimed to characterize the prevalence of IgG among children and estimate the annual force of infection of HEV.MethodsFrom April 2020 to June 2021, we collected 856 “residual sera” in 13 medical biology laboratories. Sera were tested using the Wantaï HEV IgG assay. Data were weighted according to the distribution by sex and age of the real Corsican population. Serocatalytic models were applied to assess the annual force of infection of HEV.ResultsThe weighted seroprevalence was 30.33% [27.15–34.0]. The seroprevalence was only associated with increasing age (7.25–40.52%; p
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- 2023
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22. Entomofauna cadavérica asociada a los restos incinerados de Sus scrofa domestica L., en el centro poblado de Chuyugual, La Libertad, Perú
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Deimy Briceño Vela, Florencio Ramírez Cruz, and Shirley Madeleine Valderrama Alfaro
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entomofauna cadavérica ,sus scrofadomestica ,biodiversidad ,índices poblacionales. ,Ecology ,QH540-549.5 ,Agriculture (General) ,S1-972 ,Plant culture ,SB1-1110 ,Animal culture ,SF1-1100 - Abstract
La determinación del intervalo post mortema través de la evidencia entomológica es un método muy utilizado para el esclarecimiento de crímenes en entomología forense. El objetivo de esta investigación fue determinar la entomofauna cadavérica y la biodiversidad ecológicaasociadas a los restos de Sus scrofa domestica L. El trabajo se realizó en el centro poblado de Chuyugual, La Libertad, seutilizó un ejemplar de “cerdo” de 15 kg, fue incinerado con petróleo diésel y protegido con una jaula de malla metálica. La colecta de los insectos se hizo con las técnicas entomológicas convencionales, determinando las especies con claves taxonómicas especializadas; para la determinación del valor ecológico de entomofauna cadavérica y familias más representativas se usaron los índices de Margalef, Simpson, Shanon y Pielou.La entomofauna encontrada se distribuyó en 2 ordenes, 7 familias, 12 especies y 4 morfotipos.El 35% de abundancia relativa corresponde a la familia Calliphoridae, el 23% pertenecen a losSarcophagidae, el 18% a los Staphilinidae y el 6% a las familias Musidae, Fannidae, Dermestidae y Silphidae. Labiodiversidad es altaen índices de dominancia e índice de Pielou; sin embargo, es baja en índices de riqueza específica y equidad de Shanon. La familia Calliphoridae, tiene índices de diversidad alto; en tanto que, los Sarcophagidae y Staphilinidae muestran índice moderado y bajo, respectivamente. Se concluyó que la entomofauna encontrada en la descomposición de Sus scrofa domestica pertenecen al orden díptera (Calliphoridae, Sarcophagidae, Muscidae y Fannidae) y coleóptera (Staphilinidae, Silphidae y Dermestidae).
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- 2022
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23. Associations of the perceived benefits and harms of COVID-19 with confidence in coping with the pandemic and mental health symptoms: a population-based survey in Hong Kong
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Ying Yao, Wei Jie Gong, Agnes Yuen Kwan Lai, Yongda Socrates Wu, Shirley Man Man Sit, Man Ping Wang, Sai Yin Ho, and Tai Hing Lam
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COVID-19 ,perceived benefit ,perceived harm ,confidence ,coping ,mental health ,Public aspects of medicine ,RA1-1270 - Abstract
IntroductionBoth perceived benefits and harms of COVID-19 have been reported, but whether they affect confidence in coping with the pandemic and mental health remains uncertain.ObjectiveTo examine the association of perceived benefits and harms of COVID-19 with confidence in coping with the pandemic and mental health symptoms.MethodsA population-based survey was conducted on 7,535 Hong Kong adults from 22 February to 23 March 2021, when the 4th wave of COVID-19 was under control. Information on sociodemographic characteristics, perceived benefits (10 options) and harms (12 options) of COVID-19, confidence in coping with the pandemic (range 0–10), loneliness (range 0–4), anxiety (General Anxiety Disorders-2, range 0–6) and depression (Patient Health Questionnaire-2, range 0–6) was collected. Latent profile analysis was used to identify the combined patterns of perceived benefits and harms of COVID-19. The associations of combined patterns with confidence in coping with COVID-19, loneliness, anxiety, and depression were examined using linear regression (β coefficient) adjusting for sociodemographic characteristics.ResultsThe combined patterns of perceived benefits and harms were classified into benefit (n = 4,338, 59.3%), harm (n = 995, 14.0%), and ambivalent (n = 2,202, 26.7%) groups. Compared with the ambivalent group, the benefit group had a significantly higher level of confidence (adjusted β 0.46, 95% CI 0.33 to 0.58), and lower levels of loneliness (−0.35, −0.40 to-0.29), anxiety (−0.67, 0.76 to-0.59), and depression (−0.65, −0.73 to-0.57). The harm group had a significantly lower level of confidence (−0.35, −0.53 to-0.16), and higher levels of loneliness (0.38, 0.30 to 0.45), anxiety (0.84, 0.73 to 0.96), and depression (0.95, 0.84 to 1.07).ConclusionPerceived greater benefit from COVID-19 was associated with better mental health and stronger confidence in coping with the pandemic.
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- 2023
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24. Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors
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Kellie Pickell, Andrew Lam, Lucas Donigan, Marcus Fischer, Satyajit Sujit Kumar Mitra, Fumiko Takada Axelrod, Hoang Tran, Aurélie Chaudhari, In-Kyung Park, Christopher J. Bond, Austin L. Gurney, Timothy Hoey, Sanjeev Satyal, Aaron K. Sato, John Lewicki, Jennifer Cain, Cecile Chartier, Michelle Stroud, Sasha Lazetic, Ann M. Kapoun, May Ji, Wan-Ching Yen, and Shirley Ma
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Frizzled ,Blotting, Western ,Genetic Vectors ,Cell ,Antineoplastic Agents ,CHO Cells ,Biology ,Epitope ,Immunoglobulin Fab Fragments ,Cricetulus ,Peptide Library ,Cricetinae ,Neoplasms ,medicine ,Animals ,Humans ,Luciferases ,Receptor ,Wnt Signaling Pathway ,Multidisciplinary ,Lentivirus ,HEK 293 cells ,Wnt signaling pathway ,Antibodies, Monoclonal ,LRP6 ,Drug Synergism ,LRP5 ,Biological Sciences ,Immunohistochemistry ,Molecular biology ,Frizzled Receptors ,Cell biology ,HEK293 Cells ,medicine.anatomical_structure - Abstract
The Wnt/β-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several coreceptors, has long been implicated in cancer. Here we demonstrate a therapeutic approach to targeting the Wnt pathway with a monoclonal antibody, OMP-18R5. This antibody, initially identified by binding to Frizzled 7, interacts with five Fzd receptors through a conserved epitope within the extracellular domain and blocks canonical Wnt signaling induced by multiple Wnt family members. In xenograft studies with minimally passaged human tumors, this antibody inhibits the growth of a range of tumor types, reduces tumor-initiating cell frequency, and exhibits synergistic activity with standard-of-care chemotherapeutic agents.
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- 2012
25. Prenatal dental practices in the city of Itacoatiara, Amazonas, from the perspective of pregnant women
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Keline Albuquerque Pereira Simões, Shirley Maria de Araújo Passos, Adriana Beatriz Silveira Pinto, Lauramaris de Arruda Regis Aranha, and Angela Xavier Monteiro
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primary health care. prenatal care. oral health. ,Medicine (General) ,R5-920 - Abstract
This study sought to investigate the practices of prenatal dental care from the perspective of pregnant women in the city of Itacoatiara, Amazonas. An instrument composed of 14 objective questions was used, applied to 146 pregnant women, over 18 years of age, followed up in seven family health units in the city of Itacoatiara, Amazonas. The data were descriptively analyzed using absolute and relative frequencies, using the chi-squared test (p
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- 2022
26. Adversity coping capability and its associations with mental health and family wellbeing amid the COVID-19 pandemic in Hong Kong
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Wei Jie Gong, Shirley Man Man Sit, Agnes Yuen Kwan Lai, Nancy Xiaonan Yu, Man Ping Wang, Sai Yin Ho, and Tai Hing Lam
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Adversity coping capability ,Resilience ,COVID-19 ,Mental health ,Family wellbeing ,Psychiatry ,RC435-571 - Abstract
Abstract Background Adversity coping capability (ACC) is important amid the COVID-19 pandemic. We examined the associations of ACC as measured by our one-item ACC scale (ACC-1) with mental health, family well-being and validity of ACC-1 in Hong Kong. Methods A cross-sectional survey was conducted on Hong Kong Chinese adults aged ≥ 18 years by landline, mobile phone, and online survey from February to March 2021, when the fourth wave of COVID-19 was under control. ACC-1 consisted of the question: “How do you rate your capability to cope with adversities?” with higher scores (0–10) indicating stronger ACC. The associations of ACC with socioeconomic characteristics, resilience, mental health, and family wellbeing were examined by linear regression coefficients (βs). Data were weighted by sex, age, and education of the general population. Results Of 7441 respondents, after weighing, 52.2% were female and 79.1% were aged 18 to 64 years. ACC-1 showed good construct validity, with higher ACC being associated with higher levels of resilience (adjusted β = 0.29), personal happiness (0.55), family happiness (0.42), family wellbeing (0.41), and family communication quality (0.41), and lower levels of depressive symptoms (-0.30), anxiety (-0.30), loneliness (-0.15); incremental validity with additional contributions of ACC to mental health and family wellbeing; and known-group validity with older age and favorable socioeconomic characteristics showing higher ACC (all P
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- 2022
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27. Error-constant estimation under the maximum norm for linear Lagrange interpolation
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Shirley Mae Galindo, Koichiro Ike, and Xuefeng Liu
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Lagrange interpolation ,Finite-element method ,Fujino–Morley interpolation ,Bernstein polynomial ,Mathematics ,QA1-939 - Abstract
Abstract For the linear Lagrange interpolation over a triangular domain, we propose an efficient algorithm to rigorously evaluate the interpolation error constant under the maximum norm by using the finite-element method (FEM). In solving the optimization problem corresponding to the interpolation error constant, the maximum norm in the constraint condition is the most difficult part to process. To handle this difficulty, a novel method is proposed by combining the orthogonality of the space decomposition using the Fujino–Morley FEM space and the convex-hull property of the Bernstein representation of functions in the FEM space. Numerical results for the lower and upper bounds of the interpolation error constant for triangles of various types are presented to verify the efficiency of the proposed method.
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- 2022
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28. Sound evoked fos-like immunoreactivity in the big brown bat
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Angeles Salles, Shirley Marino Lee, and Cynthia F. Moss
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Bats ,C-fos ,Social ,Communication ,Vocalizations ,Echolocation ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Most bat species have highly developed audio-vocal systems, which allow them to adjust the features of echolocation calls that are optimized for different sonar tasks, such as detecting, localizing, discriminating and tracking targets. Furthermore, bats can also produce a wide array of social calls to communicate with conspecifics. The acoustic properties of some social calls differ only subtly from echolocation calls, yet bats have the ability to distinguish them and reliably produce appropriate behavioral responses. Little is known about the underlying neural processes that enable the correct classification of bat social communication sounds. One approach to this question is to identify the brain regions that are involved in the processing of sounds that carry behavioral relevance. Here, we present preliminary data on neuronal activation, as measured by c-fos expression, in big brown bats (Eptesicus fuscus) exposed to either social calls, echolocation calls or kept in silence. We focused our investigation on five relevant brain areas; three within the canonical auditory pathway (auditory cortex, inferior colliculus and medial geniculate body) and two that are involved in the processing of emotive stimulus content (amygdala and nucleus accumbens). In this manuscript we report c-fos staining of the areas of interest after exposure to conspecific calls. We discuss future work designed to overcome experimental limitations and explore whether c-fos staining reveals anatomical segregation of neurons activated by echolocation and social call categories.
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- 2022
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29. Family context as a double-edged sword for psychological distress amid the COVID-19 pandemic with the mediating effect of individual fear and the moderating effect of household income
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Bowen Chen, Weijie Gong, Agnes Yuen Kwan Lai, Shirley Man Man Sit, Sai Yin Ho, Nancy Xiaonan Yu, Man Ping Wang, and Tai Hing Lam
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COVID-19 ,family ,fear ,household income ,psychological distress ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundThe COVID-19 pandemic drives psychological distress. Previous studies have mostly focused on individual determinants but overlooked family factors. The present study aimed to examine the associations of individual and family factors with psychological distress, and the mediating effect of individual fear and the moderating role of household income on the above associations.MethodsWe conducted a population-based cross-sectional survey on Chinese adults in Hong Kong from February to March 2021 (N = 2,251) to measure the independent variables of anti-epidemic fatigue, anti-epidemic confidence, individual and family members’ fear of COVID-19, and family well-being (range 0–10), and the dependent variable of psychological distress (through four-item Patient Health Questionnaire, range 0–4).ResultsHierarchical regression showed that anti-epidemic fatigue was positively (β = 0.23, 95% CI [0.18, 0.28]) while anti-epidemic confidence was negatively (β = −0.29, 95% CI [−0.36, −0.22]) associated with psychological distress. Family members’ fear of COVID-19 was positively (β = 0.11, 95% CI [0.05, 0.16]) while family well-being was negatively (β = −0.57, 95% CI [−0.63, −0.51]) associated with psychological distress. Structural equation model showed that individual fear mediated the above associations except for family well-being. Multi-group analyses showed a non-significant direct effect of anti-epidemic confidence and a slightly stronger direct effect of family well-being on psychological distress among participants with lower incomes, compared to those with higher incomes.ConclusionWe have first reported the double-edged effect of family context on psychological distress, with the positive association between family members’ fear of COVID-19 and psychological distress fully mediated by individual fear and the negative association between family well-being and psychological distress moderated by income level. Future studies are warranted to investigate how the contagion of fear develops in the family and how the inequality of family resources impacts family members’ mental health amid the pandemic.
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- 2023
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30. Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates β-Catenin Signaling and Tumorigenesis in Multiple Cancer Types
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John Lewicki, Andrew Lam, Michelle Stroud, Janak Raval, May Ji, Belinda Cancilla, Jie Wei, Fumiko Takada Axelrod, Gilbert O'Young, Wan-Ching Yen, Min Wang, Timothy Hoey, Ann M. Kapoun, Cecile Chartier, Cristina Dee-Hoskins, Austin L. Gurney, Pete Yeung, Shirley Ma, Christopher J. Bond, Jalpa Shah, Jennifer Cain, and Marcus Fischer
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0301 basic medicine ,Cancer Research ,Carcinogenesis ,Mice, SCID ,Biology ,medicine.disease_cause ,Bioinformatics ,03 medical and health sciences ,Mice ,Mice, Inbred NOD ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,RSPO2 ,beta Catenin ,HEK 293 cells ,Wnt signaling pathway ,Cancer ,Antibodies, Monoclonal ,medicine.disease ,Xenograft Model Antitumor Assays ,Wnt Proteins ,030104 developmental biology ,HEK293 Cells ,Oncology ,Cancer cell ,Cancer research ,Signal transduction ,Stem cell ,Thrombospondins ,Signal Transduction - Abstract
Deregulation of the β-catenin signaling has long been associated with cancer. Intracellular components of this pathway, including axin, APC, and β-catenin, are frequently mutated in a range of human tumors, but the contribution of specific extracellular ligands that promote cancer development through this signaling axis remains unclear. We conducted a reporter-based screen in a panel of human tumors to identify secreted factors that stimulate β-catenin signaling. Through this screen and further molecular characterization, we found that R-spondin (RSPO) proteins collaborate with Wnt proteins to activate β-catenin. RSPO family members were expressed in several human tumors representing multiple malignancies, including ovarian, pancreatic, colon, breast, and lung cancer. We generated specific monoclonal antibody antagonists of RSPO family members and found that anti-RSPO treatment markedly inhibited tumor growth in human patient-derived tumor xenograft models, either as single agents or in combination with chemotherapy. Furthermore, blocking RSPO signaling reduced the tumorigenicity of cancer cells based on serial transplantation studies. Moreover, gene-expression analyses revealed that anti-RSPO treatment in responsive tumors strongly inhibited β-catenin target genes known to be associated with cancer and normal stem cells. Collectively, our results suggest that the RSPO family is an important stimulator of β-catenin activity in many human tumors and highlight a new effective approach for therapeutically modulating this fundamental signaling axis. Cancer Res; 76(3); 713–23. ©2015 AACR.
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- 2015
31. Multiple stakeholder perspectives of factors influencing differential outcomes for ethnic minority students on health and social care placements: a qualitative exploration
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Julie Nightingale, Jackie Parkin, Pete Nelson, Shirley Masterson-Ng, Jacqui Brewster, Temitope Labinjo, Deborah Amoakoh, David Lomas, Ifrah Salih, and Deborah Harrop
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Ethnicity ,BAME ,BME ,Student experience ,Clinical placements ,Allied health professions ,Special aspects of education ,LC8-6691 ,Medicine - Abstract
Abstract Background Despite considerable efforts there continues to be a degree awarding gap within the United Kingdom (UK) between the proportion of White British students receiving higher classifications, compared to ethnic minority UK-domiciled students. Practice placement elements constitute approximately 50% of most health and social care programmes, yet surprisingly little research exists related to the factors which may contribute to ethnic minority student placement outcomes or experiences. This study bridges this evidence gap by exploring factors influencing differential placement outcomes of ethnic minority students from the perspectives of key stakeholders. Methods The study followed a descriptive qualitative research design and was multi-disciplinary, with participants drawn from across nursing, midwifery, social work and the allied health professions. Participants from four stakeholder categories (ethnic minority students, academic staff, placement educators and student union advisors) were invited to join separate focus groups. Focus groups were recorded and transcribed and analysed thematically. Results Ten separate focus groups [n = 66] yielded three primary themes: 1) recognition, which highlighted stakeholder perceptions of the issues [sub-themes: acknowledging concerns; cultural norms; challenging environments]; 2) the lived experience, which primarily captured ethnic minority student perspectives [sub-themes: problematising language and stereotyping, and being treated differently]; 3) surviving not thriving, which outlines the consequences of the lived experience [sub-themes: withdrawing mentally, feeling like an alien]. Conclusion This study presents a rich exploration of the factors affecting differential outcomes of ethnic minority students on practice placements through the lens of four different stakeholder groups. To our knowledge this is the first study in which this comprehensive approach has been taken to enable multiple viewpoints to be accessed across a wide range of health and social care professions. The issues and challenges raised appear to be common to most if not all of these disciplines. This study highlights the urgent need to value and support our ethnic minority students to remove the barriers they face in their practice learning settings. This is a monumental challenge and requires both individuals and organisations to step up and take collective responsibility.
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- 2022
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32. Factors associated with willingness and preferences to attend family services in Hong Kong: A population-based survey
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Yingpei Zeng, Weijie Gong, Agnes Yuen Kwan Lai, Shirley Man Man Sit, Man Ping Wang, Sai Yin Ho, and Tai Hing Lam
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family wellbeing ,family communication ,family support ,social service ,family service ,Public aspects of medicine ,RA1-1270 - Abstract
ObjectiveFamily services are open to the community at large as well as vulnerable groups; however, little is known about the willingness of communities to attend such services. We investigated the willingness and preferences to attend family services and their associated factors (including sociodemographic characteristics, family wellbeing, and family communication quality) in Hong Kong.MethodsA population-based survey was conducted on residents aged over 18 years from February to March 2021. Data included sociodemographic characteristics (sex, age, education, housing type, monthly household income, and the number of cohabitants), willingness to attend family services to promote family relationships (yes/no), family service preferences (healthy living, emotion management, family communication promotion, stress management, parent-child activities, family relationship fostering, family life education, and social network building; each yes/no), family wellbeing, and family communication quality (both scores 0–10). Family wellbeing was assessed using the average scores of perceived family harmony, happiness and health (each score 0–10). Higher scores indicate better family wellbeing or family communication quality. Prevalence estimates were weighted by sex, age and educational level of the general population. Adjusted prevalence ratios (aPR) for the willingness and preferences to attend family services were calculated in relation to sociodemographic characteristics, family wellbeing, and family communication quality.ResultsOverall, 22.1% (1,355/6,134) and 51.6% (996/1,930) of respondents were willing to attend family services to promote relationships or when facing problems, respectively. Older age (aPR = 1.37–2.30, P < 0.001–0.034) and having four or more cohabitants (aPR = 1.44–1.53, P = 0.002–0.003) were associated with increased aPR of willingness for both situations. Lower family wellbeing and communication quality were associated with lower aPR for such willingness (aPR = 0.43–0.86, P = 0.018–
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- 2023
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33. The Calling
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Shirley Maria Batista
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Language and Literature - Published
- 2021
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34. Substantial increase in perceived benefits over harms of COVID-19 outbreak but persistent socioeconomic disparities: Comparison of two cross-sectional surveys in Hong Kong from 2020 to 2021
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Hiu Tin Leung, Wei Jie Gong, Shirley Man Man Sit, Agnes Yuen Kwan Lai, Sai Yin Ho, Man Ping Wang, and Tai Hing Lam
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COVID-19 ,perceived benefits ,perceived harms ,socioeconomic disparities ,cross-sectional study ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundWe have reported both perceived benefits and harms of the COVID-19 outbreak and their socioeconomic disparities amid the pandemic in Hong Kong. We further investigated whether such perceptions and disparities had changed after 10 months.MethodsUnder the Hong Kong Jockey Club SMART Family-Link Project, we conducted two cross-sectional surveys online on perceived personal and family benefits and harms of the COVID-19 outbreak in Hong Kong adults in May 2020 (after Wave 2 was under control; N = 4,891) and in February and March 2021 (after Wave 4 was under control; N = 6,013). We collected sociodemographic information, including sex, age, education, household income, and housing. Using multivariate models of analysis of covariance (MANCOVA), we compared perceived benefits and harms and socioeconomic disparities between the two surveys.ResultsAdjusting for sex and age, the prevalence of 17 out of 18 perceived personal and family benefits of COVID-19 outbreak increased (Ps < 0.001). Six of 11 perceived personal and family harms decreased (Ps < 0.001) and 4 increased (Ps < 0.001). The total number of perceived personal and family benefits increased substantially (Ps < 0.001), whereas that of perceived personal harms decreased (P = 0.01) and family harms remained stable (P > 0.05). Socioeconomic disparities, however, persisted—more perceived benefits in those with higher socioeconomic status (Ps < 0.001) and more perceived harms in those with lower (Ps ≤ 0.005).ConclusionWe have first reported that perceived personal and family benefits of the COVID-19 outbreak increased substantially over 10 months amid the pandemic, while perceived personal and family harms were lower and stable, respectively. Socioeconomic disparities of the perceived benefits and harms persisted, which need to be monitored and addressed urgently.
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- 2022
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35. Development and evaluation of two brief digital health promotion game booths utilizing augmented reality and motion detection to promote well-being at a gerontechnology summit in Hong Kong
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Shirley Man-Man Sit, Agnes Yuen-Kwan Lai, Tai-on Kwok, Hoi-wa Wong, Yiu-lun Wong, Edward Chow, Yu-kwong Kwok, Man-Ping Wang, Sai-Yin Ho, and Tai-Hing Lam
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family happiness ,health promotion ,gerontechnology ,digital technologies ,augmented reality ,Hong Kong ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundThe acceleration of population aging calls for simple and effective interventions catered for older people. Gerontechnology, the combination of gerontology and technology, can promote quality of life in older adults. However, public health-related events incorporating information communication technology (ICT) for older people have seldom been evaluated.ObjectiveWe reported the development and evaluation of two simple and brief digital health promotion games hosted at the annual Hong Kong Gerontech and Innovation Expo cum Summit (GIES) in 2018 and 2019 to promote well-being.MethodsTwo game booths (Dinosaur Augmented Reality photo-taking in 2018, Sit-and-Stand fitness challenge in 2019) were designed by our interdisciplinary team. Four gaming technologies were employed: augmented reality, chroma key (green screen), motion detection and 3D modeling. Immediately after the game, we administered a brief questionnaire survey to assess participant satisfaction, happiness and perceived benefits, and collected qualitative data through observations and informal interviews.ResultsMajority of 1,186 and 729 game booth participants in 2018 and 2019, respectively, were female (73.4% and 64.7%) and older adults (65.5 and 65.2%). Overall satisfaction toward the game booths was high (4.64 ± 0.60 and 4.54 ± 0.68 out of 5), with females and older adults reporting higher scores. Average personal and family happiness of participants in 2018 were 8.2 and 8.0 (out of 10). 90.3 and 18.4% of participants in 2019 chose one or more personal (e.g. enhance healthy living habits 62.4%, enhance personal happiness 61.6%) and family (e.g. enhance family happiness 15.6%, improve family relationships 10.8%) benefits of the game booth, respectively. Participants showed enthusiasm toward the technologies, and pride in their physical abilities in the fitness challenge.ConclusionOur report on the development and evaluation of brief game interventions with ICT showed high satisfaction and immediate perceived benefits in community participants. Females and older adults reported higher satisfaction. Simple tools measuring happiness and perceived benefits showed positive results. Older adults were receptive and enthusiastic about the new technologies. Our findings can inform researchers and organizers of similar events. More research on simple and enjoyable ICT interventions is needed to attract older adults and promote their well-being.Trial registrationThe research protocol was registered at the National Institutes of Health (Identifier number: NCT03960372) on May 23, 2019.
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- 2022
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36. Transgenic East African Highland Banana Plants Are Protected against Radopholus similis through Host-Delivered RNAi
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Henry Shaykins Mwaka, Lander Bauters, Josephine Namaganda, Shirley Marcou, Priver Namanya Bwesigye, Jerome Kubiriba, Guy Smagghe, Wilberforce Kateera Tushemereirwe, and Godelieve Gheysen
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banana ,Radopholus similis ,nematodes ,RNAi ,transgenic ,pest control ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The burrowing nematode Radopholus similis is considered a major problem of intensive banana cultivation. It can cause extensive root damage resulting in the toppling disease of banana, which means that plants fall to the ground. Soaking R. similis in double-stranded (ds) RNA of the nematode genes Rps13, chitin synthase (Chs-2), Unc-87, Pat-10 or beta-1,4-endoglucanase (Eng1a) suppressed reproduction on carrot discs, from 2.8-fold (Chs-2) to 7-fold (Rps13). The East African Highland Banana cultivar Nakitembe was then transformed with constructs for expression of dsRNA against the same genes, and for each construct, 30 independent transformants were tested with nematode infection. Four months after transfer from in vitro culture to the greenhouse, the banana plants were transferred to a screenhouse and inoculated with 2000 nematodes per plant, and thirteen weeks later, they were analyzed for several parameters including plant growth, root necrosis and final nematode population. Plants with dsRNA constructs against the nematode genes were on average showing lower nematode multiplication and root damage than the nontransformed controls or the banana plants expressing dsRNA against the nonendogenous gene. In conclusion, RNAi seems to efficiently protect banana against damage caused by R. similis, opening perspectives to control this pest.
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- 2023
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37. Overview and Management of the Most Common Eukaryotic Diseases of Flax (Linum usitatissimum)
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Julie Moyse, Sylvain Lecomte, Shirley Marcou, Gaëlle Mongelard, Laurent Gutierrez, and Monica Höfte
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Linum usitatissimum ,eukaryotic pathogens ,disease management ,biocontrol ,breeding ,genetic resistance ,Botany ,QK1-989 - Abstract
Flax is an important crop cultivated for its seeds and fibers. It is widely grown in temperate regions, with an increase in cultivation areas for seed production (linseed) in the past 50 years and for fiber production (fiber flax) in the last decade. Among fiber-producing crops, fiber flax is the most valuable species. Linseed is the highest omega-3 oleaginous crop, and its consumption provides several benefits for animal and human health. However, flax production is impacted by various abiotic and biotic factors that affect yield and quality. Among biotic factors, eukaryotic diseases pose a significant threat to both seed production and fiber quality, which highlights the economic importance of controlling these diseases. This review focuses on the major eukaryotic diseases that affect flax in the field, describing the pathogens, their transmission modes and the associated plant symptoms. Moreover, this article aims to identify the challenges in disease management and provide future perspectives to overcome these biotic stresses in flax cultivation. By emphasizing the key diseases and their management, this review can aid in promoting sustainable and profitable flax production.
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- 2023
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38. Encapsulation of factor IX–engineered mesenchymal stem cells in fibrinogen–alginate microcapsules enhances their viability and transgene secretion
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Shirley Ma, Jianping Wen, Anna Janowska-Wieczorek, Leah A. Marquez-Curtis, Megan Dodd, Bahareh Sayyar, and Gonzalo Hortelano
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Transgene ,Cell ,Biomedical Engineering ,Medicine (miscellaneous) ,cell encapsulation ,Article ,Biomaterials ,lcsh:Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,hemophilia ,medicine ,alginate ,Secretion ,lcsh:QD415-436 ,Cell encapsulation ,030304 developmental biology ,Factor IX ,0303 health sciences ,mesenchymal stem cells ,business.industry ,Mesenchymal stem cell ,Chondrogenesis ,3. Good health ,Cell biology ,Biotechnology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cord blood ,fibrinogen ,business ,medicine.drug - Abstract
Cell microencapsulation holds significant promise as a strategy for cellular therapies; however, inadequate survival and functionality of the enclosed cells limit its application in hemophilia treatment. Here, we evaluated the use of alginate-based microcapsules to enhance the viability and transgene secretion of human cord blood–derived mesenchymal stem cells in three-dimensional cultures. Given the positive effects of extracellular matrix molecules on mesenchymal stem cell growth, we tested whether fibrinogen-supplemented alginate microcapsules can improve the efficiency of encapsulated factor IX–engineered mesenchymal stem cells as a treatment of hemophilia B. We found that fibrinogen-supplemented alginate microcapsules (a) significantly enhanced the viability and proliferation of factor IX–engineered mesenchymal stem cells and (b) increased factor IX secretion by mesenchymal stem cells compared to mesenchymal stem cells in nonsupplemented microcapsules. Moreover, we observed the osteogenic, but not chondrogenic or adipogenic, differentiation capability of factor IX–engineered cord blood mesenchymal stem cells and their efficient factor IX secretion while encapsulated in fibrinogen-supplemented alginate microcapsules. Thus, the use of engineered mesenchymal stem cells encapsulated in fibrinogen-modified microcapsules may have potential application in the treatment of hemophilia or other protein deficiency diseases.
- Published
- 2012
39. Association of family wellbeing with forwarding and verifying COVID-19-related information, and mediation of family communication quality
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Bonny Yee-Man Wong, Sai Yin Ho, Shirley Man Man Sit, Wei Jie Gong, Agnes Yuen Kwan Lai, Man Ping Wang, and Tai Hing Lam
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COVID-19 ,information sharing ,fact-check ,information overload ,misinformation ,family wellbeing ,Public aspects of medicine ,RA1-1270 - Abstract
ObjectiveWe assessed the associations of family wellbeing with verifying and subsequently forwarding COVID-19-related information to family members and the mediating effect of the quality of family communication on these associations among Chinese adults in Hong Kong.MethodsUnder the Jockey Club SMART Family-Link Project, we conducted an online population-based survey, using Family wellbeing Scale and questions related to the family communication quality and forwarding and verifying COVID-19 information. Data were collected from 4,891 adults in May 2020. Prevalence estimates of forwarding and verifying COVID-19 information were weighted by sex, age, and education of the general population, and their associations with family wellbeing (ranged 0–10) were analyzed using generalized linear models with mutual adjustment. Their interactive effects on family wellbeing and the mediating effects of family communication quality were examined.ResultsIn total, 53.9% of respondents usually/always forwarded COVID-19 information related to their family, 68.7% usually/always verified it before forwarding, and 40.9% did both. Greater family wellbeing was associated with usually/always forwarding [adjusted β (95% CI): 0.82 (0.72–0.92)] and usually/always verifying [0.43 (0.32–0.55)] (both P < 0.001) the information. Forwarding and verifying such information showed an additive effect on family wellbeing [1.25 (1.11–1.40)]. Family communication quality mediated the associations of family wellbeing with forwarding (83.7%) and verifying (86.6%) COVID-19-related information.ConclusionForwarding COVID-19 information to family, verifying such information, and especially doing both, were associated with greater family wellbeing, being strongly mediated by the quality of family communication. Individuals should be encouraged to verify COVID-19-related information before forwarding it to family members amidst the COVID-19 pandemic.
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- 2022
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40. Successful Aging: Using Information Technology to Enhance the Lives of Older Adults
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Bluethmann, Shirley, MA
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According to the 2007 State of Aging report from the US Centers of Disease Control and Prevention (CDC), the population growth of older adults today is unprecedented in American history. Experts agree that the growth is due in part to medical advances that have dramatically changed the landscape of aging in America. Today, chronic diseases have replaced infectious diseases and acute illness as the leading causes of death. In fact, some 80 percent of older adults are believed to have at least one chronic or degenerative disease. The report cites two forces- a longer lifespan and the maturing of the 77 million babyboomers- that will result in the doubling of the population of Americans 65 years and older by 2030. This dramatic change is also expected to raise existing healthcare costs by 25 percent. These factors are bringing attention to the capabilities of aging services in America. The impetus is strong to mitigate factors contributing to age-related, debilitating diseases such as heart disease, diabetes and cancer and in tum to achieve a better quality of life through healthier aging options. Community-based intervention models have achieved some success in addressing these concerns. But, as the aging population continues to grow, opportunities are emerging to integrate information technology in the approach to maximize the ability to age successfully, including opportunities to promote independence and quality of life.
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- 2007
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41. Abstract 2322: The Hippo signaling pathway mediates BMP inhibition of cancer stem cells
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Cecile Chartier, Ann M. Kapoun, Austin L. Gurney, Cristina Dee-Hoskins, Tim Hoey, Elsa Quintana, Janak Raval, Dragana Antic, Min Wang, Shirley Ma, and John Lewicki
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YAP1 ,Genetics ,Cancer Research ,Hippo signaling pathway ,Transactivation ,Oncology ,Hippo signaling ,Cancer stem cell ,SMAD ,Signal transduction ,Biology ,Actin cytoskeleton ,Cell biology - Abstract
Multiple developmental signaling pathways cooperatively regulate cancer stem cell (CSC) function. Among them, the BMP pathway has been implicated in brain CSC tumorigenicity. To examine whether BMP is a general regulator of CSCs across diverse organ systems we utilized lentivirus-mediated BMP4 expression in patient-derived xenograft models in NOD/SCID mice. The prevention of tumor growth was observed in breast, colon, ovarian, and melanoma models. Similarly, adenovirus-mediated systemic delivery of BMP4 inhibited tumor growth, dramatically affected CSC-specific cell surface markers and decreased CSC frequency. Microarray analysis of BMP4-treated tumors showed that a set of genes encoding for components of the actin cytoskeleton was significantly enriched amongst regulated genes and identified Hippo pathway genes as potential mediators of the BMP4 anti-tumor response with up-regulation of SAV1 and LATS2 and down-regulation of BIRC5. Hippo signaling regulates organ size, stem cell biology and cancer through a protein kinase complex including MST1/2, SAV1, and LATS1/2, which phosphorylates the downstream nuclear effector YAP/TAZ. Phosphorylated YAP/TAZ is unable to induce the expression of cell proliferation and anti-apoptotic genes through interaction with transcriptional co-activators such as TEAD. The Hippo pathway, known to cross-talk with BMP signaling at multiple levels, recently emerged as a cellular sensor of the physical environment through the actin cytoskeleton. We thus asked whether modulating Hippo signaling affected tumor growth. YAP1 overexpression resulted in tumor growth decrease. A deletion variant of YAP, YAP1-291, possessing a deletion of the transactivation domain has been shown to act as a dominant-negative through binding to TEAD. Intriguingly YAP1-291 was also sufficient to strongly attenuate growth of diverse BMP4-sensitive and BMP4-insensitive tumor models suggesting that transactivation through TEAD is not the only route by which YAP modulates tumor growth. YAP anti-proliferative properties were reported before. In order to reconcile the dual function of YAP in cancer, we propose that the transcriptional co-activator's TEAD-mediated oncogenic function may be counter-balanced by its potentiation of SMAD signaling in response to BMP. Citation Format: Cecile Chartier, Shirley Ma, Dragana Antic, Elsa Quintana, Janak Raval, Min Wang, Cristina Dee-Hoskins, Ann Kapoun, Tim Hoey, John Lewicki, Austin Gurney. The Hippo signaling pathway mediates BMP inhibition of cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2322. doi:10.1158/1538-7445.AM2015-2322
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- 2015
42. Associations of Face-to-Face and Instant Messaging Family Communication and Their Contents With Family Wellbeing and Personal Happiness Amidst the COVID-19 Pandemic
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Wei Jie Gong, Shirley Man Man Sit, Bonny Yee Man Wong, Socrates Yong Da Wu, Agnes Yuen Kwan Lai, Sai Yin Ho, Man Ping Wang, and Tai Hing Lam
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communication contents ,family wellbeing ,happiness ,instant messaging (IM) ,face-to-face (F2F) ,Psychiatry ,RC435-571 - Abstract
BackgroundBoth face-to-face and instant messaging (IM) communication are important for families, but face-to-face communication has reduced amidst the COVID-19 pandemic. We examined the use and contents of both communication methods amidst the pandemic, their associations with family wellbeing and personal happiness, and the mediation effects of communication quality in Hong Kong Chinese adults.MethodsThis population-based online survey enrolled 4,921 respondents in May 2020, who reported (i) any face-to-face or IM family communication when the pandemic was severe; (ii) communication contents being classified as neutral, positive, supportive, and negative; and (iii) communication quality, family wellbeing and personal happiness (score 0–10). Associations of family wellbeing and personal happiness with communication methods and contents (no communication excluded) were examined using linear regressions (β), adjusting for each other, sex, age, socioeconomic status, and the number of cohabitants. Mediating effects of communication quality on these associations were examined. Prevalence estimates were weighted by sex, age, and education of the general population. Interactions of methods and contents were examined.ResultsOf 4,891 included respondents (female: 52.9%, 45–54 years: 37.7%, ≥65 years: 21.3%), 7.1% reported no communication, 12.7% face-to-face communication only, 26.7% IM only, and 53.4% both methods. More males and those at younger ages, had lower socioeconomic status, or fewer cohabitants showed no family communication or face-to-face only. More respondents reported neutral (83.1–99.3%) than positive (42.1–62.2%), supportive (37.5–54.8%), and negative (10.9–34.5%) contents despite communication methods. Communication quality was higher with both methods than IM only, face-to-face only, and no communication (scores: 6.7 vs. 4.5–6.6, all P ≤ 0.02). Better family wellbeing and personal happiness were associated with using IM only (adjusted βs: 0.37 and 0.48) and both methods (0.37 and 0.42) than face-to-face only, and positive (0.62 and 0.74) or supportive (0.45 and 0.46) contents (all P ≤ 0.001). Communication quality mediated 35.2–93.5% of these associations. Stronger associations between positive contents and family wellbeing showed in both methods and face-to-face only than IM only (P for interaction = 0.006).ConclusionsWe have first shown that, amidst the COVID-19 pandemic, family IM communication and positive and supportive contents may promote family wellbeing and personal happiness. People with no family communication may need assistance.
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- 2022
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43. Transferring structural knowledge across cognitive maps in humans and models
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Shirley Mark, Rani Moran, Thomas Parr, Steve W. Kennerley, and Timothy E. J. Behrens
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Science - Abstract
Humans are able to exploit patterns or schemas when performing new tasks, but the mechanism for this ability is still unknown. Using graph-learning tasks, we show that humans are able to transfer abstract structural knowledge and suggest a computational mechanism by which such transfer can occur.
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- 2020
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44. Conhecimento e prática universitária no uso de imagens de pacientes
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Isabela Cristina de Miranda Gonçalves, Jacqueline de Almeida Gonçalves Sachett, Waldeyde O. Magalhães dos Santos, and Shirley Maria de Araújo Passos
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Ética ,Legislação ,Privacidade ,Fotografia ,Medical philosophy. Medical ethics ,R723-726 - Abstract
Resumo O uso de tecnologias da informação e comunicação na área da saúde tem crescido paralelamente ao avanço tecnológico. Por meio de pesquisa exploratória, descritiva, transversal e de abordagem quantitativa, objetivou-se identificar o conhecimento e a prática de discentes e docentes de universidade pública estadual sobre captação e reprodução de imagens de pacientes atendidos durante a prática acadêmica. Participaram do estudo 200 discentes matriculados nos cursos de odontologia, medicina e enfermagem, assim como 33 docentes que ministram alguma disciplina do ciclo profissional em qualquer dos referidos cursos. A pesquisa revelou preocupação com aspectos éticos e legais referentes a captura, armazenamento e disseminação de imagens clínicas de pacientes pelos profissionais e estudantes da saúde durante o processo de ensino e aprendizagem.
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- 2020
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45. Characteristics of fungemia in a peruvian referral center: 5-year retrospective analysis
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Freddy Villanueva, Janet Veliz, Karol Canasa Calvo, Esther Bellido, Shirley Martell, Sherly Ortega, and Ines Cajamarca
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epidemiología ,tendencias ,etiología ,micosis invasivas ,candidemia ,hospitales de cáncer ,Medicine ,Medicine (General) ,R5-920 - Abstract
Retrospective descriptive study carried out to determine the characteristics of fungemia in 285 cancer patients hospitalized from 2012 to 2016 at the Instituto Nacional de Enfermedades Neoplásicas (INEN). Demographic, clinical and microbiological information was evaluated. Fungemia by C. albicans predominated in patients with solid tumors and without neutropenia, while those caused by C. tropicalis predominated in patients with hematological neoplasia and neutropenia. C. tropicalis was the agent isolated in most cases (47.0%). Fungemia increased over time in patients without neutropenia. Fungemia caused by C. albicans increases with age in patients with solid tumors without neutropenia. It is concluded that fungemia are mainly caused by C. tropicalis in patients with hematological neoplasia with neutropenia and by C. albicans in patients with solid tumors without neutropenia. In addition, fungemia in patients without neutropenia increases over time; and those caused by C. albicans increase with age in patients with solid tumors without neutropenia.
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- 2020
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46. Corrigendum: Associations of Delay in Doctor Consultation With COVID-19 Related Fear, Attention to Information, and Fact-Checking
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Agnes Yuen-Kwan Lai, Shirley Man-Man Sit, Socrates Yong-Da Wu, Man-Ping Wang, Bonny Yee-Man Wong, Sai-Yin Ho, and Tai-Hing Lam
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COVID-19 ,coronavirus ,infodemic ,infodemiology ,delay in doctor consultation ,patient delay ,Public aspects of medicine ,RA1-1270 - Published
- 2022
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47. Detection of porcine enteric viruses (Kobuvirus, Mamastrovirus and Sapelovirus) in domestic pigs in Corsica, France.
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Lisandru Capai, Géraldine Piorkowski, Oscar Maestrini, François Casabianca, Shirley Masse, Xavier de Lamballerie, Rémi N Charrel, and Alessandra Falchi
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Medicine ,Science - Abstract
Many enteric viruses are found in pig farms around the world and can cause death of animals or important production losses for breeders. Among the wide spectrum of enteric viral species, porcine Sapelovirus (PSV), porcine Kobuvirus (PKoV) and porcine Astrovirus (PAstV) are frequently found in pig feces. In this study we investigated sixteen pig farms in Corsica, France, to evaluate the circulation of three enteric viruses (PKoV, PAstV-1 and PSV). In addition to the three viruses studied by RT-qPCR (908 pig feces samples), 26 stool samples were tested using the Next Generation Sequencing method (NGS). Our results showed viral RNA detection rates (i) of 62.0% [58.7-65.1] (n = 563/908) for PSV, (ii) of 44.8% [41.5-48.1] (n = 407/908) for PKoV and (iii) of 8.6% [6.8-10.6] (n = 78/908) for PAstV-1. Significant differences were observed for all three viruses according to age (P-value = 2.4e-13 for PAstV-1; 2.4e-12 for PKoV and 0.005 for PSV). The type of breeding was significantly associated with RNA detection only for PAstV-1 (P-value = 9.6e-6). Among the 26 samples tested with NGS method, consensus sequences corresponding to 10 different species of virus were detected. This study provides first insight on the presence of three common porcine enteric viruses in France. We also showed that they are frequently encountered in pigs born and bred in Corsica, which demonstrates endemic local circulation.
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- 2022
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48. Abstract 207: Dual targeting of DLL4 and VEGF signaling by a novel bispecific antibody inhibits tumor growth and reduces cancer stem cell frequency
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Jalpa Shah, Jennifer Cain, Christopher J. Bond, Fumiko Takada Axelrod, John Lewicki, Timothy Hoey, Austin L. Gurney, Rene Meisner, Marcus Fischer, Cecile Chartier, Janak Raval, Wan-Ching Yen, and Shirley Ma
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Cancer Research ,Bispecific monoclonal antibody ,biology ,Angiogenesis ,business.industry ,Cancer ,medicine.disease ,Vascular endothelial growth factor ,Endothelial stem cell ,chemistry.chemical_compound ,Oncology ,chemistry ,In vivo ,Cancer stem cell ,Immunology ,cardiovascular system ,medicine ,Cancer research ,biology.protein ,Antibody ,business - Abstract
Both Notch/Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) pathways play a critical role in angiogenesis and tumor growth. Due to differential regulatory effects of VEGF and DLL4 on the vasculature, inhibition of DLL4 or VEGF inhibits tumor growth by distinct mechanisms: anti-DLL4 treatment induces an abnormal increase of poorly perfused blood vessels, which results in a nonproductive angiogenesis unable to support tumor growth, whereas the anti-VEGF therapy significantly decreases vasculature reducing the blood supply to tumors. We have recently developed a high binding affinity bispecific monoclonal antibody that targets both human DLL4 and human VEGF. In vitro, this antibody exhibited nanomolar affinity to hVEGF and hDLL4, and reduced HUVEC proliferation induced by VEGF. The bispecific antibody demonstrated significant in vivo anti-tumor efficacy in various solid tumors, delayed tumor recurrence following termination of chemotherapy, and decreased the frequency of tumor initiating cells. Analysis of tumor vasculature after treatment with anti-DLL4/VEGF revealed inhibition of vascular gene expression and endothelial cell proliferation, indicating that the anti-VEGF effect on the vasculature is dominant over the anti-DLL4 effect. Notably, at doses where both anti-DLL4 and anti-VEGF alone produced suboptimal anti-tumor effect, dual targeting resulted in additive tumor growth inhibition. These results indicate that our bispecific anti-DLL4/VEGF is broadly efficacious and may be useful for treatment of a variety of solid tumors. Citation Format: Wan-Ching Yen, Fumiko Axelrod, Chris Bond, Jennifer Cain, Cecile Chartier, Marcus Fischer, Shirley Ma, Rene Meisner, Janak Raval, Jalpa Shah, Austin Gurney, John Lewicki, Timothy Hoey. Dual targeting of DLL4 and VEGF signaling by a novel bispecific antibody inhibits tumor growth and reduces cancer stem cell frequency. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 207. doi:10.1158/1538-7445.AM2014-207
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- 2014
49. A Phenomenological Study on the Positive and Negative Experiences of Chinese International University Students From Hong Kong Studying in the U.K. and U.S. in the Early Stage of the COVID-19 Pandemic
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Agnes Yuen-kwan Lai, Shirley Man-man Sit, Stanley Kam-ki Lam, Asa Ching-man Choi, Denise Yee-shan Yiu, Theresa Tze-kwan Lai, Mary Sau-man Ip, and Tai-hing Lam
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stress ,coping ,university students ,international ,positive and negative experience ,phenomenological study ,Psychiatry ,RC435-571 - Abstract
Background: The COVID-19 pandemic has caused distress in students globally. The mental health of international students studying abroad has been neglected during the COVID-19 pandemic, especially Chinese students who have been unfairly targeted.Objective: To explore and document the positive and negative experiences of a group of Hong Kong Chinese international students studying in the U.K. and U.S. from an insider perspective in the early stage of the COVID-19 pandemic.Methods: The qualitative study used four 1.5-h online focus group interviews of 20 Chinese international students from Hong Kong aged 18 or older studying in universities in the United Kingdom or the United States, from 3 May to 12 May 2020. A framework approach with a semi-structured interview guide was used to reflect students' stressors, cognitive appraisals, coping, and outcomes (negative impacts and positive gains), in the early stages of COVID-19. Different strategies were used to ensure the credibility, dependability, confirmability, and transferability of the study. Transcripts were analyzed using qualitative thematic content analysis.Results: Twenty full-time international University students (60% female, 90% aged 18–25 years and 65% undergraduates) were recruited. Students reported (i) stress from personal (e.g., worries about health and academic attainment), interpersonal (e.g., perceived prejudice and lack of social support), and environmental factors (e.g., uncertainties about academic programme and unclear COVID-19-related information); (ii) significant differences in culture and cognitive appraisal in the levels of perceived susceptibility and severity; (iii) positive thinking and using alternative measures in meeting challenges, which included effective emotion and problem coping strategies, and the importance of support from family, friends and schools; and (iv) negative psychological impact (e.g., worries and stress) and positive personal growth in crisis management and gains in family relationships.Conclusions: With the rise in sinophobia and uncertain developments of the pandemic, proactive support from government and academic institutions are urgently needed to reduce stress and promote the well-being of international students, especially Chinese students in the U.K. and U.S. Clear information, public education and policies related to the pandemic, appropriate academic arrangements from universities and strong support systems play important roles in maintaining students' psychological health.Clinical Trial Registration: The study was registered with the National Institutes of Health (https://clinicaltrials.gov/, identifier: NCT04365361).
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- 2021
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50. Associations of Delay in Doctor Consultation With COVID-19 Related Fear, Attention to Information, and Fact-Checking
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Agnes Yuen-Kwan Lai, Shirley Man-Man Sit, Socrates Yong-Da Wu, Man-Ping Wang, Bonny Yee-Man Wong, Sai-Yin Ho, and Tai-Hing Lam
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COVID-19 ,coronavirus ,infodemic ,infodemiology ,delay in doctor consultation ,patient delay ,Public aspects of medicine ,RA1-1270 - Abstract
Background: Delaying doctor consultation is harmful. Fear of COVID-19 leads to delays in seeking medical care at a time when pandemic information overflows. However, little is known about the role of COVID-19 related fear, attention to information, and fact-checking in such delay.Objective: Under the Hong Kong Jockey Club SMART Family-Link Project, we examined the associations of delay in doctor consultation amidst the pandemic with sociodemographic characteristics, COVID-19 related fear, attention to information, and fact-checking.Methods: We conducted a population-based online cross-sectional survey in May 2020 on Hong Kong Chinese adults. Respondents reported whether the pandemic caused any delay in doctor consultation (yes/no), level of COVID-19 related fear, attention to information and fact-checking (all on a scale of 0 to 10 and recoded into tertiles of low, moderate, high). Regression analyses were used to examine the associations of delay and fear with sociodemographic characteristics, attention and fact-checking, adjusting for covariates. Data were weighted by sex, age and education level of the population.Results: Of 4,551 respondents (46.5% male, 59.7% aged over 45 years), 10.1% reported delay in doctor consultation. The mean score was 6.4 for fear, 8.0 for attention and 7.4 for fact-checking. Delay was more common in males and increased with age and fear. High vs. low level of fear was associated with delay [adjusted odd ratios (AOR) 2.68, 95% confidence interval (CI) 2.08, 3.47]. Moderate level of fact-checking was negatively associated with delay (AOR 0.72, 95% CI 0.56, 0.92). Females reported greater fear and fear decreased with age. Fear increased with attention to information and decreased with fact-checking. Fear substantially mediated the association of delay with attention (96%) and fact-checking (30%).Conclusions: We have first shown that delay in doctor consultation increased with fear of COVID-19 and decreased with fact-checking amidst the pandemic. Fear also increased with attention to COVID-19 related information and decreased with fact-checking. Understanding these associations can help policymakers develop targeted communication and support to the public to reduce delayed doctor consultations and the associated COVID-19-related or unrelated morbidity and mortality in the community.
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- 2021
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